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Sample records for experimental autoimmune vasculitis

  1. Antineutrophil Cytoplasmic Antibodies, Autoimmune Neutropenia, and Vasculitis

    Science.gov (United States)

    Grayson, Peter C.; Sloan, J. Mark; Niles, John L.; Monach, Paul A.; Merkel, Peter A.

    2011-01-01

    Objectives Reports of an association between antineutrophil cytoplasmic antibodies (ANCA) and autoimmune neutropenia have rarely included cases of proven vasculitis. A case of ANCA-associated vasculitis (AAV) with recurrent neutropenia is described and relevant literature on the association between ANCA, neutropenia, and vasculitis is reviewed. Methods Longitudinal clinical assessments and laboratory findings are described in a patient with AAV and recurrent episodes of profound neutropenia from December 2008 – October 2010. A PubMed database search of the medical literature was performed for papers published from 1960 through October 2010 to identify all reported cases of ANCA and neutropenia. Results A 49 year-old man developed recurrent neutropenia, periodic fevers, arthritis, biopsy-proven cutaneous vasculitis, sensorineural hearing loss, epididymitis, and positive tests for ANCA with specificity for antibodies to both proteinase 3 and myeloperoxidase. Antineutrophil membrane antibodies were detected during an acute neutropenic phase and were not detectable in a post-recovery sample, whereas ANCA titers did not seem to correlate with neutropenia. An association between ANCA and neutropenia has been reported in 74 cases from 24 studies in the context of drug/toxin exposure, underlying autoimmune disease, or chronic neutropenia without underlying autoimmune disease. In these cases, the presence of atypical ANCA patterns and other antibodies were common; however, vasculitis was uncommon and when it occurred was usually limited to the skin and in cases of underlying toxin exposure. Conclusions ANCA is associated with autoimmune neutropenia, but systemic vasculitis rarely occurs in association with ANCA and neutropenia. The interaction between neutrophils and ANCA may provide insight into understanding both autoimmune neutropenia and AAV. PMID:21507463

  2. Vasculitis

    Science.gov (United States)

    Vasculitis is an inflammation of the blood vessels. It happens when the body's immune system attacks the ... or another disease. The cause is often unknown. Vasculitis can affect arteries, veins and capillaries. Arteries are ...

  3. A rare association of localized scleroderma type morphea, vitiligo, autoimmune hypothyroidism, pneumonitis, autoimmune thrombocytopenic purpura and central nervous system vasculitis. Case report.

    Science.gov (United States)

    Bonilla-Abadía, Fabio; Muñoz-Buitrón, Evelyn; Ochoa, Carlos D; Carrascal, Edwin; Cañas, Carlos A

    2012-12-20

    The localized scleroderma (LS) known as morphea, presents a variety of clinical manifestations that can include systemic involvement. Current classification schemes divide morphea into categories based solely on cutaneous morphology, without reference to systemic disease or autoimmune phenomena. This classification is likely incomplete. Autoimmune phenomena such as vitiligo and Hashimoto thyroiditis associated with LS have been reported in some cases suggesting an autoimmune basis. To our knowledge this is the first case of a morphea forming part of a multiple autoimmune syndrome (MAS) and presenting simultaneously with autoimmune thrombocytopenic purpura and central nervous system vasculitis. We report an uncommon case of a white 53 year old female patient with LS as part of a multiple autoimmune syndrome associated with pneumonitis, autoimmune thrombocytopenic purpura and central nervous system vasculitis presenting a favorable response with thrombopoietin receptor agonists, pulses of methylprednisolone and cyclophosphamide. Is likely that LS have an autoimmune origin and in this case becomes part of MAS, which consist on the presence of three or more well-defined autoimmune diseases in a single patient.

  4. A rare association of localized scleroderma type morphea, vitiligo, autoimmune hypothyroidism, pneumonitis, autoimmune thrombocytopenic purpura and central nervous system vasculitis. Case report

    Directory of Open Access Journals (Sweden)

    Bonilla-Abadía Fabio

    2012-12-01

    Full Text Available Abstract Background The localized scleroderma (LS known as morphea, presents a variety of clinical manifestations that can include systemic involvement. Current classification schemes divide morphea into categories based solely on cutaneous morphology, without reference to systemic disease or autoimmune phenomena. This classification is likely incomplete. Autoimmune phenomena such as vitiligo and Hashimoto thyroiditis associated with LS have been reported in some cases suggesting an autoimmune basis. To our knowledge this is the first case of a morphea forming part of a multiple autoimmune syndrome (MAS and presenting simultaneously with autoimmune thrombocytopenic purpura and central nervous system vasculitis. Case presentation We report an uncommon case of a white 53 year old female patient with LS as part of a multiple autoimmune syndrome associated with pneumonitis, autoimmune thrombocytopenic purpura and central nervous system vasculitis presenting a favorable response with thrombopoietin receptor agonists, pulses of methylprednisolone and cyclophosphamide. Conclusion Is likely that LS have an autoimmune origin and in this case becomes part of MAS, which consist on the presence of three or more well-defined autoimmune diseases in a single patient.

  5. [Humoral immune diseases: Cutaneous vasculitis and auto-immune bullous dermatoses].

    Science.gov (United States)

    Wechsler, Janine

    2018-02-01

    Humoral immunity is the cause of multiple diseases related to antibodies (IgA, IgG, IgM) produced by the patient. Two groups of diseases are identified. The first group is related to circulating antigen-antibody complexes. The antigens are various. They are often unknown. These immune complexes cause a vascular inflammation due to the complement fixation. Consequently, this group is dominated by inflammatory vasculitis. In the second group, the pathology is due to the fixation in situ of antibodies to a target antigen of the skin that is no more recognized by the patient. This group is represented by the auto-immune bullous dermatoses. Copyright © 2017. Published by Elsevier Masson SAS.

  6. Interferon-¿ regulates oxidative stress during experimental autoimmune encephalomyelitis

    DEFF Research Database (Denmark)

    Espejo, C.; Penkowa, Milena; Saez-Torres, I.

    2002-01-01

    Neurobiology, experimental autoimmune encephalomyelitis IFN-d, multiple sclerosis, neurodegeneration, oxidative stress......Neurobiology, experimental autoimmune encephalomyelitis IFN-d, multiple sclerosis, neurodegeneration, oxidative stress...

  7. Hypersensitivity vasculitis

    Science.gov (United States)

    Cutaneous small vessel vasculitis; Allergic vasculitis; Leukocytoclastic vasculitis ... Hypersensitivity vasculitis, or cutaneous small vessel vasculitis, is caused by: An allergic reaction to a drug or other foreign ...

  8. Cerebral Vasculitis

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    Fariborz Khorvash

    2017-02-01

    protocol for cerebral vasculitis should include initial MRI to assess the degree of parenchymal damage and to detect vessel wall changes, in particular in large-vessel vasculitis. If the results are ambiguous or medium-sized arteries are affected (beyond the spatial resolution of MRI DSA should follow. Small-vessel vasculitides entirely evade detection by vascular imaging and consequently require brain or leptomeningeal biopsy . Exclusion of differential diagnoses: Important differential diagnoses include RCVS,  intracranial atherosclerosis Moyamoy disease, autoimmune encephalopathies and infectious disorder such as varicella zoster virus (VZV vasculopathies or endocarditis. Therapy: Vasculitis is a serious disease that is potentially fatal or leads to permanent disability and requires rapid institution of immunosuppressive treatment. Possible therapeutic options include glucocorticoids, cyclophosphamide, azathioprine, intravenous immunoglobulins and mycophenolate mofetil.

  9. Proteinase 3 on apoptotic cells disrupts immune silencing in autoimmune vasculitis

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    Millet, Arnaud; Martin, Katherine R.; Bonnefoy, Francis; Saas, Philippe; Mocek, Julie; Alkan, Manal; Terrier, Benjamin; Kerstein, Anja; Tamassia, Nicola; Satyanarayanan, Senthil Kumaran; Ariel, Amiram; Ribeil, Jean-Antoine; Guillevin, Loïc; Cassatella, Marco A.; Mueller, Antje; Thieblemont, Nathalie; Lamprecht, Peter; Mouthon, Luc; Perruche, Sylvain; Witko-Sarsat, Véronique

    2015-01-01

    Granulomatosis with polyangiitis (GPA) is a systemic necrotizing vasculitis that is associated with granulomatous inflammation and the presence of anti-neutrophil cytoplasmic antibodies (ANCAs) directed against proteinase 3 (PR3). We previously determined that PR3 on the surface of apoptotic neutrophils interferes with induction of antiinflammatory mechanisms following phagocytosis of these cells by macrophages. Here, we demonstrate that enzymatically active membrane-associated PR3 on apoptotic cells triggered secretion of inflammatory cytokines, including granulocyte CSF (G-CSF) and chemokines. This response required the IL-1R1/MyD88 signaling pathway and was dependent on the synthesis of NO, as macrophages from animals lacking these pathways did not exhibit a PR3-associated proinflammatory response. The PR3-induced microenvironment facilitated recruitment of inflammatory cells, such as macrophages, plasmacytoid DCs (pDCs), and neutrophils, which were observed in close proximity within granulomatous lesions in the lungs of GPA patients. In different murine models of apoptotic cell injection, the PR3-induced microenvironment instructed pDC-driven Th9/Th2 cell generation. Concomitant injection of anti-PR3 ANCAs with PR3-expressing apoptotic cells induced a Th17 response, revealing a GPA-specific mechanism of immune polarization. Accordingly, circulating CD4+ T cells from GPA patients had a skewed distribution of Th9/Th2/Th17. These results reveal that PR3 disrupts immune silencing associated with clearance of apoptotic neutrophils and provide insight into how PR3 and PR3-targeting ANCAs promote GPA pathophysiology. PMID:26436651

  10. Experimental models of autoimmune inflammatory ocular diseases

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    Fabio Gasparin

    2012-04-01

    Full Text Available Ocular inflammation is one of the leading causes of blindness and loss of vision. Human uveitis is a complex and heterogeneous group of diseases characterized by inflammation of intraocular tissues. The eye may be the only organ involved, or uveitis may be part of a systemic disease. A significant number of cases are of unknown etiology and are labeled idiopathic. Animal models have been developed to the study of the physiopathogenesis of autoimmune uveitis due to the difficulty in obtaining human eye inflamed tissues for experiments. Most of those models are induced by injection of specific photoreceptors proteins (e.g., S-antigen, interphotoreceptor retinoid-binding protein, rhodopsin, recoverin, phosducin. Non-retinal antigens, including melanin-associated proteins and myelin basic protein, are also good inducers of uveitis in animals. Understanding the basic mechanisms and pathogenesis of autoimmune ocular diseases are essential for the development of new treatment approaches and therapeutic agents. The present review describes the main experimental models of autoimmune ocular inflammatory diseases.

  11. A rare association of localized scleroderma type morphea, vitiligo, autoimmune hypothyroidism, pneumonitis, autoimmune thrombocytopenic purpura and central nervous system vasculitis. Case report.

    OpenAIRE

    Bonilla Abadía, Fabio; Muñoz Buitrón, Evelyn; Ochoa, Carlos D.; Carrascal, Edwin; Cañas Dávila, Carlos Alberto

    2012-01-01

    The localized scleroderma (LS) known as morphea, presents a variety of clinical manifestations that can include systemic involvement. Current classification schemes divide morphea into categories based solely on cutaneous morphology, without reference to systemic disease or autoimmune phenomena. This classification is likely incomplete. Autoimmune phenomena such as vitiligo and Hashimoto thyroiditis associated with LS have been reported in some cases suggesting an autoimmune basis. To our kno...

  12. Establishment of a vascular endothelial cell-reactive type II NKT cell clone from a rat model of autoimmune vasculitis.

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    Iinuma, Chihiro; Waki, Masashi; Kawakami, Ai; Yamaguchi, Madoka; Tomaru, Utano; Sasaki, Naomi; Masuda, Sakiko; Matsui, Yuki; Iwasaki, Sari; Baba, Tomohisa; Kasahara, Masanori; Yoshiki, Takashi; Paletta, Daniel; Herrmann, Thomas; Ishizu, Akihiro

    2015-02-01

    We previously generated a rat model that spontaneously developed small vessel vasculitis (SVV). In this study, a T cell clone reactive with rat vascular endothelial cells (REC) was established and named VASC-1. Intravenous injection of VASC-1 induced SVV in normal recipients. VASC-1 was a TCRαβ/CD3-positive CD4/CD8 double-negative T cell clone with expression of NKG2D. The cytokine mRNA profile under unstimulated condition was positive for IL-4 and IFN-γ but negative for IL-2 and IL-10. After interaction with REC, the mRNA expression of IL-2, IL-5 and IL-6 was induced in VASC-1, which was inhibited by blocking of CD1d on the REC surface. Although the protein levels of these cytokines seemed to be lower than the detection limit in the culture medium, IFN-γ was detectable. The production of IFN-γ from the VASC-1 stimulated with LPS-pre-treated REC was inhibited by the CD1d blockade on the REC. These findings indicated VASC-1 as an NKT cell clone. The NKT cell pool includes two major subsets, namely types I and II. Type I NKT cells are characterized by expression of semi-invariant TCRs and the potential to bind to marine sponge-derived α-galactosylceramide (α-GalCer) loaded on CD1d; whereas, type II NKT cells do not manifest these characteristics. VASC-1 exhibited a usage of TCR other than the type I invariant TCR α chain and did not bind to α-GalCer-loaded CD1d; therefore, it was determined as a type II NKT cell clone. The collective evidence suggested that REC-reactive type II NKT cells could be involved in the pathogenesis of SVV in rats. © The Japanese Society for Immunology. 2014. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  13. T cells in multiple sclerosis and experimental autoimmune encephalomyelitis.

    LENUS (Irish Health Repository)

    Fletcher, J M

    2012-02-01

    Multiple sclerosis (MS) is a demyelinating inflammatory disorder of the central nervous system (CNS), which involves autoimmune responses to myelin antigens. Studies in experimental autoimmune encephalomyelitis (EAE), an animal model for MS, have provided convincing evidence that T cells specific for self-antigens mediate pathology in these diseases. Until recently, T helper type 1 (Th1) cells were thought to be the main effector T cells responsible for the autoimmune inflammation. However more recent studies have highlighted an important pathogenic role for CD4(+) T cells that secrete interleukin (IL)-17, termed Th17, but also IL-17-secreting gammadelta T cells in EAE as well as other autoimmune and chronic inflammatory conditions. This has prompted intensive study of the induction, function and regulation of IL-17-producing T cells in MS and EAE. In this paper, we review the contribution of Th1, Th17, gammadelta, CD8(+) and regulatory T cells as well as the possible development of new therapeutic approaches for MS based on manipulating these T cell subtypes.

  14. Vasculitis in the autoinflammatory diseases.

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    Peleg, Hagit; Ben-Chetrit, Eldad

    2017-01-01

    This article addresses the prevalence and relationship between autoinflammatory diseases and vasculitis. Autoimmune diseases (AIDs) are a group of syndromes characterized by episodes of unprovoked inflammation due to dysregulation of the innate immune system. Despite the common occurrence of rashes and other skin lesions in these diseases, vasculitis is reported in only a few. On the other hand, neutrophilic dermatoses are more prevalent. Large vessel vasculitis is reported in patients with Behcet's and Blau's syndromes. Small and medium size vasculitides are reported in familial Mediterranean fever mainly as Henoch-Schonlein purpura and polyarteritis nodosa, respectively. It is rarely described in hyper IgD with periodic fever syndrome, cryopyrin associated periodic syndromes, TNF receptor-associated periodic syndrome, deficiency of interleukin-1 receptor antagonist and pyoderma gangrenosum and acne syndrome. In most AID where bones and skin are mainly involved (CRMO, Majeed syndrome, Cherubism and DITRA) - vasculitis has not been described at all. In AID small vessel vasculitis affects mainly the skin with no involvement of internal organs. In AID, neutrophilic dermatoses are more common and prominent than vasculitis. This may reflect a minor role for interleukin-1 in the pathogenesis of vasculitis. The rarity of vasculitis in AID suggests that in most reported cases its occurrence has been probably coincidental rather than being an integral feature of the disease.

  15. Livedo vasculitis Livedo vasculitis

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    RE Achenbach

    Full Text Available La livedo vasculitis representa un patrón de respuesta a múltiples causas, que confluyen en un estado procoagulante de los vasos de la dermis y subcutis superficial, resultando en úlceras dolorosas con localización en miembros inferiores y cicatrices características. Efectuamos una revisión de las múltiples sinonimias, aspectos clínicos e histológicos de tres casos, los que respondieron aceptablemente al tratamiento con pentoxifilina vía bucal.Livedo is not a specific disease, but a distinctive clinicopathologic pattern of changes, that may occur in a variety of different circunstances. The main pathogenic mechanism is considered to be intraluminal thrombosis of dermal vessels, with a common pathway and a prothrombotic state. A glossary, clinical, histological and therapeutic aspects are reviewed.

  16. Individual behavioral characteristics of wild-type rats predict susceptibility to experimental autoimmune encephalomyelitis

    NARCIS (Netherlands)

    Kavelaars, A; Heijnen, CJ; Tennekes, R; Bruggink, JE; Koolhaas, JM

    1999-01-01

    Neuroendocrine-immune interactions are thought to be important in determining susceptibility to autoimmune disease. Animal studies have revealed that differences in susceptibility to experimental autoimmune encephalomyelitis (EAE) are related to:reactivity in the hypothalamo-pituitary-adrenal axis.

  17. Costimulatory signal blockade in murine relapsing experimental autoimmune encephalomyelitis

    DEFF Research Database (Denmark)

    Schaub, M; Issazadeh-Navikas, Shohreh; Stadlbauer, T H

    1999-01-01

    Blockade of the CD28-B7 or CD40L-CD40 T cell costimulatory signals prevents induction of experimental autoimmune encephalomyelitis (EAE). However, the effect of simultaneous blockade of these signals in EAE is unknown. We show that administration of either MR1 (to block CD40L) or CTLA4Ig (to block...... B7) after immunization or after the first attack protects from EAE. Treatment with a combination of CTLA4Ig and MR1 provides additive protection, and is associated with complete absence of mononuclear cell infiltrates in the central nervous system, and marked suppression of proliferation of primed T...... cells in the periphery. Selective B7-1 blockade did not protect from EAE. These observations have implications for therapy of autoimmune diseases....

  18. Refractory vasculitis

    NARCIS (Netherlands)

    Rutgers, Bram; Kallenberg, Cees G. M.

    Refractory vasculitis occurs in 4-5% of patients with anti-neutrophil cytoplasmic antibody associated vasculitis (AAV). Differences between therapies used for refractory disease are mostly reflected in the percentages of complete and partial remissions, but also in the number of serious side

  19. Retinal Vasculitis

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    Rosenbaum, James T.; Sibley, Cailin H.; Lin, Phoebe

    2016-01-01

    Purpose of review Ophthalmologists and rheumatologists frequently miscommunicate in consulting on patients with retinal vasculitis. This report seeks to establish a common understanding of the term, retinal vasculitis, and to review recent papers on this diagnosis. Recent findings 1) The genetic basis of some rare forms of retinal vascular disease have recently been described. Identified genes include CAPN5, TREX1, and TNFAIP3; 2) Behçet’s disease is a systemic illness that is very commonly associated with occlusive retinal vasculitis; 3) retinal imaging including fluorescein angiography and other newer imaging modalities has proven crucial to the identification and characterization of retinal vasculitis and its complications; 4) although monoclonal antibodies to IL-17A or IL-1 beta failed in trials for Behçet’s disease, antibodies to TNF alpha, either infliximab or adalimumab, have demonstrated consistent benefit in managing this disease. Interferon treatment and B cell depletion therapy via rituximab may be beneficial in certain types of retinal vasculitis. Summary Retinal vasculitis is an important entity for rheumatologists to understand. Retinal vasculitis associated with Behçet’s disease responds to monoclonal antibodies that neutralize TNF, but the many other forms of non-infectious retinal vasculitis may require alternate therapeutic management. PMID:26945335

  20. Pediatric vasculitis.

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    Barut, Kenan; Sahin, Sezgin; Kasapcopur, Ozgur

    2016-01-01

    The aim of this review is to define childhood vasculitis and to highlight new causative factors and treatment modalities under the guidance of recently published studies. Childhood vasculitis is difficult to diagnose because of the wide variation in the symptoms and signs. New nomenclature and classification criteria were proposed for the diagnosis of pediatric vasculitis. Recently, progress has been made toward understanding the genetic susceptibility to pediatric vasculitis as it was in other diseases. Various radiological techniques provide great opportunities in establishing the diagnosis of pediatric vasculitis. Mild central nervous system disease can accompany Henoch-Schonlein purpura and can go unnoticed. Antineutrophilic cytoplasmic antibody-associated vasculitis is rare in children. Increased severity of the disease, subglottic stenosis, and renal disease are described more frequently among children. Biological therapies are used with success in children as in adults. Future studies, whose aims are to evaluate treatment responses, prognosis and to design guidelines for activity, and damage index of vasculitis for children are required. Henoch-Schonlein purpura and Kawasaki disease are the most frequent vasculitides of children. Experience from adult studies for treatment and prognosis are usually used because of low incidence of other vasculitides in children. Multicenter studies of pediatric vasculitis should be conducted to detail treatment responses and prognosis in children.

  1. Cerebral vasculitis

    International Nuclear Information System (INIS)

    Greenan, T.J.; Grossman, R.I.

    1990-01-01

    This paper reviews retrospectively MR, CT, and angiographic findings in patients with cerebral vasculitis in order to understand the strengths and weaknesses of the various imaging modalities, as well as the spectrum of imaging abnormalities in this disease entity. Studies were retrospectively reviewed in 12 patients with cerebral vasculitis proved by means of angiography and/or brain biopsy

  2. Vasculitis mimics.

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    Molloy, Eamonn S; Langford, Carol A

    2008-01-01

    There are many disorders that may closely resemble the clinical, radiologic and/or pathologic features of the primary vasculitides. In this review, we focus on recently described and under-recognized syndromes that may mimic vasculitis. Hereditary causes of large-artery aneurysms such as Marfan's syndrome have long been recognized; recent years have seen a greater understanding of the genetics of Marfan's and other such disorders, including Loeys-Dietz syndrome and Ehler-Danlos syndrome type IV. Under-recognized mimics of medium-vessel vasculitis include segmental arterial mediolysis and Grange syndrome. A large number of entities can mimic small-vessel vasculitis. Recent descriptions of antibodies to human neutrophil elastase have provided insight into the occurrence of antineutrophil cytoplasmic antibodies in cocaine-induced midline destructive lesions. The differential diagnosis of cerebral vasculitis can be particularly difficult. Reversible cerebral vasoconstriction syndromes represent an important class of entities that can readily mimic cerebral vasculitis but have a very different management approach and outcome. The diagnosis of vasculitis requires careful assessment of all available clinical, laboratory, radiologic and pathologic information, and consideration of many competing differential diagnoses. Awareness of noninflammatory mimics of vasculitis is essential to avoid unnecessary and potentially harmful treatment with immunosuppressive agents.

  3. Retinal vasculitis.

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    Abu El-Asrar, Ahmed M; Herbort, Carl P; Tabbara, Khalid F

    2005-12-01

    Retinal vasculitis is a sight-threatening intraocular inflammation affecting the retinal vessels. It may occur as an isolated ocular condition, as a manifestation of infectious or neoplastic disorders, or in association with a systemic inflammatory disease. The search for an underlying etiology should be approached in a multidisciplinary fashion based on a thorough history, review of systems, physical examination, and laboratory evaluation. Discrimination between infectious and noninfectious etiologies of retinal vasculitis is important because their treatment is different. This review is based on recently published articles on retinal vasculitis and deals with its clinical diagnosis, its link with systemic diseases, and its laboratory investigation.

  4. Urticarial Vasculitis

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    ... Our Board Our Team Anniversary Vasculitis Foundation Newsletters Annual Reports Press Page Literature Order Form Join Contact Us Awareness Donate Donate Support the VF Through the Amazon Smile Program United Way Giving Ways to Give ...

  5. Hypersensitivity Vasculitis

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    ... Our Board Our Team Anniversary Vasculitis Foundation Newsletters Annual Reports Press Page Literature Order Form Join Contact Us Awareness Donate Donate Support the VF Through the Amazon Smile Program United Way Giving Ways to Give ...

  6. Vasculitis Foundation

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    ... Our Board Our Team Anniversary Vasculitis Foundation Newsletters Annual Reports Press Page Literature Order Form Join Contact Us Dream Big Donate Donate Support the VF Through the Amazon Smile Program United Way Giving Ways to Give ...

  7. Central Nervous System Vasculitis

    Science.gov (United States)

    ... of Vasculitis / Central Nervous System (CNS) Vasculitis Central Nervous System (CNS) Vasculitis Swap out your current Facebook Profile ... Facebook personal page. Replace with this image. Central nervous system (CNS) vasculitis is inflammation of blood vessel walls ...

  8. IL17 Mediates Pelvic Pain in Experimental Autoimmune Prostatitis (EAP.

    Directory of Open Access Journals (Sweden)

    Stephen F Murphy

    Full Text Available Chronic pelvic pain syndrome (CPPS is the most common form of prostatitis, accounting for 90-95% of all diagnoses. It is a complex multi-symptom syndrome with unknown etiology and limited effective treatments. Previous investigations highlight roles for inflammatory mediators in disease progression by correlating levels of cytokines and chemokines with patient reported symptom scores. It is hypothesized that alteration of adaptive immune mechanisms results in autoimmunity and subsequent development of pain. Mouse models of CPPS have been developed to delineate these immune mechanisms driving pain in humans. Using the experimental autoimmune prostatitis (EAP in C57BL/6 mice model of CPPS we examined the role of CD4+T-cell subsets in the development and maintenance of prostate pain, by tactile allodynia behavioral testing and flow cytometry. In tandem with increased CD4+IL17A+ T-cells upon EAP induction, prophylactic treatment with an anti-IL17 antibody one-day prior to EAP induction prevented the onset of pelvic pain. Therapeutic blockade of IL17 did not reverse pain symptoms indicating that IL17 is essential for development but not maintenance of chronic pain in EAP. Furthermore we identified a cytokine, IL7, to be associated with increased symptom severity in CPPS patients and is increased in patient prostatic secretions and the prostates of EAP mice. IL7 is fundamental to development of IL17 producing cells and plays a role in maturation of auto-reactive T-cells, it is also associated with autoimmune disorders including multiple sclerosis and type-1 diabetes. More recently a growing body of research has pointed to IL17's role in development of neuropathic and chronic pain. This report presents novel data on the role of CD4+IL17+ T-cells in development and maintenance of pain in EAP and CPPS.

  9. IL17 Mediates Pelvic Pain in Experimental Autoimmune Prostatitis (EAP).

    Science.gov (United States)

    Murphy, Stephen F; Schaeffer, Anthony J; Done, Joseph; Wong, Larry; Bell-Cohn, Ashlee; Roman, Kenny; Cashy, John; Ohlhausen, Michelle; Thumbikat, Praveen

    2015-01-01

    Chronic pelvic pain syndrome (CPPS) is the most common form of prostatitis, accounting for 90-95% of all diagnoses. It is a complex multi-symptom syndrome with unknown etiology and limited effective treatments. Previous investigations highlight roles for inflammatory mediators in disease progression by correlating levels of cytokines and chemokines with patient reported symptom scores. It is hypothesized that alteration of adaptive immune mechanisms results in autoimmunity and subsequent development of pain. Mouse models of CPPS have been developed to delineate these immune mechanisms driving pain in humans. Using the experimental autoimmune prostatitis (EAP) in C57BL/6 mice model of CPPS we examined the role of CD4+T-cell subsets in the development and maintenance of prostate pain, by tactile allodynia behavioral testing and flow cytometry. In tandem with increased CD4+IL17A+ T-cells upon EAP induction, prophylactic treatment with an anti-IL17 antibody one-day prior to EAP induction prevented the onset of pelvic pain. Therapeutic blockade of IL17 did not reverse pain symptoms indicating that IL17 is essential for development but not maintenance of chronic pain in EAP. Furthermore we identified a cytokine, IL7, to be associated with increased symptom severity in CPPS patients and is increased in patient prostatic secretions and the prostates of EAP mice. IL7 is fundamental to development of IL17 producing cells and plays a role in maturation of auto-reactive T-cells, it is also associated with autoimmune disorders including multiple sclerosis and type-1 diabetes. More recently a growing body of research has pointed to IL17's role in development of neuropathic and chronic pain. This report presents novel data on the role of CD4+IL17+ T-cells in development and maintenance of pain in EAP and CPPS.

  10. Mononuclear cell secretome protects from experimental autoimmune myocarditis.

    Science.gov (United States)

    Hoetzenecker, Konrad; Zimmermann, Matthias; Hoetzenecker, Wolfram; Schweiger, Thomas; Kollmann, Dagmar; Mildner, Michael; Hegedus, Balazs; Mitterbauer, Andreas; Hacker, Stefan; Birner, Peter; Gabriel, Christian; Gyöngyösi, Mariann; Blyszczuk, Przemyslaw; Eriksson, Urs; Ankersmit, Hendrik Jan

    2015-03-14

    Supernatants of serum-free cultured mononuclear cells (MNC) contain a mix of immunomodulating factors (secretome), which have been shown to attenuate detrimental inflammatory responses following myocardial ischaemia. Inflammatory dilated cardiomyopathy (iDCM) is a common cause of heart failure in young patients. Experimental autoimmune myocarditis (EAM) is a CD4+ T cell-dependent model, which mirrors important pathogenic aspects of iDCM. The aim of this study was to determine the influence of MNC secretome on myocardial inflammation in the EAM model. BALB/c mice were immunized twice with an alpha myosin heavy chain peptide together with Complete Freund adjuvant. Supernatants from mouse mononuclear cells were collected, dialysed, and injected i.p. at Day 0, Day 7, or Day 14, respectively. Myocarditis severity, T cell responses, and autoantibody formation were assessed at Day 21. The impact of MNC secretome on CD4+ T cell function and viability was evaluated using in vitro proliferation and cell viability assays. A single high-dose application of MNC secretome, injected at Day 14 after the first immunization, effectively attenuated myocardial inflammation. Mechanistically, MNC secretome induced caspase-8-dependent apoptosis in autoreactive CD4+ T cells. MNC secretome abrogated myocardial inflammation in a CD4+ T cell-dependent animal model of autoimmune myocarditis. This anti-inflammatory effect of MNC secretome suggests a novel and simple potential treatment concept for inflammatory heart diseases. © The Author 2013. Published by Oxford University Press on behalf of the European Society of Cardiology.

  11. Combined short-term immunotherapy for experimental autoimmune myasthenia gravis

    International Nuclear Information System (INIS)

    Pestronk, A.; Drachman, D.B.; Teoh, R.; Adams, R.N.

    1983-01-01

    A therapeutic strategy was designed to eliminate the humoral immune response to acetylcholine receptor (AChR) in ongoing experimental autoimmune myasthenia gravis (EAMG). Rats with EAMG were treated with a protocol consisting of three components: (1) A single high dose of cyclophosphamide (200 mg/kg) was used to produce a rapid and sustained fall in the anti-AChR antibody levels by preferential destruction of antibody-producing B-lymphocytes. ''Memory'' lymphocytes were not eliminated by cyclophosphamide. (2) Irradiation (600 rads) was used to eliminate the ''memory'' cells. It eliminated the anamnestic response to a challenge with the antigen AChR. (3) Bone marrow transplantation was used to repopulate the hematopoietic system after the otherwise lethal dose of cyclophosphamide. We used bone marrow from syngeneic rats with active EAMG to simulate an autologous transplant. Rats with EAMG treated with this combined protocol showed a prompt and sustained fall in the anti-AChR antibody levels and had no anamnestic response to a challenge with AChR. Thus, an affected animal's own marrow could be stored and used later for repopulation after cyclophosphamide-irradiation treatment. This treatment eliminates the animal's ongoing immune responses and reconstitutes the immune system in its original state. The success of this approach suggests that, if their safety could be established, similar ''curative'' strategies might be developed for the treatment of patients with severe antibody-mediated autoimmune disorders, such as myasthenia gravis

  12. Vasculitis Pregnancy Registry

    Science.gov (United States)

    2018-04-30

    Vasculitis; Behcet's Disease; CNS Vasculitis; Cryoglobulinemic Vasculitis; Eosinophilic Granulomatosis With Polyangiitis (EGPA); Churg-Strauss Syndrome (CSS); Granulomatosis With Polyangiitis (GPA); Wegener's Granulomatosis; IgA Vasculitis; Henoch-Schoenlein Purpura (HSP); Microscopic Polyangiitis (MPA); Polyarteritis Nodosa (PAN); Takayasu Arteritis (TAK); Urticarial Vasculitis; Systemic Vasculitis

  13. Amelioration of ongoing experimental autoimmune encephalomyelitis with fluoxetine.

    Science.gov (United States)

    Bhat, Roopa; Mahapatra, Sidharth; Axtell, Robert C; Steinman, Lawrence

    2017-12-15

    In patients with multiple sclerosis, the selective serotonin reuptake inhibitor, fluoxetine, resulted in less acute disease activity. We tested the immune modulating effects of fluoxetine in a mouse model of multiple sclerosis, i.e. experimental autoimmune encephalomyelitis (EAE). We show that fluoxetine delayed the onset of disease and reduced clinical paralysis in mice with established disease. Fluoxetine had abrogating effects on proliferation of immune cells and inflammatory cytokine production by both antigen-presenting cells and T cells. Specifically, in CD 4 T cells, fluoxetine increased Fas-induced apoptosis. We conclude that fluoxetine possesses immune-modulating effects resulting in the amelioration of symptoms in EAE. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Combined short-term immunotherapy for experimental autoimmune myasthenia gravis

    Energy Technology Data Exchange (ETDEWEB)

    Pestronk, A.; Drachman, D.B.; Teoh, R.; Adams, R.N.

    1983-08-01

    A therapeutic strategy was designed to eliminate the humoral immune response to acetylcholine receptor (AChR) in ongoing experimental autoimmune myasthenia gravis (EAMG). Rats with EAMG were treated with a protocol consisting of three components: (1) A single high dose of cyclophosphamide (200 mg/kg) was used to produce a rapid and sustained fall in the anti-AChR antibody levels by preferential destruction of antibody-producing B-lymphocytes. ''Memory'' lymphocytes were not eliminated by cyclophosphamide. (2) Irradiation (600 rads) was used to eliminate the ''memory'' cells. It eliminated the anamnestic response to a challenge with the antigen AChR. (3) Bone marrow transplantation was used to repopulate the hematopoietic system after the otherwise lethal dose of cyclophosphamide. We used bone marrow from syngeneic rats with active EAMG to simulate an autologous transplant. Rats with EAMG treated with this combined protocol showed a prompt and sustained fall in the anti-AChR antibody levels and had no anamnestic response to a challenge with AChR. Thus, an affected animal's own marrow could be stored and used later for repopulation after cyclophosphamide-irradiation treatment. This treatment eliminates the animal's ongoing immune responses and reconstitutes the immune system in its original state. The success of this approach suggests that, if their safety could be established, similar ''curative'' strategies might be developed for the treatment of patients with severe antibody-mediated autoimmune disorders, such as myasthenia gravis.

  15. R-flurbiprofen attenuates experimental autoimmune encephalomyelitis in mice.

    Science.gov (United States)

    Schmitz, Katja; de Bruin, Natasja; Bishay, Philipp; Männich, Julia; Häussler, Annett; Altmann, Christine; Ferreirós, Nerea; Lötsch, Jörn; Ultsch, Alfred; Parnham, Michael J; Geisslinger, Gerd; Tegeder, Irmgard

    2014-11-01

    R-flurbiprofen is the non-cyclooxygenase inhibiting R-enantiomer of the non-steroidal anti-inflammatory drug flurbiprofen, which was assessed as a remedy for Alzheimer's disease. Because of its anti-inflammatory, endocannabinoid-modulating and antioxidative properties, combined with low toxicity, the present study assessed R-flurbiprofen in experimental autoimmune encephalomyelitis (EAE) models of multiple sclerosis in mice. Oral R-flurbiprofen prevented and attenuated primary progressive EAE in C57BL6/J mice and relapsing-remitting EAE in SJL mice, even if the treatment was initiated on or after the first flare of the disease. R-flurbiprofen reduced immune cell infiltration and microglia activation and inflammation in the spinal cord, brain and optic nerve and attenuated myelin destruction and EAE-evoked hyperalgesia. R-flurbiprofen treatment increased CD4(+)CD25(+)FoxP3(+) regulatory T cells, CTLA4(+) inhibitory T cells and interleukin-10, whereas the EAE-evoked upregulation of pro-inflammatory genes in the spinal cord was strongly reduced. The effects were associated with an increase of plasma and cortical endocannabinoids but decreased spinal prostaglandins, the latter likely due to R to S inversion. The promising results suggest potential efficacy of R-flurbiprofen in human MS, and its low toxicity may justify a clinical trial. © 2014 The Authors. Published under the terms of the CC BY 4.0 license.

  16. Hydroxychloroquine reduces microglial activity and attenuates experimental autoimmune encephalomyelitis.

    Science.gov (United States)

    Koch, Marcus W; Zabad, Rana; Giuliani, Fabrizio; Hader, Walter; Lewkonia, Ray; Metz, Luanne; Wee Yong, V

    2015-11-15

    Microglial activation is thought to be a key pathophysiological mechanism underlying disease activity in all forms of MS. Hydroxychloroquine (HCQ) is an antimalarial drug with immunomodulatory properties that is widely used in the treatment of rheumatological diseases. In this series of experiments, we explore the effect of HCQ on human microglial activation in vitro and on the development of experimental autoimmune encephalitis (EAE) in vivo. We activated human microglia with lipopolysaccharide (LPS), and measured concentrations of several pro- and anti-inflammatory cytokines in untreated and HCQ pretreated cultures. We investigated the effect of HCQ pretreatment at two doses on the development of EAE and spinal cord histology. HCQ pretreatment reduced the production of pro-inflammatory (TNF-alpha, IL-6, and IL-12) and anti-inflammatory (IL-10 and IL-1 receptor antagonist) cytokines in LPS-stimulated human microglia. HCQ pretreatment delayed the onset of EAE, and reduced the number of Iba-1 positive microglia/macrophages and signs of demyelination in the spinal cords of HCQ treated animals. HCQ treatment reduces the activation of human microglia in vitro, delays the onset of EAE, and decreases the representation of activated macrophages/microglia and demyelination in the spinal cord of treated mice. HCQ is a plausible candidate for further clinical studies in MS. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. Pediatric Vasculitis Initiative

    Science.gov (United States)

    2017-05-01

    Wegeners Granulomatosis (Granulomatosis With Polyangiitis); Microscopic Polyangiitis; Churg Strauss Syndrome (Eosinophilic Granulomatosis With Polyangiitis); Polyarteritis Nodosa; Takayasu Arteritis; Primary CNS Vasculitis; Unclassified Vasculitis

  18. Vasculitis and inflammatory arthritis.

    Science.gov (United States)

    Watts, Richard A; Scott, David G I

    2016-10-01

    Vasculitis has been described in most types of inflammatory arthritis. The best described and most widely recognised form is rheumatoid vasculitis. The incidence of systemic rheumatoid vasculitis has declined significantly following the general early use of methotrexate in the 1990s, and it is now a rare form of vasculitis. Treatment of rheumatoid vasculitis is conventionally with glucocorticoids and cyclophosphamide, but there is an increasing role for rituximab similar to that in other types of vasculitis. Despite these developments the mortality of rheumatoid vasculitis remains high. Vasculitis in other types of inflammatory arthritis is less well described and the treatment remains empirical. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. Oral delivery of ACE2/Ang-(1-7) bioencapsulated in plant cells protects against experimental uveitis and autoimmune uveoretinitis.

    Science.gov (United States)

    Shil, Pollob K; Kwon, Kwang-Chul; Zhu, Ping; Verma, Amrisha; Daniell, Henry; Li, Qiuhong

    2014-12-01

    Hyperactivity of the renin-angiotensin system (RAS) resulting in elevated Angiotensin II (Ang II) contributes to all stages of inflammatory responses including ocular inflammation. The discovery of angiotensin-converting enzyme 2 (ACE2) has established a protective axis of RAS involving ACE2/Ang-(1-7)/Mas that counteracts the proinflammatory and hypertrophic effects of the deleterious ACE/AngII/AT1R axis. Here we investigated the hypothesis that enhancing the systemic and local activity of the protective axis of the RAS by oral delivery of ACE2 and Ang-(1-7) bioencapsulated in plant cells would confer protection against ocular inflammation. Both ACE2 and Ang-(1-7), fused with the non-toxic cholera toxin subunit B (CTB) were expressed in plant chloroplasts. Increased levels of ACE2 and Ang-(1-7) were observed in circulation and retina after oral administration of CTB-ACE2 and Ang-(1-7) expressing plant cells. Oral feeding of mice with bioencapsulated ACE2/Ang-(1-7) significantly reduced endotoxin-induced uveitis (EIU) in mice. Treatment with bioencapsulated ACE2/Ang-(1-7) also dramatically decreased cellular infiltration, retinal vasculitis, damage and folding in experimental autoimmune uveoretinitis (EAU). Thus, enhancing the protective axis of RAS by oral delivery of ACE2/Ang-(1-7) bioencapsulated in plant cells provide an innovative, highly efficient and cost-effective therapeutic strategy for ocular inflammatory diseases.

  20. Experimental autoimmune prostatitis induces microglial activation in the spinal cord.

    Science.gov (United States)

    Wong, Larry; Done, Joseph D; Schaeffer, Anthony J; Thumbikat, Praveen

    2015-01-01

    The pathogenesis of chronic prostatitis/chronic pelvic pain syndrome is unknown and factors including the host's immune response and the nervous system have been attributed to the development of CP/CPPS. We previously demonstrated that mast cells and chemokines such as CCL2 and CCL3 play an important role in mediating prostatitis. Here, we examined the role of neuroinflammation and microglia in the CNS in the development of chronic pelvic pain. Experimental autoimmune prostatitis (EAP) was induced using a subcutaneous injection of rat prostate antigen. Sacral spinal cord tissue (segments S14-S5) was isolated and utilized for immunofluorescence or QRT-PCR analysis. Tactile allodynia was measured at baseline and at various points during EAP using Von Frey fibers as a function for pelvic pain. EAP mice were treated with minocycline after 30 days of prostatitis to test the efficacy of microglial inhibition on pelvic pain. Prostatitis induced the expansion and activation of microglia and the development of inflammation in the spinal cord as determined by increased expression levels of CCL3, IL-1β, Iba1, and ERK1/2 phosphorylation. Microglial activation in mice with prostatitis resulted in increased expression of P2X4R and elevated levels of BDNF, two molecular markers associated with chronic pain. Pharmacological inhibition of microglia alleviated pain in mice with prostatitis and resulted in decreased expression of IL-1β, P2X4R, and BDNF. Our data show that prostatitis leads to inflammation in the spinal cord and the activation and expansion of microglia, mechanisms that may contribute to the development and maintenance of chronic pelvic pain. © 2014 Wiley Periodicals, Inc.

  1. Chondroitin 6-O-sulfate ameliorates experimental autoimmune encephalomyelitis.

    Science.gov (United States)

    Miyamoto, Katsuichi; Tanaka, Noriko; Moriguchi, Kota; Ueno, Rino; Kadomatsu, Kenji; Kitagawa, Hiroshi; Kusunoki, Susumu

    2014-05-01

    Chondroitin sulfate proteoglycans (CSPGs) are the main component of the extracellular matrix in the central nervous system (CNS) and influence neuroplasticity. Although CSPG is considered an inhibitory factor for nerve repair in spinal cord injury, it is unclear whether CSPG influences the pathogenetic mechanisms of neuroimmunological diseases. We induced experimental autoimmune encephalomyelitis (EAE) in chondroitin 6-O-sulfate transferase 1-deficient (C6st1(-/-)) mice. C6ST1 is the enzyme that transfers sulfate residues to position 6 of N-acetylgalactosamine in the sugar chain of CSPG. The phenotypes of EAE in C6st1(-/-) mice were more severe than those in wild-type (WT) mice were. In adoptive-transfer EAE, in which antigen-reactive T cells from WT mice were transferred to C6st1(-/-) and WT mice, phenotypes were significantly more severe in C6st1(-/-) than in WT mice. The recall response of antigen-reactive T cells was not significantly different among the groups. Furthermore, the number of pathogenic T cells within the CNS was also not considerably different. When EAE was induced in C6ST1 transgenic mice with C6ST1 overexpression, the mice showed considerably milder symptoms compared with those in WT mice. In conclusion, the presence of sulfate at position 6 of N-acetylgalactosamine of CSPG may influence the effecter phase of EAE to prevent the progression of pathogenesis. Thus, modification of the carbohydrate residue of CSPG may be a novel therapeutic strategy for neuroimmunological diseases such as multiple sclerosis.

  2. Ageing and recurrent episodes of neuroinflammation promote progressive experimental autoimmune encephalomyelitis in Biozzi ABH mice

    NARCIS (Netherlands)

    Peferoen, Laura A. N.; Breur, Marjolein; van de Berg, Sarah; Peferoen-Baert, Regina; Boddeke, Erik H. W. G. M.; van der Valk, Paul; Pryce, Gareth; van Noort, Johannes M.; Baker, David; Amor, Sandra

    2016-01-01

    Current therapies for multiple sclerosis (MS) reduce the frequency of relapses by modulating adaptive immune responses but fail to limit the irreversible neurodegeneration driving progressive disability. Experimental autoimmune encephalomyelitis (EAE) in Biozzi ABH mice recapitulates clinical

  3. Minocycline Effects on the Cerebrospinal Fluid Proteome of Experimental Autoimmune Encephalomyelitis Rats

    NARCIS (Netherlands)

    Stoop, Marcel P.; Rosenling, Therese; Attali, Amos; Meesters, Roland J. W.; Stingl, Christoph; Dekker, Lennard J.; van Aken, Hans; Suidgeest, Ernst; Hintzen, Rogier Q.; Tuinstra, Tinka; van Gool, Alain; Luider, Theo M.; Bischoff, Rainer

    2012-01-01

    To identify response biomarkers for pharmaceutical treatment of multiple sclerosis, we induced experimental autoimmune encephalomyelitis (EAE) in rats and treated symptomatic animals with minocycline. Cerebrospinal fluid (CSF) samples were collected 14 days after EAE induction at the peak of

  4. Minocycline effects on the cerebrospinal fluid proteome of experimental autoimmune encephalomyelitis rats

    NARCIS (Netherlands)

    Stoop, M.P.; Rosenling, T.; Attali, A.; Meesters, R.J.; Stingl, C.; Dekker, L.J.; van Aken, H.; Suidgeest, E.; Hintzen, R.Q.; Tuinstra, T.; Gool, A.J. van; Luider, T.M.; Bischoff, R.

    2012-01-01

    To identify response biomarkers for pharmaceutical treatment of multiple sclerosis, we induced experimental autoimmune encephalomyelitis (EAE) in rats and treated symptomatic animals with minocycline. Cerebrospinal fluid (CSF) samples were collected 14 days after EAE induction at the peak of

  5. Cryoglobulinemia Vasculitis.

    Science.gov (United States)

    Cacoub, Patrice; Comarmond, Cloe; Domont, Fanny; Savey, Léa; Saadoun, David

    2015-09-01

    Cryoglobulinemic vasculitis (CryoVas) is a small-vessel vasculitis involving mainly the skin, the joints, the peripheral nervous system, and the kidneys. Type I CryoVas is single monoclonal immunoglobulins related to an underlying B-cell lymphoproliferative disorder. Type II and III cryoglobulins, often referred to as mixed cryoglobulinemia, consist of polyclonal immunoglobulin (Ig)G with or without monoclonal IgM with rheumatoid factor activity. Hepatitis C virus (HCV) infection represents the main cause of mixed CryoVas. The 10-year survival rates are 63%, 65%, and 87% in HCV-positive mixed CryoVas, HCV-negative mixed CryoVas, and type I CryoVas patients, respectively. In HCV-positive patients, baseline poor prognostic factors include the presence of severe liver fibrosis, and central nervous system, kidney, and heart involvement. Treatment with antivirals is associated with a good prognosis, whereas use of immunosuppressants (including corticosteroids) is associated with a poor outcome. In HCV-negative patients, pulmonary and gastrointestinal involvement, renal insufficiency, and age > 65 years are independently associated with death. Increased risk of lymphoma also should be underlined. Treatment of type I CryoVas is that of the hemopathy; specific treatment also includes plasma exchange, corticosteroids, rituximab, and ilomedine. In HCV-CryoVas with mild-to-moderate disease, an optimal antiviral treatment should be given. For HCV-CryoVas with severe vasculitis (ie, worsening of renal function, mononeuritis multiplex, extensive skin disease, intestinal ischemia…) control of disease with rituximab, with or without plasmapheresis, is required before initiation of antiviral therapy. Other immunosuppressants should be given only in case of refractory forms of CryoVas, frequently associated with underlying B-cell lymphoma. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. Beneficial role of rapamycin in experimental autoimmune myositis.

    Directory of Open Access Journals (Sweden)

    Nicolas Prevel

    Full Text Available We developed an experimental autoimmune myositis (EAM mouse model of polymyositis where we outlined the role of regulatory T (Treg cells. Rapamycin, this immunosuppressant drug used to prevent rejection in organ transplantation, is known to spare Treg. Our aim was to test the efficacy of rapamycin in vivo in this EAM model and to investigate the effects of the drug on different immune cell sub-populations.EAM is induced by 3 injections of myosin emulsified in CFA. Mice received rapamycin during 25 days starting one day before myosin immunization (preventive treatment, or during 10 days following the last myosin immunization (curative treatment.Under preventive or curative treatment, an increase of muscle strength was observed with a parallel decrease of muscle inflammation, both being well correlated (R(2 = -0.645, p<0.0001. Rapamycin induced a general decrease in muscle of CD4 and CD8 T cells in lymphoid tissues, but spared B cells. Among T cells, the frequency of Treg was increased in rapamycin treated mice in draining lymph nodes (16.9 ± 2.2% vs. 9.3 ± 1.4%, p<0.001, which were mostly activated regulatory T cells (CD62L(lowCD44(high: 58.1 ± 5.78% vs. 33.1 ± 7%, treated vs. untreated, p<0.001. In rapamycin treated mice, inhibition of proliferation (Ki-67(+ is more important in effector T cells compared to Tregs cells (p<0.05. Furthermore, during preventive treatment, rapamycin increased the levels of KLF2 transcript in CD44(low CD62L(high naive T cell and in CD62L(low CD44(high activated T cell.Rapamycin showed efficacy both as curative and preventive treatment in our murine model of experimental myositis, in which it induced an increase of muscle strength with a parallel decrease in muscle inflammation. Rapamycin administration was also associated with a decrease in the frequency of effector T cells, an increase in Tregs, and, when administered as preventive treatment, an upregulation of KFL2 in naive and activated T cells.

  7. Impact of Vasculitis on Employment and Income

    Science.gov (United States)

    2016-01-26

    Vasculitis; Systemic Vasculitis; Behcet's Disease; CNS Vasculitis; Cryoglobulinemic Vasculitis; Eosinophilic Granulomatosis; Temporal Arteritis; Wegener Granulomatosis; Henoch-Schoenlein Purpura; Microscopic Polyangiitis; Polyarteritis Nodosa (PAN); Takayasu's Arteritis; Urticarial Vasculitis

  8. Neuroprotective effects of gypenosides in experimental autoimmune optic neuritis

    Directory of Open Access Journals (Sweden)

    Hong-Kan Zhang

    2017-04-01

    Full Text Available AIM: To determine whether gypenosides have protective effects in experimental autoimmune optic neuritis (EAON. METHODS: Mice were randomly divided into seven groups: control group, model group, three different density gypenosides monotherapy, methylprednisolone monotherapy, combination of gypenosides and methylprednisolone group. The control group was subcutaneously injected with oil emulsion adjuvant and all other groups were subcutaneously immunized with an emulsified mixture of myelin oligodendrocyte glycoprotein (MOG 35-55 peptide to induce EAON. Mice in the gypenosides groups were administered injections daily with three concentrations (15 mg/kg, 30 mg/kg, 45 mg/kg of gypenosides respectively. Mice in the methylprednisolone group and the combination treatment group were injected daily with methylprednisolone (20 mg/kg or methylprednisolone (20 mg/kg + gypenosides (30 mg/kg, respectively. After MOG immunization, visual evoked potential (VEP, optical coherence tomography (OCT, and histopathologic examination were performed at 14, 20, 30, and 40d post-inoculation (p.i.. All results were expressed as mean±SEM. The data were evaluated by one-way ANOVA followed by Tukey or Games-Howell test. RESULTS: Compared with the control group, p2 latency was prolonged in the model group (P=0.041. Combination treatment can alleviated the change in VEP at 20d p.i. (P=0.012. Average peripapillary retinal nerve fiber layer (RNFL thickness was reduced in the model group (P= 0.000, 30d; P=0.000, 40d and gypenosides treatment remarkably diminished the degree of RNFL degeneration at 30d and 40d p.i (P=0.000, 30d; P=0.000, 40d. The pathomorphological results showed a decrease in demye-lination (P=0.020 and inflammatory reactions in the combination group compared with the model group (20d p.i.. Gypenosides treatment also alleviated the degree of axonal loss (40d p.i. (P=0.003. CONCLUSION: Treatment with gypenosides exerts protective effects on retinal nerve fibers

  9. Pathogenesis of pulmonary vasculitis

    NARCIS (Netherlands)

    Heeringa, P; Schreiber, A; Falk, RJ; Jennette, JC

    2004-01-01

    Vasculitis is inflammation of blood vessels and can affect any type of vessel in any organ. Pulmonary vasculitis usually is a component of a systemic small vessel vasculitis. Three major forms of small vessel vasculitis that often affect the lungs are Wegener's granulomatosis, microscopic

  10. Acute vasculitis after endovascular brachytherapy

    International Nuclear Information System (INIS)

    Fajardo L-G, Luis F.; Prionas, Stavros D.; Kaluza, Grzegorz L.; Raizner, Albert E.

    2002-01-01

    using 32 P results in vascular effects beyond the adventitia of the target vessel. This necrotizing vasculitis is causally related to radiation, but its mechanism is unclear and a dose effect is not evident. Quite possibly, local upregulation of inflammatory cytokines contributes to this radiation-associated vasculitis, which only involved some of the arterioles in each sample. It is likely that radiation-associated vasculitis also occurs around human coronary arteries and may result in foci of ischemia. To our knowledge, this lesion has not been previously recognized, either in experimental models or in human specimens examined after angioplasty/brachytherapy

  11. Single-Organ Gallbladder Vasculitis

    Science.gov (United States)

    Hernández-Rodríguez, José; Tan, Carmela D.; Rodríguez, E. René; Hoffman, Gary S.

    2014-01-01

    GB-SV was higher than in GB-SOV (35.5% vs 10%; p = 0.05). Nongranulomatous inflammation with fibrinoid necrosis of medium-sized vessels occurred equally in both groups (>90%). Forms of SV affecting the gallbladder included polyarteritis nodosa (n = 10), hepatitis B virus-associated vasculitis (n = 8), cryoglobulinemic (essential or hepatitis C virus-associated) vasculitis (n = 6), vasculitis associated with autoimmune diseases (n = 6), microscopic polyangiitis (n = 4), eosinophilic granulomatosis with polyangiitis (Churg-Strauss) (n = 4), IgA vasculitis (Henoch-Schönlein) (n = 2), and giant cell arteritis (n = 1). GV is uncommon. Its histology most often consists of a nongranulomatous necrotizing vasculitis affecting medium-sized vessels. GB-SOV is usually discovered after routine cholecystectomy performed because of the presence of local symptoms, gallstone-associated cholecystitis, and contrary to GB-SV, GB-SOV is usually not associated with systemic symptoms. Acute phase reactants and surrogate markers of autoimmunity are usually normal or negative in GB-SOV. GB-SOV does not require systemic antiinflammatory or immunosuppressive therapy; surgery is adequate to achieve cure. GB-SV always warrants immunosuppressant therapy and is associated with high mortality. The finding of GV may precede the generalized manifestations of SV. Therefore, once GV is discovered, studies to determine disease extent and a vigilant follow-up are mandatory. PMID:25500710

  12. Clinical Transcriptomics in Systemic Vasculitis (CUTIS)

    Science.gov (United States)

    2018-04-10

    Cryoglobulinemic Vasculitis (CV); Drug-induced Vasculitis; Eosinophilic Granulomatosis With Polyangiitis (EGPA); IgA Vasculitis; Isolated Cutaneous Vasculitis; Granulomatosis With Polyangiitis (GPA); Microscopic Polyangiitis (MPA); Polyarteritis Nodosa (PAN); Urticarial Vasculitis; Vasculitis

  13. Immunomodulatory effects of helminths and protozoa in multiple sclerosis and experimental autoimmune encephalomyelitis

    DEFF Research Database (Denmark)

    Hasseldam, Henrik; Hansen, C S; Johansen, F F

    2013-01-01

    hygiene standards that exist in the western world, with reduced exposure to various pathogens, including parasites, as a consequence. Parasites are known to employ various immunomodulatory and anti-inflammatory strategies, which enable them to evade destruction by the immune system. This is most likely...... one of the reasons for the disease-dampening effects, reported in numerous studies investigating parasite infections and autoimmunity. This review will focus on recent advances in the field of parasites as beneficial immunomodulators, in multiple sclerosis and the animal model experimental autoimmune...

  14. Increased KPI containing amyloid precursor protein in experimental autoimmune encephalomyelitis brains.

    Science.gov (United States)

    Beilin, Orit; Karussis, Dimitrios M; Korczyn, Amos D; Gurwitz, David; Aronovich, Ramona; Mizrachi-Kol, Rachel; Chapman, Joab

    2007-04-16

    Amyloid precursor protein can be translated from three alternatively spliced mRNAs. We measured levels of amyloid precursor protein isoforms containing the Kunitz protease inhibitor domain (KPIAPP), and amyloid precursor protein without the Kunitz protease inhibitor domain (KPIAPP) in brain homogenates of acute experimental autoimmune encephalomyelitis mice. At the preclinical phase of the disease, both KPIAPP and KPIAPP levels were significantly higher in homogenates from brains of autoimmune encephalomyelitis mice, whereas at the acute phase of the disease only KPIAPP remained significantly elevated compared with controls. At the recovery phase, no differences were observed between the groups. The early and isoform-specific elevation of KPIAPP in autoimmune encephalomyelitis mice suggests a possible role for amyloid precursor protein in the immune response mediating the disease.

  15. Systemic Toll-like receptor stimulation suppresses experimental allergic asthma and autoimmune diabetes in NOD mice.

    Directory of Open Access Journals (Sweden)

    Aude Aumeunier

    Full Text Available BACKGROUND: Infections may be associated with exacerbation of allergic and autoimmune diseases. Paradoxically, epidemiological and experimental data have shown that some microorganisms can also prevent these pathologies. This observation is at the origin of the hygiene hypothesis according to which the decline of infections in western countries is at the origin of the increased incidence of both Th1-mediated autoimmune diseases and Th2-mediated allergic diseases over the last decades. We have tested whether Toll-like receptor (TLR stimulation can recapitulate the protective effect of infectious agents on allergy and autoimmunity. METHODS AND FINDINGS: Here, we performed a systematic study of the disease-modifying effects of a set of natural or synthetic TLR agonists using two experimental models, ovalbumin (OVA-induced asthma and spontaneous autoimmune diabetes, presenting the same genetic background of the non obese diabetic mouse (NOD that is highly susceptible to both pathologies. In the same models, we also investigated the effect of probiotics. Additionally, we examined the effect of the genetic invalidation of MyD88 on the development of allergic asthma and spontaneous diabetes. We demonstrate that multiple TLR agonists prevent from both allergy and autoimmunity when administered parenterally. Probiotics which stimulate TLRs also protect from these two diseases. The physiological relevance of these findings is further suggested by the major acceleration of OVA-induced asthma in MyD88 invalidated mice. Our results strongly indicate that the TLR-mediated effects involve immunoregulatory cytokines such as interleukin (IL-10 and transforming growth factor (TGF-beta and different subsets of regulatory T cells, notably CD4+CD25+FoxP3+ T cells for TLR4 agonists and NKT cells for TLR3 agonists. CONCLUSIONS/SIGNIFICANCE: These observations demonstrate that systemic administration of TLR ligands can suppress both allergic and autoimmune responses

  16. Vasculitis and infectious diseases.

    Science.gov (United States)

    Satta, R; Biondi, G

    2015-04-01

    Vasculitis usually presents without a well-known underline cause (idiopathic vasculitis), nevertheless, it is sometimes possible to find out one or more causative agents (secondary vasculitis). Nowadays, thanks to the increasing amount of precise diagnostic tools, a piece of idiopathic vasculitis is reclassified as associated with probable etiology, which can be set off by several factors, such as infections. Infections are considered to be the most common cause of secondary vasculitis. Virtually, every infectious agent can trigger a vasculitis by different mechanisms which can be divided in two main categories: direct and indirect. In the former, infectious agents destroy directly the vascular wall leading, eventually, to a subsequent inflammatory response. In the latter, indirect form, they stimulate an immune response against blood vessels. Different infectious agents are able to directly damage the vascular wall. Among these, it is possible to recognize Staphylococcus spp, Streptococcus spp, Salmonella spp, Treponema spp, Rickettsia spp, Cytomegalovirus, Herpes Simplex Virus 1 and 2, and many others which have a peculiar tropism for endothelial cells. Conversely, another group of microbial agents, such as Mycobacterium tuberculosis, Mycobacterium leprae, Hepatits B Virus, Human Immunodeficiency Virus and others, trigger vasculitis in the indirect way. This is due to the fact that they can share epitopes with the host or modify self-antigens, thus leading to a cross-self reaction of the immune system. These mechanism, in turn, leads to immunological responses classified as type I-IV by Gell-Coombs. Nevertheless, it is difficult to strictly separate the direct and indirect forms, because most infectious agents can cause vasculitis in both ways (mixed forms). This paper will analyze the link between infectious agents and vasculitis, focusing on direct and indirect secondary vasculitis, and on a group of probable infection-related idiopathic vasculitis, and finally

  17. Nanoparticle-mediated codelivery of myelin antigen and a tolerogenic small molecule suppresses experimental autoimmune encephalomyelitis

    Science.gov (United States)

    Yeste, Ada; Nadeau, Meghan; Burns, Evan J.; Weiner, Howard L.; Quintana, Francisco J.

    2012-01-01

    The immune response is normally controlled by regulatory T cells (Tregs). However, Treg deficits are found in autoimmune diseases, and therefore the induction of functional Tregs is considered a potential therapeutic approach for autoimmune disorders. The activation of the ligand-activated transcription factor aryl hydrocarbon receptor by 2-(1′H-indole-3′-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE) or other ligands induces dendritic cells (DCs) that promote FoxP3+ Treg differentiation. Here we report the use of nanoparticles (NPs) to coadminister ITE and a T-cell epitope from myelin oligodendrocyte glycoprotein (MOG)35–55 to promote the generation of Tregs by DCs. NP-treated DCs displayed a tolerogenic phenotype and promoted the differentiation of Tregs in vitro. Moreover, NPs carrying ITE and MOG35–55 expanded the FoxP3+ Treg compartment and suppressed the development of experimental autoimmune encephalomyelitis, an experimental model of multiple sclerosis. Thus, NPs are potential new tools to induce functional Tregs in autoimmune disorders. PMID:22745170

  18. Implication of the intestinal microbiome as a potential surrogate marker of immune responsiveness to experimental therapies in autoimmune diabetes

    NARCIS (Netherlands)

    Needell, J.C.; Dinarello, C.A.; Ir, D.; Robertson, C.E.; Ryan, S.M.; Kroehl, M.E.; Frank, D.N.; Zipris, D.

    2017-01-01

    Type 1 diabetes (T1D) is an autoimmune proinflammatory disease with no effective intervention. A major obstacle in developing new immunotherapies for T1D is the lack of means for monitoring immune responsiveness to experimental therapies. The LEW1.WR1 rat develops autoimmunity following infection

  19. Neuroimaging of cerebral vasculitis

    International Nuclear Information System (INIS)

    Wengenroth, M.; Saam, T.; Haehnel, S.

    2016-01-01

    Cerebral vasculitis can have a variety of origins. Furthermore, there are no vasculitis-specific symptoms or imaging signs and vasculitis of the CNS can mimic many other neurological diseases, which require different treatment approaches. Thus, the clinical and radiological diagnosis of cerebral vasculitis is challenging. Magnetic resonance imaging (MRI) and MR angiography (MRA) should be the radiological imaging methods of choice to assess the degree of parenchymal damage and to detect vessel wall changes. If the results are unclear digital subtraction angiography (DSA) should be pursued in order to also detect changes in medium sized vessels. Vasculitis of small vessels cannot be detected by vascular imaging and requires brain or leptomeningeal biopsy. In this review we present the current diagnostic approach and a variety of imaging findings in cerebral vasculitis and discuss the main radiological differential diagnoses. (orig.) [de

  20. Pulmonary vasculitis: imaging features

    International Nuclear Information System (INIS)

    Seo, Joon Beom; Im, Jung Gi; Chung, Jin Wook; Goo, Jin Mo; Park, Jae Hyung; Yeon, Kyung Mo; Song, Jae Woo

    1999-01-01

    Vasculitis is defined as an inflammatory process involving blood vessels, and can lead to destruction of the vascular wall and ischemic damage to the organs supplied by these vessels. The lung is commonly affected. A number of attempts have been made to classify and organize pulmonary vasculitis, but because the clinical manifestations and pathologic features of the condition overlap considerably, these afforts have failed to achieve a consensus. We classified pulmonary vasculitis as belonging to either the angitiis-granulomatosis group, the diffuse pulmonary hemorrhage with capillaritis group, or 'other'. Characteristic radiographic and CT findings of the different types of pulmonary vasculitis are illustrated, with a brief discussion of the respective disease entities

  1. Vasculitis and Pregnancy.

    Science.gov (United States)

    Machen, Leah; Clowse, Megan E B

    2017-05-01

    Vasculitis is more often a disease of women beyond their reproductive years, leaving the challenges of pregnancy management difficult to study. Pregnancy complications, including pregnancy loss and preterm birth, are higher among women with all forms of vasculitis. It seems that controlling the disease before pregnancy may improve the chances of pregnancy success. Many medications used for vasculitis are considered low risk in pregnancy, including prednisone, colchicine, azathioprine, and tumor necrosis factor inhibitors. Cyclophosphamide, methotrexate, and mycophenolate mofetil should be avoided in pregnancy. Controlling disease with low-risk medications may allow women with vasculitis to have the pregnancies they desire. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Regulatory T cells control strain specific resistance to Experimental Autoimmune Prostatitis

    Science.gov (United States)

    Breser, Maria L.; Lino, Andreia C.; Motrich, Ruben D.; Godoy, Gloria J.; Demengeot, Jocelyne; Rivero, Virginia E.

    2016-01-01

    Susceptibility to autoimmune diseases results from the encounter of a complex and long evolved genetic context with a no less complex and changing environment. Major actors in maintaining health are regulatory T cells (Treg) that primarily dampen a large subset of autoreactive lymphocytes escaping thymic negative selection. Here, we directly asked whether Treg participate in defining susceptibility and resistance to Experimental Autoimmune Prostatitis (EAP). We analyzed three common laboratory strains of mice presenting with different susceptibility to autoimmune prostatitis upon immunization with prostate proteins. The NOD, the C57BL/6 and the BALB/c mice that can be classified along a disease score ranging from severe, mild and to undetectable, respectively. Upon mild and transient depletion of Treg at the induction phase of EAP, each model showed an increment along this score, most remarkably with the BALB/c mice switching from a resistant to a susceptible phenotype. We further show that disease associates with the upregulation of CXCR3 expression on effector T cells, a process requiring IFNγ. Together with recent advances on environmental factors affecting Treg, these findings provide a likely cellular and molecular explanation to the recent rise in autoimmune diseases incidence. PMID:27624792

  3. Gut Microbiota Confers Resistance of Albino Oxford Rats to the Induction of Experimental Autoimmune Encephalomyelitis.

    Science.gov (United States)

    Stanisavljević, Suzana; Dinić, Miroslav; Jevtić, Bojan; Đedović, Neda; Momčilović, Miljana; Đokić, Jelena; Golić, Nataša; Mostarica Stojković, Marija; Miljković, Đorđe

    2018-01-01

    Albino Oxford (AO) rats are extremely resistant to induction of experimental autoimmune encephalomyelitis (EAE). EAE is an animal model of multiple sclerosis, a chronic inflammatory disease of the central nervous system (CNS), with established autoimmune pathogenesis. The autoimmune response against the antigens of the CNS is initiated in the peripheral lymphoid tissues after immunization of AO rats with CNS antigens. Subsequently, limited infiltration of the CNS occurs, yet without clinical sequels. It has recently become increasingly appreciated that gut-associated lymphoid tissues (GALT) and gut microbiota play an important role in regulation and propagation of encephalitogenic immune response. Therefore, modulation of AO gut microbiota by antibiotics was performed in this study. The treatment altered composition of gut microbiota in AO rats and led to a reduction in the proportion of regulatory T cells in Peyer's patches, mesenteric lymph nodes, and in lymph nodes draining the site of immunization. Upregulation of interferon-γ and interleukin (IL)-17 production was observed in the draining lymph nodes. The treatment led to clinically manifested EAE in AO rats with more numerous infiltrates and higher production of IL-17 observed in the CNS. Importantly, transfer of AO gut microbiota into EAE-prone Dark Agouti rats ameliorated the disease. These results clearly imply that gut microbiota is an important factor in AO rat resistance to EAE and that gut microbiota transfer is an efficacious way to treat CNS autoimmunity. These findings also support the idea that gut microbiota modulation has a potential as a future treatment of multiple sclerosis.

  4. Proinflammatory effects of exogenously administered IL-10 in experimental autoimmune orchitis

    DEFF Research Database (Denmark)

    Kaneko, Tetsushi; Itoh, Masahiro; Nakamura, Yoichi

    2003-01-01

    We studied the effects of exogenously administered recombinant murine interleukin (IL)-10 on the development of experimental autoimmune orchitis (EAO) in C3H/He mice. IL-10 significantly augments histological signs of EAO when administered for 6 consecutive days from days 15 to 20 after primary...... immunisations with testicular germ cells. These data demonstrate that IL-10, in addition to its well-known antiinflammatory property, also has proinflammatory functions capable of up-regulating testicular immunoinflammatory processes in vivo....

  5. Drug-Induced Vasculitis: New Insights and a Changing Lineup of Suspects.

    Science.gov (United States)

    Grau, Rafael G

    2015-12-01

    An increasing number of therapeutic agents have been associated with a vasculitic syndrome. This usually involves small vessels, primarily capillaries, venules, and arterioles in leukocytoclastic vasculitis, small-vessel disease similar to an antineutrophil cytoplasmic antibody-related vasculitis, or mid-sized muscular arteries in a polyarteritis-like picture. Antineutrophil cytoplasmic antibodies are present in many cases of vasculitis regardless of the size of the vessel involved. Monoclonal antibodies used to treat many autoimmune disorders have become the most common agents associated with drug-induced vasculitis. Important advances in epigenetics, genetics, and neutrophil apoptosis are providing new insights into the pathogenesis of both drug-induced vasculitis and idiopathic vasculitis. Although management has not changed significantly in the past few years where withdrawal of the offending agent is the primary intervention, increasing awareness of drug-induced vasculitis can lead to earlier diagnosis and prevention of severe organ damage and fatalities.

  6. Omalizumab for Urticarial Vasculitis

    DEFF Research Database (Denmark)

    Ghazanfar, Misbah Nasheela; Thomsen, Simon Francis

    2015-01-01

    include oral antihistamines, oral corticosteroids, dapsone, colchicine or hydroxychloroquine. We describe a male patient with urticarial vasculitis who was treated with omalizumab (anti-IgE) with convincing results and provide a review of previous reports of patients with urticarial vasculitis treated...

  7. Phenotype of Antigen Unexperienced TH Cells in the Inflamed Central Nervous System in Experimental Autoimmune Encephalomyelitis.

    Science.gov (United States)

    Franck, Sophia; Paterka, Magdalena; Birkenstock, Jerome; Zipp, Frauke; Siffrin, Volker; Witsch, Esther

    2017-06-01

    Multiple sclerosis is a chronic, disseminated inflammation of the central nervous system which is thought to be driven by autoimmune T cells. Genetic association studies in multiple sclerosis and a large number of studies in the animal model of the disease support a role for effector/memory T helper cells. However, the mechanisms underlying relapses, remission and chronic progression in multiple sclerosis or the animal model experimental autoimmune encephalomyelitis, are not clear. In particular, there is only scarce information on the role of central nervous system-invading naive T helper cells in these processes. By applying two-photon laser scanning microscopy we could show in vivo that antigen unexperienced T helper cells migrated into the deep parenchyma of the inflamed central nervous system in experimental autoimmune encephalomyelitis, independent of their antigen specificity. Using flow cytometric analyses of central nervous system-derived lymphocytes we found that only antigen-specific, formerly naive T helper cells became activated during inflammation of the central nervous system encountering their corresponding antigen.

  8. Gut Microbiota in Multiple Sclerosis and Experimental Autoimmune Encephalomyelitis: Current Applications and Future Perspectives

    Science.gov (United States)

    Lang, Yue

    2018-01-01

    The gut environment and gut microbiome dysbiosis have been demonstrated to significantly influence a range of disorders in humans, including obesity, diabetes, rheumatoid arthritis, and multiple sclerosis (MS). MS is an autoimmune disease affecting the central nervous system (CNS). The etiology of MS is not clear, and it should involve both genetic and extrinsic factors. The extrinsic factors responsible for predisposition to MS remain elusive. Recent studies on MS and its animal model, experimental autoimmune encephalomyelitis (EAE), have found that gastrointestinal microbiota may play an important role in the pathogenesis of MS/EAE. Thus, gut microbiome adjustment may be a future direction of treatment in MS. In this review, we discuss the characteristics of the gut microbiota, the connection between the brain and the gut, and the changes in gut microbiota in MS/EAE, and we explore the possibility of applying microbiota therapies in patients with MS. PMID:29805314

  9. Managing mesenteric vasculitis.

    Science.gov (United States)

    Angle, John Fritz; Nida, Berhanemeskel A; Matsumoto, Alan H

    2015-03-01

    Mesenteric vasculitis is a rare diagnosis, but it comprises a group of disorders that may have devastating manifestations. It is often difficult to diagnose using clinical symptoms and biomarkers. Vascular imaging often provides the best opportunity for the noninvasive diagnosis of vasculitis and obviates the need for performing a biopsy. The medical management of vasculitis involves controlling the inflammatory process with the use of steroids or other immunosuppressants, but medical therapy does not consistently provide regression of the vascular changes (ie, aneurysms or vascular occlusions) seen at the time of the initial diagnosis. Operative management remains the mainstay of therapy for focal occlusive or aneurysms, but the treatment options for multifocal disease remain challenging. Endovascular treatment is increasingly being used as a first line of treatment for symptomatic vasculitis. Interventionalists should be familiar with the indications and outcomes associated with the various therapeutic options for mesenteric vasculitis-associated occlusive disease and aneurysms. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. Journey of Patients With Vasculitis From First Symptom to Diagnosis

    Science.gov (United States)

    2018-01-18

    Vasculitis; Systemic Vasculitis; Behcet's Disease; CNS Vasculitis; Cryoglobulinemic Vasculitis; Eosinophilic Granulomatous Vasculitis; Temporal Arteritis; Giant Cell Arteritis; Granulomatosis With Polyangiitis; Wegener Granulomatosis; Henoch Schonlein Purpura; IgA Vasculitis; Microscopic Polyangiitis; Polyarteritis Nodosa; Takayasu Arteritis; Urticarial Vasculitis

  11. Blockade of Extracellular ATP Effect by Oxidized ATP Effectively Mitigated Induced Mouse Experimental Autoimmune Uveitis (EAU.

    Directory of Open Access Journals (Sweden)

    Ronglan Zhao

    Full Text Available Various pathological conditions are accompanied by ATP release from the intracellular to the extracellular compartment. Extracellular ATP (eATP functions as a signaling molecule by activating purinergic P2 purine receptors. The key P2 receptor involved in inflammation was identified as P2X7R. Recent studies have shown that P2X7R signaling is required to trigger the Th1/Th17 immune response, and oxidized ATP (oxATP effectively blocks P2X7R activation. In this study we investigated the effect of oxATP on mouse experimental autoimmune uveitis (EAU. Our results demonstrated that induced EAU in B6 mice was almost completely abolished by the administration of small doses of oxATP, and the Th17 response, but not the Th1 response, was significantly weakened in the treated mice. Mechanistic studies showed that the therapeutic effects involve the functional change of a number of immune cells, including dendritic cells (DCs, T cells, and regulatory T cells. OxATP not only directly inhibits the T cell response; it also suppresses T cell activation by altering the function of DCs and Foxp3+ T cell. Our results demonstrated that inhibition of P2X7R activation effectively exempts excessive autoimmune inflammation, which may indicate a possible therapeutic use in the treatment of autoimmune diseases.

  12. Evaluation of Marijuana Compounds on Neuroimmune Endpoints in Experimental Autoimmune Encephalomyelitis.

    Science.gov (United States)

    Kaplan, Barbara L F

    2018-02-21

    Cannabinoid compounds refer to a group of more than 60 plant-derived compounds in Cannabis sativa, more commonly known as marijuana. Exposure to marijuana and cannabinoid compounds has been increasing due to increased societal acceptance for both recreational and possible medical use. Cannabinoid compounds suppress immune function, and while this could compromise one's ability to fight infections, immune suppression is the desired effect for therapies for autoimmune diseases. It is critical, therefore, to understand the effects and mechanisms by which cannabinoid compounds alter immune function, especially immune responses induced in autoimmune disease. Therefore, this unit will describe induction and assessment of the experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis (MS), and its potential alteration by cannabinoid compounds. The unit includes three approaches to induce EAE, two of which provide correlations to two forms of MS, and the third specifically addresses the role of autoreactive T cells in EAE. © 2018 by John Wiley & Sons, Inc. Copyright © 2018 John Wiley & Sons, Inc.

  13. Experimental Autoimmune Encephalomyelitis (EAE) as Animal Models of Multiple Sclerosis (MS).

    Science.gov (United States)

    Glatigny, Simon; Bettelli, Estelle

    2018-01-08

    Multiple sclerosis (MS) is a multifocal demyelinating disease of the central nervous system (CNS) leading to the progressive destruction of the myelin sheath surrounding axons. It can present with variable clinical and pathological manifestations, which might reflect the involvement of distinct pathogenic processes. Although the mechanisms leading to the development of the disease are not fully understood, numerous evidences indicate that MS is an autoimmune disease, the initiation and progression of which are dependent on an autoimmune response against myelin antigens. In addition, genetic susceptibility and environmental triggers likely contribute to the initiation of the disease. At this time, there is no cure for MS, but several disease-modifying therapies (DMTs) are available to control and slow down disease progression. A good number of these DMTs were identified and tested using animal models of MS referred to as experimental autoimmune encephalomyelitis (EAE). In this review, we will recapitulate the characteristics of EAE models and discuss how they help shed light on MS pathogenesis and help test new treatments for MS patients. Copyright © 2018 Cold Spring Harbor Laboratory Press; all rights reserved.

  14. Thromboembolic disease in vasculitis

    Science.gov (United States)

    Tomasson, Gunnar; Monach, Paul A.; Merkel, Peter A.

    2011-01-01

    Purpose of review To give an overview of recent clinical findings of thromboembolic disease in vasculitis and provide insight into possible explanations of the association between thrombosis and inflammation. Recent findings A high incidence of venous thrombotic events has recently been described in four distinct cohorts of patients with antineutrophil cytoplasmic antibodies-associated vasculitis (AAV), especially during periods of active disease. No factors other than the vasculitis itself have been identified that explain this high occurrence of thrombosis. Several studies have shown an increased rate of thrombosis in Behçet’s disease, with a different clinical presentation than that observed in AAV. Recent laboratory findings provide exciting insights into a bidirectional feedback loop between coagulation and inflammation that may be applicable to vasculitis. Summary Thrombosis is an important clinical manifestation of some types of vasculitis. Better understanding of the association of thrombosis with inflammation in vasculitis might lead to development of clinically useful biomarkers and new approaches to therapy. Additionally, study of the specific factors involved in thrombosis in systemic vasculitis could help explain the role of inflammation in more common settings of venous thrombotic events. PMID:19077717

  15. Administration of Mycobacterium leprae rHsp65 aggravates experimental autoimmune uveitis in mice.

    Directory of Open Access Journals (Sweden)

    Eliana B Marengo

    Full Text Available The 60 kDa heat shock protein family, Hsp60, constitutes an abundant and highly conserved class of molecules that are highly expressed in chronic-inflammatory and autoimmune processes. Experimental autoimmune uveitis [EAU] is a T cell mediated intraocular inflammatory disease that resembles human uveitis. Mycobacterial and homologous Hsp60 peptides induces uveitis in rats, however their participation in aggravating the disease is poorly known. We here evaluate the effects of the Mycobacterium leprae Hsp65 in the development/progression of EAU and the autoimmune response against the eye through the induction of the endogenous disequilibrium by enhancing the entropy of the immunobiological system with the addition of homologous Hsp. B10.RIII mice were immunized subcutaneously with interphotoreceptor retinoid-binding protein [IRBP], followed by intraperitoneally inoculation of M. leprae recombinant Hsp65 [rHsp65]. We evaluated the proliferative response, cytokine production and the percentage of CD4(+IL-17(+, CD4(+IFN-gamma(+ and CD4(+Foxp3(+ cells ex vivo, by flow cytometry. Disease severity was determined by eye histological examination and serum levels of anti-IRBP and anti-Hsp60/65 measured by ELISA. EAU scores increased in the Hsp65 group and were associated with an expansion of CD4(+IFN-gamma(+ and CD4(+IL-17(+ T cells, corroborating with higher levels of IFN-gamma. Our data indicate that rHsp65 is one of the managers with a significant impact over the immune response during autoimmunity, skewing it to a pathogenic state, promoting both Th1 and Th17 commitment. It seems comprehensible that the specificity and primary function of Hsp60 molecules can be considered as a potential pathogenic factor acting as a whistleblower announcing chronic-inflammatory diseases progression.

  16. Neuroprotection in Experimental Autoimmune Encephalomyelitis and Progressive Multiple Sclerosis by Cannabis-Based Cannabinoids.

    Science.gov (United States)

    Pryce, Gareth; Riddall, Dieter R; Selwood, David L; Giovannoni, Gavin; Baker, David

    2015-06-01

    Multiple sclerosis (MS) is the major immune-mediated, demyelinating, neurodegenerative disease of the central nervous system. Compounds within cannabis, notably Δ9-tetrahydrocannabinol (Δ9-THC) can limit the inappropriate neurotransmissions that cause MS-related problems and medicinal cannabis is now licenced for the treatment of MS symptoms. However, the biology indicates that the endocannabinoid system may offer the potential to control other aspects of disease. Although there is limited evidence that the cannabinoids from cannabis are having significant immunosuppressive activities that will influence relapsing autoimmunity, we and others can experimentally demonstrate that they may limit neurodegeneration that drives progressive disability. Here we show that synthetic cannabidiol can slow down the accumulation of disability from the inflammatory penumbra during relapsing experimental autoimmune encephalomyelitis (EAE) in ABH mice, possibly via blockade of voltage-gated sodium channels. In addition, whilst non-sedating doses of Δ9-THC do not inhibit relapsing autoimmunity, they dose-dependently inhibit the accumulation of disability during EAE. They also appear to slow down clinical progression during MS in humans. Although a 3 year, phase III clinical trial did not detect a beneficial effect of oral Δ9-THC in progressive MS, a planned subgroup analysis of people with less disability who progressed more rapidly, demonstrated a significant slowing of progression by oral Δ9-THC compared to placebo. Whilst this may support the experimental and biological evidence for a neuroprotective effect by the endocannabinoid system in MS, it remains to be established whether this will be formally demonstrated in further trials of Δ9-THC/cannabis in progressive MS.

  17. The murine gammaherpesvirus-68 chemokine-binding protein M3 inhibits experimental autoimmune encephalomyelitis

    DEFF Research Database (Denmark)

    Millward, Jason M; Holst, Peter J; Høgh-Petersen, Mette

    2010-01-01

    M3 (AdM3) directly to the CNS to evaluate the capacity of this protein to inhibit neuroinflammation using the experimental autoimmune encephalomyelitis (EAE) model. Treatment with the AdM3 vector significantly reduced the clinical severity of EAE, attenuated CNS histopathology, and reduced numbers......Chemokines are critical mediators of immune cell entry into the central nervous system (CNS), as occurs in neuroinflammatory disease such as multiple sclerosis. Chemokines are also implicated in the immune response to viral infections. Many viruses encode proteins that mimic or block chemokine...... of immune cells infiltrating the CNS. These results suggest that M3 may represent a novel therapeutic approach to neuroinflammatory disease....

  18. Differential expression of metallothioneins in the CNS of mice with experimental autoimmune encephalomyelitis

    DEFF Research Database (Denmark)

    Espejo, C; Carrasco, J; Hidalgo, J

    2001-01-01

    Multiple sclerosis is an inflammatory, demyelinating disease of the CNS. Metallothioneins-I+II are antioxidant proteins induced in the CNS by immobilisation stress, trauma or degenerative diseases which have been postulated to play a neuroprotective role, while the CNS isoform metallothionein......-III has been related to Alzheimer's disease. We have analysed metallothioneins-I-III expression in the CNS of mice with experimental autoimmune encephalomyelitis. Moreover, we have examined the putative role of interferon-gamma, a pro-inflammatory cytokine, in the control of metallothioneins expression...

  19. Key metalloproteinases are expressed by specific cell types in experimental autoimmune encephalomyelitis

    DEFF Research Database (Denmark)

    Toft-Hansen, Henrik; Nuttall, Robert K; Edwards, Dylan R

    2004-01-01

    animal model, experimental autoimmune encephalomyelitis (EAE). We used real-time RT-PCR to profile the expression of all 22 known mouse MMPs, seven ADAMs, and all four known TIMPs in spinal cord from SJL/J mice and mice with adoptively transferred myelin basic protein (MBP)-specific EAE. A significant...... cellular sources of these strongly affected proteins in the inflamed CNS, we isolated macrophages, granulocytes, microglia, and T cells by cell sorting from the CNS of mice with EAE and analyzed their expression by real-time RT-PCR. This identified macrophages as a major source of MMP-12 and TIMP-1...

  20. A rheumatology perspective on cutaneous vasculitis: assessment and investigation for the non-rheumatologist.

    Science.gov (United States)

    Rawlings, Charlotte R; Fremlin, Georgina A; Nash, Julian; Harding, Keith

    2016-02-01

    Vasculitis, by definition, is inflammation of the vasculature. This inflammation can result in either vessel wall destruction causing aneurysm or rupture, or stenosis causing ischaemia or necrosis. This autoimmune response does not always have a clear cause. Vasculitis is a heterogeneous group of disorders that has been categorised not only by primary and secondary causes, but also by the size of the affected vessel. The secondary causes that can trigger vasculitis include infection (particularly hepatitis B and C and haemorrhagic fever);cancer, autoimmune diseases such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and Sjogren's; drugs or allergic reactions. As vasculitis can affect any part of the vasculature, it can result in a wide range of signs and symptoms. However, one of the most common presentations of vasculitis is a rash, due to small vessel vasculitis, which is most common. A vasculitic rash has certain characteristics that are easily identifiable and differentiate it from other rashes. This is a review from a rheumatologist's perspective of how to identify vasculitis skin changes. If cutaneous vasculitis is suspected, this article identifies other areas of skin that can be affected that need identification, in addition to what to screen for in the history and other differential diagnoses to consider. Subsequently, the article addresses the key investigations to request and a brief overview of the treatment principles for primary vasculitis. © 2015 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

  1. Interleukin-12 promotes activation of effector cells that induce a severe destructive granulomatous form of murine experimental autoimmune thyroiditis.

    OpenAIRE

    Braley-Mullen, H.; Sharp, G. C.; Tang, H.; Chen, K.; Kyriakos, M.; Bickel, J. T.

    1998-01-01

    Granulomatous inflammatory lesions are a major histopathological feature of a wide spectrum of human infectious and autoimmune diseases. Experimental autoimmune thyroiditis (EAT) with granulomatous histopathological features can be induced by mouse thyroglobulin (MTg)-sensitized spleen cells activated in vitro with MTg and anti-interleukin-2 receptor (anti-IL-2R), anti-IL-2, or anti-interferon-gamma (anti-IFN-gamma) monoclonal antibody (MAb). These studies suggested that IFN-gamma-producing T...

  2. [Pulmonary Manifestations of Vasculitis].

    Science.gov (United States)

    von Vietinghoff, S

    2016-11-01

    The variable symptoms and signs of pulmonary vasculitis are a diagnostic and therapeutic challenge. Vasculitis should be considered in rapidly progressing, severe and unusual manifestations of pulmonary disease. Clinical examination of other organ systems typically affected by vasculitis such as skin and kidney and autoantibody measurements are complementary approaches to manage this situation. Pulmonary involvement is common in small vessel vasculitis including anti-GBM disease (Goodpasture syndrome) and the ANCA-associated vasculitides. Life threatening pulmonary hemorrhage and irreversible damage of other organs, frequently the kidney, are important complications necessitating rapid diagnosis of these conditions.Vasculitides are rare diseases of multiple organs and therapies including biologics are evolving rapidly, requiring cooperation of specialities and with specialized centres to achieve best patient care. All involved physicians should be aware of typical complications of immunosuppressive therapy. © Georg Thieme Verlag KG Stuttgart · New York.

  3. Vasculitis in children.

    Science.gov (United States)

    Eleftheriou, Despina; Batu, Ezgi Deniz; Ozen, Seza; Brogan, Paul A

    2015-04-01

    Primary systemic vasculitides of the young are relatively rare diseases, but are associated with significant morbidity and mortality, particularly if there is diagnostic delay. We provide an overview of paediatric vasculitides with emphasis on key differences in vasculitis presentation and management between children and adults. Significant advances in the field of paediatric vasculitis research include the development of classification criteria and disease outcome tools for paediatric disease; inclusion of paediatric patients in international multicentre randomized controlled trials of therapies in vasculitis; and development of rare disease trial designs for therapeutic trials of paediatric vasculitis. The continuation of unmet needs as well as the exploration of potential therapeutic avenues and considerations in the design of future trials are also discussed. © The Author 2014. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

  4. Glucagon-Like Peptide-1 Analog, Liraglutide, Delays Onset of Experimental Autoimmune Encephalitis in Lewis Rats

    DEFF Research Database (Denmark)

    DellaValle, Brian; Brix, Gitte S; Brock, Birgitte

    2016-01-01

    (GLP-1) family, is also anti-diabetic and weight-reducing and is, moreover, directly neuroprotective and anti-inflammatory in a broad spectrum of experimental models of brain disease. In this study we investigate the potential for this FDA-approved drug, liraglutide, as a treatment for MS by utilizing...... the experimental model, experimental autoimmune encephalitis (EAE). Methods: EAE was induced in 30 female Lewis rats that subsequently received twice-daily liraglutide (200 μg/kg s.c.) or saline. Healthy controls were included (saline, n = 6, liraglutide, n = 7). Clinical score and weight were assessed daily...... treatment delayed disease onset (group clinical score significantly >0) by 2 days and markedly reduced disease severity (median clinical score 2 vs. 5; p = 0.0003). Fourteen of 15 (93%) of vehicle-treated rats reached the humane endpoint (clinical score ≥4) by day 11 compared to 5 of 15 (33%) of liraglutide...

  5. Pathogenesis of ANCA-Associated Vasculitis, an Update

    NARCIS (Netherlands)

    Kallenberg, Cees G. M.

    2011-01-01

    Clinical observations, including a report of neonatal vasculitis occurring in a child born from a mother with anti-neutrophil cytoplasmic antibody directed to myeloperoxidase (MPO-ANCA)-associated vasculitis, suggest a pathogenic role for ANCA. Such a role is supported by in vitro experimental data

  6. Prophylactic Effect of Probiotics on the Development of Experimental Autoimmune Myasthenia Gravis

    Science.gov (United States)

    Chae, Chang-Suk; Kwon, Ho-Keun; Hwang, Ji-Sun; Kim, Jung-Eun; Im, Sin-Hyeog

    2012-01-01

    Probiotics are live bacteria that confer health benefits to the host physiology. Although protective role of probiotics have been reported in diverse diseases, no information is available whether probiotics can modulate neuromuscular immune disorders. We have recently demonstrated that IRT5 probiotics, a mixture of 5 probiotics, could suppress diverse experimental disorders in mice model. In this study we further investigated whether IRT5 probiotics could modulate the progression of experimental autoimmune myasthenia gravis (EAMG). Myasthenia gravis (MG) is a T cell dependent antibody mediated autoimmune disorder in which acetylcholine receptor (AChR) at the neuromuscular junction is the major auto-antigen. Oral administration of IRT5 probiotics significantly reduced clinical symptoms of EAMG such as weight loss, body trembling and grip strength. Prophylactic effect of IRT5 probiotics on EMAG is mediated by down-regulation of effector function of AChR-reactive T cells and B cells. Administration of IRT5 probiotics decreased AChR-reactive lymphocyte proliferation, anti-AChR reactive IgG levels and inflammatory cytokine levels such as IFN-γ, TNF-α, IL-6 and IL-17. Down-regulation of inflammatory mediators in AChR-reactive lymphocytes by IRT5 probiotics is mediated by the generation of regulatory dendritic cells (rDCs) that express increased levels of IL-10, TGF-β, arginase 1 and aldh1a2. Furthermore, DCs isolated from IRT5 probiotics-fed group effectively converted CD4+ T cells into CD4+Foxp3+ regulatory T cells compared with control DCs. Our data suggest that IRT5 probiotics could be applicable to modulate antibody mediated autoimmune diseases including myasthenia gravis. PMID:23284891

  7. Study of the immune response to thyroglobulin through a model of experimental autoimmune thyroiditis

    International Nuclear Information System (INIS)

    Santos Castro, M. dos.

    1981-01-01

    The cellular and humoral immune response to thyroglobulin of different species was studied in guinea pigs. The experiments described suggested that the immune system can be activated against self-determinants. Human and pork thyroglobulin were able to induce the experimental thyroiditis as well as some immune responses, such as in vitro proliferative response, delayed hypersensitivity and antibodies. Although guinea pig thyroglobulin was unable to induce specific T-lymphocyte proliferation in vitro, delayed hypersensitivity response and antibodies, it was very efficient in inducing the autoimmune thyroiditis. On the contrary, bovine thyroglobulin did not induce experimental autoimmune thyroiditis despite producing good responses as determined by similar in vitro proliferative response, delayed hypersensitivity and on the humoral level. These results suggest that the assays utilised were not able to evaluate the relevant immune response to genesis of the thyroiditis. The determinant selection mechanisms operating in these immune responses are probably selecting determinants not responsible for self-recognition in vivo. It was suggested that the macrophage could be the cell responsible for the presentation of these determinants to the lymphocyte in an immunogenic form. (Author) [pt

  8. Strain-related effects of fenbendazole treatment on murine experimental autoimmune encephalomyelitis.

    Science.gov (United States)

    Ramp, A A; Hall, C; Orian, J M

    2010-07-01

    Parasitic infections are a concern in animal facilities, in view of their influence on physiological processes and the immune status of animals. Pinworms are effectively controlled with the anthelminthic fenbendazole (FBZ, [5-(phenylthio)-1H-benzamidazol-2-yl]carbamic acid methyl ester; C(15)H(13)N(3)O(2)S); however, questions remain as to whether prolonged FBZ exposure alters the disease course in specific experimental models, such as those pertaining to the immune system. We report that a three-month regimen of FBZ-medicated feed severely affected the onset and disease severity of murine experimental autoimmune encephalomyelitis (EAE), a disease that mimics multiple sclerosis. Differences were recorded between mouse strains used. Our data suggest that where the use of FBZ is mandatory, its full effect should be verified on the particular EAE variant adopted by the laboratory.

  9. The severity of experimental autoimmune cystitis can be ameliorated by anti-CXCL10 Ab treatment.

    Directory of Open Access Journals (Sweden)

    Udai P Singh

    Full Text Available Interstitial cystitis (IC, more recently called painful bladder syndrome (PBS is a complex disease associated with chronic bladder inflammation that primarily affects women. Its symptoms include frequent urinary urgency accompanied by discomfort or pain in the bladder and lower abdomen. In the United States, eight million people, mostly women, have IC/PBS. New evidence that autoimmune mechanisms are important in the pathogenesis of IC/PBS triggered interest.SWXJ mice immunized with a homogenate of similar mice's urinary bladders develop an autoimmune phenotype comparable to clinical IC with functional and histological alterations confined to the urinary bladder. Using the murine model of experimental autoimmune cystitis (EAC, we found that serum levels of CXCR3 ligand and local T helper type 1 (Th1 cytokine are elevated. Also, IFN-γ-inducible protein10 (CXCL10 blockade attenuated overall cystitis severity scores; reversed the development of IC; decreased local production of CXCR3 and its ligands, IFN-γ, and tumor necrosis factor-α (TNF-α; and lowered systemic levels of CXCR3 ligands. Urinary bladder CD4(+ T cells, mast cells, and neutrophils infiltrates were reduced following anti-CXCL10 antibody (Ab treatment of mice. Anti-CXCL10 Ab treatment also reversed the upregulated level of CXCR3 ligand mRNA at urinary bladder sites. The decreased number and percentage of systemic CD4(+ T cells in EAC mice returned to normal after anti-CXCL10 Ab treatment.Taken together, our findings provide important new information about the mechanisms underlying EAC pathogenesis, which has symptoms similar to those of IC/PBS. CXCL10 has the potential for use in developing new therapy for IC/PBS.

  10. Epitope-Specific Tolerance Modes Differentially Specify Susceptibility to Proteolipid Protein-Induced Experimental Autoimmune Encephalomyelitis

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    Lei Wang

    2017-11-01

    Full Text Available Immunization with myelin components can elicit experimental autoimmune encephalomyelitis (EAE. EAE susceptibility varies between mouse strains, depending on the antigen employed. BL/6 mice are largely resistant to EAE induction with proteolipid protein (PLP, probably a reflection of antigen-specific tolerance. However, the extent and mechanism(s of tolerance to PLP remain unclear. Here, we identified three PLP epitopes in PLP-deficient BL/6 mice. PLP-sufficient mice did not respond against two of these, whereas tolerance was “leaky” for an epitope with weak predicted MHCII binding, and only this epitope was encephalitogenic. In TCR transgenic mice, the “EAE-susceptibility-associated” epitope was “ignored” by specific CD4 T cells, whereas the “resistance-associated” epitope induced clonal deletion and Treg induction in the thymus. Central tolerance was autoimmune regulator dependent and required expression and presentation of PLP by thymic epithelial cells (TECs. TEC-specific ablation of PLP revealed that peripheral tolerance, mediated by dendritic cells through recessive tolerance mechanisms (deletion and anergy, could largely compensate for a lack of central tolerance. However, adoptive EAE was exacerbated in mice lacking PLP in TECs, pointing toward a non-redundant role of the thymus in dominant tolerance to PLP. Our findings reveal multiple layers of tolerance to a central nervous system autoantigen that vary among epitopes and thereby specify disease susceptibility. Understanding how different modalities of tolerance apply to distinct T cell epitopes of a target in autoimmunity has implications for antigen-specific strategies to therapeutically interfere with unwanted immune reactions against self.

  11. 5-Androstenediol Ameliorates Pleurisy, Septic Shock, and Experimental Autoimmune Encephalomyelitis in Mice

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    Ferdinando Nicoletti

    2010-01-01

    Full Text Available Androstenediol (androst-5-ene-3β,17β-diol; 5-AED, a natural adrenal steroid, has been shown to suppress experimental autoimmune encephalomyelitis (EAE in female SJL/J mice. We here report that 5-AED limits inflammation and proinflammatory cytokines including TNFα in murine models of carrageenan-induced pleurisy and lippopolysaccaride- (LPS induced septic shock. 5-AED binds to and transactivates sex steroid receptors with the same general rank order of potency (ERβ > ERα ≫ AR. 5-AED provides benefit in EAE in a dose-dependent fashion, even when treatment is delayed until onset of disease. The minimally effective dose may be as low as 4 mg/kg in mice. However, benefit was not observed when 5-AED was given in soluble formulation, leading to a short half-life and rapid clearance. These observations suggest that treatment with 5-AED limits the production of pro-inflammatory cytokines in these animal models and, ultimately, when formulated and administered properly, may be beneficial for patients with multiple sclerosis and other Th1-driven autoimmune diseases.

  12. Helminth Products Potently Modulate Experimental Autoimmune Encephalomyelitis by Downregulating Neuroinflammation and Promoting a Suppressive Microenvironment

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    Alberto N. Peón

    2017-01-01

    Full Text Available A negative correlation between the geographical distribution of autoimmune diseases and helminth infections has been largely associated in the last few years with a possible role for such type of parasites in the regulation of inflammatory diseases, suggesting new pathways for drug development. However, few helminth-derived immunomodulators have been tested in experimental autoimmune encephalomyelitis (EAE, an animal model of the human disease multiple sclerosis (MS. The immunomodulatory activities of Taenia crassiceps excreted/secreted products (TcES that may suppress EAE development were sought for. Interestingly, it was discovered that TcES was able to suppress EAE development with more potency than dexamethasone; moreover, TcES treatment was still effective even when inoculated at later stages after the onset of EAE. Importantly, the TcES treatment was able to induce a range of Th2-type cytokines, while suppressing Th1 and Th17 responses. Both the polyclonal and the antigen-specific proliferative responses of lymphocytes were also inhibited in EAE-ill mice receiving TcES in association with a potent recruitment of suppressor cell populations. Peritoneal inoculation of TcES was able to direct the normal inflammatory cell traffic to the site of injection, thus modulating CNS infiltration, which may work along with Th2 immune polarization and lymphocyte activation impairment to downregulate EAE development.

  13. Small heat shock protein αA-crystallin prevents photoreceptor degeneration in experimental autoimmune uveitis.

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    Narsing A Rao

    Full Text Available The small heat shock protein, αA-crystallin null (αA-/- mice are known to be more prone to retinal degeneration than the wild type mice in Experimental Autoimmune Uveoretinitis (EAU. In this report we demonstrate that intravenous administration of αA preserves retinal architecture and prevents photoreceptor damage in EAU. Interestingly, only αA and not αB-crystallin (αB, a closely related small heat shock protein works, pointing to molecular specificity in the observed retinal protection. The possible involvement of αA in retinal protection through immune modulation is corroborated by adaptive transfer experiments, (employing αA-/- and wild type mice with EAU as donors and Rag2-/- as the recipient mice, which indicate that αA protects against the autoimmune challenge by modulating the systemic B and T cell immunity. We show that αA administration causes marked reduction in Th1 cytokines (TNF-α, IL-12 and IFN-γ, both in the retina and in the spleen; notably, IL-17 was only reduced in the retina suggesting local intervention. Importantly, expression of Toll-like receptors and their associated adaptors is also inhibited suggesting that αA protection, against photoreceptor loss in EAU, is associated with systemic suppression of both the adaptive and innate immune responses.

  14. Small heat shock protein αA-crystallin prevents photoreceptor degeneration in experimental autoimmune uveitis.

    Science.gov (United States)

    Rao, Narsing A; Saraswathy, Sindhu; Pararajasegaram, Geeta; Bhat, Suraj P

    2012-01-01

    The small heat shock protein, αA-crystallin null (αA-/-) mice are known to be more prone to retinal degeneration than the wild type mice in Experimental Autoimmune Uveoretinitis (EAU). In this report we demonstrate that intravenous administration of αA preserves retinal architecture and prevents photoreceptor damage in EAU. Interestingly, only αA and not αB-crystallin (αB), a closely related small heat shock protein works, pointing to molecular specificity in the observed retinal protection. The possible involvement of αA in retinal protection through immune modulation is corroborated by adaptive transfer experiments, (employing αA-/- and wild type mice with EAU as donors and Rag2-/- as the recipient mice), which indicate that αA protects against the autoimmune challenge by modulating the systemic B and T cell immunity. We show that αA administration causes marked reduction in Th1 cytokines (TNF-α, IL-12 and IFN-γ), both in the retina and in the spleen; notably, IL-17 was only reduced in the retina suggesting local intervention. Importantly, expression of Toll-like receptors and their associated adaptors is also inhibited suggesting that αA protection, against photoreceptor loss in EAU, is associated with systemic suppression of both the adaptive and innate immune responses.

  15. Identification of gene expression patterns crucially involved in experimental autoimmune encephalomyelitis and multiple sclerosis

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    Martin M. Herrmann

    2016-10-01

    Full Text Available After encounter with a central nervous system (CNS-derived autoantigen, lymphocytes leave the lymph nodes and enter the CNS. This event leads only rarely to subsequent tissue damage. Genes relevant to CNS pathology after cell infiltration are largely undefined. Myelin-oligodendrocyte-glycoprotein (MOG-induced experimental autoimmune encephalomyelitis (EAE is an animal model of multiple sclerosis (MS, a chronic autoimmune disease of the CNS that results in disability. To assess genes that are involved in encephalitogenicity and subsequent tissue damage mediated by CNS-infiltrating cells, we performed a DNA microarray analysis from cells derived from lymph nodes and eluted from CNS in LEW.1AV1 (RT1av1 rats immunized with MOG 91-108. The data was compared to immunizations with adjuvant alone or naive rats and to immunizations with the immunogenic but not encephalitogenic MOG 73-90 peptide. Here, we show involvement of Cd38, Cxcr4 and Akt and confirm these findings by the use of Cd38-knockout (B6.129P2-Cd38tm1Lnd/J mice, S1P-receptor modulation during EAE and quantitative expression analysis in individuals with MS. The hereby-defined underlying pathways indicate cellular activation and migration pathways mediated by G-protein-coupled receptors as crucial events in CNS tissue damage. These pathways can be further explored for novel therapeutic interventions.

  16. Erythropoietin-derived nonerythropoietic peptide ameliorates experimental autoimmune neuritis by inflammation suppression and tissue protection.

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    Yuqi Liu

    Full Text Available Experimental autoimmune neuritis (EAN is an autoantigen-specific T-cell-mediated disease model for human demyelinating inflammatory disease of the peripheral nervous system. Erythropoietin (EPO has been known to promote EAN recovery but its haematopoiesis stimulating effects may limit its clinic application. Here we investigated the effects and potential mechanisms of an EPO-derived nonerythropoietic peptide, ARA 290, in EAN. Exogenous ARA 290 intervention greatly improved EAN recovery, improved nerve regeneration and remyelination, and suppressed nerve inflammation. Furthermore, haematopoiesis was not induced by ARA 290 during EAN treatment. ARA 290 intervention suppressed lymphocyte proliferation and altered helper T cell differentiation by inducing increase of Foxp3+/CD4+ regulatory T cells and IL-4+/CD4+ Th2 cells and decrease of IFN-γ+/CD4+ Th1 cells in EAN. In addition, ARA 290 inhibited inflammatory macrophage activation and promoted its phagocytic activity. In vitro, ARA 290 was shown to promote Schwann cell proliferation and inhibit its inflammatory activation. In summary, our data demonstrated that ARA 290 could effectively suppress EAN by attenuating inflammation and exerting direct cell protection, indicating that ARA 290 could be a potent candidate for treatment of autoimmune neuropathies.

  17. Gut-associated lymphoid tissue, gut microbes and susceptibility to experimental autoimmune encephalomyelitis.

    Science.gov (United States)

    Stanisavljević, S; Lukić, J; Momčilović, M; Miljković, M; Jevtić, B; Kojić, M; Golić, N; Mostarica Stojković, M; Miljković, D

    2016-06-01

    Gut microbiota and gut-associated lymphoid tissue have been increasingly appreciated as important players in pathogenesis of various autoimmune diseases, including multiple sclerosis. Experimental autoimmune encephalomyelitis (EAE) is an animal model of multiple sclerosis that can be induced with an injection of spinal cord homogenate emulsified in complete Freund's adjuvant in Dark Agouti (DA) rats, but not in Albino Oxford (AO) rats. In this study, mesenteric lymph nodes (MLN), Peyer's patches (PP) and gut microbiota were analysed in these two rat strains. There was higher proportion of CD4(+) T cells and regulatory T cells in non-immunised DA rats in comparison to AO rats. Also, DA rat MLN and PP cells were higher producers of pro-inflammatory cytokines interferon-γ and interleukin-17. Finally, microbial analyses showed that uncultivated species of Turicibacter and Atopostipes genus were exclusively present in AO rats, in faeces and intestinal tissue, respectively. Thus, it is clear that in comparison of an EAE-susceptible with an EAE-resistant strain of rats, various discrepancies at the level of gut associated lymphoid tissue, as well as at the level of gut microbiota can be observed. Future studies should determine if the differences have functional significance for EAE pathogenesis.

  18. T Follicular Helper-Like Cells Are Involved in the Pathogenesis of Experimental Autoimmune Encephalomyelitis

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    Jun Guo

    2018-05-01

    Full Text Available Multiple sclerosis (MS and experimental autoimmune encephalomyelitis (EAE have been proved to be T cell-mediated autoimmune diseases. Recent researches indicate that humoral immunity is also involved in the pathogenesis of these disorders. T follicular helper (Tfh cells are critical for B cell differentiation and antibody production. However, the role of Tfh cells in MS and EAE remains unclear. Here, we found elevated frequencies of CD4+CXCR5+PD-1+ Tfh-like cells in both MS patients and EAE. In EAE mice, Tfh-like cells, together with B cells, were found in the ectopic lymphoid structures in spinal cords. Moreover, Tfh-like cells promoted the antibody production via IL-21/IL-21R and CD40 ligand/CD40 interaction and the synergy effect of STAT3 and non-canonical NF-κB signaling pathway inside B cells. Moreover, adoptive transfer of Tfh-like cells could increase the severity and delay the remission of EAE. In conclusion, our data indicate that Tfh-like cells contribute to the pathogenesis of EAE.

  19. Novel CFI mutation in a patient with leukocytoclastic vasculitis may redefine the clinical spectrum of Complement Factor I deficiency

    DEFF Research Database (Denmark)

    Bay, Jakob Thaning; Katzenstein, Terese Lea; Kofoed, Kristian

    2015-01-01

    presentation of Factor I deficiency varies and includes severe recurrent bacterial infections, glomerulonephritis and autoimmune diseases. The patient, a 28-years old woman with consanguineous parents, presented with recurrent leukocytoclastic vasculitis in the lower extremities with no associated systemic...... mutations vary among patients sole association with leukocytoclastic vasculitis redefines the clinical spectrum of complete Factor I deficiency....

  20. Total glucosides of peony attenuates experimental autoimmune encephalomyelitis in C57BL/6 mice.

    Science.gov (United States)

    Huang, Qiling; Ma, Xiaomeng; Zhu, Dong Liang; Chen, Li; Jiang, Ying; Zhou, Linli; Cen, Lei; Pi, Rongbiao; Chen, Xiaohong

    2015-07-15

    Total glucosides of peony (TGP), an active compound extracted from the roots of Paeonia lactiflora Pall, has wide pharmacological effects on nervous system. Here we examined the effects of TGP on experimental autoimmune encephalomyelitis (EAE), an established model of multiple sclerosis (MS). The results showed that TGP can reduce the severity and progression of EAE in C57 BL/6 mice. In addition, TGP also down-regulated the Th1/Th17 inflammatory response and prevented the reduced expression of brain-derived neurotrophic factor and 2',3'-cyclic nucleotide 3'-phosphodiesterase of EAE. These findings suggest that TGP could be a potential therapeutic agent for MS. Copyright © 2015 Elsevier B.V. All rights reserved.

  1. Specific removal of autoantibodies by extracorporeal immunoadsorption ameliorates experimental autoimmune myasthenia gravis.

    Science.gov (United States)

    Lazaridis, Konstantinos; Dalianoudis, Ioannis; Baltatzidi, Vasiliki; Tzartos, Socrates J

    2017-11-15

    Myasthenia gravis (MG) is caused by autoantibodies, the majority of which target the muscle acetylcholine receptor (AChR). Plasmapheresis and IgG-immunoadsorption are useful therapy options, but are highly non-specific. Antigen-specific immunoadsorption would remove only the pathogenic autoantibodies, reducing the possibility of side effects while maximizing the benefit. We have extensively characterized such adsorbents, but in vivo studies are missing. We used rats with experimental autoimmune MG to perform antigen-specific immunoadsorptions over three weeks, regularly monitoring symptoms and autoantibody titers. Immunoadsorption was effective, resulting in a marked autoantibody titer decrease while the immunoadsorbed, but not the mock-treated, animals showed a dramatic symptom improvement. Overall, the procedure was found to be efficient, suggesting the subsequent initiation of clinical trials. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Experimental autoimmune encephalomyelitis from a tissue energy perspective [version 1; referees: 2 approved

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    Roshni A Desai

    2017-11-01

    Full Text Available Increasing evidence suggests a key role for tissue energy failure in the pathophysiology of multiple sclerosis (MS. Studies in experimental autoimmune encephalomyelitis (EAE, a commonly used model of MS, have been instrumental in illuminating the mechanisms that may be involved in compromising energy production. In this article, we review recent advances in EAE research focussing on factors that conspire to impair tissue energy metabolism, such as tissue hypoxia, mitochondrial dysfunction, production of reactive oxygen/nitrogen species, and sodium dysregulation, which are directly affected by energy insufficiency, and promote cellular damage. A greater understanding of how inflammation affects tissue energy balance may lead to novel and effective therapeutic strategies that ultimately will benefit not only people affected by MS but also people affected by the wide range of other neurological disorders in which neuroinflammation plays an important role.

  3. Increased demyelination and axonal damage in metallothionein I+II-deficient mice during experimental autoimmune encephalomyelitis

    DEFF Research Database (Denmark)

    Penkowa, M; Espejo, C; Martínez-Cáceres, E M

    2003-01-01

    Metallothioneins I+II (MT-I+II) are antioxidant, neuroprotective factors. We previously showed that MT-I+II deficiency during experimental autoimmune encephalomyelitis (EAE) leads to increased disease incidence and clinical symptoms. Moreover, the inflammatory response of macrophages and T cells......, oxidative stress, and apoptotic cell death during EAE were increased by MT-I+II deficiency. We now show for the first time that demyelination and axonal damage are significantly increased in MT-I+II deficient mice during EAE. Furthermore, oligodendroglial regeneration, growth cone formation, and tissue...... repair including expression of trophic factors were significantly reduced in MT-I+II-deficient mice during EAE. Accordingly, MT-I+II have protective and regenerative roles in the brain....

  4. A role for VAV1 in experimental autoimmune encephalomyelitis and multiple sclerosis

    DEFF Research Database (Denmark)

    Jagodic, Maja; Colacios, Celine; Nohra, Rita

    2009-01-01

    Multiple sclerosis, the most common cause of progressive neurological disability in young adults, is a chronic inflammatory disease. There is solid evidence for a genetic influence in multiple sclerosis, and deciphering the causative genes could reveal key pathways influencing the disease. A genome...... region on rat chromosome 9 regulates experimental autoimmune encephalomyelitis, a model for multiple sclerosis. Using interval-specific congenic rat lines and association of single-nucleotide polymorphisms with inflammatory phenotypes, we localized the gene of influence to Vav1, which codes for a signal......-transducing protein in leukocytes. Analysis of seven human cohorts (12,735 individuals) demonstrated an association of rs2546133-rs2617822 haplotypes in the first VAV1 intron with multiple sclerosis (CA: odds ratio, 1.18; CG: odds ratio, 0.86; TG: odds ratio, 0.90). The risk CA haplotype also predisposed for higher...

  5. Strain-specific induction of experimental autoimmune prostatitis (EAP) in mice.

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    Jackson, Christopher M; Flies, Dallas B; Mosse, Claudio A; Parwani, Anil; Hipkiss, Edward L; Drake, Charles G

    2013-05-01

    Prostatitis, a clinical syndrome characterized by pelvic pain and inflammation, is common in adult males. Although several induced and spontaneous murine models of prostatitis have been explored, the role of genetic background on induction has not been well-defined. Using a standard methodology for the induction of experimental autoimmune prostatitis (EAP), we investigated both acute and chronic inflammation on several murine genetic backgrounds. In our colony, nonobese diabetic (NOD) mice evinced spontaneous prostatitis that was not augmented by immunization with rat prostate extract (RPE). In contrast, the standard laboratory strain Balb/c developed chronic inflammation in response to RPE immunization. Development of EAP in other strains was variable. These data suggest that Balb/c mice injected with RPE may provide a useful model for chronic prostatic inflammation. Copyright © 2012 Wiley Periodicals, Inc.

  6. Intravitreal injection of anti-Interleukin (IL)-6 antibody attenuates experimental autoimmune uveitis in mice.

    Science.gov (United States)

    Tode, Jan; Richert, Elisabeth; Koinzer, Stefan; Klettner, Alexa; Pickhinke, Ute; Garbers, Christoph; Rose-John, Stefan; Nölle, Bernhard; Roider, Johann

    2017-08-01

    To evaluate the effect of an intravitreally applied anti-IL-6 antibody for the treatment of experimental autoimmune uveitis (EAU). EAU was induced in female B10.RIII mice by Inter-Photoreceptor-Binding-Protein (IRBP) in complete Freund's adjuvant, boosted by Pertussis toxin. Single blinded intravitreal injections of anti-IL-6 antibody were applied 5-7days as well as 8-10days (3day interval) after EAU induction into the randomized treatment eye and phosphate buffered saline (PBS) into the fellow control eye. Clinical and fluorescein angiography scoring (6 EAU grades) was done at each injection day and at enucleation day 14. Enucleated eyes were either scored histologically (6 EAU grades) or examined by ELISA for levels of IL-6, IL-17 and IL-6 soluble Receptor (sIL-6R). Uveitis developed in all 12 mice. Clinical uveitis score was significantly reduced (p=0.035) in treated eyes (median 2.0, range 0-4.0, n=12) compared to the fellow control eyes (median 3.0, range 1.0-4.0, n=12). Angiography scores were reduced in 9/12 treated eyes and histological scores in 3/4 treated eyes compared to the fellow control eyes. Cytokine levels were determined in 8 mice, of which 4 responded to anti-IL-6 treatment and 4 did not respond. All mice responding to treatment had a significant reduction of IL-6 (ptreatment significantly attenuates experimental autoimmune uveitis in mice. EAU activity correlates with ocular IL-6 and IL-17 levels. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Autoimmune diseases in asthma.

    Science.gov (United States)

    Tirosh, Amir; Mandel, Dror; Mimouni, Francis B; Zimlichman, Eyal; Shochat, Tzippora; Kochba, Ilan

    2006-06-20

    Previous research has suggested an inverse relationship between T-helper 2-related atopic disorders, such as asthma, and T-helper 1-related autoimmune diseases. One controversial hypothesis postulates that asthma provides a protective effect for the development of autoimmune-related disorders. To assess the rate of newly diagnosed autoimmune disorders in a large cohort of young adults. Using cross-sectional data from the Israeli Defense Force database, the authors analyzed the prevalence of autoimmune disorders in asthmatic and nonasthmatic military personnel between 1980 and 2003. A follow-up study traced newly diagnosed autoimmune disorders among asthmatic and nonasthmatic individuals from the time of enrollment in military service until discharge (22 and 36 months for women and men, respectively). General community. 307,367 male and 181,474 female soldiers in compulsory military service who were between 18 and 21 years of age. Cases of type 1 diabetes mellitus, vasculitis, immune thrombocytopenic purpura, inflammatory bowel disease, rheumatoid arthritis, and the antiphospholipid syndrome. Of 488,841 participants at enrollment, significantly more women than men had autoimmune disorders. Compared with asthmatic women, nonasthmatic women had a significantly higher prevalence of all autoimmune disorders except for the antiphospholipid syndrome. Type 1 diabetes mellitus, vasculitis, and rheumatoid arthritis were less prevalent in men with asthma than in those without. During the follow-up period, vasculitis and rheumatoid arthritis were more frequently diagnosed in nonasthmatic persons of both sexes. There was a significantly higher incidence of immune thrombocytopenic purpura, inflammatory bowel disease, and the antiphospholipid syndrome in nonasthmatic women and a statistically significantly higher incidence of type 1 diabetes mellitus in nonasthmatic men. The study was limited to a population of young military recruits; therefore, its findings are not necessarily

  8. A cannabigerol derivative suppresses immune responses and protects mice from experimental autoimmune encephalomyelitis.

    Science.gov (United States)

    Carrillo-Salinas, Francisco J; Navarrete, Carmen; Mecha, Miriam; Feliú, Ana; Collado, Juan A; Cantarero, Irene; Bellido, María L; Muñoz, Eduardo; Guaza, Carmen

    2014-01-01

    Phytocannabinoids that do not produce psychotropic effects are considered of special interest as novel therapeutic agents in CNS diseases. A cannabigerol quinone, the compound VCE-003, has been shown to alleviate symptoms in a viral model of multiple sclerosis (MS). Hence, we studied T cells and macrophages as targets for VCE-003 and its efficacy in an autoimmune model of MS. Proliferation, cell cycle, expression of activation markers was assessed by FACs in human primary T cells, and cytokine and chemokine production was evaluated. Transcription was studied in Jurkat cells and RAW264.7 cells were used to study the effects of VCE-003 on IL-17-induced macrophage polarization to a M1 phenotype. Experimental autoimmune encephalomyelitis (EAE) was induced by myelin oligodendrocyte glycoprotein (MOG₃₅₋₅₅) immunization and spinal cord pathology was assessed by immunohistochemistry. Neurological impairment was evaluated using disease scores. We show here that VCE-003 inhibits CD3/CD28-induced proliferation, cell cycle progression and the expression of the IL-2Rα and ICAM-1 activation markers in human primary T cells. VCE-003 inhibits the secretion of Th1/Th17 cytokines and chemokines in primary murine T cells, and it reduces the transcriptional activity of the IL-2, IL-17 and TNFα promoters induced by CD3/CD28. In addition, VCE-003 and JWH-133, a selective CB2 agonist, dampened the IL-17-induced polarization of macrophages to a pro-inflammatory M1 profile. VCE-003 also prevented LPS-induced iNOS expression in microglia. VCE-003 ameliorates the neurological defects and the severity of MOG-induced EAE in mice through CB2 and PPARγ receptor activation. A reduction in cell infiltrates, mainly CD4+ T cells, was observed, and Th1 and Th17 responses were inhibited in the spinal cord of VCE-003-treated mice, accompanied by weaker microglial activation, structural preservation of myelin sheets and reduced axonal damage. This study highlights the therapeutic potential

  9. Correlation of gut microbiota composition with resistance to experimental autoimmune encephalomyelitis in rats

    Directory of Open Access Journals (Sweden)

    Suzana Stanisavljevic

    2016-12-01

    Full Text Available Multiple sclerosis is a chronic inflammatory disease of the central nervous system (CNS. It is widely accepted that autoimmune response against the antigens of the CNS is the essential pathogenic force in the disease. It has recently become increasingly appreciated that activated encephalitogenic cells tend to migrate towards gut associated lymphoid tissues (GALT and that interrupted balance between regulatory and inflammatory immunity within the GALT might have decisive role in the initiation and propagation of the CNS autoimmunity. Gut microbiota composition and function has the major impact on the balance in the GALT. Thus, our aim was to perform analyses of gut microbiota in experimental autoimmune encephalomyelitis (EAE, an animal model of multiple sclerosis. Albino Oxford (AO rats that are highly resistant to EAE induction and Dark Agouti (DA rats that develop EAE after mild immunization were compared for gut microbiota composition in different phases after EAE induction. Microbial analyses of the genus Lactobacillus and related lactic acid bacteria showed higher diversity of Lactobacillus spp. in EAE-resistant AO rats, while some members of Firmicutes and Proteobacteria (Undibacterium oligocarboniphilum were detected only in faeces of DA rats at the peak of the disease (between 13 and 16 days after induction. Interestingly, Turicibacter sp. that was found exclusively in non-immunized AO, but not in DA rats in our previous study was detected in DA rats that remained healthy 16 days after induction. Similar observation was obtained for the members of Lachnospiraceae. As dominant presence of the members of Lachnospiraceae family in gut microbial community has been linked with mild symptoms of various diseases, it is tempting to assume that Turicibacter sp. and Lachnospiraceae contribute to the prevention of EAE development and the alleviation of the disease symptoms. Further, production of a typical regulatory cytokine interleukin-10 was

  10. A cannabigerol derivative suppresses immune responses and protects mice from experimental autoimmune encephalomyelitis.

    Directory of Open Access Journals (Sweden)

    Francisco J Carrillo-Salinas

    Full Text Available Phytocannabinoids that do not produce psychotropic effects are considered of special interest as novel therapeutic agents in CNS diseases. A cannabigerol quinone, the compound VCE-003, has been shown to alleviate symptoms in a viral model of multiple sclerosis (MS. Hence, we studied T cells and macrophages as targets for VCE-003 and its efficacy in an autoimmune model of MS. Proliferation, cell cycle, expression of activation markers was assessed by FACs in human primary T cells, and cytokine and chemokine production was evaluated. Transcription was studied in Jurkat cells and RAW264.7 cells were used to study the effects of VCE-003 on IL-17-induced macrophage polarization to a M1 phenotype. Experimental autoimmune encephalomyelitis (EAE was induced by myelin oligodendrocyte glycoprotein (MOG₃₅₋₅₅ immunization and spinal cord pathology was assessed by immunohistochemistry. Neurological impairment was evaluated using disease scores. We show here that VCE-003 inhibits CD3/CD28-induced proliferation, cell cycle progression and the expression of the IL-2Rα and ICAM-1 activation markers in human primary T cells. VCE-003 inhibits the secretion of Th1/Th17 cytokines and chemokines in primary murine T cells, and it reduces the transcriptional activity of the IL-2, IL-17 and TNFα promoters induced by CD3/CD28. In addition, VCE-003 and JWH-133, a selective CB2 agonist, dampened the IL-17-induced polarization of macrophages to a pro-inflammatory M1 profile. VCE-003 also prevented LPS-induced iNOS expression in microglia. VCE-003 ameliorates the neurological defects and the severity of MOG-induced EAE in mice through CB2 and PPARγ receptor activation. A reduction in cell infiltrates, mainly CD4+ T cells, was observed, and Th1 and Th17 responses were inhibited in the spinal cord of VCE-003-treated mice, accompanied by weaker microglial activation, structural preservation of myelin sheets and reduced axonal damage. This study highlights the

  11. Invariant NKT cells regulate experimental autoimmune uveitis through inhibition of Th17 differentiation.

    Science.gov (United States)

    Oh, Keunhee; Byoun, Ok-Jin; Ham, Don-Il; Kim, Yon Su; Lee, Dong-Sup

    2011-02-01

    Although NKT cells have been implicated in diverse immunomodulatory responses, the effector mechanisms underlying the NKT cell-mediated regulation of pathogenic T helper cells are not well understood. Here, we show that invariant NKT cells inhibited the differentiation of CD4(+) T cells into Th17 cells both in vitro and in vivo. The number of IL-17-producing CD4(+) T cells was reduced following co-culture with purified NK1.1(+) TCR(+) cells from WT, but not from CD1d(-/-) or Jα18(-/-) , mice. Co-cultured NKT cells from either cytokine-deficient (IL-4(-/-) , IL-10(-/-) , or IFN-γ(-/-) ) or WT mice efficiently inhibited Th17 differentiation. The contact-dependent mechanisms of NKT cell-mediated regulation of Th17 differentiation were confirmed using transwell co-culture experiments. On the contrary, the suppression of Th1 differentiation was dependent on IL-4 derived from the NKT cells. The in vivo regulatory capacity of NKT cells on Th17 cells was confirmed using an experimental autoimmune uveitis model induced with human IRBP(1-20) (IRBP, interphotoreceptor retinoid-binding protein) peptide. NKT cell-deficient mice (CD1d(-/-) or Jα18(-/-) ) demonstrated an increased disease severity, which was reversed by the transfer of WT or cytokine-deficient (IL-4(-/-) , IL-10(-/-) , or IFN-γ(-/-) ) NKT cells. Our results indicate that invariant NKT cells inhibited autoimmune uveitis predominantly through the cytokine-independent inhibition of Th17 differentiation. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. Exercise training attenuates experimental autoimmune encephalomyelitis by peripheral immunomodulation rather than direct neuroprotection.

    Science.gov (United States)

    Einstein, Ofira; Fainstein, Nina; Touloumi, Olga; Lagoudaki, Roza; Hanya, Ester; Grigoriadis, Nikolaos; Katz, Abram; Ben-Hur, Tamir

    2018-01-01

    Conflicting results exist on the effects of exercise training (ET) on Experimental Autoimmune Encephalomyelitis (EAE), nor is it known how exercise impacts on disease progression. We examined whether ET ameliorates the development of EAE by modulating the systemic immune system or exerting direct neuroprotective effects on the CNS. Healthy mice were subjected to 6weeks of motorized treadmill running. The Proteolipid protein (PLP)-induced transfer EAE model in mice was utilized. To assess effects of ET on systemic autoimmunity, lymph-node (LN)-T cells from trained- vs. sedentary donor mice were transferred to naïve recipients. To assess direct neuroprotective effects of ET, PLP-reactive LN-T cells were transferred into recipient mice that were trained prior to EAE transfer or to sedentary mice. EAE severity was assessed in vivo and the characteristics of encephalitogenic LN-T cells derived from PLP-immunized mice were evaluated in vitro. LN-T cells obtained from trained mice induced an attenuated clinical and pathological EAE in recipient mice vs. cells derived from sedentary animals. Training inhibited the activation, proliferation and cytokine gene expression of PLP-reactive T cells in response to CNS-derived autoantigen, but strongly enhanced their proliferation in response to Concanavalin A, a non-specific stimulus. However, there was no difference in EAE severity when autoreactive encephalitogenic T cells were transferred to trained vs. sedentary recipient mice. ET inhibits immune system responses to an auto-antigen to attenuate EAE, rather than generally suppressing the immune system, but does not induce a direct neuro-protective effect against EAE. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Transplantation of autologous adipose stem cells lacks therapeutic efficacy in the experimental autoimmune encephalomyelitis model.

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    Xiujuan Zhang

    Full Text Available Multiple sclerosis (MS, characterized by chronic inflammation, demyelination, and axonal damage, is a complicated neurological disease of the human central nervous system. Recent interest in adipose stromal/stem cell (ASCs for the treatment of CNS diseases has promoted further investigation in order to identify the most suitable ASCs. To investigate whether MS affects the biologic properties of ASCs and whether autologous ASCs from MS-affected sources could serve as an effective source for stem cell therapy, cells were isolated from subcutaneous inguinal fat pads of mice with established experimental autoimmune encephalomyelitis (EAE, a murine model of MS. ASCs from EAE mice and their syngeneic wild-type mice were cultured, expanded, and characterized for their cell morphology, surface antigen expression, osteogenic and adipogenic differentiation, colony forming units, and inflammatory cytokine and chemokine levels in vitro. Furthermore, the therapeutic efficacy of the cells was assessed in vivo by transplantation into EAE mice. The results indicated that the ASCs from EAE mice displayed a normal phenotype, typical MSC surface antigen expression, and in vitro osteogenic and adipogenic differentiation capacity, while their osteogenic differentiation capacity was reduced in comparison with their unafflicted control mice. The ASCs from EAE mice also demonstrated increased expression of pro-inflammatory cytokines and chemokines, specifically an elevation in the expression of monocyte chemoattractant protein-1 and keratin chemoattractant. In vivo, infusion of wild type ASCs significantly ameliorate the disease course, autoimmune mediated demyelination and cell infiltration through the regulation of the inflammatory responses, however, mice treated with autologous ASCs showed no therapeutic improvement on the disease progression.

  14. In acute experimental autoimmune encephalomyelitis, infiltrating macrophages are immune activated, whereas microglia remain immune suppressed.

    Science.gov (United States)

    Vainchtein, I D; Vinet, J; Brouwer, N; Brendecke, S; Biagini, G; Biber, K; Boddeke, H W G M; Eggen, B J L

    2014-10-01

    Multiple sclerosis (MS) is an autoimmune demyelinating disorder of the central nervous system (CNS) characterized by loss of myelin accompanied by infiltration of T-lymphocytes and monocytes. Although it has been shown that these infiltrates are important for the progression of MS, the role of microglia, the resident macrophages of the CNS, remains ambiguous. Therefore, we have compared the phenotypes of microglia and macrophages in a mouse model for MS, experimental autoimmune encephalomyelitis (EAE). In order to properly discriminate between these two cell types, microglia were defined as CD11b(pos) CD45(int) Ly-6C(neg) , and infiltrated macrophages as CD11b(pos) CD45(high) Ly-6C(pos) . During clinical EAE, microglia displayed a weakly immune-activated phenotype, based on the expression of MHCII, co-stimulatory molecules (CD80, CD86, and CD40) and proinflammatory genes [interleukin-1β (IL-1β) and tumour necrosis factor- α (TNF-α)]. In contrast, CD11b(pos) CD45(high) Ly-6C(pos) infiltrated macrophages were strongly activated and could be divided into two populations Ly-6C(int) and Ly-6C(high) , respectively. Ly-6C(high) macrophages contained less myelin than Ly-6C(int) macrophages and expression levels of the proinflammatory cytokines IL-1β and TNF-α were higher in Ly-6C(int) macrophages. Together, our data show that during clinical EAE, microglia are only weakly activated whereas infiltrated macrophages are highly immune reactive. © 2014 Wiley Periodicals, Inc.

  15. Regulation of Th1 cells and experimental autoimmune encephalomyelitis (EAE) by glycogen synthase kinase-3

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    Beurel, Eléonore; Kaidanovich-Beilin, Oksana; Yeh, Wen-I; Song, Ling; Palomo, Valle; Michalek, Suzanne M.; Woodgett, James R.; Harrington, Laurie E.; Eldar-Finkelman, Hagit; Martinez, Ana; Jope, Richard S.

    2013-01-01

    Experimental autoimmune encephalomyelitis (EAE) is a rodent model of multiple sclerosis (MS), a debilitating autoimmune disease of the central nervous system, for which only limited therapeutic interventions are available. Since MS is mediated in part by autoreactive T cells, particularly Th17 and Th1 cells, in the present study, we tested if inhibitors of glycogen synthase kinase-3 (GSK3), previously reported to reduce Th17 cell generation, also alter Th1 cell production or ameliorate EAE. GSK3 inhibitors were found to impede the production of Th1 cells by reducing STAT1 activation. Molecularly reducing the expression of either of the two GSK3 isoforms demonstrated that Th17 cell production was sensitive to reduced levels of GSK3β, and Th1 cell production was inhibited in GSK3α-deficient cells. Administration of the selective GSK3 inhibitors TDZD-8, VP2.51, VP0.7, or L803-mts, significantly reduced the clinical symptoms of MOG35-55-induced EAE in mice, nearly eliminating the chronic progressive phase, and reduced the number of Th17 and Th1 cells in the spinal cord. Administration of TDZD-8 or L803-mts after the initial disease episode ameliorated clinical symptoms in a relapsing/remitting model of PLP139-151-induced EAE. Furthermore, deletion of GSK3β specifically in T cells was sufficient to ameliorate MOG35-55-induced EAE. These results demonstrate isoform-selective effects of GSK3 on T cell generation, therapeutic effects of GSK3 inhibitors in EAE, and that GSK3 inhibition in T cells is sufficient to reduce the severity of EAE, suggesting that GSK3 may be a feasible target for developing new therapeutic interventions for MS. PMID:23606540

  16. Astragaloside IV attenuates experimental autoimmune encephalomyelitis of mice by counteracting oxidative stress at multiple levels.

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    Yixin He

    Full Text Available Multiple sclerosis (MS is a chronic autoimmune neuroinflammatory disease found mostly in young adults in the western world. Oxidative stress induced neuronal apoptosis plays an important role in the pathogenesis of MS. In current study, astragaloside IV (ASI, a natural saponin molecule isolated from Astragalus membranceus, given at 20 mg/kg daily attenuated the severity of experimental autoimmune encephalomyelitis (EAE in mice significantly. Further studies disclosed that ASI treatment inhibited the increase of ROS and pro-inflammatory cytokine levels, down-regulation of SOD and GSH-Px activities, and elevation of iNOS, p53 and phosphorylated tau in central nervous system (CNS as well as the leakage of BBB of EAE mice. Meanwhile, the decreased ratio of Bcl-2/Bax was reversed by ASI. Moreover, ASI regulated T-cell differentiation and infiltration into CNS. In neuroblast SH-SY5Y cells, ASI dose-dependently reduced cellular ROS level and phosphorylation of tau in response to hydrogen peroxide challenge by modulation of Bcl-2/Bax ratio. ASI also inhibited activation of microglia both in vivo and in vitro. iNOS up-regulation induced by IFNγ stimulation was abolished by ASI dose-dependently in BV-2 cells. In summary, ASI prevented the severity of EAE progression possibly by counterbalancing oxidative stress and its effects via reduction of cellular ROS level, enhancement of antioxidant defense system, increase of anti-apoptotic and anti-inflammatory pathways, as well as modulation of T-cell differentiation and infiltration into CNS. The study suggested ASI may be effective for clinical therapy/prevention of MS.

  17. Astragaloside IV attenuates experimental autoimmune encephalomyelitis of mice by counteracting oxidative stress at multiple levels.

    Science.gov (United States)

    He, Yixin; Du, Min; Gao, Yan; Liu, Hongshuai; Wang, Hongwei; Wu, Xiaojun; Wang, Zhengtao

    2013-01-01

    Multiple sclerosis (MS) is a chronic autoimmune neuroinflammatory disease found mostly in young adults in the western world. Oxidative stress induced neuronal apoptosis plays an important role in the pathogenesis of MS. In current study, astragaloside IV (ASI), a natural saponin molecule isolated from Astragalus membranceus, given at 20 mg/kg daily attenuated the severity of experimental autoimmune encephalomyelitis (EAE) in mice significantly. Further studies disclosed that ASI treatment inhibited the increase of ROS and pro-inflammatory cytokine levels, down-regulation of SOD and GSH-Px activities, and elevation of iNOS, p53 and phosphorylated tau in central nervous system (CNS) as well as the leakage of BBB of EAE mice. Meanwhile, the decreased ratio of Bcl-2/Bax was reversed by ASI. Moreover, ASI regulated T-cell differentiation and infiltration into CNS. In neuroblast SH-SY5Y cells, ASI dose-dependently reduced cellular ROS level and phosphorylation of tau in response to hydrogen peroxide challenge by modulation of Bcl-2/Bax ratio. ASI also inhibited activation of microglia both in vivo and in vitro. iNOS up-regulation induced by IFNγ stimulation was abolished by ASI dose-dependently in BV-2 cells. In summary, ASI prevented the severity of EAE progression possibly by counterbalancing oxidative stress and its effects via reduction of cellular ROS level, enhancement of antioxidant defense system, increase of anti-apoptotic and anti-inflammatory pathways, as well as modulation of T-cell differentiation and infiltration into CNS. The study suggested ASI may be effective for clinical therapy/prevention of MS.

  18. Myeloid-derived suppressor cells as a potential therapy for experimental autoimmune myasthenia gravis.

    Science.gov (United States)

    Li, Yan; Tu, Zhidan; Qian, Shiguang; Fung, John J; Markowitz, Sanford D; Kusner, Linda L; Kaminski, Henry J; Lu, Lina; Lin, Feng

    2014-09-01

    We recently demonstrated that hepatic stellate cells induce the differentiation of myeloid-derived suppressor cells (MDSCs) from myeloid progenitors. In this study, we found that adoptive transfer of these MDSCs effectively reversed disease progression in experimental autoimmune myasthenia gravis (EAMG), a T cell-dependent and B cell-mediated model for myasthenia gravis. In addition to ameliorated disease severity, MDSC-treated EAMG mice showed suppressed acetylcholine receptor (AChR)-specific T cell responses, decreased levels of serum anti-AChR IgGs, and reduced complement activation at the neuromuscular junctions. Incubating MDSCs with B cells activated by anti-IgM or anti-CD40 Abs inhibited the proliferation of these in vitro-activated B cells. Administering MDSCs into mice immunized with a T cell-independent Ag inhibited the Ag-specific Ab production in vivo. MDSCs directly inhibit B cells through multiple mechanisms, including PGE2, inducible NO synthase, and arginase. Interestingly, MDSC treatment in EAMG mice does not appear to significantly inhibit their immune response to a nonrelevant Ag, OVA. These results demonstrated that hepatic stellate cell-induced MDSCs concurrently suppress both T and B cell autoimmunity, leading to effective treatment of established EAMG, and that the MDSCs inhibit AChR-specific immune responses at least partially in an Ag-specific manner. These data suggest that MDSCs could be further developed as a novel approach to treating myasthenia gravis and, even more broadly, other diseases in which T and B cells are involved in pathogenesis. Copyright © 2014 by The American Association of Immunologists, Inc.

  19. Vorinostat Modulates the Imbalance of T Cell Subsets, Suppresses Macrophage Activity, and Ameliorates Experimental Autoimmune Uveoretinitis.

    Science.gov (United States)

    Fang, Sijie; Meng, Xiangda; Zhang, Zhuhong; Wang, Yang; Liu, Yuanyuan; You, Caiyun; Yan, Hua

    2016-03-01

    The purpose of the study was to investigate the anti-inflammatory efficiency of vorinostat, a histone deacetylase inhibitor, in experimental autoimmune uveitis (EAU). EAU was induced in female C57BL/6J mice immunized with interphotoreceptor retinoid-binding protein peptide. Vorinostat or the control treatment, phosphate-buffered saline, was administrated orally from 3 days before immunization until euthanasia at day 21 after immunization. The clinical and histopathological scores of mice were graded, and the integrity of the blood-retinal barrier was examined by Evans blue staining. T helper cell subsets were measured by flow cytometry, and the macrophage functions were evaluated with immunohistochemistry staining and immunofluorescence assays. The mRNA levels of tight junction proteins were measured by qRT-PCR. The expression levels of intraocular cytokines and transcription factors were examined by western blotting. Vorinostat relieved both clinical and histopathological manifestations of EAU in our mouse model, and the BRB integrity was maintained in vorinostat-treated mice, which had less vasculature leakage and higher mRNA and protein expressions of tight junction proteins than controls. Moreover, vorinostat repressed Th1 and Th17 cells and increased Th0 and Treg cells. Additionally, the INF-γ and IL-17A expression levels were significantly decreased, while the IL-10 level was increased by vorinostat treatment. Furthermore, due to the reduced TNF-α level, the macrophage activity was considerably inhibited in EAU mice. Finally, transcription factors, including STAT1, STAT3, and p65, were greatly suppressed by vorinostat treatment. Our data suggest that vorinostat might be a potential anti-inflammatory agent in the management of uveitis and other autoimmune inflammatory diseases.

  20. Biomarkers in Vasculitis

    Science.gov (United States)

    Monach, Paul A.

    2014-01-01

    Purpose of review Better biomarkers are needed for guiding management of patients with vasculitis. Large cohorts and technological advances had led to an increase in pre-clinical studies of potential biomarkers. Recent findings The most interesting markers described recently include a gene expression signature in CD8+ T cells that predicts tendency to relapse or remain relapse-free in ANCA-associated vasculitis, and a pair of urinary proteins that are elevated in Kawasaki disease but not other febrile illnesses. Both of these studies used “omics” technologies to generate and then test hypotheses. More conventional hypothesis-based studies have indicated that the following circulating proteins have potential to improve upon clinically available tests: pentraxin-3 in giant cell arteritis and Takayasu’s arteritis; von Willebrand factor antigen in childhood central nervous system vasculitis; eotaxin-3 and other markers related to eosinophils or Th2 immune responses in eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome); and MMP-3, TIMP-1, and CXCL13 in ANCA-associated vasculitis. Summary New markers testable in blood and urine have the potential to assist with diagnosis, staging, assessment of current disease activity, and prognosis. However, the standards for clinical usefulness, in particular the demonstration of either very high sensitivity or very high specificity, have yet to be met for clinically relevant outcomes. PMID:24257367

  1. Fibroblasts express OvHV-2 capsid protein in vasculitis lesions of American bison (Bison bison) with experimental sheep-associated malignant catarrhal fever

    Science.gov (United States)

    Sheep-associated malignant catarrhal fever (SA-MCF) caused by ovine herpesvirus-2 (OvHV-2), a '-herpesvirus, is an often fatal disease characterized by lymphoproliferation, vasculitis, and mucosal ulceration in American bison (Bison bison), cattle (Bos taurus), and other clinically susceptible speci...

  2. Chloroquine treatment enhances regulatory T cells and reduces the severity of experimental autoimmune encephalomyelitis.

    Directory of Open Access Journals (Sweden)

    Rodolfo Thomé

    Full Text Available BACKGROUND: The modulation of inflammatory processes is a necessary step, mostly orchestrated by regulatory T (Treg cells and suppressive Dendritic Cells (DCs, to prevent the development of deleterious responses and autoimmune diseases. Therapies that focused on adoptive transfer of Treg cells or their expansion in vivo achieved great success in controlling inflammation in several experimental models. Chloroquine (CQ, an anti-malarial drug, was shown to reduce inflammation, although the mechanisms are still obscure. In this context, we aimed to access whether chloroquine treatment alters the frequency of Treg cells and DCs in normal mice. In addition, the effects of the prophylactic and therapeutic treatment with CQ on Experimental Autoimmune Encephalomyelitis (EAE, an experimental model for human Multiple Sclerosis, was investigated as well. METHODOLOGY/PRINCIPAL FINDINGS: EAE was induced in C57BL/6 mice by immunization with myelin oligodendrocyte glycoprotein (MOG35-55 peptide. C57BL/6 mice were intraperitoneally treated with chloroquine. Results show that the CQ treatment provoked an increase in Treg cells frequency as well as a decrease in DCs. We next evaluated whether prophylactic CQ administration is capable of reducing the clinical and histopathological signs of EAE. Our results demonstrated that CQ-treated mice developed mild EAE compared to controls that was associated with lower infiltration of inflammatory cells in the central nervous system CNS and increased frequency of Treg cells. Also, proliferation of MOG35-55-reactive T cells was significantly inhibited by chloroquine treatment. Similar results were observed when chloroquine was administrated after disease onset. CONCLUSION: We show for the first time that CQ treatment promotes the expansion of Treg cells, corroborating previous reports indicating that chloroquine has immunomodulatory properties. Our results also show that CQ treatment suppress the inflammation in the CNS of

  3. Functional Magnetic Resonance Imaging of Rats with Experimental Autoimmune Encephalomyelitis Reveals Brain Cortex Remodeling

    Science.gov (United States)

    Tambalo, Stefano; Peruzzotti-Jametti, Luca; Rigolio, Roberta; Fiorini, Silvia; Bontempi, Pietro; Mallucci, Giulia; Balzarotti, Beatrice; Marmiroli, Paola; Sbarbati, Andrea; Cavaletti, Guido

    2015-01-01

    Cortical reorganization occurring in multiple sclerosis (MS) patients is thought to play a key role in limiting the effect of structural tissue damage. Conversely, its exhaustion may contribute to the irreversible disability that accumulates with disease progression. Several aspects of MS-related cortical reorganization, including the overall functional effect and likely modulation by therapies, still remain to be elucidated. The aim of this work was to assess the extent of functional cortical reorganization and its brain structural/pathological correlates in Dark Agouti rats with experimental autoimmune encephalomyelitis (EAE), a widely accepted preclinical model of chronic MS. Morphological and functional MRI (fMRI) were performed before disease induction and during the relapsing and chronic phases of EAE. During somatosensory stimulation of the right forepaw, fMRI demonstrated that cortical reorganization occurs in both relapsing and chronic phases of EAE with increased activated volume and decreased laterality index versus baseline values. Voxel-based morphometry demonstrated gray matter (GM) atrophy in the cerebral cortex, and both GM and white matter atrophy were assessed by ex vivo pathology of the sensorimotor cortex and corpus callosum. Neuroinflammation persisted in the relapsing and chronic phases, with dendritic spine density in the layer IV sensory neurons inversely correlating with the number of cluster of differentiation 45-positive inflammatory lesions. Our work provides an innovative experimental platform that may be pivotal for the comprehension of key mechanisms responsible for the accumulation of irreversible brain damage and for the development of innovative therapies to reduce disability in EAE/MS. SIGNIFICANCE STATEMENT Since the early 2000s, functional MRI (fMRI) has demonstrated profound modifications in the recruitment of cortical areas during motor, cognitive, and sensory tasks in multiple sclerosis (MS) patients. Experimental autoimmune

  4. Headache in autoimmune diseases.

    Science.gov (United States)

    John, Seby; Hajj-Ali, Rula A

    2014-03-01

    Autoimmune diseases are a group of heterogeneous inflammatory disorders characterized by systemic or localized inflammation, leading to ischemia and tissue destruction. These include disorders like systemic lupus erythematosus and related diseases, systemic vasculitides, and central nervous system (CNS) vasculitis (primary or secondary). Headache is a very common manifestation of CNS involvement of these diseases. Although headache characteristics can be unspecific and often non-diagnostic, it is important to recognize because headache can be the first manifestation of CNS involvement. Prompt recognition and treatment is necessary not only to treat the headache, but also to help prevent serious neurological sequelae that frequently accompany autoimmune diseases. In this review, we discuss headache associated with autoimmune diseases along with important mimics. © 2014 American Headache Society.

  5. Systemic vasculitis and the gut.

    Science.gov (United States)

    Hatemi, Ibrahim; Hatemi, Gulen; Çelik, Aykut F

    2017-01-01

    Gastrointestinal system can be involved in primary and secondary vasculitides. The recent data regarding the pathophysiology, clinical findings, diagnosis, management, and outcome of gastrointestinal involvement in different types of vasculitis are reviewed. Diagnosis of gastrointestinal vasculitis may be difficult and relies mostly on imaging, because biopsy samples are hard to obtain and superficial mucosal biopsies have a low yield. There are conflicting reports on the association of antineutrophilic cytoplasmic antibodies (ANCA) type with the frequency of gastrointestinal involvement in ANCA-associated vasculitis. Pancreatitis is a rare but serious complication of ANCA-associated vasculitis. Terminal ileitis may be observed in immunoglobulin A vasculitis and can be hard to distinguish from Crohn's disease. High fecal calprotectin levels can indicate active gastrointestinal involvement in both immunoglobulin A vasculitis and Behçet's syndrome. Refractory gastrointestinal involvement in Behçet's syndrome can be treated with thalidomide and/or TNF-α antagonists. The outcome of mesenteric vasculitis in systemic lupus erythematosus can be improved with high-dose glucocorticoids and cyclophosphamide or rituximab. Gastrointestinal system can be commonly involved in immunoglobulin A vasculitis, ANCA-associated vasculitis, polyarteritis nodosa, and Behçet's syndrome and can be an important cause of morbidity and mortality. Treatment depends on the type of vasculitis and is usually with high-dose corticosteroids and immunosuppressives.

  6. Genetically Distinct Subsets within ANCA-Associated Vasculitis

    Science.gov (United States)

    Lyons, Paul A.; Rayner, Tim F.; Trivedi, Sapna; Holle, Julia U.; Watts, Richard A.; Jayne, David R.W.; Baslund, Bo; Brenchley, Paul; Bruchfeld, Annette; Chaudhry, Afzal N.; Tervaert, Jan Willem Cohen; Deloukas, Panos; Feighery, Conleth; Gross, Wolfgang L.; Guillevin, Loic; Gunnarsson, Iva; P, Lorraine Harper M.R.C; Hrušková, Zdenka; Little, Mark A.; Martorana, Davide; Neumann, Thomas; Ohlsson, Sophie; Padmanabhan, Sandosh; Pusey, Charles D.; Salama, Alan D.; Sanders, Jan-Stephan F.; Savage, Caroline O.; Segelmark, Mårten; Stegeman, Coen A.; Tesař, Vladimir; Vaglio, Augusto; Wieczorek, Stefan; Wilde, Benjamin; Zwerina, Jochen; Rees, Andrew J.; Clayton, David G.; Smith, Kenneth G.C.

    2013-01-01

    BACKGROUND Antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis is a severe condition encompassing two major syndromes: granulomatosis with polyangiitis (formerly known as Wegener’s granulomatosis) and microscopic polyangiitis. Its cause is unknown, and there is debate about whether it is a single disease entity and what role ANCA plays in its pathogenesis. We investigated its genetic basis. METHODS A genomewide association study was performed in a discovery cohort of 1233 U.K. patients with ANCA-associated vasculitis and 5884 controls and was replicated in 1454 Northern European case patients and 1666 controls. Quality control, population stratification, and statistical analyses were performed according to standard criteria. RESULTS We found both major-histocompatibility-complex (MHC) and non-MHC associations with ANCA-associated vasculitis and also that granulomatosis with polyangiitis and microscopic polyangiitis were genetically distinct. The strongest genetic associations were with the antigenic specificity of ANCA, not with the clinical syndrome. Anti–proteinase 3 ANCA was associated with HLA-DP and the genes encoding α1-antitrypsin (SERPINA1) and proteinase 3 (PRTN3) (P = 6.2×10−89, P = 5.6×10−12, and P = 2.6×10−7, respectively). Anti–myeloperoxidase ANCA was associated with HLA-DQ (P = 2.1×10−8). CONCLUSIONS This study confirms that the pathogenesis of ANCA-associated vasculitis has a genetic component, shows genetic distinctions between granulomatosis with polyangiitis and microscopic polyangiitis that are associated with ANCA specificity, and suggests that the response against the autoantigen proteinase 3 is a central pathogenic feature of proteinase 3 ANCA–associated vasculitis. These data provide preliminary support for the concept that proteinase 3 ANCA–associated vasculitis and myeloperoxidase ANCA–associated vasculitis are distinct autoimmune syndromes. (Funded by the British Heart Foundation and others.) PMID

  7. Protective influences on experimental autoimmune encephalomyelitis by MHC class I and class II alleles

    DEFF Research Database (Denmark)

    Mustafa, M; Vingsbo, C; Olsson, T

    1994-01-01

    are resistant. Interestingly, rats with the MHC u haplotype develop an immune response to the MBP 63-88, but do not get EAE. In this study we have used intra-MHC recombinant rat strains to compare the influences of the MHC u with the a haplotype. We discovered the following: 1) The class II region of the MHC...... a haplotype permits EAE and a Th1 type of immune response as measured by IFN-gamma production after in vitro challenge of in vivo-primed T cells with MBP 63-88. 2) The class II region of the u haplotype is associated with a disease-protective immune response characterized by production of not only IFN......Experimental autoimmune encephalomyelitis (EAE) is influenced by polymorphism of the MHC. We have previously found that Lewis rats with certain MHC haplotypes are susceptible to disease induced with the myelin basic protein (MBP) peptide 63-88, whereas Lewis rats with other MHC haplotypes...

  8. The experimental autoimmune encephalomyelitis disease course is modulated by nicotine and other cigarette smoke components.

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    Zhen Gao

    Full Text Available Epidemiological studies have reported that cigarette smoking increases the risk of developing multiple sclerosis (MS and accelerates its progression. However, the molecular mechanisms underlying these effects remain unsettled. We have investigated here the effects of the nicotine and the non-nicotine components in cigarette smoke on MS using the experimental autoimmune encephalomyelitis (EAE model, and have explored their underlying mechanism of action. Our results show that nicotine ameliorates the severity of EAE, as shown by reduced demyelination, increased body weight, and attenuated microglial activation. Nicotine administration after the development of EAE symptoms prevented further disease exacerbation, suggesting that it might be useful as an EAE/MS therapeutic. In contrast, the remaining components of cigarette smoke, delivered as cigarette smoke condensate (CSC, accelerated and increased adverse clinical symptoms during the early stages of EAE, and we identify a particular cigarette smoke compound, acrolein, as one of the potential mediators. We also show that the mechanisms underlying the opposing effects of nicotine and CSC on EAE are likely due to distinct effects on microglial viability, activation, and function.

  9. Differential effects of B7-1 blockade in the rat experimental autoimmune encephalomyelitis model

    DEFF Research Database (Denmark)

    Gallon, L; Chandraker, A; Issazadeh-Navikas, Shohreh

    1997-01-01

    that CD28-B7 blockade by systemic administration of CTLA4Ig prevents actively induced EAE. Since CTLA4Ig binds to both B7-1 and B7-2, we used a mutant form of CTLA4Ig (CTLA4IgY100F) that binds only B7-1, to study the role of B7-1 blockade in this model. Such a reagent avoids the potential of signaling...... treated with systemic CTLA4gY100F did not. More importantly, systemic administration of CTLA4IgY100F abrogated the protective effect of ex vivo treated APCs. These data suggest an important regulatory role for B7-1, perhaps through binding to CTLA4, in this model of EAE. Understanding the role......Blocking the CD28-B7 T cell costimulatory activation pathway protects animals from developing experimental autoimmune encephalomyelitis (EAE). In the mouse EAE model, selective blockade of B7-1 by specific mAbs has been shown to protect animals from EAE. In the Lewis rat model, we have shown...

  10. SAP Suppresses the Development of Experimental Autoimmune Encephalomyelitis in C57BL6 Mice

    Science.gov (United States)

    Ji, Zhe; Ke, Zun-Ji; Geng, Jian-Guo

    2012-01-01

    Experimental autoimmune encephalomyelitis (EAE) is a CD4+ T cell-mediated disease of the CNS. Serum amyloid P component (SAP) is a highly conserved plasma protein named for its universal presence in amyloid deposits. Here we report SAP transgenic mice had unexpectedly attenuated EAE due to impaired encephalitogenic responses. Following induction with myelin oligodendroglial glycoprotein (MOG) peptide 35–55 in CFA, SAP transgenic mice showed reduced spinal cord inflammation with lower severity of EAE attacks as compared with control C57BL/6 mice. However in SAP-KO mice, the severity of EAE is enhanced. Adoptive transfer of Ag-restimulated T cells from wild-type to SAP transgenic mice or transfer of SAP transgenic Ag-restimulated T cells to control mice induced milder EAE. T cells from MOG-primed SAP transgenic mice showed weak proliferative responses. Furthermore, in SAP transgenic mice, there is little infiltration of CD45-positive cells in the spinal cord. In vitro, SAP suppressed the secretion of IL-2 stimulated by P-selectin, and blocked P-selectin binding to T cells. Moreover, SAP could change the affinity between α4-integrin and T cells. These data suggested that SAP could antagonize the development of the acute phase of inflammation accompanying EAE by modulating the function of P-selectin. PMID:21647172

  11. Augmentation of transfer of experimental autoimmune thyroiditis (EAT) in mice by irradiation of recipients

    International Nuclear Information System (INIS)

    Williams, W.V.; Kyriakos, M.; Sharp, G.C.; Braley-Mullen, H.

    1987-01-01

    Experimental autoimmune thyroiditis (EAT) can be adoptively transferred to normal syngeneic recipients using spleen cells from susceptible strains of mice primed in vivo with mouse thyroglobulin (MTg) and lipopolysaccharide (LPS) following in vitro activation of spleen cells by culture with MTg. Irradiation of recipient animals markedly augments the severity of thyroiditis induced in this system. Irradiation of recipients does not alter the time course of the development of thyroiditis, nor does it alter the requirement for both in vivo priming and in vitro activation of spleen cells for the development of EAT. Spleen cells from EAT-resistant strains of mice (e.g., Balb/c) do not induce EAT in irradiated recipients. Irradiated recipients develop significant levels of anti-MTg antibodies while unirradiated recipients have little detectable antibody response. The augmenting effect of irradiation can be substantially reversed by transferring naive spleen cells to recipients prior to the transfer of MTg/LPS-primed in vitro-activated spleen cells. In addition athymic CBA/Tufts nude mice develop more severe EAT than CBA/Tufts nude/+ littermates following transfer of activated CBA/J spleen cells. These data suggest that natural suppressor cells may regulate the development of EAT at the effector cell level

  12. The mechanism of effective electroacupuncture on T cell response in rats with experimental autoimmune encephalomyelitis.

    Directory of Open Access Journals (Sweden)

    Yumei Liu

    Full Text Available Previously, we demonstrated that electroacupuncture (EA decreased lymphocyte infiltration into the spinal cords of rats presenting with experimental autoimmune encephalomyelitis (EAE, a disease model used in the study of multiple sclerosis (MS. The aim of this study was to characterize the effects of EA on the EAE. Female Lewis rats were divided into either CFA, EAE, EA, or injection with naloxone after electroacupuncture (NAL groups. Electroacupuncture was administered every day for 21 days. To evaluate proliferation and apoptosis, lymphocytes from rats presenting with EAE were collected and cultured with β-endorphin. Immunohistochemisty, flow cytometry and radio-immunity methods were applied to detect the expression of β-endorphin. Results presented in this report demonstrate that the beneficial anti-inflammatory effects of EA on EAE were related to β-endorphin production that balances the Thl/Th2 and Th17/Treg responses. These results suggest that β-endorphin could be an important component in the development of EA-based therapies used for the treatment of EAE.

  13. Immune mechanisms in the transfer of experimental autoimmune encephalomyelitis without adjuvant

    International Nuclear Information System (INIS)

    Silberg, D.G.

    1985-01-01

    Experimental autoimmune encephalomyelitis (EAE) can be induced in Lewis rats without the use of adjuvant. Spleen cells of naive rats were sensitized to myelin basic protein (MBP) in vitro. Transfer of these cells did not result in the development of EAE. However, spleen cells from primary recipients, taken 10 days post transfer, and cultured with MBP (secondary culture, transferred EAE to secondary recipients. EAE can be induced in primary recipients by the transfer of secondary cultured cells or cultured cells or challenge with MBP in complete Freund's adjuvant (CFA) or incomplete Freund's adjuvant (IFA) 10 days after injection of naive cultured cells. The finding that MBP-CFA challenged 1' recipients developed EAE, suggests that the rats have been primed to MBP through the naive cultured cell transfer. The cells from naive culture that sensitize the primary recipient were radioresistant (1500 R), probably macrophages. This is in contrast to the cells transferring EAE to the secondary recipient, which were radiosensitive. Unlike the spleen cells which transfer EAE from MBP-CFA sensitized rats, the cells in the secondary transfer could not be activated to transfer EAE when cultured with concanavalin A. Clinical EAE in the secondary recipient was more severe when these rats were irradiated (200 R) prior to transfer. There is evidence that low dose irradiation eliminates naturally occurring suppressor cells. EAE also developed in lethally irradiated (850 R) recipients of secondary cultured cells, suggesting that the transferred cells can induce EAE alone or by recruiting radioresistant cells in the secondary host

  14. Neuropathic pain in experimental autoimmune neuritis is associated with altered electrophysiological properties of nociceptive DRG neurons.

    Science.gov (United States)

    Taha, Omneya; Opitz, Thoralf; Mueller, Marcus; Pitsch, Julika; Becker, Albert; Evert, Bernd Oliver; Beck, Heinz; Jeub, Monika

    2017-11-01

    Guillain-Barré syndrome (GBS) is an acute, immune-mediated polyradiculoneuropathy characterized by rapidly progressive paresis and sensory disturbances. Moderate to severe and often intractable neuropathic pain is a common symptom of GBS, but its underlying mechanisms are unknown. Pathology of GBS is classically attributed to demyelination of large, myelinated peripheral fibers. However, there is increasing evidence that neuropathic pain in GBS is associated with impaired function of small, unmyelinated, nociceptive fibers. We therefore examined the functional properties of small DRG neurons, the somata of nociceptive fibers, in a rat model of GBS (experimental autoimmune neuritis=EAN). EAN rats developed behavioral signs of neuropathic pain. This was accompanied by a significant shortening of action potentials due to a more rapid repolarization and an increase in repetitive firing in a subgroup of capsaicin-responsive DRG neurons. Na + current measurements revealed a significant increase of the fast TTX-sensitive current and a reduction of the persistent TTX-sensitive current component. These changes of Na + currents may account for the significant decrease in AP duration leading to an overall increase in excitability and are therefore possibly directly linked to pathological pain behavior. Thus, like in other animal models of neuropathic and inflammatory pain, Na + channels seem to be crucially involved in the pathology of GBS and may constitute promising targets for pain modulating pharmaceuticals. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Autophagy regulates the therapeutic potential of mesenchymal stem cells in experimental autoimmune encephalomyelitis.

    Science.gov (United States)

    Dang, Shipeng; Xu, Huanbai; Xu, Congfeng; Cai, Wei; Li, Qian; Cheng, Yiji; Jin, Min; Wang, Ru-Xing; Peng, Yongde; Zhang, Yi; Wu, Changping; He, Xiaozhou; Wan, Bing; Zhang, Yanyun

    2014-07-01

    Mesenchymal stem cell (MSC)-based therapy is a promising approach to treat various inflammatory disorders including multiple sclerosis. However, the fate of MSCs in the inflammatory microenvironment is largely unknown. Experimental autoimmune encephalomyelitis (EAE) is a well-studied animal model of multiple sclerosis. We demonstrated that autophagy occurred in MSCs during their application for EAE treatment. Inflammatory cytokines, e.g., interferon gamma and tumor necrosis factor, induced autophagy in MSCs synergistically by inducing expression of BECN1/Beclin 1. Inhibition of autophagy by knockdown of Becn1 significantly improved the therapeutic effects of MSCs on EAE, which was mainly attributable to enhanced suppression upon activation and expansion of CD4(+) T cells. Mechanistically, inhibition of autophagy increased reactive oxygen species generation and mitogen-activated protein kinase 1/3 activation in MSCs, which were essential for PTGS2 (prostaglandin-endoperoxide synthase 2 [prostaglandin G/H synthase and cyclooxygenase]) and downstream prostaglandin E2 expression to exert immunoregulatory function. Furthermore, pharmacological treatment of MSCs to inhibit autophagy increased their immunosuppressive effects on T cell-mediated EAE. Our findings indicate that inflammatory microenvironment-induced autophagy downregulates the immunosuppressive function of MSCs. Therefore, modulation of autophagy in MSCs would provide a novel strategy to improve MSC-based immunotherapy.

  16. Recombinant human acetylcholine receptor alpha-subunit induces chronic experimental autoimmune myasthenia gravis.

    Science.gov (United States)

    Lennon, V A; Lambert, E H; Leiby, K R; Okarma, T B; Talib, S

    1991-04-01

    A synthetic gene encoding the 210 N-terminal residues of the alpha-subunit of the nicotinic acetylcholine receptor (AChR) of human skeletal muscle was cloned into an inducible expression plasmid to produce a fusion protein in high yield in Escherichia coli. Like native human AChR, the recombinant human alpha 1-210 protein induced AChR-binding, AChR-modulating, and AChR-blocking autoantibodies in rats when injected once intradermally as an emulsion in CFA, with Bordetella pertussis vaccine as supplementary adjuvant. The minimum dose of recombinant protein required to induce biochemical signs of experimental autoimmune myasthenia gravis (EAMG) with 100% incidence was 2.2 micrograms. With 6.6 to 22 micrograms, serum levels of autoantibodies were persistent, and clinically apparent EAMG lasted more than a month. Clinical, electrophysiological, and biochemical indices of EAMG induced by doses of 66 micrograms or more were more uniformly severe and persistent, with 33% fatality. Rats receiving a control extract of E. coli containing plasmid without the alpha 1-210 codon insert, with adjuvants, did not develop autoantibodies or signs of EAMG. This highly reproducible new model of EAMG induced by a recombinant human autoantigen should be valuable for testing Ag-specific immunotherapeutic strategies that might be applicable to treating acquired myasthenia gravis in humans.

  17. Regulation of adenosine deaminase (ADA) on induced mouse experimental autoimmune uveitis (EAU) ‡

    Science.gov (United States)

    Liang, Dongchun; Zuo, Aijun; Zhao, Ronglan; Shao, Hui; Kaplan, Henry J.; Sun, Deming

    2016-01-01

    Adenosine is an important regulator of the immune response and adenosine deaminase (ADA) inhibits this regulatory effect by converting adenosine into functionally inactive molecules. Studies have shown that adenosine receptor (AR) agonists can be either anti- or pro-inflammatory. Clarification of the mechanisms that cause these opposing effects should provide a better guide for therapeutic intervention. In this study, we investigated the effect of ADA on the development of experimental autoimmune uveitis (EAU) induced by immunizing EAU-prone mice with a known uveitogenic peptide, IRBP1–20. Our results showed that the effective time to administer a single dose of ADA to suppress induction of EAU was 8–14 days post-immunization, shortly before EAU expression, but ADA treatment at other time points exacerbated disease. ADA preferentially inhibited Th17 responses and this effect was γδ T cell-dependent. Our results demonstrated that the existing immune status strongly influences the anti- or proinflammatory effects of ADA. Our observations should help improve the design of ADA- and AR-targeted therapies. PMID:26856700

  18. Vorinostat, a histone deacetylase inhibitor, suppresses dendritic cell function and ameliorates experimental autoimmune encephalomyelitis.

    Science.gov (United States)

    Ge, Zhenzhen; Da, Yurong; Xue, Zhenyi; Zhang, Kai; Zhuang, Hao; Peng, Meiyu; Li, Yan; Li, Wen; Simard, Alain; Hao, Junwei; Yao, Zhi; Zhang, Rongxin

    2013-03-01

    Vorinostat, a histone deacetylase inhibitor, has been used clinically as an anticancer drug and also has immunosuppressive properties. However, the underlying mechanisms of effects of vorinostat on central nervous system (CNS) inflammatory diseases remain incomplete. Here, this study investigates the effects of vorinostat on human CD14(+) monocyte-derived dendritic cells (DCs) and mouse immature DC in vitro. Furthermore, we explore the therapeutic effects and cellular mechanisms of vorinostat on animal model of multiple sclerosis, experimental autoimmune encephalomyelitis (EAE) in vivo. Our findings demonstrate that vorinostat inhibited human CD14(+) monocyte-derived DCs differentiation, maturation, endocytosis, and further inhibited mDCs' stimulation of allogeneic T-cell proliferation. In addition, vorinostat inhibited DC-directed Th1- (Type 1T helper) and Th17-polarizing cytokine production. Furthermore, vorinostat ameliorated Th1- and Th17-mediated EAE by reducing CNS inflammation and demyelination. What's more, Th1 and Th17 cell functions were suppressed in vorinostat-treated EAE mice. Finally, vorinostat suppressed expression of costimulatory molecules of DC in EAE mice. These suggest therapeutic effects of vorinostat on EAE which may by suppress DCs and DCs-mediated Th1 and Th17 cell functions. Our findings warrant further investigation in the potential of vorinostat for the treatment of human multiple sclerosis. Copyright © 2012. Published by Elsevier Inc.

  19. Combined treatment with ribavirin and tiazofurin attenuates response of glial cells in experimental autoimmune encephalomyelitis

    Directory of Open Access Journals (Sweden)

    Nedeljković Nadežda

    2012-01-01

    Full Text Available Experimental autoimmune encephalomyelitis (EAE is an animal model of multiple sclerosis (MS, a human inflammatory and demyelinating disease. Microglia and astrocytes are glial cells of the central nervous system (CNS that play a dual role in MS and EAE pathology. The aim of this study was to examine the effect of combined treatment with two nucleoside analogues, ribavirin and tiazofurin, on microglia and astrocytes in actively induced EAE. Therapeutic treatment with a combination of these two nucleoside analogues reduced disease severity, mononuclear cell infiltration and demyelination. The obtained histological results indicate that ribavirin and tiazofurin changed activated microglia into an inactive type and attenuated astrocyte reactivity at the end of the treatment period. Since reduction of reactive microgliosis and astrogliosis correlated with EAE suppression, the present study also suggests that the obtained beneficial effect of ribavirin and tiazofurin could be a consequence of their action inside as well as outside the CNS. [Acknowledgments. This work was supported by the Serbian Ministry of Education and Science, Project No: III41014.

  20. Isolated vasculitis of the CNS

    International Nuclear Information System (INIS)

    Block, F.; Reith, W.

    2000-01-01

    Vasculitis is a rare cause for disease of the CNS. The isolated vasculitis of the CNS is restricted to the CNS whereas other forms of vasculitis affect various organs including the CNS. Headache, encephalopathy, focal deficits and epileptic seizures are the major symptoms suggestive for vasculitis. One major criterion of the isolated vasculitis of the CNS is the lack of evidence for other vasculitis forms or for pathology of other organs. Angiography displays multifocal segmental stenosis of intracranial vessels. MRI demonstrates multiple lesions which in part show enhancement after gadolinium. A definite diagnosis can only be made on the grounds of biopsy from leptomeninges and parenchyma. Therapy consists of corticosteroids and cyclophosphamid. (orig.) [de

  1. Experimental autoimmune myasthenia gravis may occur in the context of a polarized Th1- or Th2-type immune response in rats

    DEFF Research Database (Denmark)

    Saoudi, A; Bernard, I; Hoedemaekers, A

    1999-01-01

    Experimental autoimmune myasthenia gravis (EAMG) is a T cell-dependent, Ab-mediated autoimmune disease induced in rats by a single immunization with acetylcholine receptor (AChR). Although polarized Th1 responses have been shown to be crucial for the development of mouse EAMG, the role of Th cell...

  2. Gray Matter Hypoxia in the Brain of the Experimental Autoimmune Encephalomyelitis Model of Multiple Sclerosis

    Science.gov (United States)

    Johnson, Thomas W.; Wu, Ying; Nathoo, Nabeela; Rogers, James A.; Wee Yong, V.; Dunn, Jeff F.

    2016-01-01

    Background Multiple sclerosis (MS) has a significant inflammatory component and may have significant gray matter (GM) pathophysiology. Brain oxygenation is a sensitive measurement of the balance between metabolic need and oxygen delivery. There is evidence that inflammation and hypoxia are interdependent. In this paper, we applied novel, implanted PO2 sensors to measure hypoxia in cortical and cerebellar GM, in an inflammation-induced mouse model of MS. Objective Quantify oxygenation in cortical and cerebellar GM in the awake, unrestrained experimental autoimmune encephalomyelitis (EAE) mouse model and to relate the results to symptom level and disease time-course. Methods C57BL/6 mice were implanted with a fiber-optic sensor in the cerebellum (n = 13) and cortex (n = 24). Animals were induced with stimulation of the immune response and sensitization to myelin oligodendrocyte glycoprotein (MOG). Controls did not have MOG. We measured PO2 in awake, unrestrained animals from pre-induction (baseline) up to 36 days post-induction for EAE and controls. Results There were more days with hypoxia than hyperoxia (cerebellum: 34/67 vs. 18/67 days; cortex: 85/112 vs. 22/112) compared to time-matched controls. The average decline in PO2 on days that were significantly lower than time-matched controls was -8.8±6.0 mmHg (mean ± SD) for the cerebellum and -8.0±4.6 for the cortex. Conversely, the average increase in PO2 on days that were significantly hyperoxic was +3.2±2.8 mmHg (mean ± SD) for the cerebellum and +0.8±2.1 for the cortex. Cortical hypoxia related to increased behavioral deficits. Evidence for hypoxia occurred before measurable behavioral deficits. Conclusions A highly inflammatory condition primed to a white matter (WM) autoimmune response correlates with significant hypoxia and increased variation in oxygenation in GM of both cerebellum and cortex in the mouse EAE model of MS. PMID:27907119

  3. Coagulopathy triggered autoimmunity: experimental antiphospholipid syndrome in factor V Leiden mice

    Science.gov (United States)

    2013-01-01

    Background We investigated interactions between genetically and autoimmune-mediated coagulopathies by inducing experimental antiphospholipid syndrome (eAPS) in mice carrying the factor V Leiden (FVL) mutation. Methods eAPS was induced in heterozygous and homozygous FVL transgenic mice (C57BL/6 background) by immunization with β2-glycoprotein I (β2-GPI). Autoantibody levels were measured at 1 and 5 months post-immunization. Mice were tested at 4 months post-immunization for behavior and cognitive function in the staircase, elevated plus-maze, and swim T-maze tests. Brains were removed and analyzed by immunohistochemistry for inflammatory markers and neurodegenerative processes. Results A single immunization with β2-GPI induced significantly higher and longer-lasting immune responses, and this was dependent on the number of FVL alleles. At 1 and 5 months post-immunization, levels of antibodies rose from 1.17 ± 0.07 to 1.62 ± 0.17 (optical density units; ODU) in homozygous FVL mice, compared with stable levels of 0.59 ± 0.17 and 0.48 ± 0.16 ODU in heterozygous FVL mice and a drop from 1.62 ± 0.21 to 0.61 ± 0.13 ODU in wild-type mice. Behavioral and cognitive clinical features of eAPS were also correlated with FVL allele load, as assessed by the elevated plus-maze (altered anxiety), staircase (hyperactivity and higher exploration), and swim T-maze (impaired learning) tests. Histological studies identified significant neurodegenerative changes in both grey and white matter in the eAPS-FVL brains. In spite of the potential interaction of two prothrombotic disease states, there were no ischemic lesions seen in this group. Conclusions The results indicate that genetically mediated coagulopathies increase the risk of developing coagulation-targeted autoimmune responses, and suggest the importance of antibody-mediated neurodegenerative processes in the brain in APS. PMID:23566870

  4. Cerebral MR imaging in vasculitis

    International Nuclear Information System (INIS)

    Ott, D.; Geissler, A.; Peter, H.H.

    1990-01-01

    This paper evaluates the diagnostic sensitivity and specificity of MR imaging for the detection of cerebral involvement in vasculitis. Seventy-six patient with proved systematic vasculitis and two with isolated cerebral vasculitis were examined. Half of them had central nervous system symptoms. T2-weighted sequences were performed at 2 T in most cases. All but two symptomatic and one-third of the asymptomatic patients showed pathologic changes in the white matter. The distribution and shape of lesions depend on the caliber of the involved vessel. In small-vessel vasculitis, the distribution was mostly subcortical, the average size was 0.5--10 mm, and lesions were predominantly round

  5. Vasculitis of the mesenteric circulation.

    Science.gov (United States)

    Koster, Matthew J; Warrington, Kenneth J

    2017-02-01

    Vasculitis of the mesenteric circulation is an uncommon but life-threatening manifestation of systemic vasculitis. Initial symptoms are frequently non-specific and therefore patients often present to primary care physicians and gastroenterologists with abdominal pain or gastrointestinal bleeding. Given the severity of the conditions associated with mesenteric vasculitis, it is imperative to appropriately diagnose and initiate treatment of suspected cases. This review will focus on diseases commonly associated with vasculitis of the mesenteric vessels. Imaging characteristics and clinical features assisting in diagnosis as well as initial approaches to treatment are emphasized. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. Diagnosis and classification of autoimmune orchitis.

    Science.gov (United States)

    Silva, C A; Cocuzza, M; Carvalho, J F; Bonfá, E

    2014-01-01

    Autoimmune orchitis is characterized by testis inflammation and the presence of specific antisperm antibodies (ASA). It is classified in two categories. Primary autoimmune orchitis is defined by infertility and asymptomatic orchitis associated with ASA (100%) directed to the basement membrane or seminiferous tubules in infertile men, without any systemic disease and usually asymptomatic. Secondary autoimmune orchitis is characterized by symptomatic orchitis and/or testicular vasculiti`s associated with a systemic autoimmune disease, particularly vasculitis. These patients typically demonstrate testicular pain, erythema and/or swelling. ASA in secondary autoimmune orchitis have been reported in up to 50% of patients, especially in systemic lupus erythematosus patients. The pathogenesis of primary as well as secondary autoimmune orchitis is still unknown. Although the etiology is likely to be multifactorial, testicular inflammation, infection or trauma may induce T cell response with pro-inflammatory cytokine production with a consequent blood-testis-barrier permeability alteration, ASA production and apoptosis of spermatocytes and spermatids. ASA is known to cause immobilization and/or agglutination of spermatozoa, which may block sperm-egg interaction resulting in infertility. Assisted reproduction has been used as an efficient option in primary cases and immunosuppressive therapy for secondary autoimmune orchitis, although there is no double-blind, randomized trial to confirm the efficacy of any treatment regimens for these conditions. Copyright © 2014 Elsevier B.V. All rights reserved.

  7. Specific and strain-independent effects of dexamethasone in the prevention and treatment of experimental autoimmune encephalomyelitis in rodents

    DEFF Research Database (Denmark)

    Donia, M; Mangano, K; Quattrocchi, C

    2010-01-01

    Experimental autoimmune encephalomyelitis in rodents (EAE) is a generally accepted in vivo model for immunopathogenic mechanisms underlying multiple sclerosis (MS). There are, however, different forms of rodent EAE, and therapeutic regimens may affect these forms differently. We have therefore te...... predictors of drug efficacy in at least some variants of human MS. Better understanding of the clinical and immunopharmacologic features of these models might prove useful when testing new drug candidates for MS treatment....

  8. Hyperinducibility of Ia antigen on astrocytes correlates with strain-specific susceptibility to experimental autoimmune encephalomyelitis

    International Nuclear Information System (INIS)

    Massa, P.T.; ter Meulen, V.; Fontana, A.

    1987-01-01

    In search of a phenotypic marker determining genetically controlled susceptibility to delayed-type hypersensitivity (DTH) reactions in the brain-in particular, experimental autoimmune encephalomyelitis (EAE)- the authors have compared the γ-interferon (IFN-γ) induction of Ia molecules on astrocytes and macrophages from rat and mouse strains that are susceptible or resistant to this disease. They focused on Ia expression because DTH reactions to self or foreign antigens are largely mediated by lymphocytes restricted by class II (Ia) antigens of the major histocompatibility complex (MHC). The data demonstrate that Lewis (fully susceptible) and Brown Norway (BN) (fully resistant) rats are very different in that Lewis astrocytes express much higher levels of Ia than BN astrocytes. Similar data were obtained from an analysis of EAE-susceptible and -resistant mouse strains (SJL and BALB/c, respectively), which suggest that this phenomenon may be universal and not limited to only one mammalian species. At least one gene responsible for Ia hyperinduction is located outside the rat RT-1 or the mouse MHC locus. Animals congenic at the RT-1 or MHC locus of the resistant strain but with background genes of the susceptible strain exhibit intermediate levels of Ia compared to fully resistant and susceptible rodents, which fits well with the reduced EAE susceptibility of these congenic animals. Furthermore, hyperinduction of Ia is astrocyte specific, since peritoneal macrophages of susceptible and resistant strains exhibit identical profiles of Ia induction. Thus, astrocyte Ia hyperinducibility may be a major strain- and tissue-specific factor that contributes to Ia-restricted DTH reactions in the brain

  9. Partial deficiency of sphingosine-1-phosphate lyase confers protection in experimental autoimmune encephalomyelitis.

    Directory of Open Access Journals (Sweden)

    Andreas Billich

    Full Text Available BACKGROUND: Sphingosine-1-phosphate (S1P regulates the egress of T cells from lymphoid organs; levels of S1P in the tissues are controlled by S1P lyase (Sgpl1. Hence, Sgpl1 offers a target to block T cell-dependent inflammatory processes. However, the involvement of Sgpl1 in models of disease has not been fully elucidated yet, since Sgpl1 KO mice have a short life-span. METHODOLOGY: We generated inducible Sgpl1 KO mice featuring partial reduction of Sgpl1 activity and analyzed them with respect to sphingolipid levels, T-cell distribution, and response in models of inflammation. PRINCIPAL FINDINGS: The partially Sgpl1 deficient mice are viable but feature profound reduction of peripheral T cells, similar to the constitutive KO mice. While thymic T cell development in these mice appears normal, mature T cells are retained in thymus and lymph nodes, leading to reduced T cell numbers in spleen and blood, with a skewing towards increased proportions of memory T cells and T regulatory cells. The therapeutic relevance of Sgpl1 is demonstrated by the fact that the inducible KO mice are protected in experimental autoimmune encephalomyelitis (EAE. T cell immigration into the CNS was found to be profoundly reduced. Since S1P levels in the brain of the animals are unchanged, we conclude that protection in EAE is due to the peripheral effect on T cells, leading to reduced CNS immigration, rather than on local effects in the CNS. SIGNIFICANCE: The data suggest Sgpl1 as a novel therapeutic target for the treatment of multiple sclerosis.

  10. Voluntary wheel running delays disease onset and reduces pain hypersensitivity in early experimental autoimmune encephalomyelitis (EAE).

    Science.gov (United States)

    Benson, Curtis; Paylor, John W; Tenorio, Gustavo; Winship, Ian; Baker, Glen; Kerr, Bradley J

    2015-09-01

    Multiple sclerosis (MS) is classically defined by motor deficits, but it is also associated with the secondary symptoms of pain, depression, and anxiety. Up to this point modifying these secondary symptoms has been difficult. There is evidence that both MS and the animal model experimental autoimmune encephalomyelitis (EAE), commonly used to study the pathophysiology of the disease, can be modulated by exercise. To examine whether limited voluntary wheel running could modulate EAE disease progression and the co-morbid symptoms of pain, mice with EAE were allowed access to running wheels for 1h every day. Allowing only 1h every day of voluntary running led to a significant delay in the onset of clinical signs of the disease. The development of mechanical allodynia was assessed using Von Frey hairs and indicated that wheel running had a modest positive effect on the pain hypersensitivity associated with EAE. These behavioral changes were associated with reduced numbers of cFOS and phosphorylated NR1 positive cells in the dorsal horn of the spinal cord compared to no-run EAE controls. In addition, within the dorsal horn, voluntary wheel running reduced the number of infiltrating CD3(+) T-cells and reduced the overall levels of Iba1 immunoreactivity. Using high performance liquid chromatography (HPLC), we observed that wheel-running lead to significant changes in the spinal cord levels of the antioxidant glutathione. Oxidative stress has separately been shown to contribute to EAE disease progression and neuropathic pain. Together these results indicate that in mice with EAE, voluntary motor activity can delay the onset of clinical signs and reduce pain symptoms associated with the disease. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. Cerebral biochemical pathways in experimental autoimmune encephalomyelitis and adjuvant arthritis: a comparative metabolomic study.

    Directory of Open Access Journals (Sweden)

    Norbert W Lutz

    Full Text Available Many diseases, including brain disorders, are associated with perturbations of tissue metabolism. However, an often overlooked issue is the impact that inflammations outside the brain may have on brain metabolism. Our main goal was to study similarities and differences between brain metabolite profiles of animals suffering from experimental autoimmune encephalomyelitis (EAE and adjuvant arthritis (AA in Lewis rat models. Our principal objective was the determination of molecular protagonists involved in the metabolism underlying these diseases. EAE was induced by intraplantar injection of complete Freund's adjuvant (CFA and spinal-cord homogenate (SC-H, whereas AA was induced by CFA only. Naive rats served as controls (n = 9 for each group. Two weeks after inoculation, animals were sacrificed, and brains were removed and processed for metabolomic analysis by NMR spectroscopy or for immunohistochemistry. Interestingly, both inflammatory diseases caused similar, though not identical, changes in metabolites involved in regulation of brain cell size and membrane production: among the osmolytes, taurine and the neuronal marker, N-acetylaspartate, were decreased, and the astrocyte marker, myo-inositol, slightly increased in both inoculated groups compared with controls. Also ethanolamine-containing phospholipids, sources of inflammatory agents, and several glycolytic metabolites were increased in both inoculated groups. By contrast, the amino acids, aspartate and isoleucine, were less concentrated in CFA/SC-H and control vs. CFA rats. Our results suggest that inflammatory brain metabolite profiles may indicate the existence of either cerebral (EAE or extra-cerebral (AA inflammation. These inflammatory processes may act through distinct pathways that converge toward similar brain metabolic profiles. Our findings open new avenues for future studies aimed at demonstrating whether brain metabolic effects provoked by AA are pain/stress-mediated and

  12. RAE-1 expression is induced during experimental autoimmune encephalomyelitis and is correlated with microglia cell proliferation.

    Science.gov (United States)

    Djelloul, Mehdi; Popa, Natalia; Pelletier, Florence; Raguénez, Gilda; Boucraut, José

    2016-11-01

    Retinoic acid early induced transcript-1 (RAE-1) glycoproteins are ligands of the activating immune receptor NKG2D. They are known as stress molecules induced in pathological conditions. We previously reported that progenitor cells express RAE-1 in physiological conditions and we described a correlation between RAE-1 expression and cell proliferation. In addition, we showed that Raet1 transcripts are induced in the spinal cord of experimental autoimmune encephalomyelitis (EAE) mice. EAE is a model for multiple sclerosis which is accompanied by microglia proliferation and activation, recruitment of immune cells and neurogenesis. We herein studied the time course expression of the two members of the Raet1 gene family present in C57BL/6 mice, namely Raet1d and Raet1e, in the spinal cord during EAE. We report that Raet1d and Raet1e genes are induced early upon EAE onset and reach a maximal expression at the peak of the pathology. We show that myeloid cells, i.e. macrophages as well as microglia, are cellular sources of Raet1 transcripts. We also demonstrate that only Raet1d expression is induced in microglia, whereas macrophages expressed both Raet1d and Raet1e. Furthermore, we investigated the dynamics of RAE-1 expression in microglia cultures. RAE-1 induction correlated with cell proliferation but not with M1/M2 phenotypic orientation. We finally demonstrate that macrophage colony-stimulating factor (M-CSF) is a major factor controlling RAE-1 expression in microglia. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Delayed onset of experimental autoimmune encephalomyelitis in Olig1 deficient mice.

    Directory of Open Access Journals (Sweden)

    Xiaoli Guo

    Full Text Available BACKGROUND: Olig1 is a basic helix-loop-helix (bHLH transcription factor that is essential for oligodendrogenesis and efficient remyelination. However, its role in neurodegenerative disorders has not been well-elucidated. METHODOLOGY/PRINCIPAL FINDINGS: Here we investigated the effects of Olig1 deficiency on experimental autoimmune encephalomyelitis (EAE, an animal model of multiple sclerosis (MS. We show that the mean disease onset of myelin oligodendrocyte glycoprotein (MOG-induced EAE in Olig1(-/- mice is significantly slower than wide-type (WT mice (19.8 ± 2.2 in Olig1(-/- mice and 9.5 ± 0.3 days in WT mice. In addition, 10% of Olig1(-/- mice did not develop EAE by the end of the observation periods (60 days. The severity of EAE, the extent of demyelination, and the activation of microglial cells and astrocytes in spinal cords, were significantly milder in Olig1(-/- mice compared with WT mice in the early stage. Moreover, the visual function, as assessed by the second-kernel of multifocal electroretinograms, was better preserved, and the number of degenerating axons in the optic nerve was significantly reduced in Olig1(-/- mice. Interestingly, Olig1 deficiency had no effect on T cell response capability, however, it reduced the expression of myelin proteins such as MOG, myelin basic protein (MBP and myelin-associated glycoprotein (MAG. The expression of Olig2 remained unchanged in the optic nerve and brain, and it was reduced in the spinal cord of Olig1(-/- mice. CONCLUSIONS/SIGNIFICANCE: Our results suggest that the Olig1 signaling pathways may be involved in the incidence rate and the severity of neurological symptoms in MS.

  14. Mechanisms of action of cannabidiol in adoptively transferred experimental autoimmune encephalomyelitis.

    Science.gov (United States)

    González-García, Coral; Torres, Irene Moreno; García-Hernández, Ruth; Campos-Ruíz, Lucía; Esparragoza, Luis Rodríguez; Coronado, María José; Grande, Aranzazu García; García-Merino, Antonio; Sánchez López, Antonio J

    2017-12-01

    Cannabidiol (CBD) is one of the most important compounds in Cannabis sativa, lacks psychotropic effects, and possesses a high number of therapeutic properties including the amelioration of experimental autoimmune encephalomyelitis (EAE). The aim of this study was to analyse the relative efficacy of CBD in adoptively transferred EAE (at-EAE), a model that allows better delineation of the effector phase of EAE. Splenocytes and lymph nodes from mice with actively induced EAE were cultured in the presence of MOG 35-55 and IL-12 and inoculated intraperitoneally in recipient female C57BL/6J mice. The effects of CBD were evaluated using clinical scores and magnetic resonance imaging (MRI). In the central nervous system, the extent of cell infiltration, axonal damage, demyelination, microglial activation and cannabinoid receptors expression was assessed by immunohistochemistry. Lymph cell viability, apoptosis, oxidative stress and IL-6 production were measured in vitro. Preventive intraperitoneal treatment with CBD ameliorated the clinical signs of at-EAE, and this improvement was accompanied by a reduction of the apparent diffusion coefficient in the subiculum area of the brain. Inflammatory infiltration, axonal damage, and demyelination were reduced, and cannabinoid receptor expression was modulated. Incubation with CBD decreased encephalitogenic cell viability, increasing early apoptosis and reactive oxygen species (ROS) and decreasing IL-6 production. The reduction in viability was not mediated by CB 1 , CB 2 or GPR55 receptors. CBD markedly improved the clinical signs of at-EAE and reduced infiltration, demyelination and axonal damage. The CBD-mediated decrease in the viability of encephalitogenic cells involves ROS generation, apoptosis and a decrease in IL-6 production and may contribute to the therapeutic effect of this compound. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Cerebral biochemical pathways in experimental autoimmune encephalomyelitis and adjuvant arthritis: a comparative metabolomic study.

    Science.gov (United States)

    Lutz, Norbert W; Fernandez, Carla; Pellissier, Jean-François; Cozzone, Patrick J; Béraud, Evelyne

    2013-01-01

    Many diseases, including brain disorders, are associated with perturbations of tissue metabolism. However, an often overlooked issue is the impact that inflammations outside the brain may have on brain metabolism. Our main goal was to study similarities and differences between brain metabolite profiles of animals suffering from experimental autoimmune encephalomyelitis (EAE) and adjuvant arthritis (AA) in Lewis rat models. Our principal objective was the determination of molecular protagonists involved in the metabolism underlying these diseases. EAE was induced by intraplantar injection of complete Freund's adjuvant (CFA) and spinal-cord homogenate (SC-H), whereas AA was induced by CFA only. Naive rats served as controls (n = 9 for each group). Two weeks after inoculation, animals were sacrificed, and brains were removed and processed for metabolomic analysis by NMR spectroscopy or for immunohistochemistry. Interestingly, both inflammatory diseases caused similar, though not identical, changes in metabolites involved in regulation of brain cell size and membrane production: among the osmolytes, taurine and the neuronal marker, N-acetylaspartate, were decreased, and the astrocyte marker, myo-inositol, slightly increased in both inoculated groups compared with controls. Also ethanolamine-containing phospholipids, sources of inflammatory agents, and several glycolytic metabolites were increased in both inoculated groups. By contrast, the amino acids, aspartate and isoleucine, were less concentrated in CFA/SC-H and control vs. CFA rats. Our results suggest that inflammatory brain metabolite profiles may indicate the existence of either cerebral (EAE) or extra-cerebral (AA) inflammation. These inflammatory processes may act through distinct pathways that converge toward similar brain metabolic profiles. Our findings open new avenues for future studies aimed at demonstrating whether brain metabolic effects provoked by AA are pain/stress-mediated and/or due to the

  16. Excess circulating alternatively activated myeloid (M2 cells accelerate ALS progression while inhibiting experimental autoimmune encephalomyelitis.

    Directory of Open Access Journals (Sweden)

    Ilan Vaknin

    Full Text Available Circulating immune cells including autoreactive T cells and monocytes have been documented as key players in maintaining, protecting and repairing the central nervous system (CNS in health and disease. Here, we hypothesized that neurodegenerative diseases might be associated, similarly to tumors, with increased levels of circulating peripheral myeloid derived suppressor cells (MDSCs, representing a subset of suppressor cells that often expand under pathological conditions and inhibit possible recruitment of helper T cells needed for fighting off the disease.We tested this working hypothesis in amyotrophic lateral sclerosis (ALS and its mouse model, which are characterized by a rapid progression once clinical symptoms are evident. Adaptive transfer of alternatively activated myeloid (M2 cells, which homed to the spleen and exhibited immune suppressive activity in G93A mutant superoxide dismutase-1 (mSOD1 mice at a stage before emergence of disease symptoms, resulted in earlier appearance of disease symptoms and shorter life expectancy. The same protocol mitigated the inflammation-induced disease model of multiple sclerosis, experimental autoimmune encephalomyelitis (EAE, which requires circulating T cells for disease induction. Analysis of whole peripheral blood samples obtained from 28 patients suffering from sporadic ALS (sALS, revealed a two-fold increase in the percentage of circulating MDSCs (LIN(-/LowHLA-DR(-CD33(+ compared to controls.Taken together, these results emphasize the distinct requirements for fighting the inflammatory neurodegenerative disease, multiple sclerosis, and the neurodegenerative disease, ALS, though both share a local inflammatory component. Moreover, the increased levels of circulating MDSCs in ALS patients indicates the operation of systemic mechanisms that might lead to an impairment of T cell reactivity needed to overcome the disease conditions within the CNS. This high level of suppressive immune cells might

  17. Cell Fusion along the Anterior-Posterior Neuroaxis in Mice with Experimental Autoimmune Encephalomyelitis.

    Directory of Open Access Journals (Sweden)

    Sreenivasa R Sankavaram

    Full Text Available It is well documented that bone marrow-derived cells can fuse with a diverse range of cells, including brain cells, under normal or pathological conditions. Inflammation leads to robust fusion of bone marrow-derived cells with Purkinje cells and the formation of binucleate heterokaryons in the cerebellum. Heterokaryons form through the fusion of two developmentally differential cells and as a result contain two distinct nuclei without subsequent nuclear or chromosome loss.In the brain, fusion of bone marrow-derived cells appears to be restricted to the complex and large Purkinje cells, raising the question whether the size of the recipient cell is important for cell fusion in the central nervous system. Purkinje cells are among the largest neurons in the central nervous system and accordingly can harbor two nuclei.Using a well-characterized model for heterokaryon formation in the cerebellum (experimental autoimmune encephalomyelitis - a mouse model of multiple sclerosis, we report for the first time that green fluorescent protein-labeled bone marrow-derived cells can fuse and form heterokaryons with spinal cord motor neurons. These spinal cord heterokaryons are predominantly located in or adjacent to an active or previously active inflammation site, demonstrating that inflammation and infiltration of immune cells are key for cell fusion in the central nervous system. While some motor neurons were found to contain two nuclei, co-expressing green fluorescent protein and the neuronal marker, neuron-specific nuclear protein, a number of small interneurons also co-expressed green fluorescent protein and the neuronal marker, neuron-specific nuclear protein. These small heterokaryons were scattered in the gray matter of the spinal cord.This novel finding expands the repertoire of neurons that can form heterokaryons with bone marrow-derived cells in the central nervous system, albeit in low numbers, possibly leading to a novel therapy for spinal cord

  18. Huperzine A inhibits CCL2 production in experimental autoimmune encephalomyelitis mice and in cultured astrocyte.

    Science.gov (United States)

    Tian, G X; Zhu, X Q; Chen, Y; Wu, G C; Wang, J

    2013-01-01

    The active role of chemokines and inflammatory cytokines in the central nervous system (CNS) during the pathogenesis of experimental autoimmune encephalomyelitis (EAE) has been clearly established. Recent studies from our laboratory reported that Huperzine A (HupA) can attenuate the disease process in EAE by the inhibition of inflammation, demyelination, and axonal injury in the spinal cord as well as encephalomyelitic T-cell proliferation. In this study, the effects of low dose HupA on CCL2, TNF-alpha, IL-6, and IL-1beta expression were evaluated in EAE. The effect of HupA on lipopolysachharide (LPS)-induced inflammatory molecule secretion was investigated in cultured-astrocytes in vitro. In MOG35-55-induced EAE mice, intraperitoneal injections of HupA (0.1 mg/kg•d−1) significantly suppressed the expression of CCL2, IL-6, TNF-alpha, and IL-1beta in the spinal cord. HupA also repressed LPS-induced CCL2 production, but with little influence on pro-inflammatory cytokines in primary cultured astrocytes. The inhibition effect of HupA on CCL2 is PPARgamma-dependent and nicotine receptor-independent. Conditioned culture media from HupA-treated astrocyte decreased PBMC migration in vitro. Collectively, these results suggest that HupA can ameliorate EAE by inhibiting CCL2 production in astrocyte, which may consequently decrease inflammatory cell infiltration in the spinal cord. HupA may have a potential therapeutic value for the treatment of MS and other neuroinflammatory diseases.

  19. Neutrophil extracellular traps in vasculitis, friend or foe?

    Science.gov (United States)

    Söderberg, Daniel; Segelmark, Mårten

    2018-01-01

    Neutrophil extracellular traps (NETs) can be found at the sites of vascular lesions and in the circulation of patients with active small vessel vasculitis. Neutrophils from vasculitis patients release more NETs in vitro, and NETs have properties that can harm the vasculature both directly and indirectly. There are several ways to interfere with NET formation, which open for new therapeutic options. However, there are several types of NETs and different mechanisms of NET formation, and these might have different effects on inflammation. Here we review recent findings regarding the pathogenesis and therapeutic potentials of NETs in vasculitis. Experimental mouse models support a role for NETs in promoting vascular damage, where histones and mitochondrial DNA appear to be driving forces. Impaired formation of NETs, however, in an SLE-like mouse model leads to more severe disease, suggesting that NETs can be important in limiting inflammation. Studies on drug-induced vasculitis reveal that levamisole can induce NETosis via muscarinic receptors, predisposing for the generation of autoantibodies, including antineutrophil cytoplasmic autoantibodies (ANCA). This supports the notion that NETs can bridge the innate and adaptive immune systems. NETs can participate in the pathogenesis of vasculitis, but in some models there also seem to be protective effects of NETs. This complexity needs further evaluation with experimental models that are as specific as possible for human primary vasculitis.

  20. Hypocomplementemic Urticarial Vasculitis Syndrome With Crescentic Glomerulonephritis.

    Science.gov (United States)

    Salim, Sohail Abdul; Yousuf, Tauqeer; Patel, Asha; Fülöp, Tibor; Agarwal, Mohit

    2018-02-01

    Hypocomplementemic urticarial vasculitis syndrome (HUVS) is a rare autoimmune disease characterized by multiple organ system involvement, including renal disease, with low complement levels. We report the case of a 31-year-old woman who presented with nonspecific symptoms including fatigue, diarrhea, macular rash and abdominal pain with acute renal failure leading to end-stage kidney disease. Laboratory results showed hematuria, nephrotic range proteinuria, worsening creatinine and low C1q levels. Left kidney biopsy showed proliferative glomerulonephritis with crescent formation. She was treated with 6 months of intravenous cyclophosphamide, followed by 2 doses of intravenous rituximab (1g each), thereafter maintained on mycophenolate mofetil and glucocorticoid-based therapy. She experienced a full recovery of renal function after 12 months of dialysis dependence. Hypocomplementemic urticarial vasculitis syndrome with crescentic glomerulonephritis is a rare disease with only 5 other reported cases in literature. In our case, we document a delayed but excellent renal recovery during a 2-year follow-up. Copyright © 2018 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.

  1. ANCA-associated vasculitis and malignancy

    DEFF Research Database (Denmark)

    Mahr, Alfred; Heijl, Caroline; Le Guenno, Guillaume

    2013-01-01

    of individual therapeutic agents is difficult to dissect, but cyclophosphamide has emerged as a major contributor to cancer development because of its direct carcinogenic properties. Awareness of cancer risk in AAV calls for increased implementation of measures to prevent or screen for cancer and development......In this review, we summarise the current understanding of the potential link between cancer and anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV), including granulomatosis with polyangiitis (Wegener's; GPA) and microscopic polyangiitis (MPA). As is true for many autoimmune...... or inflammatory rheumatic diseases, AAV diagnosis and therapy are associated with an increased risk of de novo cancer development, likely as a result of impaired immunosurveillance, direct oncogenicity of immunosuppressive agents and perhaps malignant degeneration of tissues undergoing chronic immune stimulation...

  2. Infections and vasculitis.

    Science.gov (United States)

    Thomas, Konstantinos; Vassilopoulos, Dimitrios

    2017-01-01

    To review recent evidence for infection rates in patients with systemic vasculitides, the role of specific infectious agents in the pathogenesis of vasculitis and recent breakthroughs in the treatment of virus-associated vasculitides. In well designed recent studies, infections were found to be common during the first 6-12 months in patients with anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitides (AAV) and giant cell arteritis (GCA) and to contribute significantly to increased mortality during this period. New therapeutic schemes with lower cyclophosphamide doses and shorter corticosteroid courses were associated with decreased infectious rates in elderly patients with AAV whereas a prednisone dose greater than 10 mg/day at the end of the first year were associated with increased infectious-related mortality in patients with GCA. Recently, a potential role for varicella zoster virus in GCA pathogenesis has been proposed but more data are needed in order to establish a causal relationship. Finally, preliminary data show excellent short-term efficacy and safety of the new, interferon-free, oral antiviral agents in the treatment of hepatitis C virus-associated cryoglobulinemic vasculitis. Infections continue to be one of the main causes of mortality in patients with systemic vasculitides, emphasizing the need for safer immunosuppressive therapies and appropriate prophylaxis.

  3. Role of passive T-cell death in chronic experimental autoimmune encephalomyelitis

    DEFF Research Database (Denmark)

    Issazadeh-Navikas, Shohreh; Abdallah, K; Chitnis, T

    2000-01-01

    central nervous system (CNS) compared with controls. There was also a decreased number of apoptotic cells in the CNS of Bcl-x(L) transgenic mice when compared with littermates at all time points tested. This is the first report of an autoimmune disease model in Bcl-x(L) transgenic mice. Our data indicate...

  4. In Acute Experimental Autoimmune Encephalomyelitis, Infiltrating Macrophages Are Immune Activated, Whereas Microglia Remain Immune Suppressed

    NARCIS (Netherlands)

    Vainchtein, I. D.; Vinet, J.; Brouwer, N.; Brendecke, S.; Biagini, G.; Biber, K.; Boddeke, H. W. G. M.; Eggen, B. J. L.

    2014-01-01

    Multiple sclerosis (MS) is an autoimmune demyelinating disorder of the central nervous system (CNS) characterized by loss of myelin accompanied by infiltration of T-lymphocytes and monocytes. Although it has been shown that these infiltrates are important for the progression of MS, the role of

  5. GM-CSF-Producing Th Cells in Rats Sensitive and Resistant to Experimental Autoimmune Encephalomyelitis.

    Science.gov (United States)

    Stojić-Vukanić, Zorica; Pilipović, Ivan; Vujnović, Ivana; Nacka-Aleksić, Mirjana; Petrović, Raisa; Arsenović-Ranin, Nevena; Dimitrijević, Mirjana; Leposavić, Gordana

    2016-01-01

    Given that granulocyte macrophage colony-stimulating factor (GM-CSF) is identified as the key factor to endow auto-reactive Th cells with the potential to induce neuroinflammation in experimental autoimmune encephalomyelitis (EAE) models, the frequency and phenotype of GM-CSF-producing (GM-CSF+) Th cells in draining lymph nodes (dLNs) and spinal cord (SC) of Albino Oxford (AO) and Dark Agouti (DA) rats immunized for EAE were examined. The generation of neuroantigen-specific GM-CSF+ Th lymphocytes was impaired in dLNs of AO rats (relatively resistant to EAE induction) compared with their DA counterparts (susceptible to EAE) reflecting impaired CD4+ lymphocyte proliferation and less supportive of GM-CSF+ Th cell differentiation dLN cytokine microenvironment. Immunophenotyping of GM-CSF+ Th cells showed their phenotypic heterogeneity in both strains and revealed lower frequency of IL-17+IFN-γ+, IL-17+IFN-γ-, and IL-17-IFN-γ+ cells accompanied by higher frequency of IL-17-IFN-γ- cells among them in AO than in DA rats. Compared with DA, in AO rats was also found (i) slightly lower surface density of CCR2 (drives accumulation of highly pathogenic GM-CSF+IFN-γ+ Th17 cells in SC) on GM-CSF+IFN-γ+ Th17 lymphocytes from dLNs, and (ii) diminished CCL2 mRNA expression in SC tissue, suggesting their impaired migration into the SC. Moreover, dLN and SC cytokine environments in AO rats were shown to be less supportive of GM-CSF+IFN-γ+ Th17 cell differentiation (judging by lower expression of mRNAs for IL-1β, IL-6 and IL-23/p19). In accordance with the (i) lower frequency of GM-CSF+ Th cells in dLNs and SC of AO rats and their lower GM-CSF production, and (ii) impaired CCL2 expression in the SC tissue, the proportion of proinflammatory monocytes among peripheral blood cells and their progeny (CD45hi cells) among the SC CD11b+ cells were reduced in AO compared with DA rats. Collectively, the results indicate that the strain specificities in efficacy of several mechanisms

  6. Sulforaphane ameliorates the development of experimental autoimmune encephalomyelitis by antagonizing oxidative stress and Th17-related inflammation in mice.

    Science.gov (United States)

    Li, Bin; Cui, Wei; Liu, Jia; Li, Ru; Liu, Qian; Xie, Xiao-Hua; Ge, Xiao-Li; Zhang, Jing; Song, Xiu-Juan; Wang, Ying; Guo, Li

    2013-12-01

    Sulforaphane (SFN) is an organosulfur compound present in vegetables and has potent anti-oxidant and anti-inflammatory activities. This study was aimed at investigating the effect of treatment with SFN on inflammation and oxidative stress, and the potential mechanisms underlying the action of SFN in experimental autoimmune encephalomyelitis (EAE) in C57BL/6 mice. Treatment with SFN significantly inhibited the development and severity of EAE in mice, accompanied by mitigating inflammatory infiltration and demyelination in the spinal cord of mice. The protective effect of SFN was associated with significantly improved distribution of claudin-5 and occludin, and decreased levels of MMP-9 expression, preserving the blood-brain barrier. Furthermore, the protection of SFN was also related to decreased levels of oxidative stress in the brains of mice by enhanced activation of the Nrf2/ARE pathway and increased levels of anti-oxidant HO-1 and NQO1 expression. In addition, treatment with SFN inhibited antigen-specific Th17 responses and enhanced IL-10 responses. Our data indicated that treatment with SFN inhibited EAE development and severity in mice by its anti-oxidant activity and antagonizing autoimmune inflammation. Our findings suggest that SFN and its analogues may be promising reagents for intervention of multiple sclerosis and other autoimmune diseases. © 2013.

  7. Arctigenin Suppress Th17 Cells and Ameliorates Experimental Autoimmune Encephalomyelitis Through AMPK and PPAR-γ/ROR-γt Signaling.

    Science.gov (United States)

    Li, Wen; Zhang, Zhihui; Zhang, Kai; Xue, Zhenyi; Li, Yan; Zhang, Zimu; Zhang, Lijuan; Gu, Chao; Zhang, Qi; Hao, Junwei; Da, Yurong; Yao, Zhi; Kong, Ying; Zhang, Rongxin

    2016-10-01

    Arctigenin is a herb compound extract from Arctium lappa and is reported to exhibit pharmacological properties, including neuronal protection and antidiabetic, antitumor, and antioxidant properties. However, the effects of arctigenin on autoimmune inflammatory diseases of the CNS, multiple sclerosis (MS), and its animal model experimental autoimmune encephalomyelitis (EAE) are still unclear. In this study, we demonstrated that arctigenin-treated mice are resistant to EAE; the clinical scores of arctigenin-treated mice are significantly reduced. Histochemical assays of spinal cord sections also showed that arctigenin reduces inflammation and demyelination in mice with EAE. Furthermore, the Th1 and Th17 cells in peripheral immune organs are inhibited by arctigenin in vivo. In addition, the Th1 cytokine IFN-γ and transcription factor T-bet, as well as the Th17 cytokines IL-17A, IL-17F, and transcription factor ROR-γt are significantly suppressed upon arctigenin treatment in vitro and in vivo. Interestedly, Th17 cells are obviously inhibited in CNS of mice with EAE, while Th1 cells do not significantly change. Besides, arctigenin significantly restrains the differentiation of Th17 cells. We further demonstrate that arctigenin activates AMPK and inhibits phosphorylated p38, in addition, upregulates PPAR-γ, and finally suppresses ROR-γt. These findings suggest that arctigenin may have anti-inflammatory and immunosuppressive properties via inhibiting Th17 cells, indicating that it could be a potential therapeutic drug for multiple sclerosis or other autoimmune inflammatory diseases.

  8. Comparative Effects of Human Neural Stem Cells and Oligodendrocyte Progenitor Cells on the Neurobehavioral Disorders of Experimental Autoimmune Encephalomyelitis Mice

    Directory of Open Access Journals (Sweden)

    Dae-Kwon Bae

    2016-01-01

    Full Text Available Since multiple sclerosis (MS is featured with widespread demyelination caused by autoimmune response, we investigated the recovery effects of F3.olig2 progenitors, established by transducing human neural stem cells (F3 NSCs with Olig2 transcription factor, in myelin oligodendrocyte glycoprotein- (MOG- induced experimental autoimmune encephalomyelitis (EAE model mice. Six days after EAE induction, F3 or F3.olig2 cells (1 × 106/mouse were intravenously transplanted. MOG-injected mice displayed severe neurobehavioral deficits which were remarkably attenuated and restored by cell transplantation, in which F3.olig2 cells were superior to its parental F3 cells. Transplanted cells migrated to the injured spinal cord, matured to oligodendrocytes, and produced myelin basic proteins (MBP. The F3.olig2 cells expressed growth and neurotrophic factors including brain-derived neurotrophic factor (BDNF, nerve growth factor (NGF, ciliary neurotrophic factor (CNTF, and leukemia inhibitory factor (LIF. In addition, the transplanted cells markedly attenuated inflammatory cell infiltration, reduced cytokine levels in the spinal cord and lymph nodes, and protected host myelins. The results indicate that F3.olig2 cells restore neurobehavioral symptoms of EAE mice by regulating autoimmune inflammatory responses as well as by stimulating remyelination and that F3.olig2 progenitors could be a candidate for the cell therapy of demyelinating diseases including MS.

  9. Systemic vasculitis and the lung.

    Science.gov (United States)

    Talarico, Rosaria; Barsotti, Simone; Elefante, Elena; Baldini, Chiara; Tani, Chiara; Mosca, Marta

    2017-01-01

    The purpose of this review is to provide a critical analysis of the recent literature on this topic, with particular focus on the most relevant studies published over the last year. Many studies are published every year on the diagnosis, pathogenesis and treatment of pulmonary involvement in antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV). The main subjects covered by this article are the pathogenesis, diagnosis and clinical aspects of lung involvement in ANCA-associated vasculitis and non-ANCA-associated vasculitis. Lung involvement is a common feature in systemic vasculitis. The lungs are one of the most frequently involved organs in systemic vasculitis. In order to provide an update on the recent advances in the pathogenesis, clinical features and novel treatments of lung involvement in systemic vasculitis, a systematic MedLine search has been performed.Most of the data analyzed have confirmed that lung involvement seems to develop more frequently in patients with myeloperoxidase-ANCA-positive AAV, mainly in those with a diagnosis of microscopic polyangiitis (MPA), compared with patients with proteinase 3 ANCA-positive AAV. Moreover, among non-ANCA-associated vasculitis lung involvement may represent a worrying complication of the disease, mainly when associated with vascular involvement.

  10. A B Cell-Driven Autoimmune Pathway Leading to Pathological Hallmarks of Progressive Multiple Sclerosis in the Marmoset Experimental Autoimmune Encephalomyelitis Model

    Directory of Open Access Journals (Sweden)

    Bert A. ’t Hart

    2017-07-01

    Full Text Available The absence of pathological hallmarks of progressive multiple sclerosis (MS in commonly used rodent models of experimental autoimmune encephalomyelitis (EAE hinders the development of adequate treatments for progressive disease. Work reviewed here shows that such hallmarks are present in the EAE model in marmoset monkeys (Callithrix jacchus. The minimal requirement for induction of progressive MS pathology is immunization with a synthetic peptide representing residues 34–56 from human myelin oligodendrocyte glycoprotein (MOG formulated with a mineral oil [incomplete Freund’s adjuvant (IFA]. Pathological aspects include demyelination of cortical gray matter with microglia activation, oxidative stress, and redistribution of iron. When the peptide is formulated in complete Freund’s adjuvant, which contains mycobacteria that relay strong activation signals to myeloid cells, oxidative damage pathways are strongly boosted leading to more intensive pathology. The proven absence of immune potentiating danger signals in the MOG34–56/IFA formulation implies that a narrow population of antigen-experienced T cells present in the monkey’s immune repertoire is activated. This novel pathway involves the interplay of lymphocryptovirus-infected B cells with MHC class Ib/Caja-E restricted CD8+ CD56+ cytotoxic T lymphocytes.

  11. [Treatment of cryoglobulinemic vasculitis associated with hepatitis C virus infection].

    Science.gov (United States)

    Retamozo, Soledad; Brito-Zerón, Pilar; Ramos-Casals, Manuel

    2015-05-08

    Cryoglobulinemia is a heterogeneous systemic autoimmune disease with a wide variety of causes, symptoms and outcomes, and different etiopathogenic pathways involved in the vasculitic organ damage. The discovery of the hepatitis C virus (HCV) in 1989 changed radically the focus of research of the so-called "essential" cryoglobulinemia. Cryoglobulins can be detected in 25-30% of patients with HCV, overwhelmingly representing mixed cryoglobulins. However, only 10-15% of patients present with cryoglobulinemic vasculitis, with a broad spectrum of symptoms including mild or life-threatening manifestations. Consequently, not all patients can be uniformly treated. The key therapeutic points in HCV+ patients with cryoglobulinemic vasculitis cover different aspects. The first is to treat the underlying cause of cryoglobulinemia whenever possible, hence the use of antiviral therapies must always be considered in these patients. An individualized diagnostic approach to assess the number of organs involved and the severity of organ involvement is also essential in the therapeutic planning. This complex clinical scenario leads to an equally complex therapeutic scenario. There are three main treatment strategies for HCV-associated cryoglobulinemic vasculitis: conventional immunosuppression, antiviral treatment and biological therapies. The most recent studies are suggesting a change from the classical therapeutic approach (monotherapeutic regimens) to combination/sequential regimens, including treatments targeting the virus and those directed against the induced autoimmune disease, with the aim of blocking the various etiopathogenic pathways involved. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

  12. Short- and long-term effects of T-cell modulating agents in experimental autoimmunity

    International Nuclear Information System (INIS)

    Mellergaard, Johan; Havarinasab, Said; Hultman, Per

    2004-01-01

    Due to the easy and reliable induction of a disease condition with many of the features present in human autoimmunity, mercury-induced autoimmunity (mHgAI) in rodents is a favourable autoimmune model. Genetically susceptible (H-2 s ) mice develop in response to mercury (Hg) a systemic autoimmune condition with antinucleolar antibodies (ANoA) targeting the protein fibrillarin, transient polyclonal B-cell activation, hyperimmunoglobulinemia, and systemic immune-complex (IC) deposits. In order to study the short- and long-term effects of treatment with immunomodulating agents on the disease parameters in HgAI, groups of B10.S (H-2 s ) mice were given 6 mg HgCl 2 /l drinking water for 22 weeks. Three weeks initial treatment with cyclosporin A (CyA), a high dose of tacrolimus (HD tacrolimus), or anti-CD4 monoclonal antibody (a-CD4) inhibited induction of ANoA and IC deposit by Hg. This effect persisted for the subsequent 19 weeks when the mice were only treated with Hg. Initial treatment with anti-IL-4 monoclonal antibody (a-IL-4) for 3 weeks inhibited induction of IgE and IC deposits by Hg, but not ANoA. However, subsequent treatment with Hg without a-IL-4 for 19 weeks induced IC deposits. The T-cell modulating agents aggravated some of the HgAI disease parameters: a-CD4 stimulated the polyclonal B-cell activation, a-IL-4 increased the IgG antichromatin antibody response, and a low dose of tacrolimus (LD tacrolimus) enhanced the ANoA, the polyclonal B-cell activation, and the IC deposits. We conclude that a short initial treatment with a-CD4 or CyA efficiently protects against induction of systemic autoimmunity for an extended period of time. However, some of the T-cell modulating agents, especially a low dose of tacrolimus, aggravate autoimmune manifestations not only during ongoing treatment, but also after treatment with these agents has ceased

  13. A case of central nervous system vasculitis related to an episode of Guillain-Barrè syndrome

    OpenAIRE

    Sinardi, Daniele; Spada, Antonella; Marino, Antonella; Mondello, Epifanio

    2000-01-01

    The authors report their knowledge about an uncommon case of isolated vasculitis, restricted to the left sylvian artery during an auto-immune Guillain-Barrè syndrome (GBS), sustained by cytomegalovirus (CMV). An acute cardiopulmonary failure requiring a ventilator and vasopressor support manifested, notwithstanding plasma exchanging and immune-modulating therapy. An IgM-enriched formula administration coincided with a rapid amelioration of GBS and vasculitis to a complete recovery the next mo...

  14. Arg deficiency does not influence the course of Myelin Oligodendrocyte Glycoprotein (MOG35-55)-induced experimental autoimmune encephalomyelitis

    DEFF Research Database (Denmark)

    Jacobsen, Freja Aksel; Hulst, Camilla; Bäckström, Thomas

    2016-01-01

    Background: Inhibition of Abl kinases has an ameliorating effect on the rodent model for multiple sclerosis, experimental autoimmune encephalomyelitis, and arrests lymphocyte activation. The family of Abl kinases consists of the Abl1/Abl and Abl2/Arg tyrosine kinases. While the Abl kinase has bee...... encephalomyelitis is not dependent on Arg, but Arg plays a role for the number of B cells in immunized mice. This might suggest a novel role for the Arg kinase in B-cell trafficking or regulation. Furthermore, the results suggest that Arg is important for normal embryonic development....

  15. Treatment with metallothionein prevents demyelination and axonal damage and increases oligodendrocyte precursors and tissue repair during experimental autoimmune encephalomyelitis

    DEFF Research Database (Denmark)

    Penkowa, Milena; Hidalgo, Juan

    2003-01-01

    Experimental autoimmune encephalomyelitis (EAE) is an animal model for the human demyelinating disease multiple sclerosis (MS). EAE and MS are characterized by significant inflammation, demyelination, neuroglial damage, and cell death. Metallothionein-I and -II (MT-I + II) are antiinflammatory an......)beta, neurotrophin-3 (NT-3), NT-4/5, and nerve growth factor (NGF). These beneficial effects of Zn-MT-II treatment could not be attributable to its zinc content per se. The present results support further the use of Zn-MT-II as a safe and successful therapy for multiple sclerosis....

  16. Insulinotropic and anti-inflammatory effects of rosiglitazone in experimental autoimmune diabetes.

    Science.gov (United States)

    Awara, Wageh M; el-Sisi, Alaa E; el-Refaei, Mohamed; el-Naa, Mona M; el-Desoky, Karima

    2005-01-01

    Cytokines and nitric oxide (NO) are involved in the pathogenesis of autoimmune diabetes mellitus (DM). Rosiglitazone is an insulin-sensitizing drug that is a ligand for the nuclear receptor peroxisome proliferator-activated receptor-gamma (PPAR-gamma). The anti-inflammatory and immunomodulating properties of PPAR-gamma have been documented. The aim of this study is to investigate the effectiveness of rosiglitazone in autoimmune DM and to clarify the possible mechanism(s) involved. Autoimmune DM was induced in adult male Balb/c mice by co-administration of cyclosporin A and multiple low doses of streptozotocin. Diabetic mice were treated daily with rosiglitazone (7 mg/kg, p.o.) for 21 days. Blood glucose level (BGL), serum insulin level and pancreatic levels of tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma) and NO were measured. Histopathological examination and immunohistochemical determination of CD4 and CD8 T lymphocytes in the pancreatic islets were performed. In addition, analysis of pancreatic protein expression was carried out. The results showed that rosiglitazone treatment resulted in a significant decrease in the BGL and the pancreatic levels of TNF-alpha, IFN-gamma and NO compared to diabetic mice. The serum insulin level was significantly increased after rosiglitazone treatment compared to diabetic mice. The destroyed pancreatic islets were regenerated and became free from both CD4 and CD8 T cells after treatment. Furthermore, many changes in pancreatic protein expression were observed. These results suggest that rosiglitazone has a beneficial effect in the treatment of autoimmune diabetes, an effect that seemed to be a secondary consequence of its anti-inflammatory and immunomodulating properties and might be reflected at the level of protein expression.

  17. The last classification of vasculitis

    NARCIS (Netherlands)

    Kallenberg, Cees G. M.

    2008-01-01

    Systemic vasculitides are a group of diverse conditions characterized by inflammation of the blood vessels. To obtain homogeneity in clinical characteristics, prognosis, and response to treatment, patients with vasculitis should be classified into defined disease categories. Many classification

  18. Vasculitis Terms A to Z

    Science.gov (United States)

    ... Our Board Our Team Anniversary Vasculitis Foundation Newsletters Annual Reports Press Page Literature Order Form Join Contact Us Awareness Donate Donate Support the VF Through the Amazon Smile Program United Way Giving Ways to Give ...

  19. Differential diagnosis of retinal vasculitis.

    Science.gov (United States)

    Abu El-Asrar, Ahmed M; Herbort, Carl P; Tabbara, Khalid F

    2009-10-01

    Retinal vaculitis is a sight-threatening inflammatory eye condition that involves the retinal vessels. Detection of retinal vasculitis is made clinically, and confirmed with the help of fundus fluorescein angiography. Active vascular disease is characterized by exudates around retinal vessels resulting in white sheathing or cuffing of the affected vessels. In this review, a practical approach to the diagnosis of retinal vasculitis is discussed based on ophthalmoscopic and fundus fluorescein angiographic findings.

  20. Leukocytoclastic vasculitis associated with clarithromycin.

    Science.gov (United States)

    Gavura, S R; Nusinowitz, S

    1998-05-01

    To report a possible case of leukocytoclastic vasculitis associated with clarithromycin therapy. An 83-year-old white woman was prescribed clarithromycin for pneumonia. Six days after her initial presentation, she developed lesions on her palms. Clarithromycin was discontinued at that time. The following day she developed purpuric eccymotic nonblanching lesions that primarily appeared on the lower extremities, buttocks, and abdomen. Colonoscopy revealed generalized erythema and edema of the bowel mucosa. Gastroscopy revealed duodenitis and gastritis, but no bleeding or ulceration. Skin biopsy of the lesions was compatible with leukocytoclastic vasculitis. Renal function was not affected, although hematuria was noted. All symptoms resolved after drug withdrawal and a short course of corticosteroids. Searches were performed on MEDLINE, Embase, International Pharmaceutical Abstracts, and major adverse drug reaction databases to identify reports and articles discussing clarithromycin- and macrolide-induced leukocytoclastic vasculitis. Leukocytoclastic vasculitis is one category of drug hypersensitivity reactions characterized by distinctive patterns of perivascular inflammation. The case described here is consistent with the diagnosis of leukocytoclastic vasculitis, and is similar to the other single published case report associated with clarithromycin. Leukocytoclastic vasculitis induced by clarithromycin is a rare but serious potential adverse effect.

  1. BCG and BCG/DNAhsp65 Vaccinations Promote Protective Effects without Deleterious Consequences for Experimental Autoimmune Encephalomyelitis

    Directory of Open Access Journals (Sweden)

    Sofia Fernanda Gonçalves Zorzella-Pezavento

    2013-01-01

    Full Text Available A prime-boost strategy conserving BCG is considered the most promising vaccine to control tuberculosis. A boost with a DNA vaccine containing the mycobacterial gene of a heat shock protein (pVAXhsp65 after BCG priming protected mice against experimental tuberculosis. However, anti-hsp65 immunity could worsen an autoimmune disease due to molecular mimicry. In this investigation, we evaluated the effect of a previous BCG or BCG/pVAXhsp65 immunization on experimental autoimmune encephalomyelitis (EAE development. Female Lewis rats were immunized with BCG or BCG followed by pVAXhsp65 boosters. The animals underwent EAE induction and were daily evaluated for weight loss and clinical score. They were euthanized during recovery phase to assess immune response and inflammatory infiltration at the central nervous system. Previous immunization did not aggravate or accelerate clinical score or weight loss. In addition, this procedure clearly decreased inflammation in the brain. BCG immunization modulated the host immune response by triggering a significant reduction in IL-10 and IFN-γ levels induced by myelin basic protein. These data indicated that vaccination protocols with BCG or BCG followed by boosters with pVAXhsp65 did not trigger a deleterious effect on EAE evolution.

  2. [Therapeutic efficacy of compound Xuanju capsule on autoimmune prostatitis in rats: an experimental study].

    Science.gov (United States)

    Li, Tian-Fu; Wu, Qiu-Yue; Li, Wei-Wei; Zhang, Cui; Li, Na; Shang, Xue-Jun; Xia, Xin-Yi; Xu, Hao-Qin; Huang, Yu-Feng

    2014-05-01

    To evaluate the therapeutic effect of Compound Xuanju Capsule (CXC) on autoimmune prostatitis in rat models. Sixty healthy male Wistar rats were randomly divided into five groups of equal number: blank control, low-concentration purified prostate protein (low-conc PPP), low-conc PPP + CXC treatment, high-concentration PPP (hi-con PPP), and hi-conc PPP + CXC treatment. Autoimmune prostatitis models were established by intragastric administration of PPP solution at 15 mg/ml (low concentration) and 80 mg/ml, respectively. At 30 days after modeling, the rats in the blank control and low-conc and hi-conc PPP model groups were treated with normal saline, and those in the other two groups with CXC at a daily dose of 0.068 g/ml. At 30, 45, and 60 days, all the animals were sacrificed for observation of pathological changes in the prostate tissue and determination of the levels of IL-8, IL-10, and TNF-alpha in the serum. Compared with the PPP models, the hi-conc PPP + CXC group showed significantly reduced levels of IL-8 and TNF-alpha in the serum at 45 days ([148.54 +/- 17.23] and [62.14 +/- 5.59] pg/ml vs [100.77 +/- 11.08] and [32.63 +/- 2.91] pg/ml, P microscope. Compound Xuanju Capsule is efficacious on autoimmune prostatis in rats by reducing inflammatory changes in the prostate tissue and improving the expression of inflammatory factors.

  3. Genetic resistance in experimental autoimmune encephalomyelitis. I. Analysis of the mechanism of LeR resistance using radiation chimeras

    International Nuclear Information System (INIS)

    Pelfrey, C.M.; Waxman, F.J.; Whitacre, C.C.

    1989-01-01

    Experimental autoimmune encephalomyelitis (EAE) is a cell-mediated autoimmune disease of the central nervous system that has been extensively studied in the rat. The Lewis rat is highly susceptible to the induction of EAE, while the Lewis resistant (LeR) rat is known to be resistant. In this paper, we demonstrate that the LeR rat, which was derived from the Lewis strain by inbreeding of fully resistant animals, is histocompatible with the Lewis strain. Radiation chimeras, a tool for distinguishing between immunologic and nonimmunologic resistance mechanisms, were utilized to analyze the cellular mechanisms involved in genetic resistance to EAE. By transplanting bone marrow cells from LeR rats into irradiated Lewis recipients, Lewis rats were rendered resistant to EAE induction. Likewise, transplanting Lewis bone marrow cells into irradiated LeR recipients rendered LeR rats susceptible. Mixed lymphoid cell chimeras using bone marrow, spleen, and thymus cells in Lewis recipient rats revealed individual lymphoid cell types and cell interactions that significantly affected the incidence and severity of EAE. Our results suggest that LeR resistance is mediated by hematopoietic/immune cells, and that cells located in the spleen appear to play a critical role in the resistance/susceptibility to EAE induction. Depletion of splenic adherent cells did not change the patterns of EAE resistance. In vivo cell mixing studies suggested the presence of a suppressor cell population in the LeR spleen preparations which exerted an inhibitory effect on Lewis autoimmune responses. Thus, the mechanism of LeR resistance appears to be different from that in other EAE-resistant animals

  4. Huperzine A ameliorates experimental autoimmune encephalomyelitis via the suppression of T cell-mediated neuronal inflammation in mice.

    Science.gov (United States)

    Wang, Jun; Chen, Fu; Zheng, Peng; Deng, Weijuan; Yuan, Jia; Peng, Bo; Wang, Ruochen; Liu, Wenjun; Zhao, Hui; Wang, Yanqing; Wu, Gencheng

    2012-07-01

    Huperzine A (HupA), a sesquiterpene alkaloid and a potent and reversible inhibitor of acetylcholinesterase, possesses potential anti-inflammatory properties and is used for the treatment of certain neurodegenerative diseases such as Alzheimer's disease. However, it is still unknown whether this chemical is beneficial in the treatment of multiple sclerosis, a progressive inflammatory disease of the central nervous system. In this study, we examined the immunomodulatory properties of HupA in experimental autoimmune encephalomyelitis (EAE), a T-cell mediated murine model of multiple sclerosis. The following results were obtained: (1) intraperitoneal injections of HupA significantly attenuate the neurological severity of EAE in mice. (2) HupA decreases the accumulation of inflammatory cells, autoimmune-related demyelination and axonal injury in the spinal cords of EAE mice. (3) HupA down-regulates mRNA levels of the pro-inflammatory cytokines (IFN-γ and IL-17) and chemokines (MCP-1, RANTES, and TWEAK) while enhancing levels of anti-inflammatory cytokines (IL-4 and IL-10) in the spinal cords of EAE mice. (4) HupA inhibits MOG(35-55) stimulation-induced T-cell proliferation and IFN-γ and IL-17 secretion in cultured splenocytes. (5) HupA inhibition of T-cell proliferation is reversed by the nicotinic acetylcholinergic receptor antagonist mecamylamine. We conclude that HupA can ameliorate EAE by suppressing autoimmune responses, inflammatory reactions, subsequent demyelination and axonal injury in the spinal cord. Therefore, HupA may have a potential therapeutic value for the treatment of multiple sclerosis and as a neuroimmunomodulatory drug to control human CNS pathology. Copyright © 2012 Elsevier Inc. All rights reserved.

  5. Cutting-edge issues in autoimmune orchitis.

    Science.gov (United States)

    Silva, Clovis A; Cocuzza, Marcello; Borba, Eduardo F; Bonfá, Eloísa

    2012-04-01

    Autoimmune orchitis is a relevant cause of decreased fecundity in males, and it is defined as a direct aggression to the testis with the concomitant presence of anti-sperm antibodies (ASA). The presence of these specific antibodies has been observed in approximately 5-12% of infertile male partners. Primary autoimmune orchitis is defined by isolated infertility with ASA but without evidence of a systemic disease. Secondary causes of orchitis and/or testicular vasculitis are uniformly associated with autoimmune diseases, mainly in primary vasculitis such as polyarteritis nodosa, Behçet's disease, and Henoch-Schönlein purpura. The overall frequencies of acute orchitis and ASA in rheumatic diseases are 2-31% and 0-50%, respectively. The pathogenesis of primary/secondary autoimmune orchitis is not completely understood but probably involves the access of immune cells to the testicular microenvironment due to inflammation, infection or trauma, leading to apoptosis of spermatocytes and spermatids. Glucocorticoids and immunosuppressive drugs are indicated in autoimmune orchitis-associated active systemic autoimmune diseases. However, there are no standardized treatment options, and the real significance of ASA in infertile men is still controversial. Assisted reproductive technologies such as intrauterine insemination, in vitro fertilization, and intracytoplasmic sperm injection (ICSI) are therapeutic options for male infertility associated with these autoantibodies. ICSI is considered to be the best choice for patients with severe sperm autoimmunity, particularly in males with low semen counts or motility.

  6. Caspase-1 inhibitor regulates humoral responses in experimental autoimmune myasthenia gravis via IL-6- dependent inhibiton of STAT3.

    Science.gov (United States)

    Wang, Cong-Cong; Zhang, Min; Li, Heng; Li, Xiao-Li; Yue, Long-Tao; Zhang, Peng; Liu, Ru-Tao; Chen, Hui; Li, Yan-Bin; Duan, Rui-Sheng

    2017-08-24

    We have previously demonstrated that Cysteinyl aspartate-specific proteinase-1 (caspase-1) inhibitor ameliorates experimental autoimmune myasthenia gravis (EAMG) by inhibited cellular immune response, via suppressing DC IL-1 β, CD4 + T and γdT cells IL-17 pathways. In this study, we investigated the effect of caspase-1 inhibitor on humoral immune response of EAMG and further explore the underlying mechanisms. An animal model of MG was induced by region 97-116 of the rat AChR α subunit (R97-116 peptide) in Lewis rats. Rats were treated with caspase-1 inhibitor Ac-YVAD-cmk intraperitoneally (i.p.) every second day from day 13 after the first immunization. Flow cytometry, western blot, immunofluorescence, and enzyme-linked immunosorbent assay (ELISA) were performed to evaluate the neuroprotective effect of caspase-1 inhibitor on humoral immune response of EAMG. The results showed that caspase-1 inhibitor reduced the relative affinity of anti-R97-116 IgG, suppressed germinal center response, decreased follicular helper T cells, and increased follicular regulatory T cells and regulatory B cells. In addition, we found that caspase-1 inhibitor inhibited humoral immunity response in EAMG rats via suppressing IL-6-STAT3-Bcl-6 pathways. These results suggest that caspase-1 inhibitor ameliorates EAMG by regulating humoral immune response, thus providing new insights into the development of myasthenia gravis and other autoimmune diseases therapies. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Regulation of Th1 and Th17 cell differentiation and amelioration of experimental autoimmune encephalomyelitis by natural product compound berberine.

    Science.gov (United States)

    Qin, Xia; Guo, Bingshi T; Wan, Bing; Fang, Lei; Lu, Limin; Wu, Lili; Zang, Ying Qin; Zhang, Jingwu Z

    2010-08-01

    Berberine (BBR), an isoquinoline alkaloid derived from plants, is widely used as an anti-inflammatory remedy in traditional Chinese medicine. In this study, we showed that BBR was efficacious in the amelioration of experimental autoimmune encephalomyelitis (EAE) through novel regulatory mechanisms involving pathogenic Th1 and Th17 cells. BBR inhibited differentiation of Th17 cells and, to a lesser degree, Th1 cells through direct actions on the JAK/STAT pathway, whereas it had no effect on the relative number of CD4(+)Foxp3(+) regulatory T cells. In addition, BBR indirectly influenced Th17 and Th1 cell functions through its effect on the expression and function of costimulatory molecules and the production of IL-6, which was attributable to the inhibition of NF-kappaB activity in CD11b(+) APCs. BBR treatment completely abolished the encephalitogenicity of MOG(35-55)-reactive Th17 cells in an adoptive transfer EAE model, and the same treatment significantly inhibited the ability of MOG(35-55)-reactive Th1 cells to induce EAE. This study provides new evidence that natural compounds, such as BBR, are of great value in the search for novel anti-inflammatory agents and therapeutic targets for autoimmune diseases.

  8. Hsp65-producing Lactococcus lactis prevents experimental autoimmune encephalomyelitis in mice by inducing CD4+LAP+ regulatory T cells

    Science.gov (United States)

    Rezende, Rafael M.; Oliveira, Rafael P.; Medeiros, Samara R.; Gomes-Santos, Ana C.; Alves, Andrea C.; Loli, Flávia G.; Guimarães, Mauro A.F.; Amaral, Sylvia S.; da Cunha, André P.; Weiner, Howard L.; Azevedo, Vasco; Miyoshi, Anderson; Faria, Ana M.C.

    2013-01-01

    Heat shock proteins (Hsps) participate in the cellular response to stress and they are hiperexpressed in inflammatory conditions. They are also known to play a major role in immune modulation, controlling, for instance, autoimmune responses. In this study, we showed that oral administration of a recombinant Lactococcus lactis strain that produces and releases LPS-free Hsp65 prevented the development of experimental autoimmune encephalomyelitis (EAE) in C57BL/6 mice. This was confirmed by the reduced inflammatory cell infiltrate and absence of injury signs in the spinal cord. The effect was associated with reduced IL-17 and increased IL-10 production in mesenteric lymph node and spleen cell cultures. Hsp65-producing-L. lactis-fed mice had a remarkable increase in the number of natural and inducible CD4+Foxp3+ regulatory T (Treg) cells and CD4+LAP+ (Latency-associated peptide) Tregs - which express the membrane-bound TGF-β - in spleen, inguinal and mesenteric lymph nodes as well as in spinal cord. Moreover, many Tregs co-expressed Foxp3 and LAP. In vivo depletion of LAP+ cells abrogated the effect of Hsp65-producing L. lactis in EAE prevention and worsened disease in medium-fed mice. Thus, Hsp65-L.lactis seems to boost this critical regulatory circuit involved in controlling EAE development in mice. PMID:22939403

  9. An endogenous aryl hydrocarbon receptor ligand acts on dendritic cells and T cells to suppress experimental autoimmune encephalomyelitis

    Science.gov (United States)

    Quintana, Francisco J.; Murugaiyan, Gopal; Farez, Mauricio F.; Mitsdoerffer, Meike; Tukpah, Ann-Marcia; Burns, Evan J.; Weiner, Howard L.

    2010-01-01

    The ligand-activated transcription factor aryl hydrocarbon receptor (AHR) participates in the differentiation of FoxP3+ Treg, Tr1 cells, and IL-17–producing T cells (Th17). Most of our understanding on the role of AHR on the FoxP3+ Treg compartment results from studies using the toxic synthetic chemical 2,3,7,8-tetrachlorodibenzo-p-dioxin. Thus, the physiological relevance of AHR signaling on FoxP3+ Treg in vivo is unclear. We studied mice that carry a GFP reporter in the endogenous foxp3 locus and a mutated AHR protein with reduced affinity for its ligands, and found that AHR signaling participates in the differentiation of FoxP3+ Treg in vivo. Moreover, we found that treatment with the endogenous AHR ligand 2-(1′H-indole-3′-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE) given parenterally or orally induces FoxP3+ Treg that suppress experimental autoimmune encephalomyelitis. ITE acts not only on T cells, but also directly on dendritic cells to induce tolerogenic dendritic cells that support FoxP3+ Treg differentiation in a retinoic acid-dependent manner. Thus, our work demonstrates that the endogenous AHR ligand ITE promotes the induction of active immunologic tolerance by direct effects on dendritic and T cells, and identifies nontoxic endogenous AHR ligands as potential unique compounds for the treatment of autoimmune disorders. PMID:21068375

  10. The ANCA Vasculitis Questionnaire (AAV-PRO©)

    Science.gov (United States)

    2017-05-01

    Eosinophilic Granulomatosis With Polyangiitis (Churg-Strauss) (EGPA); Churg-Strauss Syndrome (CSS); Granulomatosis With Polyangiitis (Wegener's) (GPA); Wegener Granulomatosis (WG); Microscopic Polyangiitis (MPA); ANCA-Associated Vasculitis (AAV); Vasculitis

  11. Vasculitis associated with connective tissue diseases.

    Science.gov (United States)

    Cozzani, E; Gasparini, G; Papini, M; Burlando, M; Drago, F; Parodi, A

    2015-04-01

    Vasculitis in connective tissue disease (CTD) is quite rare, it is reported in approximately 10% of patients with CTD; systemic lupus erythematosus (SLE) shows the highest association rate. Vessels of any size may be involved, but mainly small vessels vasculitis is reported. At present the classification of these vasculitis is unsatisfactory. According to the 2012 revised International Chapel Hill Consensus Conference, vasculitides secondary to CTD are a well identified entity and are classified under the category of "vasculitis associated with systemic disease". However only lupus vasculitis and rheumatoid vasculitis are explicitly listed, while the remaining are generically included under the heading "others". Petechiae, purpura, gangrene and ulcers are the most frequent cutaneous manifestations that should investigated in order to rule out potentially dangerous systemic involvement, especially if cryoglobulinemic or necrotizing vasculitis are suspected. This review will focus on the cutaneous involvement in CTD associated vasculitis.

  12. Contrasting Roles of Islet Resident Immunoregulatory Macrophages and Dendritic Cells in Experimental Autoimmune Type 1 Diabetes

    Science.gov (United States)

    Thornley, Thomas B.; Ma, Lingzhi; Chipashvili, Vaja; Aker, Jonathan E.; Korniotis, Sarantis; Csizmadia, Eva; Strom, Terry B.; Koulmanda, Maria

    2016-01-01

    The innate immune system critically shapes diabetogenic adaptive immunity during type 1 diabetes (T1D) pathogenesis. While the role of tissue-infiltrating monocyte-derived macrophages in T1D is well established, the role of their tissue-resident counterparts remains undefined. We now demonstrate that islet resident macrophages (IRMs) from non-autoimmune mice have an immunoregulatory phenotype and powerfully induce FoxP3+ Tregs in vitro. The immunoregulatory phenotype and function of IRMs is compromised by TLR4 activation in vitro. Moreover, as T1D approaches in NOD mice, the immunoregulatory phenotype of IRMs is diminished as is their relative abundance compared to immunostimulatory DCs. Our findings suggest that maintenance of IRM abundance and their immunoregulatory phenotype may constitute a novel therapeutic strategy to prevent and/or cure T1D. PMID:26943809

  13. Contrasting Roles of Islet Resident Immunoregulatory Macrophages and Dendritic Cells in Experimental Autoimmune Type 1 Diabetes.

    Directory of Open Access Journals (Sweden)

    Thomas B Thornley

    Full Text Available The innate immune system critically shapes diabetogenic adaptive immunity during type 1 diabetes (T1D pathogenesis. While the role of tissue-infiltrating monocyte-derived macrophages in T1D is well established, the role of their tissue-resident counterparts remains undefined. We now demonstrate that islet resident macrophages (IRMs from non-autoimmune mice have an immunoregulatory phenotype and powerfully induce FoxP3+ Tregs in vitro. The immunoregulatory phenotype and function of IRMs is compromised by TLR4 activation in vitro. Moreover, as T1D approaches in NOD mice, the immunoregulatory phenotype of IRMs is diminished as is their relative abundance compared to immunostimulatory DCs. Our findings suggest that maintenance of IRM abundance and their immunoregulatory phenotype may constitute a novel therapeutic strategy to prevent and/or cure T1D.

  14. Single-organ gallbladder vasculitis: characterization and distinction from systemic vasculitis involving the gallbladder. An analysis of 61 patients.

    Science.gov (United States)

    Hernández-Rodríguez, José; Tan, Carmela D; Rodríguez, E René; Hoffman, Gary S

    2014-11-01

    higher than in GB-SOV (35.5% vs 10%; p = 0.05). Nongranulomatous inflammation with fibrinoid necrosis of medium-sized vessels occurred equally in both groups (>90%). Forms of SV affecting the gallbladder included polyarteritis nodosa (n = 10), hepatitis B virus-associated vasculitis (n = 8), cryoglobulinemic (essential or hepatitis C virus-associated) vasculitis (n = 6), vasculitis associated with autoimmune diseases (n = 6), microscopic polyangiitis (n = 4), eosinophilic granulomatosis with polyangiitis (Churg-Strauss) (n = 4), IgA vasculitis (Henoch-Schönlein) (n = 2), and giant cell arteritis (n = 1).GV is uncommon. Its histology most often consists of a nongranulomatous necrotizing vasculitis affecting medium-sized vessels. GB-SOV is usually discovered after routine cholecystectomy performed because of the presence of local symptoms, gallstone-associated cholecystitis, and contrary to GB-SV, GB-SOV is usually not associated with systemic symptoms. Acute phase reactants and surrogate markers of autoimmunity are usually normal or negative in GB-SOV. GB-SOV does not require systemic antiinflammatory or immunosuppressive therapy; surgery is adequate to achieve cure. GB-SV always warrants immunosuppressant therapy and is associated with high mortality. The finding of GV may precede the generalized manifestations of SV. Therefore, once GV is discovered, studies to determine disease extent and a vigilant follow-up are mandatory.

  15. Cerebral vasculitis associated with cocaine abuse

    International Nuclear Information System (INIS)

    Kaye, B.R.; Fainstat, M.

    1987-01-01

    A case of cerebral vasculitis in a previously healthy 22-year-old man with a history of cocaine abuse is described. Cerebral angiograms showed evidence of vasculitis. A search for possible causes other than cocaine produced no results. The authors include cocaine with methamphetamines, heroin, and ephedrine as illicit drugs that can cause cerebral vasculitis

  16. Animal models of antineutrophil cytoplasm antibody-associated vasculitis.

    LENUS (Irish Health Repository)

    Salama, Alan D

    2012-01-01

    To provide an update on the experimental models that have been developed recapitulating clinical antineutrophil cytoplasm antibody (ANCA) associated vasculitis. The application of the models in the study of pathogenesis, and the therapeutic implications of this, are covered in the article by van Timmeren and Heeringa in this issue.

  17. XY sex chromosome complement, compared with XX, in the CNS confers greater neurodegeneration during experimental autoimmune encephalomyelitis.

    Science.gov (United States)

    Du, Sienmi; Itoh, Noriko; Askarinam, Sahar; Hill, Haley; Arnold, Arthur P; Voskuhl, Rhonda R

    2014-02-18

    Women are more susceptible to multiple sclerosis (MS) and have more robust immune responses than men. However, men with MS tend to demonstrate a more progressive disease course than women, suggesting a disconnect between the severity of an immune attack and the CNS response to a given immune attack. We have previously shown in an MS model, experimental autoimmune encephalomyelitis, that autoantigen-sensitized XX lymph node cells, compared with XY, are more encephalitogenic. These studies demonstrated an effect of sex chromosomes in the induction of immune responses, but did not address a potential role of sex chromosomes in the CNS response to immune-mediated injury. Here, we examined this possibility using XX versus XY bone marrow chimeras reconstituted with a common immune system of one sex chromosomal type. We found that experimental autoimmune encephalomyelitis mice with an XY sex chromosome complement in the CNS, compared with XX, demonstrated greater clinical disease severity with more neuropathology in the spinal cord, cerebellum, and cerebral cortex. A candidate gene on the X chromosome, toll-like receptor 7, was then examined. Toll-like receptor 7 expression in cortical neurons was higher in mice with XY compared with mice with XX CNS, consistent with the known neurodegenerative role for toll-like receptor 7 in neurons. These results suggest that sex chromosome effects on neurodegeneration in the CNS run counter to effects on immune responses, and may bear relevance to the clinical enigma of greater MS susceptibility in women but faster disability progression in men. This is a demonstration of a direct effect of sex chromosome complement on neurodegeneration in a neurological disease.

  18. Transgenic expression of soluble human CD5 enhances experimentally-induced autoimmune and anti-tumoral immune responses.

    Directory of Open Access Journals (Sweden)

    Rafael Fenutría

    Full Text Available CD5 is a lymphoid-specific transmembrane glycoprotein constitutively expressed on thymocytes and mature T and B1a lymphocytes. Current data support the view that CD5 is a negative regulator of antigen-specific receptor-mediated signaling in these cells, and that this would likely be achieved through interaction with CD5 ligand/s (CD5L of still undefined nature expressed on immune or accessory cells. To determine the functional consequence of loss of CD5/CD5L interaction in vivo, a new transgenic mouse line was generated (shCD5EμTg, expressing a circulating soluble form of human CD5 (shCD5 as a decoy to impair membrane-bound CD5 function. These shCD5EμTg mice showed an enhanced response to autologous antigens, as deduced from the presentation of more severe forms of experimentally inducible autoimmune disease (collagen-induced arthritis, CIA; and experimental autoimmune encephalitis, EAE, as well as an increased anti-tumoral response in non-orthotopic cancer models (B16 melanoma. This enhancement of the immune response was in agreement with the finding of significantly reduced proportions of spleen and lymph node Treg cells (CD4+CD25+FoxP3+, and of peritoneal IL-10-producing and CD5+ B cells, as well as an increased proportion of spleen NKT cells in shCD5EμTg mice. Similar changes in lymphocyte subpopulations were observed in wild-type mice following repeated administration of exogenous recombinant shCD5 protein. These data reveal the relevant role played by CD5/CD5L interactions on the homeostasis of some functionally relevant lymphocyte subpopulations and the modulation of immune responses to autologous antigens.

  19. Autoimmune Thyroiditis and Glomerulopathies

    Directory of Open Access Journals (Sweden)

    Domenico Santoro

    2017-06-01

    Full Text Available Autoimmune thyroiditis (AIT is generally associated with hypothyroidism. It affects ~2% of the female population and 0.2% of the male population. The evidence of thyroid function- and thyroid autoantibody-unrelated microproteinuria in almost half of patients with AIT and sometimes heavy proteinuria as in the nephrotic syndrome point to a link of AIT with renal disease. The most common renal diseases observed in AIT are membranous nephropathy, membranoproliferative glomerulonephritis, minimal change disease, IgA nephropathy, focal segmental glomerulosclerosis, antineutrophil cytoplasmic autoantibody (ANCA vasculitis, and amyloidosis. Different hypotheses have been put forward regarding the relationship between AIT and glomerulopathies, and several potential mechanisms for this association have been considered. Glomerular deposition of immunocomplexes of thyroglobulin and autoantibodies as well as the impaired immune tolerance for megalin (a thyrotropin-regulated glycoprotein expressed on thyroid cells are the most probable mechanisms. Cross-reactivity between antigens in the setting of genetic predisposition has been considered as a potential mechanism that links the described association between ANCA vasculitis and AIT.

  20. Severe T-cell depletion from the PALS leads to altered spleen composition in common marmosets with experimental autoimmune encephalomyelitis (EAE)

    NARCIS (Netherlands)

    De Vos, Alex F; van Riel, Debby A J; van Meurs, Marjan; Brok, Herbert P M; Boon, Louis; Hintzen, Rogier Q; Claassen, Eric H J H M; 't Hart, Bert A; Laman, Jon D

    Recent data suggest that the spleen is a crucial component of the immune system in the development of experimental autoimmune encephalomyelitis (EAE) in marmoset monkeys. Using immunohistochemistry, we investigated changes in the distribution of leukocytes in the spleen associated with clinical

  1. Deficient p75 low-affinity neurotrophin receptor expression does alter the composition of cellular infiltrate in experimental autoimmune encephalomyelitis in C57BL/6 mice

    NARCIS (Netherlands)

    Kust, B; Mantingh-Otter, [No Value; Boddeke, E; Copray, S

    We have shown earlier that induction of experimental autoimmune encephalomyelitis (EAE)-a model for the human disease multiple sclerosis-in C5713L/6 wild-type mice resulted in the expression of the p75 low-affinity neurotrophin receptor (p75(NTR)) in endothelial cells in the CNS. In comparison to

  2. Chronic Pelvic Pain Development and Prostate Inflammation in Strains of Mice With Different Susceptibility to Experimental Autoimmune Prostatitis.

    Science.gov (United States)

    Breser, Maria L; Motrich, Ruben D; Sanchez, Leonardo R; Rivero, Virginia E

    2017-01-01

    Experimental autoimmune prostatitis (EAP) is an autoimmune inflammatory disease of the prostate characterized by peripheral prostate-specific autoimmune responses associated with prostate inflammation. EAP is induced in rodents upon immunization with prostate antigens (PAg) plus adjuvants and shares important clinical and immunological features with the human disease chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). EAP was induced in young NOD, C57BL/6, and BALB/c male mice by immunization with PAg plus complete Freund́s adjuvant. Tactile allodynia was assessed using Von Frey fibers as a measure of pelvic pain at baseline and at different time points after immunization. Using conventional histology, immunohistochemistry, FACS analysis, and protein arrays, an interstrain comparative study of prostate cell infiltration and inflammation was performed. Chronic pelvic pain development was similar between immunized NOD and C57BL/6 mice, although the severity of leukocyte infiltration was greater in the first case. Coversely, minimal prostate cell infiltration was observed in immunized BALB/c mice, who showed no pelvic pain development. Increased numbers of mast cells, mostly degranulated, were detected in prostate samples from NOD and C57BL/6 mice, while lower total counts and resting were observed in BALB/c mice. Prostate tissue from NOD mice revealed markedly increased expression levels of inflammatory cytokines, chemokines, adhesion molecules, vascular endothelial growth factor, and metalloproteinases. Similar results, but to a lesser extent, were observed when analyzing prostate tissue from C57BL/6 mice. On the contrary, the expression of the above mediators was very low in prostate tissue from immunized BALB/c mice, showing significantly slight increments only for CXCL1 and IL4. Our results provide new evidence indicating that NOD, C57BL/6, and BALB/c mice develop different degrees of chronic pelvic pain, type, and amount of prostate cell infiltration

  3. Urinary Soluble CD163 in Active Renal Vasculitis.

    Science.gov (United States)

    O'Reilly, Vincent P; Wong, Limy; Kennedy, Claire; Elliot, Louise A; O'Meachair, Shane; Coughlan, Alice Marie; O'Brien, Eoin C; Ryan, Michelle M; Sandoval, Diego; Connolly, Emma; Dekkema, Gerjan J; Lau, Jiaying; Abdulahad, Wayel H; Sanders, Jan-Stephan F; Heeringa, Peter; Buckley, Colm; O'Brien, Cathal; Finn, Stephen; Cohen, Clemens D; Lindemeyer, Maja T; Hickey, Fionnuala B; O'Hara, Paul V; Feighery, Conleth; Moran, Sarah M; Mellotte, George; Clarkson, Michael R; Dorman, Anthony J; Murray, Patrick T; Little, Mark A

    2016-09-01

    A specific biomarker that can separate active renal vasculitis from other causes of renal dysfunction is lacking, with a kidney biopsy often being required. Soluble CD163 (sCD163), shed by monocytes and macrophages, has been reported as a potential biomarker in diseases associated with excessive macrophage activation. Thus, we hypothesized that urinary sCD163 shed by crescent macrophages correlates with active glomerular inflammation. We detected sCD163 in rat urine early in the disease course of experimental vasculitis. Moreover, microdissected glomeruli from patients with small vessel vasculitis (SVV) had markedly higher levels of CD163 mRNA than did those from patients with lupus nephritis, diabetic nephropathy, or nephrotic syndrome. Both glomeruli and interstitium of patients with SVV strongly expressed CD163 protein. In 479 individuals, including patients with SVV, disease controls, and healthy controls, serum levels of sCD163 did not differ between the groups. However, in an inception cohort, including 177 patients with SVV, patients with active renal vasculitis had markedly higher urinary sCD163 levels than did patients in remission, disease controls, or healthy controls. Analyses in both internal and external validation cohorts confirmed these results. Setting a derived optimum cutoff for urinary sCD163 of 0.3 ng/mmol creatinine for detection of active renal vasculitis resulted in a sensitivity of 83%, specificity of 96%, and a positive likelihood ratio of 20.8. These data indicate that urinary sCD163 level associates very tightly with active renal vasculitis, and assessing this level may be a noninvasive method for diagnosing renal flare in the setting of a known diagnosis of SVV. Copyright © 2016 by the American Society of Nephrology.

  4. Functional genomics analysis of vitamin D effects on CD4+ T cells in vivo in experimental autoimmune encephalomyelitis ‬

    KAUST Repository

    Zeitelhofer, Manuel

    2017-02-15

    Vitamin D exerts multiple immunomodulatory functions and has been implicated in the etiology and treatment of several autoimmune diseases, including multiple sclerosis (MS). We have previously reported that in juvenile/adolescent rats, vitamin D supplementation protects from experimental autoimmune encephalomyelitis (EAE), a model of MS. Here we demonstrate that this protective effect associates with decreased proliferation of CD4+ T cells and lower frequency of pathogenic T helper (Th) 17 cells. Using transcriptome, methylome, and pathway analyses in CD4+ T cells, we show that vitamin D affects multiple signaling and metabolic pathways critical for T-cell activation and differentiation into Th1 and Th17 subsets in vivo. Namely, Jak/Stat, Erk/Mapk, and Pi3K/Akt/mTor signaling pathway genes were down-regulated upon vitamin D supplementation. The protective effect associated with epigenetic mechanisms, such as (i) changed levels of enzymes involved in establishment and maintenance of epigenetic marks, i.e., DNA methylation and histone modifications; (ii) genome-wide reduction of DNA methylation, and (iii) up-regulation of noncoding RNAs, including microRNAs, with concomitant down-regulation of their protein-coding target RNAs involved in T-cell activation and differentiation. We further demonstrate that treatment of myelin-specific T cells with vitamin D reduces frequency of Th1 and Th17 cells, down-regulates genes in key signaling pathways and epigenetic machinery, and impairs their ability to transfer EAE. Finally, orthologs of nearly 50% of candidate MS risk genes and 40% of signature genes of myelin-reactive T cells in MS changed their expression in vivo in EAE upon supplementation, supporting the hypothesis that vitamin D may modulate risk for developing MS.

  5. Functional genomics analysis of vitamin D effects on CD4+ T cells in vivo in experimental autoimmune encephalomyelitis ‬

    KAUST Repository

    Zeitelhofer, Manuel; Adzemovic, Milena Z.; Gomez-Cabrero, David; Bergman, Petra; Hochmeister, Sonja; N'diaye, Marie; Paulson, Atul; Ruhrmann, Sabrina; Almgren, Malin; Tegner, Jesper; Ekströ m, Tomas J.; Guerreiro-Cacais, André Ortlieb; Jagodic, Maja

    2017-01-01

    Vitamin D exerts multiple immunomodulatory functions and has been implicated in the etiology and treatment of several autoimmune diseases, including multiple sclerosis (MS). We have previously reported that in juvenile/adolescent rats, vitamin D supplementation protects from experimental autoimmune encephalomyelitis (EAE), a model of MS. Here we demonstrate that this protective effect associates with decreased proliferation of CD4+ T cells and lower frequency of pathogenic T helper (Th) 17 cells. Using transcriptome, methylome, and pathway analyses in CD4+ T cells, we show that vitamin D affects multiple signaling and metabolic pathways critical for T-cell activation and differentiation into Th1 and Th17 subsets in vivo. Namely, Jak/Stat, Erk/Mapk, and Pi3K/Akt/mTor signaling pathway genes were down-regulated upon vitamin D supplementation. The protective effect associated with epigenetic mechanisms, such as (i) changed levels of enzymes involved in establishment and maintenance of epigenetic marks, i.e., DNA methylation and histone modifications; (ii) genome-wide reduction of DNA methylation, and (iii) up-regulation of noncoding RNAs, including microRNAs, with concomitant down-regulation of their protein-coding target RNAs involved in T-cell activation and differentiation. We further demonstrate that treatment of myelin-specific T cells with vitamin D reduces frequency of Th1 and Th17 cells, down-regulates genes in key signaling pathways and epigenetic machinery, and impairs their ability to transfer EAE. Finally, orthologs of nearly 50% of candidate MS risk genes and 40% of signature genes of myelin-reactive T cells in MS changed their expression in vivo in EAE upon supplementation, supporting the hypothesis that vitamin D may modulate risk for developing MS.

  6. Immunization with Recombinantly Expressed LRP4 Induces Experimental Autoimmune Myasthenia Gravis in C57BL/6 Mice.

    Science.gov (United States)

    Ulusoy, Canan; Çavuş, Filiz; Yılmaz, Vuslat; Tüzün, Erdem

    2017-07-01

    Myasthenia gravis (MG) is an autoimmune disease of the neuromuscular junction (NMJ), characterized with muscle weakness. While MG develops due to acetylcholine receptor (AChR) antibodies in most patients, antibodies to muscle-specific receptor tyrosine kinase (MuSK) or low-density lipoprotein receptor-related protein 4 (LRP4) may also be identified. Experimental autoimmune myasthenia gravis (EAMG) has been previously induced by both LRP4 immunization and passive transfer of LRP4 antibodies. Our aim was to confirm previous results and to test the pathogenic effects of LRP4 immunization in a commonly used mouse strain C57BL/6 (B6) using a recombinantly expressed human LRP4 protein. B6 mice were immunized with human LRP4 in CFA, Torpedo Californica AChR in CFA or only CFA. Clinical and pathogenic aspects of EAMG were compared among groups. LRP4- and AChR-immunized mice showed comparable EAMG clinical severity. LRP4-immunized mice displayed serum antibodies to LRP4 and NMJ IgG and complement factor C3 deposits. IgG2 was the dominant anti-LRP4 isotype. Cultured lymph node cells of LRP4- and AChR-immunized mice gave identical pro-inflammatory cytokine (IL-6, IFN-γ and IL-17) responses to LRP4 and AChR stimulation, respectively. Our results confirm the EAMG-inducing action of LRP4 immunization and identify B6 as a LRP4-EAMG-susceptible mouse strain. Demonstration of complement fixing anti-LRP4 antibodies in sera and complement/IgG deposits at the NMJ of LRP4-immunized mice indicates complement activation as a putative pathogenic mechanism. We have thus developed a practical LRP4-induced EAMG model using a non-conformational protein and a widely available mouse strain for future investigation of LRP4-related MG.

  7. Thyroid autoimmunity

    NARCIS (Netherlands)

    Wiersinga, Wilmar M.

    2014-01-01

    Autoimmune thyroid disease (AITD) is a multifactorial disease in which autoimmunity against thyroid antigens develops against a particular genetic background facilitated by exposure to environmental factors. Immunogenicity of the major thyroid antigens thyroid peroxidase, thyroglobulin (TG) and

  8. Recent advances in childhood vasculitis.

    Science.gov (United States)

    Ozen, Seza; Acar-Ozen, Nazire Pinar

    2017-09-01

    The review aims to summarize the recent findings in vasculitis that may have an impact in our understanding or management of these diseases. We are learning more about monogenic diseases that closely mimic the pediatric vasculitides. Deficiency of adenosine deaminase 2 can present with a polyarteritis nodosa (PAN)-like picture and should be included in the differential of all pediatric cases of PAN with a family history or in cases with early stroke, or in cases resistant to conventional therapy. Mutations in tumor necrosis factor α-induced protein 3 results in a disease that can present as Behçet disease called haploinsufficiency of A20. In fact, these patients would also fulfill the existing criteria for PAN and Behçet disease, respectively. Additional advances in Behçet disease pathogenesis come from a large genetic study of Turkish Behçet disease using data obtained from genotyping using the Immunochip. This confirmed the HLA-B-51 locus as the most significant association and identified new risk loci. Large Iranian and Japanese cohorts were used as replication cohorts. Best treatment of pediatric vasculitis remains a challenge as we continue to lack controlled studies. There are new reports in treatment on Henoch-Schönlein purpura/Immunoglobulin A vasculitis which is one of our most frequent childhood vasculitides. Small series of new treatments for central nervous system vasculitis and Takayasu disease will also be summarized. Diagnostic criteria have been reassessed in pediatric Behçet disease as well as adult and childhood forms of antineutrophil cytoplasmic antibodies-positive vasculitis. The new pathways defined in monogenic diseases may help us better understand the pathogenesis and may help us design more targeted therapy. Although pediatric cases are being increasingly recognized, the relative rarity of the diseases presents an obstacle for studies. Thus, we can reach conclusive results for their management through multicenter studies only.

  9. The therapeutic effects of MSc1 nanocomplex, synthesized by nanochelating technology, on experimental autoimmune encephalomyelitic C57/BL6 mice

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    Fakharzadeh S

    2014-08-01

    Full Text Available Saideh Fakharzadeh,1 Mohammad Ali Sahraian,2 Maryam Hafizi,1 Somayeh Kalanaky,1 Zahra Masoumi,1 Mehdi Mahdavi,1 Nasser Kamalian,3 Alireza Minagar,4 Mohammad Hassan Nazaran1 1Department of Research and Development, Sodour Ahrar Shargh Company, Tehran, Iran; 2MS Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran; 3Department of Pathology, Medical School of Tehran University of Medical Sciences, Tehran, Iran; 4Department of Neurology, LSU Health Sciences Centre, Shreveport, LA, USA Purpose: Currently approved therapies for multiple sclerosis (MS at best only slow down its progression. Therefore, it is necessary to utilize novel technologies in order to synthesize smart multifunctional structures. In the present study, for the first time we evaluated the therapeutic potential of MSc1 nanocomplex, which was designed based on novel nanochelating technology. Materials and methods: MSc1 cell-protection capacity, with and without iron bond, was evaluated against hydrogen peroxide (H2O2-induced oxidative stress in cultured rat pheochromocytoma-12 cells. The ability of MSc1 to maintain iron bond at pH ranges of 1–7 was evaluated. Nanocomplex toxicity was examined by estimating the intraperitoneal median lethal dose (LD50. Experimental autoimmune encephalomyelitic mice were injected with MSc1 14 days after disease induction, when the clinical symptoms appeared. The clinical score, body weight, and disease-induced mortality were monitored until day 54. In the end, after collecting blood samples for assessing hemoglobin and red blood cell count, the brains and livers of the mice were isolated for hematoxylin and eosin staining and analysis of iron content, respectively. Results: The results showed that MSc1 prevented H2O2-induced cell death even after binding with iron, and it preserved its bond with iron constant at pH ranges 1–7. The nanocomplex intraperitoneal LD50 was 1,776.59 mg/kg. MSc1 prompted therapeutic

  10. Galectin-3 in autoimmunity and autoimmune diseases.

    Science.gov (United States)

    de Oliveira, Felipe L; Gatto, Mariele; Bassi, Nicola; Luisetto, Roberto; Ghirardello, Anna; Punzi, Leonardo; Doria, Andrea

    2015-08-01

    Galectin-3 (gal-3) is a β-galactoside-binding lectin, which regulates cell-cell and extracellular interactions during self/non-self-antigen recognition and cellular activation, proliferation, differentiation, migration and apoptosis. It plays a significant role in cellular and tissue pathophysiology by organizing niches that drive inflammation and immune responses. Gal-3 has some therapeutic potential in several diseases, including chronic inflammatory disorders, cancer and autoimmune diseases. Gal-3 exerts a broad spectrum of functions which differs according to its intra- or extracellular localization. Recombinant gal-3 strategy has been used to identify potential mode of action of gal-3; however, exogenous gal-3 may not reproduce the functions of the endogenous gal-3. Notably, gal-3 induces monocyte-macrophage differentiation, interferes with dendritic cell fate decision, regulates apoptosis on T lymphocytes and inhibits B-lymphocyte differentiation into immunoglobulin secreting plasma cells. Considering the influence of these cell populations in the pathogenesis of several autoimmune diseases, gal-3 seems to play a role in development of autoimmunity. Gal-3 has been suggested as a potential therapeutic agent in patients affected with some autoimmune disorders. However, the precise role of gal-3 in driving the inflammatory process in autoimmune or immune-mediated disorders remains elusive. Here, we reviewed the involvement of gal-3 in cellular and tissue events during autoimmune and immune-mediated inflammatory diseases. © 2015 by the Society for Experimental Biology and Medicine.

  11. "Warming yang and invigorating qi" acupuncture alters acetylcholine receptor expression in the neuromuscular junction of rats with experimental autoimmune myasthenia gravis

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    Hai-peng Huang

    2016-01-01

    Full Text Available Myasthenia gravis is an autoimmune disorder in which antibodies have been shown to form against the nicotinic acetylcholine nicotinic postsynaptic receptors located at the neuromuscular junction. "Warming yang and invigorating qi" acupuncture treatment has been shown to reduce serum inflammatory cytokine expression and increase transforming growth factor beta expression in rats with experimental autoimmune myasthenia gravis. However, few studies have addressed the effects of this type of acupuncture on the acetylcholine receptors at the neuromuscular junction. Here, we used confocal laser scanning microscopy to examine the area and density of immunoreactivity for an antibody to the nicotinic acetylcholine receptor at the neuromuscular junction in the phrenic nerve of rats with experimental autoimmune myasthenia gravis following "warming yang and invigorating qi" acupuncture therapy. Needles were inserted at acupressure points Shousanli (LI10, Zusanli (ST36, Pishu (BL20, and Shenshu (BL23 once daily for 7 consecutive days. The treatment was repeated after 1 day of rest. We found that area and the integrated optical density of the immunoreactivity for the acetylcholine receptor at the neuromuscular junction of the phrenic nerve was significantly increased following acupuncture treatment. This outcome of the acupuncture therapy was similar to that of the cholinesterase inhibitor pyridostigmine bromide. These findings suggest that "warming yang and invigorating qi" acupuncture treatment increases acetylcholine receptor expression at the neuromuscular junction in a rat model of autoimmune myasthenia gravis.

  12. Use of positron emission tomography (PET) for the diagnosis of large-vessel vasculitis.

    Science.gov (United States)

    Loricera, J; Blanco, R; Hernández, J L; Martínez-Rodríguez, I; Carril, J M; Lavado, C; Jiménez, M; González-Vela, C; González-Gay, M Á

    2015-01-01

    The term vasculitis encompasses a heterogeneous group of diseases that share the presence of inflammatory infiltrates in the vascular wall. The diagnosis of large-vessel vasculitis is often a challenge because the presenting clinical features are nonspecific in many cases and they are often shared by different types of autoimmune and inflammatory diseases including other systemic vasculitides. Moreover, the pathogenesis of large-vessel vasculitis is not fully understood. Nevertheless, the advent of new imaging techniques has constituted a major breakthrough to establish an early diagnosis and a promising tool to monitor the follow-up of patients with largevessel vasculitis. This is the case of the molecular imaging with the combination of positron emission tomography with computed tomography (PET/CT) using different radiotracers, especially the (18)F-fluordeoxyglucose ((18)F-FDG). In this review we have focused on the contribution of (18)F-FDG PET in the diagnosis of large-vessel vasculitis. Copyright © 2015 Elsevier España, S.L.U. and SEMNIM. All rights reserved.

  13. Leukocytoclastic vasculitis complicating cisplatin + radiation treatment for laryngeal cancer: a case report.

    Science.gov (United States)

    Quintanilha, Júlia Coelho França; Visacri, Marília Berlofa; Amaral, Laís Sampaio; Lima, Carmen Silvia Passos; Cintra, Maria Letícia; Moriel, Patricia

    2017-12-06

    Leukocytoclastic vasculitis is typically mediated by deposition of immune complexes and is related to many causes, including medication. To the best of our knowledge, leukocytoclastic vasculitis related to cisplatin has not yet been described in the scientific literature. We report a rare case of leukocytoclastic vasculitis after the first cycle of high-dose cisplatin chemotherapy in a patient with larynx carcinoma. A 48-year-old Caucasian man with larynx carcinoma received a high-dose of cisplatin monochemotherapy (100 mg/m 2 every 21 days), along with 70 Gy of radiotherapy divided into 35 sessions, as a therapeutic schedule. Twelve days after the first chemotherapy administration and after 8 sessions of radiotherapy (total of 16 Gy), the patient presented with acute onset of palpable purpura in the lower limbs. The patient was hospitalized for 10 days, and during this period, he underwent several examinations to rule out infectious, autoimmune, and neoplastic disorders. A skin biopsy showed leukocytoclastic vasculitis with a positive pattern for IgM and C3, as detected through direct immunofluorescence. Twenty-five days after cisplatin administration, the chemotherapy regimen was changed to carboplatin AUC 5, and the episodes of purpura ceased, reinforcing the hypothesis of an adverse reaction to cisplatin. Cisplatin can induce leukocytoclastic vasculitis and clinicians should be aware of this potential effect for better case management and diagnosis.

  14. Regulation of adenosine deaminase (ADA) on induced mouse experimental autoimmune uveitis (EAU) ?

    OpenAIRE

    Liang, Dongchun; Zuo, Aijun; Zhao, Ronglan; Shao, Hui; Kaplan, Henry J.; Sun, Deming

    2016-01-01

    Adenosine is an important regulator of the immune response and adenosine deaminase (ADA) inhibits this regulatory effect by converting adenosine into functionally inactive molecules. Studies have shown that adenosine receptor (AR) agonists can be either anti- or pro-inflammatory. Clarification of the mechanisms that cause these opposing effects should provide a better guide for therapeutic intervention. In this study, we investigated the effect of ADA on the development of experimental autoim...

  15. Meningococal Septicemia with Cutaneous Vasculitis

    Directory of Open Access Journals (Sweden)

    Radha Mittal

    1989-01-01

    Full Text Available Two cases-had meningococcal septicemia with vasculitis of skin. Out 9 year old female developed generalised ,asymptomatic, purpuric atrophic plaques on the limbs, trunk and face on the fourth day of high fever. The second patient was 20 year old male who developed purplish plaques. Nodules, and bullae mainly on the extensor surface of the hands and feet on the tenth day, of high fever. Bullae had clear fluid and bluish-black peripheral rim

  16. The leukotriene B{sub 4} receptor, BLT1, is required for the induction of experimental autoimmune encephalomyelitis

    Energy Technology Data Exchange (ETDEWEB)

    Kihara, Yasuyuki, E-mail: kihara-yasuyuki@umin.net [Department of Biochemistry and Molecular Biology, Faculty of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan); Yokomizo, Takehiko [Department of Medical Biochemistry, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582 (Japan); Core Research for Embryonic Science and Technology (CREST), Japan Science and Technology Agency (Japan); Kunita, Akiko; Morishita, Yasuyuki; Fukayama, Masashi [Department of Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033 (Japan); Ishii, Satoshi; Shimizu, Takao [Department of Biochemistry and Molecular Biology, Faculty of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan)

    2010-04-09

    Leukotriene B{sub 4} (LTB{sub 4}) is a potent chemoattractant and activator of neutrophils, macrophages and T cells. These cells are a key component of inflammation and all express BLT1, a high affinity G-protein-coupled receptor for LTB{sub 4}. However, little is known about the neuroimmune functions of BLT1. In this study, we describe a distinct role for BLT1 in the pathology of experimental autoimmune encephalomyelitis (EAE) and T{sub H}1/T{sub H}17 immune responses. BLT1 mRNA was highly upregulated in the spinal cord of EAE mice, especially during the induction phase. BLT1{sup -/-} mice had delayed onset and less severe symptoms of EAE than BLT1{sup +/+} mice. Additionally, inflammatory cells were recruited to the spinal cord of asymptomatic BLT1{sup +/+}, but not BLT1{sup -/-} mice before the onset of disease. Ex vivo studies showed that both the proliferation and the production of IFN-{gamma}, TNF-{alpha}, IL-17 and IL-6 were impaired in BLT1{sup -/-} cells, as compared with BLT1{sup +/+} cells. Thus, we suggest that BLT1 exacerbates EAE by regulating the migration of inflammatory cells and T{sub H}1/T{sub H}17 immune responses. Our findings provide a novel therapeutic option for the treatment of multiple sclerosis and other T{sub H}17-mediated diseases.

  17. Amelioration of experimental autoimmune encephalomyelitis in C57BL/6 mice by photobiomodulation induced by 670 nm light.

    Directory of Open Access Journals (Sweden)

    Kamaldeen A Muili

    Full Text Available The approved immunomodulatory agents for the treatment of multiple sclerosis (MS are only partially effective. It is thought that the combination of immunomodulatory and neuroprotective strategies is necessary to prevent or reverse disease progression. Irradiation with far red/near infrared light, termed photobiomodulation, is a therapeutic approach for inflammatory and neurodegenerative diseases. Data suggests that near-infrared light functions through neuroprotective and anti-inflammatory mechanisms. We sought to investigate the clinical effect of photobiomodulation in the Experimental Autoimmune Encephalomyelitis (EAE model of multiple sclerosis.The clinical effect of photobiomodulation induced by 670 nm light was investigated in the C57BL/6 mouse model of EAE. Disease was induced with myelin oligodendrocyte glycoprotein (MOG according to standard laboratory protocol. Mice received 670 nm light or no light treatment (sham administered as suppression and treatment protocols. 670 nm light reduced disease severity with both protocols compared to sham treated mice. Disease amelioration was associated with down-regulation of proinflammatory cytokines (interferon-γ, tumor necrosis factor-α and up-regulation of anti-inflammatory cytokines (IL-4, IL-10 in vitro and in vivo.These studies document the therapeutic potential of photobiomodulation with 670 nm light in the EAE model, in part through modulation of the immune response.

  18. The Anti-Inflammatory Effects of a Yin Zhi Huang Soup in an Experimental Autoimmune Prostatitis Rat Model

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    Longsheng Deng

    2017-01-01

    Full Text Available The present study aimed to investigate the therapeutic effects of the Chinese herbal medicine Yin Zhi Huang soup (YZS in an experimental autoimmune prostatitis (EAP rat model. In total, 48 rats were randomly divided into the following four groups (n=12/group: saline group, pathological model group, Qianlietai group, and YZS group. We determined the average wet weight of the prostate tissue, the ratio of the wet weight of the prostate tissue to body weight, tumor necrosis factor-alpha (TNF-α levels in the blood serum, the expression of inducible nitric oxide synthase (iNOS in the rats’ prostate tissues, and the pathological changes in the prostate tissue using light microscopy. YZS reduced the rats’ prostate wet weight, the ratio of the prostate wet weight to body weight, and TNF-α levels in the blood serum and inhibited the expression of iNOS in the rats’ prostate tissues (P<0.05. Following YZS treatment, the pathological changes in the rats’ prostates were improved compared with those in the model group (P<0.05. Furthermore, YZS treatment reduced inflammatory changes in the prostate tissue. It also significantly suppressed proinflammatory cytokines, such as TNF-α, and chemokines, such as iNOS, in the rat model of EAP.

  19. CD73 Expressed on γδ T Cells Shapes Their Regulatory Effect in Experimental Autoimmune Uveitis.

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    Dongchun Liang

    Full Text Available γδ T cells can either enhance or inhibit an adaptive immune response, but the mechanisms involved are not fully understood. Given that CD73 is the main enzyme responsible for conversion of AMP into the immunosuppressive molecule adenosine, we investigated its role in the regulatory function of γδ T cells in experimental autoimmune uveitis (EAU. We found that γδ T cells expressed different amounts of CD73 during the different stages of EAU and that low CD73 expression on γδ T cells correlated with enhanced Th17 response-promoting activity. Functional comparison of CD73-deficient and wild-type B6 (CD73+/+ mice showed that failure to express CD73 decreased both the enhancing and suppressive effects of γδ T cells on EAU. We also demonstrated that γδ T cells expressed different amounts of CD73 when activated by different pathways, which enabled them to either enhance or inhibit an adaptive immune response. Our results demonstrate that targeting CD73 expression on γδ T cells may allow us to manipulate their pro- or anti-inflammatory effect on Th17 responses.

  20. Inhibition of Myeloperoxidase at the Peak of Experimental Autoimmune Encephalomyelitis Restores Blood-Brain-Barrier Integrity and Ameliorates Disease Severity.

    Science.gov (United States)

    Zhang, Hao; Ray, Avijit; Miller, Nichole M; Hartwig, Danielle; Pritchard, Kirkwood A; Dittel, Bonnie N

    2015-11-12

    Oxidative stress is thought to contribute to disease pathogenesis in the central nervous system (CNS) disease multiple sclerosis (MS). Myeloperoxidase (MPO), a potent peroxidase that generates toxic radicals and oxidants, is increased in the CNS during MS. However, the exact mechanism whereby MPO drives MS pathology is not known. We addressed this question by inhibiting MPO in mice with experimental autoimmune encephalomyelitis (EAE) using our non-toxic MPO inhibitor KYC. We found that therapeutic administration of KYC for five days starting at the peak of disease significantly attenuated EAE disease severity, reduced myeloid cell numbers and permeability of the blood-brain-barrier (BBB). These data indicate that inhibition of MPO by KYC restores BBB integrity thereby limiting migration of myeloid cells into the CNS that drive EAE pathogenesis. In addition, these observations indicate that KYC may be an effective therapeutic agent for the treatment of MS. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  1. Tolerogenic Dendritic Cells Generated with Tofacitinib Ameliorate Experimental Autoimmune Encephalomyelitis through Modulation of Th17/Treg Balance

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    Yan Zhou

    2016-01-01

    Full Text Available It is well known that dendritic cells (DCs play a pivotal role in triggering self-specific responses. Conversely, tolerogenic DCs (tolDCs, a specialized subset, induce tolerance and negatively regulate autoreactive responses. Tofacitinib, a Janus kinase inhibitor developed by Pfizer for treatment of rheumatoid arthritis, is probable to be a promising candidate for inducing tolDCs. The aims of this study were to evaluate the effectiveness of tolDCs induced by tofacitinib in a myelin oligodendrocyte glycoprotein- (MOG- specific experimental autoimmune encephalomyelitis (EAE model and to investigate their effects on Th17/Treg balance in the animal model of multiple sclerosis (MS. Our results revealed that tofacitinib-treated DCs maintained a steady semimature phenotype with a low level of proinflammatory cytokines and costimulatory molecules. DCs treated by tofacitinib also induced antigen-specific T cells hyporesponsiveness in a concentration-dependent manner. Upon intravenous injection into EAE mice, MOG pulsed tolDCs significantly dampened disease activity, and adoptive cell therapy (ACT disturbed Th17/Treg balance with a remarkable decrease of Th1/Th17 cells and an increase in regulatory T cells (Tregs. Overall, DCs modified by tofacitinib exhibited a typical tolerogenic phenotype, and the antigen-specific tolDCs may represent a new avenue of research for the development of future clinical treatments for MS.

  2. Suppressive effects of a novel compound on interphotoreceptor retinoid-binding protein-induced experimental autoimmune uveoretinitis in rats

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    Jun-ichi Sakai

    1999-01-01

    Full Text Available The immunosuppressive effect of ethyl O-(N-(pcarboxyphenyl-carbamoyl-mycophenolate(CAM was examined in interphotoreceptor retinoid-binding protein (IRBP-induced experimental autoimmune uveoretinitis (EAU in rats. Lewis rats immunized with bovine IRBP were treated with various oral doses of CAM postimmunization. The degree of inflammation was assessed clinically each day and histologically on day 14 or day 20. Production of various cytokines and IRBP-specific antibody, as well as IRBP-specific proliferation response, was assessed. Complete inhibition of EAU in rats, both by clinical and histologic criteria, was achieved with 50 mg/kg CAM when administered daily for 14 days following IRBP immunization. Partial inhibition was observed at lesser doses of CAM. This CAM-mediated response was accompanied by diminished production of cytokines interleukin-2, interferon-γ and tumor necrosis factor-α, as well as a reduction in IRBP-specific antibody production. Furthermore, administration of CAM either in the induction phase only (days 0–7 or in the effector phase only (days 9 or 11 to day 20 was also capable of suppressing EAU, as assessed histopathologically on day 20. We conclude that CAM is effective in suppressing EAU in rats and its mechanism of action appears to involve modulation of T cell function.

  3. Scabietic vasculitis: Report of 2 cases.

    Science.gov (United States)

    Clevy, C; Brajon, D; Combes, E; Benzaquen, M; Dales, J-P; Koeppel, M-C; Berbis, P

    2017-05-01

    The infectious causes of cutaneous vasculitis are well known and include streptococcal infections among others. Cases resulting from parasitic infection are less frequent. Scabies, which is currently on the increase, has only been reported in a few isolated cases. Herein, we report two noteworthy cases of profuse scabies complicated by cutaneous vasculitis. Case 1: a 90-year-old woman, residing in a nursing home, was admitted to our dermatology department complaining of pruritus, present for one month, predominantly on the inside of the thighs and on the buttocks, associated with purpuric lesions on the lower limbs. A skin biopsy revealed leukocytoclastic vasculitis. A diagnosis of scabies was based on severe pruritus and hypereosinophilia and was confirmed by microscopic examination of the parasitology sample and the skin biopsy sample. Despite thorough investigation, no other cause of vasculitis could be found. Complete regression of the skin lesions was achieved with scabies treatment only, without any specific treatment for the vasculitis. Case 2: a 74-year-old man, living in a nursing home, was hospitalized for purpuric papules on the lower limbs, present for one month. Physical examination revealed linear patterns in the interdigital spaces associated with scabies evident on dermoscopic examination. The skin biopsy revealed signs of vasculitis. As in our first case, no aetiology of vasculitis was found and a favorable outcome was achieved by means of scabies treatment alone with no specific treatment for vasculitis. Both of our patients presented scabies and vasculitis. In view of the absence of other causes of vasculitis and of the complete regression of lesions due to vasculitis without recurrence achieved with the scabies treatment alone, a diagnosis was made of scabietic vasculitis, probably as a result of cutaneous hypersensitivity reaction to humeral mediators. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  4. Pregnancy Outcomes Among Patients With Vasculitis

    Science.gov (United States)

    Clowse, Megan E. B.; Richeson, Rachel L.; Pieper, Carl; Merkel, Peter A.

    2015-01-01

    Objective Pregnancy outcomes of patients with vasculitis are unknown, but are of great concern to patients and physicians. Through an online survey, this study assessed pregnancy outcomes among patients with vasculitis. Methods Participants in the Vasculitis Clinical Research Consortium Patient Contact Registry were invited to respond to an anonymous, internet-based survey that included questions about pregnancy outcomes, the timing of pregnancy relative to a diagnosis of vasculitis, and medication use. Results A total of 350 women and 113 men completed the survey. After a diagnosis of vasculitis, 74 pregnancies were reported by women and 18 conceptions were reported by men. The rate of pregnancy loss was higher among women who conceived after a diagnosis of vasculitis compared to those who conceived prior to diagnosis (33.8% versus 22.4%; P = 0.04). Among women, the rate of preterm births increased significantly for pregnancies conceived after a diagnosis of vasculitis relative to those conceived before diagnosis (23.3% versus 11.4%; P = 0.03). Only 18% of women reported worsening of vasculitis during pregnancy, but those who experienced increased vasculitis activity were more likely to deliver preterm. Exposure to cyclophosphamide or prednisone did not appear to impact pregnancy outcomes; however, the number of pregnancies among women taking these medications was small. Among the pregnancies conceived by men with vasculitis, the timing of diagnosis had no significant effect on the rate of pregnancy loss. Conclusion Women who conceived after a diagnosis of vasculitis had a higher rate of pregnancy loss than those who conceived prior to diagnosis. Vasculitis did not worsen during the majority of pregnancies conceived after diagnosis. PMID:23401494

  5. TH17 cells mediate inflammation in a novel model of spontaneous experimental autoimmune lacrimal keratoconjunctivitis with neural damage.

    Science.gov (United States)

    Seo, Kyoung Yul; Kitamura, Kazuya; Han, Soo Jung; Kelsall, Brian

    2017-09-27

    Dry eye disease (DED) affects one third of the population worldwide. In prior studies, experimental autoimmune lacrimal keratoconjunctivitis (EALK) induced by desiccating stress in mice has been used as a model of DED. This model is complicated by a requirement for exogenous epithelial cell injury and administration of anticholinergic agents with broad immunologic effects. We sought to develop a novel mouse model of EALK and to demonstrate the responsible pathogenic mechanisms. CD4 + CD45RB high naive T cells with and without CD4 + CD45RB low regulatory T cells were adoptively transferred to C57BL/10 recombination-activating gene 2 (Rag2) -/- mice. The eyes, draining lymph nodes, lacrimal glands, and surrounding tissues of mice with and without spontaneous keratoconjunctivitis were evaluated for histopathologic changes, cellular infiltration, and cytokine production in tissues and isolated cells. Furthermore, the integrity of the corneal nerves was evaluated using whole-tissue immunofluorescence imaging. Gene-deficient naive T cells or RAG2-deficient hosts were evaluated to assess the roles of IFN-γ, IL-17A, and IL-23 in disease pathogenesis. Finally, cytokine levels were determined in the tears of patients with DED. EALK developed spontaneously in C57BL/10 Rag2 -/- mice after adoptive transfer of CD4 + CD45RB high naive T cells and was characterized by infiltration of CD4 + T cells, macrophages, and neutrophils. In addition to lacrimal keratoconjunctivitis, mice had damage to the corneal nerve, which connects components of the lacrimal functional unit. Pathogenic T-cell differentiation was dependent on IL-23p40 and controlled by cotransferred CD4 + CD45RB low regulatory T cells. T H 17 rather than T H 1 CD4 + cells were primarily responsible for EALK, even though levels of both IL-17 and IFN-γ were increased in inflammatory tissues, likely because of their ability to drive expression of CXC chemokines within the cornea and the subsequent influx of myeloid cells

  6. Bee Venom Acupuncture Alleviates Experimental Autoimmune Encephalomyelitis by Upregulating Regulatory T Cells and Suppressing Th1 and Th17 Responses.

    Science.gov (United States)

    Lee, Min Jung; Jang, Minhee; Choi, Jonghee; Lee, Gihyun; Min, Hyun Jung; Chung, Won-Seok; Kim, Jong-In; Jee, Youngheun; Chae, Younbyoung; Kim, Sung-Hoon; Lee, Sung Joong; Cho, Ik-Hyun

    2016-04-01

    The protective and therapeutic mechanism of bee venom acupuncture (BVA) in neurodegenerative disorders is not clear. We investigated whether treatment with BVA (0.25 and 0.8 mg/kg) at the Zusanli (ST36) acupoints, located lateral from the anterior border of the tibia, has a beneficial effect in a myelin basic protein (MBP)(68-82)-induced acute experimental autoimmune encephalomyelitis (EAE) rat model. Pretreatment (every 3 days from 1 h before immunization) with BVA was more effective than posttreatment (daily after immunization) with BVA with respect to clinical signs (neurological impairment and loss of body weight) of acute EAE rats. Treatment with BVA at the ST36 acupoint in normal rats did not induce the clinical signs. Pretreatment with BVA suppressed demyelination, glial activation, expression of cytokines [interferon (IFN)-γ, IL-17, IL-17A, tumor necrosis factor-alpha (TNF-α), and IL-1β], chemokines [RANTES, monocyte chemotactic protein-1 (MCP-1), and macrophage inflammatory protein (MIP)-1α], and inducible nitric oxide synthase (iNOS), and activation of p38 mitogen-activated protein kinase (MAPK) and nuclear factor (NF)-κB (p65 and phospho-IκBα) signaling pathways in the spinal cord of acute EAE rats. Pretreatment with BVA decreased the number of CD4(+), CD4(+)/IFN-γ(+), and CD4(+)/IL-17(+) T cells, but increased the number of CD4(+)/Foxp3(+) T cells in the spinal cord and lymph nodes of acute EAE rats. Treatment with BVA at six placebo acupoints (SP9, GB39, and four non-acupoints) did not have a positive effect in acute EAE rats. Interestingly, onset and posttreatment with BVA at the ST36 acupoint markedly attenuated neurological impairment in myelin oligodendrocyte glycoprotein (MOG)(35-55)-induced chronic EAE mice compared to treatment with BVA at six placebo acupoints. Our findings strongly suggest that treatment with BVA with ST36 acupoint could delay or attenuate the development and progression of EAE by upregulating regulatory T cells and

  7. Educational Needs of Patients With Systemic Vasculitis

    Science.gov (United States)

    2014-07-11

    Behcet's Disease; Churg-Strauss Syndrome; Vasculitis, Central Nervous System; Giant Cell Arteritis; Wegener Granulomatosis; Henoch-Schoenlein Purpura; Microscopic Polyangiitis; Polyarteritis Nodosa; Takayasu's Arteritis

  8. Therapeutic Effect of CD4+CD25+ Regulatory T Cells Amplified In Vitro on Experimental Autoimmune Neuritis in Rats

    Directory of Open Access Journals (Sweden)

    Feng-Jie Wang

    2018-05-01

    Full Text Available Background/Aims: This study aimed to explore whether the adoptive transfusion of autologous CD4+CD25+ regulatory T cells (CD4+CD25+ Tregs has a therapeutic effect on Experimental autoimmune neuritis (EAN model rats, and it provides new experimental and theoretical bases for the immunotherapy of Guillain-Barre syndrome (GBS. Methods: CD4+CD25+ Tregs were sorted from the spleens of rats using immunomagnetic bead separation techniques combined with flow cytometry. Their in vitro inhibitory function was determined using a lymphocyte proliferation inhibition test, and their purity was confirmed by flow cytometry. Cells were stimulated using CD3/CD28 monoclonal antibodies and were cultured in culture medium containing interleukin 2 (IL-2, transforming growth factor-β (TGF-β and rapamycin. After 15 days of amplification, CD4+CD25+ Tregs were collected and transfused into EAN model rats. Changes in the pathology and electron microscopical morphology of rat sciatic nerves in the normal group, untreated group, low-dose group (2 × 107 and high-dose group (4 × 107 were observed, and the expression of CD4+CD25+FOXP3 in peripheral blood in the four groups of rats was detected by flow cytometry. Results: Compared with rats in the untreated group, rats in the treatment groups had significantly reduced infiltration of inflammatory cells in the sciatic nerve, as well as myelin and axonal damage. Additionally, the CD4+CD25+ Tregs levels in peripheral blood were significantly higher than those in the untreated group (P< 0. 05. Moreover, the therapeutic effect became more significant with an increase in the dose of adoptive transfusion. Conclusion: Adoptive transfusion of CD4+CD25+ Tregs into EAN model rats has significant therapeutic effects.

  9. Membrane attack complex of complement is not essential for immune mediated demyelination in experimental autoimmune neuritis.

    Science.gov (United States)

    Tran, Giang T; Hodgkinson, Suzanne J; Carter, Nicole M; Killingsworth, Murray; Nomura, Masaru; Verma, Nirupama D; Plain, Karren M; Boyd, Rochelle; Hall, Bruce M

    2010-12-15

    Antibody deposition and complement activation, especially membrane attack complex (MAC) formation are considered central for immune mediated demyelination. To examine the role of MAC in immune mediated demyelination, we studied experimental allergic neuritis (EAN) in Lewis rats deficient in complement component 6 (C6) that cannot form MAC. A C6 deficient Lewis (Lewis/C6-) strain of rats was bred by backcrossing the defective C6 gene, from PVG/C6- rats, onto the Lewis background. Lewis/C6- rats had the same C6 gene deletion as PVG/C6- rats and their sera did not support immune mediated haemolysis unless C6 was added. Active EAN was induced in Lewis and Lewis/C6- rats by immunization with bovine peripheral nerve myelin in complete Freund's adjuvant (CFA), and Lewis/C6- rats had delayed clinical EAN compared to the Lewis rats. Peripheral nerve demyelination in Lewis/C6- was also delayed but was similar in extent at the peak of disease. Compared to Lewis, Lewis/C6- nerves had no MAC deposition, reduced macrophage infiltrate and IL-17A, but similar T cell infiltrate and Th1 cytokine mRNA expression. ICAM-1 and P-selectin mRNA expression and immunostaining on vascular endothelium were delayed in Lewis C6- compared to Lewis rats' nerves. This study found that MAC was not required for immune mediated demyelination; but that MAC enhanced early symptoms and early demyelination in EAN, either by direct lysis or by sub-lytic induction of vascular endothelial expression of ICAM-1 and P-selectin. Copyright © 2010 Elsevier B.V. All rights reserved.

  10. CD8+/perforin+/WC1- gammadelta T cells, CD8+ alphabeta T cells, infiltrate vasculitis lesions of American bison (Bison bison) with experimental sheep-associated malignant catarrhal fever

    Science.gov (United States)

    Sheep-associated malignant catarrhal fever (SA-MCF) caused by ovine herpesvirus-2 (OvHV-2) is a fatal disease associated with lymphoproliferation, lymphocytic vasculitis, and mucosal ulceration in clinically susceptible species. SA-MCF is an important threat to American bison (Bison bison) due to th...

  11. A SELDI mass spectrometry study of experimental autoimmune encephalomyelitis: sample preparation, reproducibility, and differential protein expression patterns.

    Science.gov (United States)

    Azzam, Sausan; Broadwater, Laurie; Li, Shuo; Freeman, Ernest J; McDonough, Jennifer; Gregory, Roger B

    2013-05-01

    Experimental autoimmune encephalomyelitis (EAE) is an autoimmune, inflammatory disease of the central nervous system that is widely used as a model of multiple sclerosis (MS). Mitochondrial dysfunction appears to play a role in the development of neuropathology in MS and may also play a role in disease pathology in EAE. Here, surface enhanced laser desorption ionization mass spectrometry (SELDI-MS) has been employed to obtain protein expression profiles from mitochondrially enriched fractions derived from EAE and control mouse brain. To gain insight into experimental variation, the reproducibility of sub-cellular fractionation, anion exchange fractionation as well as spot-to-spot and chip-to-chip variation using pooled samples from brain tissue was examined. Variability of SELDI mass spectral peak intensities indicates a coefficient of variation (CV) of 15.6% and 17.6% between spots on a given chip and between different chips, respectively. Thinly slicing tissue prior to homogenization with a rotor homogenizer showed better reproducibility (CV = 17.0%) than homogenization of blocks of brain tissue with a Teflon® pestle (CV = 27.0%). Fractionation of proteins with anion exchange beads prior to SELDI-MS analysis gave overall CV values from 16.1% to 18.6%. SELDI mass spectra of mitochondrial fractions obtained from brain tissue from EAE mice and controls displayed 39 differentially expressed proteins (p≤ 0.05) out of a total of 241 protein peaks observed in anion exchange fractions. Hierarchical clustering analysis showed that protein fractions from EAE animals with severe disability clearly segregated from controls. Several components of electron transport chain complexes (cytochrome c oxidase subunit 6b1, subunit 6C, and subunit 4; NADH dehydrogenase flavoprotein 3, alpha subcomplex subunit 2, Fe-S protein 4, and Fe-S protein 6; and ATP synthase subunit e) were identified as possible differentially expressed proteins. Myelin Basic Protein isoform 8 (MBP8) (14.2 k

  12. Glucagon-like peptide-1 analogue, liraglutide, delays onset and reduces severity of experimental autoimmune encephalitis in Lewis rats

    Directory of Open Access Journals (Sweden)

    Brian DellaValle

    2016-11-01

    Full Text Available AbstractIntroduction: Recent findings indicate that metabolic disturbances are involved in multiple sclerosis (MS pathology and influence the susceptibility to treatment, directing attention towards anti-diabetic drugs such as metformin and pioglitazone. Liraglutide, a drug of the glucagon-like peptide-1 (GLP-1 family, is also anti-diabetic and weight-reducing and is moreover, directly neuroprotective and anti-inflammatory in a broad spectrum of experimental models of brain disease. In this study we investigate the potential for this FDA-approved drug, liraglutide, as a treatment for MS by utilizing the experimental model, experimental autoimmune encephalitis (EAE.Methods: EAE was induced in 30 female Lewis rats that subsequently received twice-daily liraglutide (200 µg/kg s.c. or saline. Healthy controls were included (saline, n=6, liraglutide, n=7. Clinical score and weight were assessed daily by blinded observers. Animals were killed at peak disease severity (day 11 or if exceeding humane endpoint (clinical score ≥4. Protein levels of manganese superoxide dismutase (MnSOD, amyloid precursor protein (APP, and glial fibrillary acidic protein (GFAP were determined.Results: Liraglutide treatment delayed disease onset (group clinical score significantly >0 by two days and markedly reduced disease severity (median clinical score 2 vs. 5; p=0.0003. Fourteen of 15 (93% of vehicle-treated rats reached the humane endpoint (clinical score ≥4 by day 11 compared to 5 of 15 (33% of liraglutide-treated rats (p=0.0004. Liraglutide substantially increased the mitochondrial antioxidant MnSOD (p<0.01 and reduced the neurodegenerative marker APP (p=0.036 in the brain. GFAP levels were not significantly changed with drug treatment (p=0.09Conclusion: We demonstrate, for the first time, that liraglutide treatment delays onset of EAE in Lewis rats and is associated with improved protective capacity against oxidative stress. These data suggest GLP-1 receptor

  13. Experimental autoimmune encephalomyelitis (EAE): lesion visualization on a 3 tesla Clinical whole-body system after intraperitoneal contrast injection

    Energy Technology Data Exchange (ETDEWEB)

    Heckl, S.; Naegele, T.; Klose, U. [Dept. of Neuroradiology, Medical School, Univ. of Tuebingen (Germany); Herrmann, M.; Gaertner, S.; Weissert, R. [Dept. of Neurology, Medical School, Univ. of Tuebingen (Germany); Schick, F. [Dept. of Radiology, Medical School, Univ. of Tuebingen (Germany); Kueker, W. [Dept. of Neuroradiology, Medical School, Univ. of Tuebingen (Germany); Dept. of Neuroradiology, Radcliffe Infirmary, Oxford, England (United Kingdom)

    2004-11-01

    Purpose: To investigate the intravital visibility of CNS lesions in rats with experimental autoimmune encephalomyelitis (EAE), the animal correlate of multiple sclerosis, using a 3-Tesla (T) wholebody MR system. Materials and Methods: Three healthy Dark Agouti (DA) rats and 16 DA rats with clinical signs of EAE were examined on a 3T whole body-system using a normal wrist coil. In total, 25 examinations were preformed using T2- and T1-weighted images in transverse and sagittal orientation with a slice thickness of 2 mm or 1 mm (voxel size up to 0.2 x 0.2 x 1 mm). Sedation was achieved by intraperitoneal injection of ketamine and xylazine. In addition, T1-weighted images were obtained after the instillation of 1.0 ml of gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA) (0.5 mmol/ml) into the peritoneal cavity. Results: T2- and T1-weighted images of the brain and spinal cord with high spatial and contrast resolution could be obtained in all animals. The anatomical details of the olfactory bulb glomeruli, cerebellum foliae, ventricles and corpus callosum were clearly visible. The EAE lesions presented as hyperintense area in T2-weighted images and could be demonstrated in all clinically affected animals by MRI and histologically verified. In total, the 16 affected rats had 28 cerebral and 2 spinal cord lesions (range 1 to 4, median 2). Contrast enhancement was noted in 12 animals and ranked as severe in ten and moderate in two cases. No adverse effects were noted due to sedation or intraperitoneal contrast injection. Conclusions: The intravital demonstration of cerebral and spinal cord EAE lesions in rats is possible on a 3T whole-body MR scanner using a normal wrist coil. Intraperitoneal injection of ketamine/xylazine and contrast agent is an easy, safe and effective procedure in rats. (orig.)

  14. Experimental autoimmune encephalomyelitis (EAE): lesion visualization on a 3 tesla Clinical whole-body system after intraperitoneal contrast injection

    International Nuclear Information System (INIS)

    Heckl, S.; Naegele, T.; Klose, U.; Herrmann, M.; Gaertner, S.; Weissert, R.; Schick, F.; Kueker, W.

    2004-01-01

    Purpose: To investigate the intravital visibility of CNS lesions in rats with experimental autoimmune encephalomyelitis (EAE), the animal correlate of multiple sclerosis, using a 3-Tesla (T) wholebody MR system. Materials and Methods: Three healthy Dark Agouti (DA) rats and 16 DA rats with clinical signs of EAE were examined on a 3T whole body-system using a normal wrist coil. In total, 25 examinations were preformed using T2- and T1-weighted images in transverse and sagittal orientation with a slice thickness of 2 mm or 1 mm (voxel size up to 0.2 x 0.2 x 1 mm). Sedation was achieved by intraperitoneal injection of ketamine and xylazine. In addition, T1-weighted images were obtained after the instillation of 1.0 ml of gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA) (0.5 mmol/ml) into the peritoneal cavity. Results: T2- and T1-weighted images of the brain and spinal cord with high spatial and contrast resolution could be obtained in all animals. The anatomical details of the olfactory bulb glomeruli, cerebellum foliae, ventricles and corpus callosum were clearly visible. The EAE lesions presented as hyperintense area in T2-weighted images and could be demonstrated in all clinically affected animals by MRI and histologically verified. In total, the 16 affected rats had 28 cerebral and 2 spinal cord lesions (range 1 to 4, median 2). Contrast enhancement was noted in 12 animals and ranked as severe in ten and moderate in two cases. No adverse effects were noted due to sedation or intraperitoneal contrast injection. Conclusions: The intravital demonstration of cerebral and spinal cord EAE lesions in rats is possible on a 3T whole-body MR scanner using a normal wrist coil. Intraperitoneal injection of ketamine/xylazine and contrast agent is an easy, safe and effective procedure in rats. (orig.)

  15. Long-Term Therapeutic Effects of Mesenchymal Stem Cells Compared to Dexamethasone on Recurrent Experimental Autoimmune Uveitis of Rats

    Science.gov (United States)

    Zhang, Lingjun; Zheng, Hui; Shao, Hui; Nian, Hong; Zhang, Yan; Bai, Lingling; Su, Chang; Liu, Xun; Dong, Lijie; Li, Xiaorong; Zhang, Xiaomin

    2014-01-01

    Purpose. We tested the long-term effects of different regimens of mesenchymal stem cell (MSC) administration in a recurrent experimental autoimmune uveitis (rEAU) model in rats, and compared the efficacy of MSC to that of dexamethasone (DEX). Methods. One or two courses of MSC treatments were applied to R16-specific T cell–induced rEAU rats before or after disease onsets. The DEX injections were given for 7 or 50 days continuously after disease onsets. Clinical appearances were observed until the 50th day after transfer. On the 10th day, T cells from control and MSC groups were analyzed by flow cytometry. Supernatants from the proliferation assay and aqueous humor were collected for cytokine detection. Functions of T cells and APCs in spleens also were studied by lymphocyte proliferation assays. Results. One course of MSC therapy, administered after disease onset, led to a lasting therapeutic effect, with a decreased incidence, reduced mean clinical score, and reduced retinal impairment after 50 days of observation, while multiple courses of treatment did not improve the therapeutic benefit. Although DEX and MSCs equally reduced the severity of the first episode of rEAU, the effect of DEX was shorter lasting, and DEX therapy failed to control the disease even with long periods of treatment. The MSCs significantly decreased T helper 1 (Th1) and Th17 responses, suppressed the function of antigen-presenting cells, and upregulated T regulatory cells. Conclusions. These results suggested that MSCs might be new corticosteroid spring agents, while providing fewer side effects and longer lasting suppressive effects for recurrent uveitis. PMID:25125599

  16. The extracellular domain of myelin oligodendrocyte glycoprotein elicits atypical experimental autoimmune encephalomyelitis in rat and Macaque species.

    Directory of Open Access Journals (Sweden)

    Alan D Curtis

    Full Text Available Atypical models of experimental autoimmune encephalomyelitis (EAE are advantageous in that the heterogeneity of clinical signs appears more reflective of those in multiple sclerosis (MS. Conversely, models of classical EAE feature stereotypic progression of an ascending flaccid paralysis that is not a characteristic of MS. The study of atypical EAE however has been limited due to the relative lack of suitable models that feature reliable disease incidence and severity, excepting mice deficient in gamma-interferon signaling pathways. In this study, atypical EAE was induced in Lewis rats, and a related approach was effective for induction of an unusual neurologic syndrome in a cynomolgus macaque. Lewis rats were immunized with the rat immunoglobulin variable (IgV-related extracellular domain of myelin oligodendrocyte glycoprotein (IgV-MOG in complete Freund's adjuvant (CFA followed by one or more injections of rat IgV-MOG in incomplete Freund's adjuvant (IFA. The resulting disease was marked by torticollis, unilateral rigid paralysis, forelimb weakness, and high titers of anti-MOG antibody against conformational epitopes of MOG, as well as other signs of atypical EAE. A similar strategy elicited a distinct atypical form of EAE in a cynomolgus macaque. By day 36 in the monkey, titers of IgG against conformational epitopes of extracellular MOG were evident, and on day 201, the macaque had an abrupt onset of an unusual form of EAE that included a pronounced arousal-dependent, transient myotonia. The disease persisted for 6-7 weeks and was marked by a gradual, consistent improvement and an eventual full recovery without recurrence. These data indicate that one or more boosters of IgV-MOG in IFA represent a key variable for induction of atypical or unusual forms of EAE in rat and Macaca species. These studies also reveal a close correlation between humoral immunity against conformational epitopes of MOG, extended confluent demyelinating plaques in

  17. The extracellular domain of myelin oligodendrocyte glycoprotein elicits atypical experimental autoimmune encephalomyelitis in rat and Macaque species.

    Science.gov (United States)

    Curtis, Alan D; Taslim, Najla; Reece, Shaun P; Grebenciucova, Elena; Ray, Richard H; Rosenbaum, Matthew D; Wardle, Robert L; Van Scott, Michael R; Mannie, Mark D

    2014-01-01

    Atypical models of experimental autoimmune encephalomyelitis (EAE) are advantageous in that the heterogeneity of clinical signs appears more reflective of those in multiple sclerosis (MS). Conversely, models of classical EAE feature stereotypic progression of an ascending flaccid paralysis that is not a characteristic of MS. The study of atypical EAE however has been limited due to the relative lack of suitable models that feature reliable disease incidence and severity, excepting mice deficient in gamma-interferon signaling pathways. In this study, atypical EAE was induced in Lewis rats, and a related approach was effective for induction of an unusual neurologic syndrome in a cynomolgus macaque. Lewis rats were immunized with the rat immunoglobulin variable (IgV)-related extracellular domain of myelin oligodendrocyte glycoprotein (IgV-MOG) in complete Freund's adjuvant (CFA) followed by one or more injections of rat IgV-MOG in incomplete Freund's adjuvant (IFA). The resulting disease was marked by torticollis, unilateral rigid paralysis, forelimb weakness, and high titers of anti-MOG antibody against conformational epitopes of MOG, as well as other signs of atypical EAE. A similar strategy elicited a distinct atypical form of EAE in a cynomolgus macaque. By day 36 in the monkey, titers of IgG against conformational epitopes of extracellular MOG were evident, and on day 201, the macaque had an abrupt onset of an unusual form of EAE that included a pronounced arousal-dependent, transient myotonia. The disease persisted for 6-7 weeks and was marked by a gradual, consistent improvement and an eventual full recovery without recurrence. These data indicate that one or more boosters of IgV-MOG in IFA represent a key variable for induction of atypical or unusual forms of EAE in rat and Macaca species. These studies also reveal a close correlation between humoral immunity against conformational epitopes of MOG, extended confluent demyelinating plaques in spinal cord and

  18. IL17/IL17RA as a Novel Signaling Axis Driving Mesenchymal Stem Cell Therapeutic Function in Experimental Autoimmune Encephalomyelitis

    Directory of Open Access Journals (Sweden)

    Mónica Kurte

    2018-04-01

    Full Text Available The therapeutic effect of mesenchymal stem cells (MSCs in multiple sclerosis (MS and the experimental autoimmune encephalomyelitis (EAE model has been well described. This effect is, in part, mediated through the inhibition of IL17-producing cells and the generation of regulatory T cells. While proinflammatory cytokines such as IFNγ, TNFα, and IL1β have been shown to enhance MSCs immunosuppressive function, the role of IL17 remains poorly elucidated. The aim of this study was, therefore, to investigate the role of the IL17/IL17R pathway on MSCs immunoregulatory effects focusing on Th17 cell generation in vitro and on Th17-mediated EAE pathogenesis in vivo. In vitro, we showed that the immunosuppressive effect of MSCs on Th17 cell proliferation and differentiation is partially dependent on IL17RA expression. This was associated with a reduced expression level of MSCs immunosuppressive mediators such as VCAM1, ICAM1, and PD-L1 in IL17RA−/− MSCs as compared to wild-type (WT MSCs. In the EAE model, we demonstrated that while WT MSCs significantly reduced the clinical scores of the disease, IL17RA−/− MSCs injected mice exhibited a clinical worsening of the disease. The disability of IL17RA−/− MSCs to reduce the progression of the disease paralleled the inability of these cells to reduce the frequency of Th17 cells in the draining lymph node of the mice as compared to WT MSCs. Moreover, we showed that the therapeutic effect of MSCs was correlated with the generation of classical Treg bearing the CD4+CD25+Foxp3+ signature in an IL17RA-dependent manner. Our findings reveal a novel role of IL17RA on MSCs immunosuppressive and therapeutic potential in EAE and suggest that the modulation of IL17RA in MSCs could represent a novel method to enhance their therapeutic effect in MS.

  19. Lipocalin 2 is a novel immune mediator of experimental autoimmune encephalomyelitis pathogenesis and is modulated in multiple sclerosis.

    Science.gov (United States)

    Berard, Jennifer L; Zarruk, Juan G; Arbour, Nathalie; Prat, Alexandre; Yong, V Wee; Jacques, Francois H; Akira, Shizuo; David, Samuel

    2012-07-01

    Experimental autoimmune encephalomyelitis (EAE) is a widely used animal model of multiple sclerosis (MS), an inflammatory, demyelinating disease of the central nervous system (CNS). EAE pathogenesis involves various cell types, cytokines, chemokines, and adhesion molecules. Given the complexity of the inflammatory response in EAE, it is likely that many immune mediators still remain to be discovered. To identify novel immune mediators of EAE pathogenesis, we performed an Affymetrix gene array screen on the spinal cords of mice at the onset stage of disease. This screening identified the gene encoding lipocalin 2 (Lcn2) as being significantly upregulated. Lcn2 is a multi-functional protein that plays a role in glial activation, matrix metalloproteinase (MMP) stabilization, and cellular iron flux. As many of these processes have been implicated in EAE, we characterized the expression and role of Lcn2 in this disease in C57BL/6 mice. We show that Lcn2 is significantly upregulated in the spinal cord throughout EAE and is expressed predominantly by monocytes and reactive astrocytes. The Lcn2 receptor, 24p3R, is also expressed on monocytes, macrophages/microglia, and astrocytes in EAE. In addition, we show that EAE severity is increased in Lcn2(-/-) mice as compared with wild-type controls. Finally, we demonstrate that elevated levels of Lcn2 are detected in the plasma and cerebrospinal fluid (CSF) in MS and in immune cells in CNS lesions in MS tissue sections. These data indicate that Lcn2 is a modulator of EAE pathogenesis and suggest that it may also play a role in MS. Copyright © 2012 Wiley Periodicals, Inc.

  20. Human periodontal ligament stem cells secretome from multiple sclerosis patients suppresses NALP3 inflammasome activation in experimental autoimmune encephalomyelitis

    Science.gov (United States)

    Soundara Rajan, Thangavelu; Giacoppo, Sabrina; Diomede, Francesca; Bramanti, Placido; Trubiani, Oriana; Mazzon, Emanuela

    2017-01-01

    Research in recent years has largely explored the immunomodulatory effects of mesenchymal stem cells (MSCs) and their secretory products, called “secretome,” in the treatment of neuroinflammatory diseases. Here, we examined whether such immunosuppressive effects might be elicited due to inflammasome inactivation. To this end, we treated experimental autoimmune encephalomyelitis (EAE) mice model of multiple sclerosis (MS) with the conditioned medium or purified exosomes/microvesicles (EMVs) obtained from relapsing-remitting-MS patients human periodontal ligament stem cells (hPDLSCs) and investigated the regulation of NALP3 inflammasome. We noticed enhanced expression of NALP3, Cleaved Caspase 1, interleukin (IL)-1β, and IL-18 in EAE mouse spinal cord. Conversely, hPDLSCs-conditioned medium and EMVs significantly blocked NALP3 inflammasome activation and provided protection from EAE. Reduction in NALP3, Cleaved Caspase 1, IL-1β, and IL-18 level was noticed in conditioned medium and EMVs-treated EAE mice. Pro-inflammatory Toll-like receptor (TLR)-4 and nuclear factor (NF)-κB were elevated in EAE, while hPDLSCs-conditioned medium and EMVs treatment reduced their expression and increased IκB-α expression. Characterization of hPDLSCs-conditioned medium showed substantial level of anti-inflammatory IL-10, transforming growth factor (TGF)-β, and stromal cell–derived factor 1α (SDF-1α). We propose that the immunosuppressive role of hPDLSCs-derived conditioned medium and EMVs in EAE mice may partly attribute to the presence of soluble immunomodulatory factors, NALP3 inflammasome inactivation, and NF-κB reduction. PMID:28764573

  1. [Primary childhood vasculitis new classification criteria

    DEFF Research Database (Denmark)

    Herlin, T.; Nielsen, Susan

    2008-01-01

    Primary vasculitis is seen in both adults and children, but some of the diseases like Kawasaki disease occur primarily in children. The Chapel Hill Classification Criteria for primary vasculitis refers to the size of vessels but has not been validated in children. Recently, new criteria...

  2. Epidemiology of ANCA associated vasculitis

    Directory of Open Access Journals (Sweden)

    Wenche Koldingsnes

    2009-10-01

    Full Text Available ANCA associated vasculitis (AAV comprises three syndromes with systemic vasculitis (Wegener’s granulomatosis (WG, Churg Strauss syndrome (CSS and icroscopic polyangiitis (MPA, which all involve small and medium sized vessels and are associated with antibodies against cytoplasmatic antibodies in neutrophils (ANCA. Polyarteritis nodosa (PAN is included in this review as it also affects medium sized vessels, and has many clinical findings in common with the AAV.Since the recognition of ANCA, increasing data have become available on the epidemiology of these vasculitidis. WG constitutes half of the AAV and its prevalence has increased from 30/million in the late 1980’s in the USA to 160/million in this century in northern Europe. The prevalence for the whole group of primary systemic vasculitides is now 300/million in Sweden. The annual incidence of WG increased from 6.0/million to 14/million during the 1990’s in Tromsø, but it is unknown if this is a true increase or the result of an increased awareness of the diagnosis. For the whole group of AAV, the annual incidence in most more recent studies is relatively constant over time and by geographical location, ranging from 13 to 21/million. Nonetheless there are interesting differences in the prevalence of specific vasculitis between different geographical areas, as well as for sub specificities of ANCA.There seems to be a South-North gradient for WG and PR3-ANCA with high figures reported from northern Europe and southern New Zealand. In European studies WG is 90% PR3-ANCA positive. MPA which is predominantly MPO-ANCA associated are more frequent in the Mediterranean countries and also has an increasing gradient towards east-Asia, as almost all AAV in China and Japan are diagnosed as MPA, predominantly MPO-ANCA positive.There are also some ethnic and gender differences. WG is most prevalent among Caucasians in the USA and in people with European ancestors in Paris and in New Zealand, less

  3. Standardization of the experimental autoimmune myasthenia gravis (EAMG) model by immunization of rats with Torpedo californica acetylcholine receptors — Recommendations for methods and experimental designs

    Science.gov (United States)

    Losen, Mario; Martinez-Martinez, Pilar; Molenaar, Peter C.; Lazaridis, Konstantinos; Tzartos, Socrates; Brenner, Talma; Duan, Rui-Sheng; Luo, Jie; Lindstrom, Jon; Kusner, Linda

    2015-01-01

    Myasthenia gravis (MG) with antibodies against the acetylcholine receptor (AChR) is characterized by a chronic, fatigable weakness of voluntary muscles. The production of autoantibodies involves the dysregulation of T cells which provide the environment for the development of autoreactive B cells. The symptoms are caused by destruction of the postsynaptic membrane and degradation of the AChR by IgG autoantibodies, predominantly of the G1 and G3 subclasses. Active immunization of animals with AChR from mammalian muscles, AChR from Torpedo or Electrophorus electric organs, and recombinant or synthetic AChR fragments generates a chronic model of MG, termed experimental autoimmune myasthenia gravis (EAMG). This model covers cellular mechanisms involved in the immune response against the AChR, e.g. antigen presentation, T cell-help and regulation, B cell selection and differentiation into plasma cells. Our aim is to define standard operation procedures and recommendations for the rat EAMG model using purified AChR from the Torpedo californica electric organ, in order to facilitate more rapid translation of preclinical proof of concept or efficacy studies into clinical trials and, ultimately, clinical practice. PMID:25796590

  4. PK11195 binding to the peripheral benzodiazepine receptor as a marker of microglia activation in multiple sclerosis and experimental autoimmune encephalomyelitis

    DEFF Research Database (Denmark)

    Vowinckel, E; Reutens, D; Becher, B

    1997-01-01

    Activated glial cells are implicated in regulating and effecting the immune response that occurs within the CNS as part of multiple sclerosis (MS) and its animal model experimental autoimmune encephalomyelitis (EAE). The peripheral benzodiazepine receptor (PBR) is expressed in glial cells. We...... examined the utility of using in vitro and in vivo ligand binding to the PBR as a measure of lesion activity in autoimmune CNS demyelinating diseases. Applying a combined autoradiography and immunohistochemical approach to spinal cord and brain tissues from mice with EAE, we found a correlation at sites...... of inflammatory lesions between [3H]-PK11195 binding and immunoreactivity for the activated microglial/macrophage marker Mac-1/CD11b. In MS tissues, [3H]-PK11195 binding correlated with sites of immunoreactivity for the microglial/macrophage marker CD68, at the edges of chronic active plaques. Positron emission...

  5. Moringin activates Wnt canonical pathway by inhibiting GSK3β in a mouse model of experimental autoimmune encephalomyelitis

    Directory of Open Access Journals (Sweden)

    Giacoppo S

    2016-10-01

    Full Text Available Sabrina Giacoppo,1 Thangavelu Soundara Rajan,1 Gina Rosalinda De Nicola,2 Renato Iori,2 Placido Bramanti,1 Emanuela Mazzon1 1IRCCS Centre Neurolesi “Bonino-Pulejo”, Messina, Italy; 2Council for Agricultural Research and Economics, Research Centre for Industrial Crops (CREA-CIN, Bologna, Italy Abstract: Aberrant canonical Wnt–β-catenin signaling has been reported in multiple sclerosis (MS, although the results are controversial. The present study aimed to examine the role of the Wnt–β-catenin pathway in experimental MS and also to test moringin (4-[α-L-rhamnopyranosyloxy]-benzyl isothiocyanate, resulting from exogenous myrosinase hydrolysis of the natural phytochemical glucomoringin 4(α-L-rhamnosyloxy-benzyl glucosinolate as a modulator of neuroinflammation via the β-catenin–PPARγ axis. Experimental autoimmune encephalomyelitis (EAE, the most common model of MS, was induced in C57BL/6 mice by immunization with MOG35–55. Released moringin (10 mg/kg glucomoringin +5 µL myrosinase/mouse was administered daily for 1 week before EAE induction and continued until mice were killed on day 28 after EAE induction. Our results clearly showed that the Wnt–β-catenin pathway was downregulated in the EAE model, whereas moringin pretreatment was able to avert this. Moringin pretreatment normalizes the aberrant Wnt–β-catenin pathway, resulting in GSK3β inhibition and β-catenin upregulation, which regulates T-cell activation (CD4 and FoxP3, suppresses the main inflammatory mediators (IL-1β, IL-6, and COX2, through activation of PPARγ. In addition, moringin attenuates apoptosis by reducing the expression of the Fas ligand and cleaved caspase 9, and in parallel increases antioxidant Nrf2 expression in EAE mice. Taken together, our results provide an interesting discovery in identifying moringin as a modulator of the Wnt–β-catenin signaling cascade and as a new potential therapeutic target for MS treatment. Keywords: Wnt

  6. Intermediate monocytes in ANCA vasculitis: increased surface expression of ANCA autoantigens and IL-1β secretion in response to anti-MPO antibodies.

    LENUS (Irish Health Repository)

    O'Brien, Eóin C

    2015-01-01

    ANCA vasculitis encompasses several autoimmune conditions characterised by destruction of small vessels, inflammation of the respiratory tract and glomerulonephritis. Most patients harbour autoantibodies to myeloperoxidase (MPO) or proteinase 3 (PR3). Clinical and experimental data suggest that pathogenesis is driven by ANCA-mediated activation of neutrophils and monocytes. We investigated a potential role for distinct monocyte subsets. We found that the relative proportion of intermediate monocytes is increased in patients versus control individuals, and both MPO and PR3 are preferentially expressed on these cells. We demonstrate that MPO and PR3 are expressed independently of each other on monocytes and that PR3 is not associated with CD177. MPO expression correlates with that of Fc receptor CD16 on intermediate monocytes. Monocyte subsets respond differently to antibodies directed against MPO and PR3, with anti-MPO but not anti-PR3 leading to increased IL-1β, IL-6 and IL-8 production. In concordance with the observed higher surface expression of MPO on intermediate monocytes, this subset produces the highest quantity of IL-1β in response to anti-MPO stimulation. These data suggest that monocytes, specifically, the intermediate subset, may play a role in ANCA vasculitis, and also indicate that substantial differences exist between the effect of anti-MPO and anti-PR3 antibodies on these cells.

  7. Behcet's disease with cerebral vasculitis

    International Nuclear Information System (INIS)

    Scardamaglia, L.; Desmond, P.M.; Gonzales, M.F.; Bendrups, A.; Brodtmann, A.

    2001-01-01

    The case presented illustrates the diagnostic dilemma off neurological involvement in Behcet's disease and other inflammatory diseases. 'Psychiatric' symptoms were present for 2 years without abnormalities on SPECT or MRI and without CSF pleocytosis. Even at the time of fitting, no CSF abnormalities were observed. The preceding psychiatric presentations may have been due to cerebral vasculitis that was exacerbated by withdrawal of steroids. Magnetic resonance imaging is currently the most sensitive imaging modality. Lesions are usually in the brainstem, cerebellum, basal ganglia region or periventricular white matter, and the pons and the mesencephalon are commonly affected. In our patient there was no diencephalic or brainstem involvement. The inflammatory process can appear as a very large lesion, with gadolinium enhancement and significant mass effect, as in our patient. Brain magnetic resonance imaging. Postgadolinium-diethylenetriamine pentaacetic acid, axial image shows two large lesions in the right frontal lobe, with the larger, posterior lesion demonstrating vivid ring enhancement. A central nodule is isodense, with the cerebral white matter within the larger lesion. Surrounding low T 1 signal involves the hemispheric white matter without cortical extension and is consistent with vasogenic oedema. Minor mass effect is demonstrated with bowing of the anterior falx cerebri to the left. Biopsy shows prominent fibrinoid necrosis in small calibre postcapillary venules and cerebral white matter. There are surrounding acute and chronic inflammatory cells and nuclear debris, consistent with vasculitis

  8. Eosinophils in Autoimmune Diseases

    Directory of Open Access Journals (Sweden)

    Daniela Čiháková

    2017-04-01

    Full Text Available Eosinophils are multifunctional granulocytes that contribute to initiation and modulation of inflammation. Their role in asthma and parasitic infections has long been recognized. Growing evidence now reveals a role for eosinophils in autoimmune diseases. In this review, we summarize the function of eosinophils in inflammatory bowel diseases, neuromyelitis optica, bullous pemphigoid, autoimmune myocarditis, primary biliary cirrhosis, eosinophilic granulomatosis with polyangiitis, and other autoimmune diseases. Clinical studies, eosinophil-targeted therapies, and experimental models have contributed to our understanding of the regulation and function of eosinophils in these diseases. By examining the role of eosinophils in autoimmune diseases of different organs, we can identify common pathogenic mechanisms. These include degranulation of cytotoxic granule proteins, induction of antibody-dependent cell-mediated cytotoxicity, release of proteases degrading extracellular matrix, immune modulation through cytokines, antigen presentation, and prothrombotic functions. The association of eosinophilic diseases with autoimmune diseases is also examined, showing a possible increase in autoimmune diseases in patients with eosinophilic esophagitis, hypereosinophilic syndrome, and non-allergic asthma. Finally, we summarize key future research needs.

  9. Eosinophils in Autoimmune Diseases

    Science.gov (United States)

    Diny, Nicola L.; Rose, Noel R.; Čiháková, Daniela

    2017-01-01

    Eosinophils are multifunctional granulocytes that contribute to initiation and modulation of inflammation. Their role in asthma and parasitic infections has long been recognized. Growing evidence now reveals a role for eosinophils in autoimmune diseases. In this review, we summarize the function of eosinophils in inflammatory bowel diseases, neuromyelitis optica, bullous pemphigoid, autoimmune myocarditis, primary biliary cirrhosis, eosinophilic granulomatosis with polyangiitis, and other autoimmune diseases. Clinical studies, eosinophil-targeted therapies, and experimental models have contributed to our understanding of the regulation and function of eosinophils in these diseases. By examining the role of eosinophils in autoimmune diseases of different organs, we can identify common pathogenic mechanisms. These include degranulation of cytotoxic granule proteins, induction of antibody-dependent cell-mediated cytotoxicity, release of proteases degrading extracellular matrix, immune modulation through cytokines, antigen presentation, and prothrombotic functions. The association of eosinophilic diseases with autoimmune diseases is also examined, showing a possible increase in autoimmune diseases in patients with eosinophilic esophagitis, hypereosinophilic syndrome, and non-allergic asthma. Finally, we summarize key future research needs. PMID:28496445

  10. Autoimmune gastritis.

    Science.gov (United States)

    Kulnigg-Dabsch, Stefanie

    2016-10-01

    Autoimmune gastritis is a chronic inflammatory disease with destruction of parietal cells of the corpus and fundus of the stomach. The known consequence is vitamin B12 deficiency and, consequently, pernicious anemia. However, loss of parietal cells reduces secretion of gastric acid which is also required for absorption of inorganic iron; thus, iron deficiency is commonly found in patients with autoimmune gastritis. This usually precedes vitamin B12 deficiency and is found mainly in young women. Patients with chronic iron deficiency, especially those refractory to oral iron therapy, should therefore be evaluated for the presence of autoimmune gastritis.

  11. Vaccines, adjuvants and autoimmunity.

    Science.gov (United States)

    Guimarães, Luísa Eça; Baker, Britain; Perricone, Carlo; Shoenfeld, Yehuda

    2015-10-01

    Vaccines and autoimmunity are linked fields. Vaccine efficacy is based on whether host immune response against an antigen can elicit a memory T-cell response over time. Although the described side effects thus far have been mostly transient and acute, vaccines are able to elicit the immune system towards an autoimmune reaction. The diagnosis of a definite autoimmune disease and the occurrence of fatal outcome post-vaccination have been less frequently reported. Since vaccines are given to previously healthy hosts, who may have never developed the disease had they not been immunized, adverse events should be carefully accessed and evaluated even if they represent a limited number of occurrences. In this review of the literature, there is evidence of vaccine-induced autoimmunity and adjuvant-induced autoimmunity in both experimental models as well as human patients. Adjuvants and infectious agents may exert their immune-enhancing effects through various functional activities, encompassed by the adjuvant effect. These mechanisms are shared by different conditions triggered by adjuvants leading to the autoimmune/inflammatory syndrome induced by adjuvants (ASIA syndrome). In conclusion, there are several case reports of autoimmune diseases following vaccines, however, due to the limited number of cases, the different classifications of symptoms and the long latency period of the diseases, every attempt for an epidemiological study has so far failed to deliver a connection. Despite this, efforts to unveil the connection between the triggering of the immune system by adjuvants and the development of autoimmune conditions should be undertaken. Vaccinomics is a field that may bring to light novel customized, personalized treatment approaches in the future. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. Human neutrophils in auto-immunity.

    Science.gov (United States)

    Thieblemont, Nathalie; Wright, Helen L; Edwards, Steven W; Witko-Sarsat, Véronique

    2016-04-01

    Human neutrophils have great capacity to cause tissue damage in inflammatory diseases via their inappropriate activation to release reactive oxygen species (ROS), proteases and other tissue-damaging molecules. Furthermore, activated neutrophils can release a wide variety of cytokines and chemokines that can regulate almost every element of the immune system. In addition to these important immuno-regulatory processes, activated neutrophils can also release, expose or generate neoepitopes that have the potential to break immune tolerance and result in the generation of autoantibodies, that characterise a number of human auto-immune diseases. For example, in vasculitis, anti-neutrophil cytoplasmic antibodies (ANCA) that are directed against proteinase 3 or myeloperoxidase are neutrophil-derived autoantigens and activated neutrophils are the main effector cells of vascular damage. In other auto-immune diseases, these neutrophil-derived neoepitopes may arise from a number of processes that include release of granule enzymes and ROS, changes in the properties of components of their plasma membrane as a result of activation or apoptosis, and via the release of Neutrophil Extracellular Traps (NETs). NETs are extracellular structures that contain chromatin that is decorated with granule enzymes (including citrullinated proteins) that can act as neo-epitopes to generate auto-immunity. This review therefore describes the processes that can result in neutrophil-mediated auto-immunity, and the role of neutrophils in the molecular pathologies of auto-immune diseases such as vasculitis, rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). We discuss the potential role of NETs in these processes and some of the debate in the literature regarding the role of this phenomenon in microbial killing, cell death and auto-immunity. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Measurement of damage in systemic vasculitis: a comparison of the Vasculitis Damage Index with the Combined Damage Assessment Index

    DEFF Research Database (Denmark)

    Suppiah, Ravi; Flossman, Oliver; Mukhtyar, Chetan

    2011-01-01

    To compare the Vasculitis Damage Index (VDI) with the Combined Damage Assessment Index (CDA) as measures of damage from vasculitis.......To compare the Vasculitis Damage Index (VDI) with the Combined Damage Assessment Index (CDA) as measures of damage from vasculitis....

  14. BJ-1108, a 6-Amino-2,4,5-trimethylpyridin-3-ol analogue, regulates differentiation of Th1 and Th17 cells to ameliorate experimental autoimmune encephalomyelitis.

    Science.gov (United States)

    Kang, Youra; Timilshina, Maheshwor; Nam, Tae-Gyu; Jeong, Byeong-Seon; Chang, Jae-Hoon

    2017-02-28

    CD4 + T cells play an important role in the initiation of an immune response by providing help to other cells. Among the helper T subsets, interferon-γ (IFN-γ)-secreting T helper 1 (Th1) and IL-17-secreting T helper 17 (Th17) cells are indispensable for clearance of intracellular as well as extracellular pathogens. However, Th1 and Th17 cells are also associated with pathogenesis and contribute to the progression of multiple inflammatory conditions and autoimmune diseases. In the current study, we found that BJ-1108, a 6-aminopyridin-3-ol analogue, significantly inhibited Th1 and Th17 differentiation in vitro in a concentration-dependent manner, with no effect on proliferation or apoptosis of activated T cells. Moreover, BJ-1108 inhibited differentiation of Th1 and Th17 cells in ovalbumin (OVA)-specific OT II mice. A complete Freund's adjuvant (CFA)/OVA-induced inflammatory model revealed that BJ-1108 can reduce generation of proinflammatory Th1 and Th17 cells. Furthermore, in vivo studies showed that BJ-1108 delayed onset of disease and suppressed experimental autoimmune encephalomyelitis (EAE) disease progression by inhibiting differentiation of Th1 and Th17 cells. BJ-1108 treatment ameliorates inflammation and EAE by inhibiting Th1 and Th17 cells differentiation. Our findings suggest that BJ-1108 is a promising novel therapeutic agent for the treatment of inflammation and autoimmune disease.

  15. Autoimmune disorders

    Science.gov (United States)

    ... exact cause of autoimmune disorders is unknown. One theory is that some microorganisms (such as bacteria or ... M. is also a founding member of Hi-Ethics and subscribes to the principles of the Health ...

  16. Autoimmune pancreatitis

    Directory of Open Access Journals (Sweden)

    Davorin Dajčman

    2007-05-01

    Full Text Available Background: Autoimmune pancreatitis is a recently described type of pancreatitis of presumed autoimmune etiology. Autoimmune pancreatitis is often misdiagnosed as pancreatic cancer difficult, since their clinical presentations are often similar. The concept of autoimmune pancreatitis was first published in 1961. Since then, autoimmune pancreatitis has often been treated not as an independent clinical entity but rather as a manifestation of systemic disease. The overall prevalence and incidence of the disease have yet to be determined, but three series have reported the prevalence as between 5 and 6 % of all patients with chronic pancreatitis. Patient vary widely in age, but most are older than 50 years. Patients with autoimmune pancreatitis usually complain of the painless jaundice, mild abdominal pain and weight loss. There is no laboratory hallmark of the disease, even if cholestatic profiles of liver dysfunction with only mild elevation of amylase and lipase levels have been reported.Conclusions: Proposed diagnostic criteria contains: (1 radiologic imaging, diffuse enlargement of the pancreas and diffusely irregular narrowing of the main pancreatic duct, (2 laboratory data, elevated levels of serum ã-globulin and/or IgG, specially IgG4, or the presence of autoantibodies and (3 histopathologic examination, fibrotic change with dense lymphoplasmacytic infiltration in the pancreas. For correct diagnosis of autoimmune pancreatitis, criterion 1 must be present with criterion 2 and/or 3. Autoimmune pancreatitis is frequently associated with rheumatoid arthritis, Sjogren’s syndrome, inflammatory bowel disease, tubulointersticial nephritis, primary sclerosing cholangitis and idiopathic retroperitoneal fibrosis. Pancreatic biopsy using an endoscopic ultrasound-guided fine needle aspiration biopsy is the most important diagnostic method today. Treatment with corticosteroids leads to the and resolution of pancreatic inflamation, obstruction and

  17. Vasculitis

    Science.gov (United States)

    ... OII) Timed Up & Go (TUG) Western Ontario & McMaster Universities Osteoarthritis Index (WOMAC) Young Investigators Resources for Doctoral Students/Post-Doctoral Fellows Evidence-Based Practice for Academic Researchers Responsible Data Management in Research Career Planning Treatments Patient ...

  18. What matters for patients with vasculitis?

    Science.gov (United States)

    Novakovich, Elaine; Grayson, Peter C

    2015-06-01

    Advances in clinical care for patients with vasculitis have improved survival rates and created new challenges related to the ongoing management of chronic disease. Lack of curative therapies, burden of disease, treatment-related side effects, and fear of relapse contribute to patient-perceived reduction in quality of life. Patient-held beliefs about disease and priorities may differ substantially from the beliefs of their health care providers, and research paradigms are shifting to reflect more emphasis on understanding vasculitis from the patient's perspective. Efforts are ongoing to develop disease outcome measures in vasculitis that better represent the patient experience. Health care providers who care for patients with vasculitis should be sensitive to the substantial burdens of disease commonly experienced by patients living with the disease and should strive to provide comprehensive care directed towards the medical and biopsychological needs of these patients. Published by Elsevier Masson SAS.

  19. A case of small vessel vasculitis

    Directory of Open Access Journals (Sweden)

    Madhulika Mahashabde

    2014-01-01

    We are reporting a case of un-specified small vessel vasculitis, which was diagnosed on the basis of positive perinuclear anti neutrophil cytoplasmic antibodies (ANCA P MPO done by Enzyme Linked Immunosorbent Assay (ELISA.

  20. Vasculitis : Clinical approach, pathophysiology and treatment

    NARCIS (Netherlands)

    Kallenberg, GGM

    2000-01-01

    Systemic vasculitides constitute a heterogeneous group of diseases characterized by inflammation of blood vessels. Classification of the disease is mandatory for the assessment of prognosis and the institution of treatment. Secondary forms of vasculitis should be distinguished from primary

  1. Renal sarcoidosis presenting as acute kidney injury with granulomatous interstitial nephritis and vasculitis.

    Science.gov (United States)

    Agrawal, Varun; Crisi, Giovanna M; D'Agati, Vivette D; Freda, Benjamin J

    2012-02-01

    Among the various renal manifestations of sarcoidosis, granulomatous inflammation confined to the tubulointerstitial compartment is the most commonly reported finding. We present the case of a 66-year-old man with acute kidney injury, hypercalcemia, mild restrictive pulmonary disease, and neurologic signs of parietal lobe dysfunction. Kidney biopsy showed diffuse interstitial inflammation with noncaseating granulomas that exhibited the unusual feature of infiltrating the walls of small arteries with destruction of the elastic lamina, consistent with granulomatous vasculitis. The findings of granulomatous interstitial nephritis on kidney biopsy, hypercalcemia, and possible cerebral and pulmonary involvement in the absence of other infectious, drug-induced, or autoimmune causes of granulomatous disease established the diagnosis of sarcoidosis. Pulse methylprednisolone followed by maintenance prednisone therapy led to improvement in kidney function, hypercalcemia, and neurologic symptoms. Vasculocentric granulomatous interstitial nephritis with granulomatous vasculitis is a rare and under-recognized manifestation of renal sarcoidosis. Copyright © 2012 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

  2. IgA vasculitis as a presentation of human immunodeficiency virus infection.

    Science.gov (United States)

    Brandy-García, Anahy M; Santos-Juanes, Jorge; Suarez, Silvia; Caminal-Montero, Luis

    2018-05-15

    IgA vasculitis is a small-vessel vasculitis mediated by immune complexes. In clinical terms, it is characterized by palpable purpura in the lower limbs, joint involvement in the form of arthralgia or arthritis, and gastrointestinal and renal involvement (this will mark a poorer prognosis in adults). Infectious processes, mainly in the upper respiratory tract, are frequently found to be triggers. On the other hand, human immunodeficiency virus (HIV) causes immune dysfunction, which triggers hypergammaglobulinemia and can trigger autoimmune disorders. At times, this can affect the vascular endothelium, giving rise to vasculitic manifestations, although there are few reports in the literature of its role in the presentation of HIV. Copyright © 2018 Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. Publicado por Elsevier España, S.L.U. All rights reserved.

  3. History of primary vasculitis in Latin America.

    Science.gov (United States)

    Iglesias Gammara, Antonio; Coral, Paola; Quintana, Gerardo; Toro, Carlos E; Flores, Luis Felipe; Matteson, Eric L; Restrepo, José Félix

    2010-03-01

    A literature review utilizing Fepafem, Bireme, LiLacs, Scielo Colombia, Scielo Internacional, former MedLine, Pubmed, and BVS Colombia as well as manual searches in the libraries of major Latin American universities was performed to study vasculitis in Latin America. Since 1945, a total of 752 articles have been published by Latin American authors. However, only a minority are devoted to primary vasculitides, and even fewer have been published in indexed journals. Approximately 126 are in OLD, Medline, Pubmed, Bireme, and Scielo. Most publications are from Mexico, followed by Brazil and Colombia. Systematic studies of the epidemiology of primary idiopathic vasculitis are available for a few countries, i.e. Brazil, Mexico, Colombia, Chile, and Peru. Takayasu arteritis and ANCA-associated vasculitis are the best studied forms of vasculitis in Latin America. Interest and expertise in vasculitis is growing in Latin America, as reflected in the increased number of published articles from this region of the world in the last decade. Racial and environmental factors are possibly responsible for the differential expression of various types of primary vasculitis observed in Latin America. With time, the unique features, epidemiology, and better treatment strategies for idiopathic vasculitides in Latin America will emerge.

  4. PR-957, a selective inhibitor of immunoproteasome subunit low-MW polypeptide 7, attenuates experimental autoimmune neuritis by suppressing Th17-cell differentiation and regulating cytokine production.

    Science.gov (United States)

    Liu, Haijie; Wan, Chunxiao; Ding, Yanan; Han, Ranran; He, Yating; Xiao, Jinting; Hao, Junwei

    2017-04-01

    Experimental autoimmune neuritis (EAN) is a CD4 + T-cell-mediated autoimmune inflammatory demyelinating disease of the peripheral nervous system. It has been replicated in an animal model of human inflammatory demyelinating polyradiculoneuropathy, Guillain-Barré syndrome. In this study, we evaluated the therapeutic efficacy of a selective inhibitor of the immunoproteasome subunit, low-MW polypeptide 7 (PR-957) in rats with EAN. Our results showed that PR-957 significantly delayed onset day, reduced severity and shortened duration of EAN, and alleviated demyelination and inflammatory infiltration in sciatic nerves. In addition to significantly regulating expression of the cytokine profile, PR-957 treatment down-regulated the proportion of proinflammatory T-helper (T h )17 cells in sciatic nerves and spleens of rats with EAN. Data presented show the role of PR-957 in the signal transducer and activator of transcription 3 (STAT3) pathway. PR-957 not only decreased expression of IL-6 and IL-23 but also led to down-regulation of STAT3 phosphorylation in CD4 + T cells. Regulation of the STAT3 pathway led to a reduction in retinoid-related orphan nuclear receptor γ t and IL-17 production. Furthermore, reduction of STAT3 phosphorylation may have directly suppressed T h 17-cell differentiation. Therefore, our study demonstrates that PR-957 could potently alleviate inflammation in rats with EAN and that it may be a likely candidate for treating Guillain-Barré syndrome.-Liu, H., Wan, C., Ding, Y., Han, R., He, Y., Xiao, J., Hao, J. PR-957, a selective inhibitor of immunoproteasome subunit low-MW polypeptide 7, attenuates experimental autoimmune neuritis by suppressing T h 17-cell differentiation and regulating cytokine production. © FASEB.

  5. In vivo evidence for CD4+ and CD8+ suppressor T cells in vaccination-induced suppression of murine experimental autoimmune thyroiditis

    International Nuclear Information System (INIS)

    Flynn, J.C.; Kong, Y.C.

    1991-01-01

    In several experimental autoimmune diseases, including experimental autoimmune thyroiditis (EAT), vaccination with attenuated autoantigen-specific T cells has provided protection against subsequent induction of disease. However, the mechanism(s) of vaccination-induced suppression remains to be clarified. Since the authors have previously shown that suppression generated by pretreatment with mouse thyroglobulin (MTg) or thyroid-stimulating hormone in EAT is mediated by CD4+, not CD8+, suppressor T cells, they examined the role of T cell subsets in vaccination-induced suppression of EAT. Mice were vaccinated with irradiated, MTg-primed, and MTg-activated spleen cells and then challenged. Pretreatment with these cells suppressed EAT induced by immunization with MTg and adjuvant, but not by adoptive transfer of thyroiditogenic cells, suggesting a mechanism of afferent suppression. The activation of suppressor mechanisms did not require CD8+ cells, since mice depleted of CD8+ cells before vaccination showed reduced EAT comparable to control vaccinated mice. Furthermore, depletion of either the CD4+ or the CD8+ subset after vaccination did not significantly abrogate suppression. However, suppression was eliminated by the depletion of both CD4+ and CD8+ cells in vaccinated mice. These results provide evidence for the cooperative effects of CD4+ and CD8+ T cells in vaccination-induced suppression of EAT

  6. Mechanisms of vasculitis : How pauci-immune is ANCA-associated renal vasculitis?

    NARCIS (Netherlands)

    van Paassen, P.; Tervaert, J. W. Cohen; Heeringa, P.

    2007-01-01

    Both the innate and the acquired immune system are involved in the pathophysiology of renal vasculitis. However, anti-neutrophil cytoplasmic antibody (ANCA)-associated renal vasculitis is characterized by a 'pauci-immune' pattern of immunofluorescence during kidney biopsy, indicating the relative

  7. A cross-sectional study of the Birmingham Vasculitis Activity Score version 3 in systemic vasculitis

    NARCIS (Netherlands)

    Suppiah, Ravi; Mukhtyar, Chetan; Flossmann, Oliver; Alberici, Federico; Baslund, Bo; Batra, Rajbir; Brown, Denise; Holle, Julia; Hruskova, Zdenka; Jayne, David R. W.; Judge, Andrew; Little, Mark A.; Palmisano, Alessandra; Stegeman, Coen; Tesar, Vladimir; Vaglio, Augusto; Westman, Kerstin; Luqmani, Raashid

    Methods. A total of 238 patients with vasculitis from seven countries in Europe were evaluated at a single time point. Spearman's correlation coefficients were calculated between BVAS v. 3 scores, vasculitis activity index (VAI), physician's global assessment (PGA), the physician's treatment

  8. A cross-sectional study of the Birmingham Vasculitis Activity Score version 3 in systemic vasculitis.

    LENUS (Irish Health Repository)

    Suppiah, Ravi

    2011-05-01

    Assessment of disease activity in vasculitis can be achieved using the BVAS, a clinical checklist of relevant symptoms, signs and features of active disease. The aim of this study was to revalidate the BVAS version 3 (BVAS v. 3) in a cohort of patients with systemic vasculitis.

  9. Grouping annotations on the subcellular layered interactome demonstrates enhanced autophagy activity in a recurrent experimental autoimmune uveitis T cell line.

    Directory of Open Access Journals (Sweden)

    Xiuzhi Jia

    Full Text Available Human uveitis is a type of T cell-mediated autoimmune disease that often shows relapse-remitting courses affecting multiple biological processes. As a cytoplasmic process, autophagy has been seen as an adaptive response to cell death and survival, yet the link between autophagy and T cell-mediated autoimmunity is not certain. In this study, based on the differentially expressed genes (GSE19652 between the recurrent versus monophasic T cell lines, whose adoptive transfer to susceptible animals may result in respective recurrent or monophasic uveitis, we proposed grouping annotations on a subcellular layered interactome framework to analyze the specific bioprocesses that are linked to the recurrence of T cell autoimmunity. That is, the subcellular layered interactome was established by the Cytoscape and Cerebral plugin based on differential expression, global interactome, and subcellular localization information. Then, the layered interactomes were grouping annotated by the ClueGO plugin based on Gene Ontology and Kyoto Encyclopedia of Genes and Genomes databases. The analysis showed that significant bioprocesses with autophagy were orchestrated in the cytoplasmic layered interactome and that mTOR may have a regulatory role in it. Furthermore, by setting up recurrent and monophasic uveitis in Lewis rats, we confirmed by transmission electron microscopy that, in comparison to the monophasic disease, recurrent uveitis in vivo showed significantly increased autophagy activity and extended lymphocyte infiltration to the affected retina. In summary, our framework methodology is a useful tool to disclose specific bioprocesses and molecular targets that can be attributed to a certain disease. Our results indicated that targeted inhibition of autophagy pathways may perturb the recurrence of uveitis.

  10. [Clinical features of 32 patients with cutaneous small vessel vasculitis].

    Science.gov (United States)

    López de Maturana, Donaldo; Amaro, Patricio; Segovia, Laura; Balestrini, Claudia

    2004-02-01

    The skin is a common target of small vessel vasculitis, with a wide assortment of pathological changes. This condition is usually associated to systemic diseases. To report the clinical and pathological features of patients with cutaneous small vessel vasculitis. A retrospective review of 32 patients with a pathological diagnosis of cutaneous vasculitis. Seventy two percent of patients were women. Cutaneous lesions were mainly located in the lower limbs (94%). The most common lesion was palpable purpura (62%). Connective tissue diseases and systemic vasculitis were the most commonly associated systemic diseases. Palpable purpura is the most common manifestation of cutaneous small vessel vasculitis, that is usually associated to connective tissue diseases or systemic vasculitis.

  11. Progranulin antibodies in autoimmune diseases.

    Science.gov (United States)

    Thurner, Lorenz; Preuss, Klaus-Dieter; Fadle, Natalie; Regitz, Evi; Klemm, Philipp; Zaks, Marina; Kemele, Maria; Hasenfus, Andrea; Csernok, Elena; Gross, Wolfgang L; Pasquali, Jean-Louis; Martin, Thierry; Bohle, Rainer Maria; Pfreundschuh, Michael

    2013-05-01

    Systemic vasculitides constitute a heterogeneous group of diseases. Autoimmunity mediated by B lymphocytes and their humoral effector mechanisms play a major role in ANCA-associated vasculitis (AAV) as well as in non-ANCA associated primary systemic vasculitides and in the different types of autoimmune connective tissue disorders and rheumatoid arthritis. In order to detect autoantibodies in systemic vasculitides, we screened protein macroarrays of human cDNA expression libraries with sera from patients with ANCA-associated and ANCA-negative primary systemic vasculitides. This approach led to the identification of antibodies against progranulin, a 88 kDA secreted glycoprotein with strong anti-inflammatory activity in the course of disease of giant-cell arteritis/polymyalgia rheumatica (14/65), Takayasu's arteritis (4/13), classical panarteritis nodosa (4/10), Behcet's disease (2/6) and in the course of disease in granulomatosis with polyangiitis (31/75), Churg-Strauss syndrome (7/23) and in microscopic polyangiitis (7/19). In extended screenings the progranulin antibodies were also detected in other autoimmune diseases such as systemic lupus erythematosus (39/91) and rheumatoid arthritis (16/44). Progranulin antibodies were detected only in 1 of 97 healthy controls. Anti-progranulin positive patients with systemic vasculitides, systemic lupus erythematosus or rheumatoid arthritis had significant lower progranulin plasma levels, indicating a neutralizing effect. In light of the anti-inflammatory effects of progranulin, progranulin antibodies might exert pro-inflammatory effects thus contributing to the pathogenesis of the respective autoimmune diseases and might serve as a marker for disease activity. This hypothesis is supported by the fact that a positive progranulin antibody status was associated with active disease in granulomatosis with polyangiitis. Copyright © 2012 Elsevier Ltd. All rights reserved.

  12. Autoimmun hypophysitis

    DEFF Research Database (Denmark)

    Krarup, Therese; Hagen, Claus

    2010-01-01

    during pregnancy or postpartum, but also occurs in males and children. AH is often associated with other autoimmune diseases, most frequently with Hashimoto's thyroiditis. The symptoms are caused by enlargement of the pituitary gland and disturbances of the hormone function. Treatment is either...

  13. Epigenetics and Vasculitis: a Comprehensive Review.

    Science.gov (United States)

    Renauer, Paul; Coit, Patrick; Sawalha, Amr H

    2016-06-01

    Vasculitides represent a group of relatively rare systemic inflammatory diseases of the blood vessels. Despite recent progress in understanding the genetic basis and the underlying pathogenic mechanisms in vasculitis, the etiology and pathogenesis of vasculitis remain incompletely understood. Epigenetic dysregulation plays an important role in immune-mediated diseases, and the contribution of epigenetic aberrancies in vasculitis is increasingly being recognized. Histone modifications in the PR3 and MPO gene loci might be mechanistically involved in the pathogenesis of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis. Similarly, other studies revealed important epigenetic contribution to other vasculitides, including Kawasaki disease and IgA vasculitis. More recently, genome-wide epigenomic studies have been performed in several vasculitides. A recent genome-wide DNA methylation study uncovered an important role for epigenetic remodeling of cytoskeleton-related genes in the pathogenesis of Behçet's disease and suggested that reversal of some of these DNA methylation changes associates with disease remission. Genome-wide DNA methylation profiling characterized the inflammatory response in temporal artery tissue from patients with giant cell arteritis and showed increased activation of calcineurin/nuclear factor of activated T cells (NFAT) signaling, prompting the suggestion that a specific calcineurin/NFAT inhibitor that is well tolerated and with the added beneficial anti-platelet activity, such as dipyridamole, might be of therapeutic potential in giant cell arteritis. While epigenetic studies in systemic vasculitis are still in their infancy, currently available data clearly indicate that investigating the epigenetic mechanisms underlying these diseases will help to better understand the pathogenesis of vasculitis and provide novel targets for the development of disease biomarkers and new therapies.

  14. Ursodeoxycholic acid attenuates experimental autoimmune arthritis by targeting Th17 and inducing pAMPK and transcriptional corepressor SMILE.

    Science.gov (United States)

    Lee, Eun-Jung; Kwon, Jeong-Eun; Park, Min-Jung; Jung, Kyung-Ah; Kim, Da-Som; Kim, Eun-Kyung; Lee, Seung Hoon; Choi, Jong Young; Park, Sung-Hwan; Cho, Mi-La

    2017-08-01

    Ursodeoxycholic acid (UDCA) has been known that UDCA has prominent effects on liver, however, there is little known about its influence on autoimmune disease. Here, the benefit of UDCA on arthritis rheumatoid (RA) in vivo was tested. RA mouse were induced using collagen II (CIA, collagen induced arthritis) where the disease severity or UDCA-related signaling pathway such as AMP-activated protein kinase (AMPK) or small heterodimer partner interacting leucine zipper protein (SMILE) was evaluated by westerblot and immunohistochemical staining. Gene expression was measured by realtime-polymerase chain reaction (PCR). The administration of UDCA effectively alleviated the arthritic score and incidence with decreased cartilage damage and lipid metabolic parameters. UDCA also suppressed the secretion of pro-inflammatory cytokines. It was confirmed that UDCA upregulated the expression of SMILE and transcriptional activity of PPARγ via controlling AMPK or p38 activity. In the present study, the therapeutic effect of UDCA inducing SMILE through AMPK activation in rheumatoid arthritis mouse as well as other autoimmune disease was proposed. Copyright © 2017 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

  15. A Novel Approach to Reinstating Tolerance in Experimental Autoimmune Myasthenia Gravis Using a Targeted Fusion Protein, mCTA1–T146

    Directory of Open Access Journals (Sweden)

    Alessandra Consonni

    2017-09-01

    Full Text Available Reinstating tissue-specific tolerance has attracted much attention as a means to treat autoimmune diseases. However, despite promising results in rodent models of autoimmune diseases, no established tolerogenic therapy is clinically available yet. In the experimental autoimmune myasthenia gravis (EAMG model several protocols have been reported that induce tolerance against the prime disease-associated antigen, the acetylcholine receptor (AChR at the neuromuscular junction. Using the whole AChR, the extracellular part or peptides derived from the receptor, investigators have reported variable success with their treatments, though, usually relatively large amounts of antigen has been required. Hence, there is a need for better formulations and strategies to improve on the efficacy of the tolerance-inducing therapies. Here, we report on a novel targeted fusion protein carrying the immunodominant peptide from AChR, mCTA1–T146, which given intranasally in repeated microgram doses strongly suppressed induction as well as ongoing EAMG disease in mice. The results corroborate our previous findings, using the same fusion protein approach, in the collagen-induced arthritis model showing dramatic suppressive effects on Th1 and Th17 autoaggressive CD4 T cells and upregulated regulatory T cell activities with enhanced IL10 production. A suppressive gene signature with upregulated expression of mRNA for TGFβ, IL10, IL27, and Foxp3 was clearly detectable in lymph node and spleen following intranasal treatment with mCTA1–T146. Amelioration of EAMG disease was accompanied by reduced loss of muscle AChR and lower levels of anti-AChR serum antibodies. We believe this targeted highly effective fusion protein mCTA1–T146 is a promising candidate for clinical evaluation in myasthenia gravis patients.

  16. Dendritic cells and anergic type I NKT cells play a crucial role in sulfatide-mediated immune regulation in experimental autoimmune encephalomyelitis.

    Science.gov (United States)

    Maricic, Igor; Halder, Ramesh; Bischof, Felix; Kumar, Vipin

    2014-08-01

    CD1d-restricted NKT cells can be divided into two groups: type I NKT cells use a semi-invariant TCR, whereas type II express a relatively diverse set of TCRs. A major subset of type II NKT cells recognizes myelin-derived sulfatides and is selectively enriched in the CNS tissue during experimental autoimmune encephalomyelitis (EAE). We have shown that activation of sulfatide-reactive type II NKT cells by sulfatide prevents induction of EAE. In this article, we have addressed the mechanism of regulation, as well as whether a single immunodominant form of synthetic sulfatide can treat ongoing chronic and relapsing EAE in SJL/J mice. We have shown that the activation of sulfatide-reactive type II NKT cells leads to a significant reduction in the frequency and effector function of myelin proteolipid proteins 139-151/I-A(s)-tetramer(+) cells in lymphoid and CNS tissues. In addition, type I NKT cells and dendritic cells (DCs) in the periphery, as well as CNS-resident microglia, are inactivated after sulfatide administration, and mice deficient in type I NKT cells are not protected from disease. Moreover, tolerized DCs from sulfatide-treated animals can adoptively transfer protection into naive mice. Treatment of SJL/J mice with a synthetic cis-tetracosenoyl sulfatide, but not α-galactosylceramide, reverses ongoing chronic and relapsing EAE. Our data highlight a novel immune-regulatory pathway involving NKT subset interactions leading to inactivation of type I NKT cells, DCs, and microglial cells in suppression of autoimmunity. Because CD1 molecules are nonpolymorphic, the sulfatide-mediated immune-regulatory pathway can be targeted for development of non-HLA-dependent therapeutic approaches to T cell-mediated autoimmune diseases. Copyright © 2014 by The American Association of Immunologists, Inc.

  17. Significance of isolated vasculitis in the gynecological tract: what clinicians do with the pathologic diagnosis of vasculitis?

    Science.gov (United States)

    Roma, Andres A; Amador-Ortiz, Catalina; Liapis, Helen

    2014-08-01

    Vasculitides includes a heterogeneous group of disorders with the common histologic findings of vascular wall inflammation. Systemic or localized disease (eg, renal vasculitis) has serious consequences. The incidence of isolated gynecologic vasculitis diagnosed on pathology specimens and its significance is little known. We performed a 20 year retrospective review including 53 cases with vasculitis diagnosis affecting the female genital tract identified in pathology reports. None had prior symptoms or were diagnosed with generalized vasculitis, while one patient had prior diagnosis of fibromyalgia. Most patients presented with abnormal bleeding and were treated for conditions unrelated to vasculitis. The different types of vasculitis were: predominantly lymphocytic (nonspecific) 30 cases, necrotizing 17 cases and granulomatous 6 cases. Only 2 patients had additional serologic tests. None of the patients with isolated gynecologic vasculitis received corticosteroids or additional treatment related to the vasculitis. None of the patients developed systemic vasculitis at follow-up (2 months-19.5 years; mean, 5.5 years). Isolated gynecologic vasculitis diagnosed on pathology slides is rarely associated with systemic vasculitis. Potential isolated gynecologic vasculitis causes include: previous surgical interventions and vascular inflammation secondary to local neoplasm. In almost all cases, clinicians did not perform a thorough laboratory analysis to exclude systemic vasculitis and therapy was not required in any case, suggesting minimal clinical significance. Copyright © 2014 Elsevier Inc. All rights reserved.

  18. Illness Perceptions and Fatigue in Systemic Vasculitis

    Science.gov (United States)

    Grayson, Peter C.; Amudala, Naomi A.; McAlear, Carol A.; Leduc, Renée L.; Shereff, Denise; Richesson, Rachel; Fraenkel, Liana; Merkel, Peter A.

    2014-01-01

    Objective To compare illness perceptions among patients with different forms of vasculitis, identify risk factors for negative illness perceptions, and determine the association between illness perceptions and fatigue. Methods Participants were recruited from an online registry in vasculitis to complete the revised Illness Perception Questionnaire (IPQ-R). Mean scores on each IPQ-R dimension were compared across types of vasculitis. Cluster analysis and stepwise regression identified predictors of negative illness perception. Fatigue was measured using the general subscale of the Multidimensional Fatigue Inventory (MFI). Patient-reported measures of disease activity and IPQ-R dimensions were assessed in relation to MFI scores using linear regression in sequential, additive models with model-fit comparisons. Results 692 participants with 9 forms of vasculitis completed the IPQ-R. For 6 out of 8 IPQ-R dimensions, there were no significant differences in mean scores between the different vasculitides. Scores in identity and cyclical dimensions were significantly higher in Behçet’s disease compared to other types of vasculitis (13.5 vs 10.7; 4.0 vs 3.2, pvasculitis, and younger age is a risk factor for negative illness perceptions. Illness perceptions explain differences in fatigue scores beyond what can be explained by measures of disease activity. PMID:23861259

  19. Renal vasculitis presenting with acute kidney injury.

    Science.gov (United States)

    Villacorta, Javier; Diaz-Crespo, Francisco; Acevedo, Mercedes; Cavero, Teresa; Guerrero, Carmen; Praga, Manuel; Fernandez-Juarez, Gema

    2017-06-01

    Renal failure secondary to ANCA-associated vasculitis represents a clinical and therapeutic challenge. In this study, we aimed to assess the treatment response rates and long-term outcomes of vasculitis patients presenting with renal failure. This retrospective study included 151 patients with renal vasculitis from three hospitals who underwent a renal biopsy between 1997 and 2014. Patients with renal failure which required dialysis at the onset were compared to those presenting with more preserved renal function. The primary end point was treatment response and patient surivival. Patients with severe renal involvement had a lower response to treatment compared to those having preserved renal function (26.6 versus 93.4%; p renal recovery (41.6 versus 12.5%; p = 0.05). A higher incidence of severe infections was observed among patients with severe renal involvement (38.4 versus 18.1%, p = 0.01). The mortality rate was significantly higher among vasculitis patients presenting with renal failure (53.8 versus 22.2%, p = 0.001). Global survival at 1 and 5 years was 60 and 47% in patients requiring dialysis compared with 90 and 80% among those with more preserved renal function (p renal dysfunction represents an independent risk factor for patient survival in renal vasculitis. Patients requiring dialysis associate a lower response rate to immunosuppressive therapy and a higher incidence of severe infections.

  20. Immunomodulatory effects of Longdan Xiegan Tang on CD4+/CD8+ T cells and associated inflammatory cytokines in rats with experimental autoimmune uveitis.

    Science.gov (United States)

    Tang, Kai; Guo, Dadong; Zhang, Lian; Guo, Junguo; Zheng, Fengming; Si, Junkang; Bi, Hongsheng

    2016-09-01

    Longdan Xiegan Tang (LXT) is a mixture of herbal extracts commonly used in traditional Chinese medicine that may exert immunomodulatory effects for the treatment of autoimmune diseases. However, the detailed mechanisms that mediate the actions of LXT are unclear. The present study induced an experimental autoimmune uveitis (EAU) model in Lewis rats via injection of IRBP1177‑1191 emulsion. The model was used to investigate the effects of LXT on EAU rats and assess the efficacy of LXT by measuring clinical manifestations and histopathological changes caused by EAU. Additionally, alterations in the ratio of CD4+/CD8+‑T cells were determined by flow cytometry, and the expression of interferon (IFN)‑γ, interleukin (IL)‑17, IL‑10 and tumor necrosis factor (TNF)‑α were measured using reverse transcription‑quantitative polymerase chain reaction and enzyme‑linked immunosorbent assay analysis. The results of the present study demonstrate that LXT can efficiently alleviate the symptoms of EAU, inhibit the differentiation of uveitogenic CD4+ T cells and reduce the expression of proinflammatory cytokines, including IFN‑γ, IL‑17 and TNF‑α. Furthermore, LXT promotes the production of IL‑10 and accelerates the recovery of EAU, indicating that the immunomodulatory effects of LXT may potentially be used for the treatment of uveitis.

  1. Treatment with NAD(+) inhibited experimental autoimmune encephalomyelitis by activating AMPK/SIRT1 signaling pathway and modulating Th1/Th17 immune responses in mice.

    Science.gov (United States)

    Wang, Jueqiong; Zhao, Congying; Kong, Peng; Sun, Huanhuan; Sun, Zhe; Bian, Guanyun; Sun, Yafei; Guo, Li

    2016-10-01

    Nicotinamide adenine dinucleotide (NAD(+)) plays vital roles in mitochondrial functions, cellular energy metabolism and calcium homeostasis. In this study, we investigated the effect of NAD(+) administration for the treatment of experimental autoimmune encephalomyelitis (EAE) in C57BL/6 mice. EAE, a classical animal model of multiple sclerosis (MS), was induced by subcutaneous injection of myelin oligodendrocyteglycoprotein (MOG). The mice were treated with 250mg/kg (body weight) NAD(+) in PBS administered intraperitoneally once daily. We observed that NAD(+) treatment could lessen the severity of EAE. Additionally, NAD(+) treatment attenuated pathological injuries of EAE mice. We also found that the AMP-activated protein kinase (AMPK)/silent mating-type information regulation 2 homolog 1(SIRT1) pathway was activated in the NAD(+)-treated mice and NAD(+) treatment suppressed pro-inflammatory T cell responses. Our findings demonstrated that NAD(+) could be an effective and promising agent to treat multiple sclerosis and its effects on other autoimmune diseases should be explored. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. Anti-inflammatory mechanisms of IFN-γ studied in experimental autoimmune encephalomyelitis reveal neutrophils as a potential target in multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Nichole M Miller

    2015-08-01

    Full Text Available Multiple sclerosis (MS is an autoimmune disease of the central nervous system (CNS mediated by T helper (h1 and/or Th17 CD4 T cells that drive inflammatory lesion development along with demyelination and neuronal damage. Defects in immune regulatory mechanisms are thought to play a role in the pathogenesis of MS. While an early clinical trial indicated that IFN-γ administration was detrimental to MS, studies in the mouse model of MS, experimental autoimmune encephalomyelitis (EAE, indicated that IFN-γ exhibits a number of anti-inflammatory properties within the CNS. These mechanisms include inhibition of IL-17 production, induction of regulatory T cells, T cell apoptosis and regulation of chemokine production. Mice deficient in IFN-γ or its receptor were instrumental in deciphering the anti-inflammatory properties of IFN-γ in the CNS. In particular, they revealed that IFN-γ is a major regulator of neutrophil recruitment into the CNS, which by a variety of mechanisms including disruption of the blood-brain-barrier (BBB and production of reactive oxygen species are thought to contribute to the onset and progression of EAE. Neutrophils were also shown to be instrumental in EAE relapses. To date neutrophils have not been appreciated as a driver of MS, but more recently based largely on the strong EAE data this view is being reevaluated by some investigators in the field.

  3. The nuclear IκB family protein IκBNS influences the susceptibility to experimental autoimmune encephalomyelitis in a murine model.

    Science.gov (United States)

    Kobayashi, Shuhei; Hara, Akira; Isagawa, Takayuki; Manabe, Ichiro; Takeda, Kiyoshi; MaruYama, Takashi

    2014-01-01

    The nuclear IκB family protein IκBNS is expressed in T cells and plays an important role in Interferon (IFN)-γ and Interleukin (IL)-2 production. IκB-ζ, the most similar homolog of IκBNS, plays an important role in the generation of T helper (Th)17 cells in cooperation with RORγt, a master regulator of Th17 cells. Thus, IκB-ζ deficient mice are resistant to Th17-dependent experimental autoimmune encephalomyelitis (EAE). However, IκB-ζ deficient mice develop the autoimmune-like Sjögren syndrome with aging. Here we found that IκBNS-deficient (Nfkbid-/-) mice show resistance against developing Th17-dependent EAE. We found that Nfkbid-/- T cells have decreased expression of IL-17-related genes and RORγt in response to Transforming Growth Factor (TGF)-β1 and IL-6 stimulation. Thus, IκBNS plays a pivotal role in the generation of Th17 cells and in the control of Th17-dependent EAE.

  4. CC chemokine receptor 4 is required for experimental autoimmune encephalomyelitis by regulating GM-CSF and IL-23 production in dendritic cells

    Science.gov (United States)

    Poppensieker, Karola; Otte, David-Marian; Schürmann, Britta; Limmer, Andreas; Dresing, Philipp; Drews, Eva; Schumak, Beatrix; Klotz, Luisa; Raasch, Jennifer; Mildner, Alexander; Waisman, Ari; Scheu, Stefanie; Knolle, Percy; Förster, Irmgard; Prinz, Marco; Maier, Wolfgang; Zimmer, Andreas; Alferink, Judith

    2012-01-01

    Dendritic cells (DCs) are pivotal for the development of experimental autoimmune encephalomyelitis (EAE). However, the mechanisms by which they control disease remain to be determined. This study demonstrates that expression of CC chemokine receptor 4 (CCR4) by DCs is required for EAE induction. CCR4−/− mice presented enhanced resistance to EAE associated with a reduction in IL-23 and GM-CSF expression in the CNS. Restoring CCR4 on myeloid cells in bone marrow chimeras or intracerebral microinjection of CCR4-competent DCs, but not macrophages, restored EAE in CCR4−/− mice, indicating that CCR4+ DCs are cellular mediators of EAE development. Mechanistically, CCR4−/− DCs were less efficient in GM-CSF and IL-23 production and also TH-17 maintenance. Intraspinal IL-23 reconstitution restored EAE in CCR4−/− mice, whereas intracerebral inoculation using IL-23−/− DCs or GM-CSF−/− DCs failed to induce disease. Thus, CCR4-dependent GM-CSF production in DCs required for IL-23 release in these cells is a major component in the development of EAE. Our study identified a unique role for CCR4 in regulating DC function in EAE, harboring therapeutic potential for the treatment of CNS autoimmunity by targeting CCR4 on this specific cell type. PMID:22355103

  5. Reproductive Health in Men and Women With Vasculitis

    Science.gov (United States)

    2014-06-25

    Giant Cell Arteritis; Takayasu's Arteritis; Polyarteritis Nodosa; Wegener's Granulomatosis; Microscopic Polyangiitis; Churg-Strauss Syndrome; Behcet's Disease; Kawasaki Disease; Henoch-schoenlein Purpura; Vasculitis, Central Nervous System; Drug-induced Necrotizing Vasculitis

  6. Public health awareness of autoimmune diseases after the death of a celebrity.

    Science.gov (United States)

    Bragazzi, Nicola Luigi; Watad, Abdulla; Brigo, Francesco; Adawi, Mohammad; Amital, Howard; Shoenfeld, Yehuda

    2017-08-01

    Autoimmune disorders impose a high burden, in terms of morbidity and mortality worldwide. Vasculitis is an autoimmune disorder that causes inflammation and destruction of blood vessels. Harold Allen Ramis, a famous American actor, director, writer, and comedian, died on the February 24, 2014, of complications of an autoimmune inflammatory vasculitis. To investigate the relation between interests and awareness of an autoimmune disease after a relevant event such as the death of a celebrity, we systematically mined Google Trends, Wikitrends, Google News, YouTube, and Twitter, in any language, from their inception until October 31, 2016. Twenty-eight thousand eight hundred fifty-two tweets; 4,133,615 accesses to Wikipedia; 6780 news; and 11,400 YouTube videos were retrieved, processed, and analyzed. The Harold Ramis death of vasculitis resulted into an increase in vasculitis-related Google searches, Wikipedia page accesses, and tweet production, documenting a peak in February 2014. No trend could be detected concerning uploading YouTube videos. The usage of Big Data is promising in the fields of immunology and rheumatology. Clinical practitioners should be aware of this emerging phenomenon.

  7. Cocaine/levamisole-associated autoimmune syndrome: a disease of neutrophil-mediated autoimmunity.

    Science.gov (United States)

    Cascio, Michael J; Jen, Kuang-Yu

    2018-01-01

    Levamisole was previously used for its immunomodulatory properties to treat rheumatoid arthritis and some cancers. However, because of serious side-effects, it was taken off the market in the United States. Recently, levamisole has reemerged as a popular cocaine adulterant. Some individuals who consume levamisole-adulterated cocaine can develop a life-threatening autoimmune syndrome. In this review, the medical consequences of levamisole exposure and postulated mechanisms by which levamisole induces these adverse effects are discussed. Although agranulocytosis and cutaneous vasculitis are the major findings in patients who develop cocaine/levamisole-associated autoimmune syndrome (CLAAS), more recent experience indicates that other organ systems can be involved as well. Current studies point to neutrophil activation and neutrophil extracellular trap formation with subsequent antineutrophil cytoplasmic antibody-mediated tissue injury as a possible mechanism of CLAAS. In the past decade, the detrimental effects of levamisole have reemerged because of its popularity as a cocaine adulterant. Although infrequent, some individuals develop a systemic autoimmune syndrome characterized by immune-mediated agranulocytosis and antineutrophil cytoplasmic antibody-mediated vasculitis. Mechanistically, neutrophil antigens appear to be a major player in inducing CLAAS. Prompt cessation of levamisole exposure is key to treatment, although relapses are frequent because of the addictive effects of cocaine and the high prevalence of levamisole within the cocaine supply.

  8. Interstital lung disease in ANCA vasculitis.

    Science.gov (United States)

    Alba, Marco A; Flores-Suárez, Luis Felipe; Henderson, Ashley G; Xiao, Hong; Hu, Peiqi; Nachman, Patrick H; Falk, Ronald J; Charles Jennette, J

    2017-07-01

    Anti-neutrophil cytoplasmic antibodies (ANCA) vasculitides are immune-mediated disorders that primarily affect small blood vessels of the airway and kidneys. Lung involvement, one of the hallmarks of microscopic polyangiitis and granulomatosis with polyangiitis, is associated with increased mortality and morbidity. In recent years, several retrospective series and case reports have described the association of interstitial lung disease (ILD) and ANCA vasculitis, particularly those positive for ANCA specific for myeloperoxidase. In the majority of these patients pulmonary fibrosis occurs concurrently or predates the diagnosis of ANCA vasculitis. More importantly, these studies have shown that ILD has an adverse impact on the long-term prognosis of ANCA vasculitis. This review focuses on the main clinical and radiologic features of pulmonary fibrosis associated with anti-neutrophil cytoplasmic antibodies. Major histopathology features, prognosis and therapeutic options are summarized. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Cardiovascular disease in autoimmune rheumatic diseases.

    Science.gov (United States)

    Hollan, Ivana; Meroni, Pier Luigi; Ahearn, Joseph M; Cohen Tervaert, J W; Curran, Sam; Goodyear, Carl S; Hestad, Knut A; Kahaleh, Bashar; Riggio, Marcello; Shields, Kelly; Wasko, Mary C

    2013-08-01

    Various autoimmune rheumatic diseases (ARDs), including rheumatoid arthritis, spondyloarthritis, vasculitis and systemic lupus erythematosus, are associated with premature atherosclerosis. However, premature atherosclerosis has not been uniformly observed in systemic sclerosis. Furthermore, although experimental models of atherosclerosis support the role of antiphospholipid antibodies in atherosclerosis, there is no clear evidence of premature atherosclerosis in antiphospholipid syndrome (APA). Ischemic events in APA are more likely to be caused by pro-thrombotic state than by enhanced atherosclerosis. Cardiovascular disease (CVD) in ARDs is caused by traditional and non-traditional risk factors. Besides other factors, inflammation and immunologic abnormalities, the quantity and quality of lipoproteins, hypertension, insulin resistance/hyperglycemia, obesity and underweight, presence of platelets bearing complement protein C4d, reduced number and function of endothelial progenitor cells, apoptosis of endothelial cells, epigenetic mechanisms, renal disease, periodontal disease, depression, hyperuricemia, hypothyroidism, sleep apnea and vitamin D deficiency may contribute to the premature CVD. Although most research has focused on systemic inflammation, vascular inflammation may play a crucial role in the premature CVD in ARDs. It may be involved in the development and destabilization of both atherosclerotic lesions and of aortic aneurysms (a known complication of ARDs). Inflammation in subintimal vascular and perivascular layers appears to frequently occur in CVD, with a higher frequency in ARD than in non-ARD patients. It is possible that this inflammation is caused by infections and/or autoimmunity, which might have consequences for treatment. Importantly, drugs targeting immunologic factors participating in the subintimal inflammation (e.g., T- and B-cells) might have a protective effect on CVD. Interestingly, vasa vasorum and cardiovascular adipose tissue may

  10. Autoimmune hepatitis.

    Science.gov (United States)

    Vergani, D; Mieli-Vergani, G

    2004-06-01

    Autoimmune hepatitis (AIH) is characterised histologically by interface hepatitis, and serologically by the presence of non-organ and liver specific autoantibodies and increased levels of immunoglobulin G. Its onset is often ill-defined, frequently mimicing acute hepatitis. AIH usually responds to immunosuppressive treatment, which should be instituted as soon as diagnosis is made. Two types of AIH are recognized according to seropositivity for smooth muscle and/or antinuclear antibody (SMA/ANA, type 1 AIH) or liver kidney microsomal type 1 antibody (LKM1, type 2 AIH). There is a female predominance in both. LKM1 positive patients tend to present more acutely, at a younger age and commonly have immunoglobulin A deficiency, while duration of symptoms before diagnosis, clinical signs, family history of autoimmunity, presence of associated autoimmune disorders, response to treatment and long-term prognosis are similar in the 2 groups. Susceptibility to AIH type 1 is conferred by possession of HLA DR3 and DR4, while to AIH type 2 by possession of HLA DR7. Liver damage is likely to derive from an immune reaction to liver cell antigens, possibly triggered by a mechanism of molecular mimicry, where immune responses to external pathogens, e.g. viruses, become directed towards structurally similar self-components. In AIH this process would be perpetuated by impairment in immune regulation.

  11. Neuroimaging of cerebral vasculitis; Bildgebung zerebraler Vaskulitiden

    Energy Technology Data Exchange (ETDEWEB)

    Wengenroth, M. [Universitaetsklinikum Schleswig-Holstein, Campus Luebeck, Institut fuer Neuroradiologie, Luebeck (Germany); Klinikum der Ludwig-Maximilians-Universitaet, Institut fuer klinische Radiologie, Muenchen (Germany); Saam, T. [Klinikum der Ludwig-Maximilians-Universitaet, Institut fuer klinische Radiologie, Muenchen (Germany); Haehnel, S. [Universitaetsklinikum Heidelberg, Abteilung Neuroradiologie, Heidelberg (Germany)

    2016-01-15

    Cerebral vasculitis can have a variety of origins. Furthermore, there are no vasculitis-specific symptoms or imaging signs and vasculitis of the CNS can mimic many other neurological diseases, which require different treatment approaches. Thus, the clinical and radiological diagnosis of cerebral vasculitis is challenging. Magnetic resonance imaging (MRI) and MR angiography (MRA) should be the radiological imaging methods of choice to assess the degree of parenchymal damage and to detect vessel wall changes. If the results are unclear digital subtraction angiography (DSA) should be pursued in order to also detect changes in medium sized vessels. Vasculitis of small vessels cannot be detected by vascular imaging and requires brain or leptomeningeal biopsy. In this review we present the current diagnostic approach and a variety of imaging findings in cerebral vasculitis and discuss the main radiological differential diagnoses. (orig.) [German] Die zerebrale Vaskulitis kann viele Ursachen haben. Daher ist die klinische und radiologische Diagnose schwierig, auch weil es etliche vaskulitistypische Symptome und MR-Befunde bei anderen Erkrankungen gibt. Die ZNS-Vaskulitis kann zahlreiche andere neurologische Erkrankungen imitieren, die unterschiedlicher Therapie beduerfen. MRT und MR-Angiographie (MRA) sind die Verfahren der Wahl, mit denen die radiologische Diagnostik begonnen werden sollte, um den Parenchymschaden und den Gefaessbefall zu beurteilen. Bei unklaren Befunden kann eine digitale Subtraktionsangiographie (DSA) ergaenzt werden, um auch mittelgrosse Gefaesse beurteilen zu koennen. Der Befall kleiner Gefaesse kann nur bioptisch nachgewiesen werden. In der folgenden Uebersicht stellen wir das diagnostische Herangehen bei zerebraler Vaskulitis vor, praesentieren zahlreiche Befunde und diskutieren die wichtigsten radiologischen Differenzialdiagnosen. (orig.)

  12. Persistent activation of microglia is associated with neuronal dysfunction of callosal projecting pathways and multiple sclerosis-like lesions in relapsing--remitting experimental autoimmune encephalomyelitis

    DEFF Research Database (Denmark)

    Rasmussen, Stine; Wang, Yue; Kivisäkk, Pia

    2007-01-01

    callosal projecting neurons. There was significant impairment of retrograde labeling of NeuN-positive callosal projecting neurons and reduction in the labelling of their transcallosal axons. These data demonstrate a novel paradigm of cortical and callosal neuropathology in a mouse model of MS, perpetuated......Cortical pathology, callosal atrophy and axonal loss are substrates of progression in multiple sclerosis (MS). Here we describe cortical, periventricular subcortical lesions and callosal demyelination in relapsing-remitting experimental autoimmune encephalomyelitis in SJL mice that are similar...... to lesions found in MS. Unlike the T-cell infiltrates that peak during acute disease, we found that microglia activation persists through the chronic disease phase. Microglia activation correlated with abnormal phosphorylation of neurofilaments in the cortex and stripping of synaptic proteins in cortical...

  13. Connective Tissue Disorder-Associated Vasculitis.

    Science.gov (United States)

    Sharma, Aman; Dhooria, Aadhaar; Aggarwal, Ashish; Rathi, Manish; Chandran, Vinod

    2016-06-01

    Vasculitides secondary to connective tissue diseases are classified under the category of 'vasculitis associated with systemic disease' in the revised International Chapel Hill Consensus Conference (CHCC) nomenclature. These secondary vasculitides may affect any of the small, medium or large vessels and usually portend a poor prognosis. Any organ system can be involved and the presentation would vary depending upon that involvement. Treatment depends upon the type and severity of presentation. In this review, we describe secondary vasculitis associated with rheumatoid arthritis, systemic lupus erythematosus, sarcoidosis, relapsing polychondritis, systemic sclerosis, Sjogren's syndrome and idiopathic inflammatory myositis, focusing mainly on recent advances in the past 3 years.

  14. 1,25-Dihydroxyvitamin D3 inhibits the differentiation and migration of T(H17 cells to protect against experimental autoimmune encephalomyelitis.

    Directory of Open Access Journals (Sweden)

    Jae-Hoon Chang

    Full Text Available BACKGROUND: Vitamin D(3, the most physiologically relevant form of vitamin D, is an essential organic compound that has been shown to have a crucial effect on the immune responses. Vitamin D(3 ameliorates the onset of the experimental autoimmune encephalomyelitis (EAE; however, the direct effect of vitamin D(3 on T cells is largely unknown. METHODOLOGY/PRINCIPAL FINDINGS: In an in vitro system using cells from mice, the active form of vitamin D(3 (1,25-dihydroxyvitamin D(3 suppresses both interleukin (IL-17-producing T cells (T(H17 and regulatory T cells (Treg differentiation via a vitamin D receptor signal. The ability of 1,25-dihydroxyvitamin D(3 (1,25(OH(2D(3 to reduce the amount of IL-2 regulates the generation of Treg cells, but not T(H17 cells. Under T(H17-polarizing conditions, 1,25(OH(2D(3 helps to increase the numbers of IL-10-producing T cells, but 1,25(OH(2D(3's negative regulation of T(H17 development is still defined in the IL-10(-/- T cells. Although the STAT1 signal reciprocally affects the secretion of IL-10 and IL-17, 1,25(OH(2D(3 inhibits IL-17 production in STAT1(-/- T cells. Most interestingly, 1,25(OH(2D(3 negatively regulates CCR6 expression which might be essential for T(H17 cells to enter the central nervous system and initiate EAE. CONCLUSIONS/SIGNIFICANCE: Our present results in an experimental murine model suggest that 1,25(OH(2D(3 can directly regulate T cell differentiation and could be applied in preventive and therapeutic strategies for T(H17-mediated autoimmune diseases.

  15. Vasculitis syndromes : Peripheral neuropathy in AAV--when vasculitis hits a nerve

    NARCIS (Netherlands)

    Rutgers, Abraham; Kallenberg, Cornelis

    Peripheral neuropathy can be a manifestation of small-vessel vasculitides such as antineutrophil cytoplasmic antibody-associated vasculitis. Diagnosing vasculitic neuropathy is, however, difficult in many cases. Early treatment focused on achieving remission of the underlying vasculitic process is

  16. AUTOIMMUNE HEPATITIS

    Directory of Open Access Journals (Sweden)

    Yusri Dianne Jurnalis

    2010-05-01

    Full Text Available AbstrakHepatitis autoimun merupakan penyakit inflamasi hati yang berat dengan penyebab pasti yang tidak diketahui yang mengakibatkan morbiditas dan mortalitas yang tinggi. Semua usia dan jenis kelamin dapat dikenai dengan insiden tertinggi pada anak perempuan usia prepubertas, meskipun dapat didiagnosis pada usia 6 bulan. Hepatitis autoimun dapat diklasifikasikan menjadi 2 bagian berdasarkan adanya antibodi spesifik: Smooth Muscle Antibody (SMA dengan anti-actin specificity dan/atau Anti Nuclear Antibody (ANA pada tipe 1 dan Liver-Kidney Microsome antibody (LKM1 dan/atau anti-liver cytosol pada tipe 2. Gambaran histologisnya berupa “interface hepatitis”, dengan infiltrasi sel mononuklear pada saluran portal, berbagai tingkat nekrosis, dan fibrosis yang progresf. Penyakit berjalan secara kronik tetapi keadaan yang berat biasanya menjadi sirosis dan gagal hati.Tipe onset yang paling sering sama dengan hepatitis virus akut dengan gagal hati akut pada beberapa pasien; sekitar sepertiga pasien dengan onset tersembunyi dengan kelemahan dan ikterik progresif ketika 10-15% asimptomatik dan mendadak ditemukan hepatomegali dan/atau peningkatan kadar aminotransferase serum. Adanya predominasi perempuan pada kedua tipe. Pasien LKM1 positif menunjukkan keadaan lebih akut, pada usia yang lebih muda, dan biasanya dengan defisiensi Immunoglobulin A (IgA, dengan durasi gejala sebelum diagnosis, tanda klinis, riwayat penyakit autoimun pada keluarga, adanya kaitan dengan gangguan autoimun, respon pengobatan dan prognosis jangka panjang sama pada kedua tipe.Kortikosteroid yang digunakan secara tunggal atau kombinasi azathioprine merupakan terapi pilihan yang dapat menimbulkan remisi pada lebih dari 90% kasus. Strategi terapi alternatif adalah cyclosporine. Penurunan imunosupresi dikaitkan dengan tingginya relap. Transplantasi hati dianjurkan pada penyakit hati dekom-pensata yang tidak respon dengan pengobatan medis lainnya.Kata kunci : hepatitis Autoimmune

  17. [Autoimmune hepatitis].

    Science.gov (United States)

    Färkkilä, Martti

    2013-01-01

    Autoimmune hepatitis is chronic liver disease with two subtypes, type 1 with anti nuclear or smooth muscle antibodies and type 2 with LKM1 or LC1 antibodies, and both with hypergammaglobulinemia and typical histology. Prevalence of AIH is between 10 to 17 per 100000 in Europe. Up to 20-40 % of cases present with acute hepatitis. Budesonide can be used as a first line induction therapy in non-cirrhotic patients, and tiopurines, mercaptopurine or mycophenolic acid as maintenance therapies. Patients not responding to conventional therapy can be treated with ciclosporin, tacrolimus or rituximab or finally with liver transplantation.

  18. Pediatric ischemic stroke due to dengue vasculitis.

    Science.gov (United States)

    Nanda, Subrat Kumar; Jayalakshmi, Sita; Mohandas, Surath

    2014-10-01

    Dengue infection is an important arboviral infection in southeast Asia, especially in India. Neurological manifestations of dengue are increasingly recognized. We report an ischemic stroke due to dengue vasculitis in an 8-year-old child. We present a girl with a short febrile illness followed by episodic severe headache, with gradually progressive hemiparesis and visual impairment. Her brain magnetic resonance imaging revealed multiple infarctions in the anterior and posterior circulation. The magnetic resonance angiogram revealed irregular narrowing of bilateral middle cerebral arteries, right anterior cerebral artery, left posterior cerebral, and bilateral vertebral arteries suggestive of vasculitis. Her dengue serology was strongly positive for immunoglobulin M with 68.9 panbio units. The rest of the evaluation for pediatric stroke was unremarkable. She was treated with intravenous followed by oral corticosteroids and recovered totally with resolution of vasculitis on magnetic resonance angiogram over the next 3 months. This child illustrates possible immune-mediated vasculitis caused by dengue infection which is rather a rare presentation in a child who subsequently recovered well. One should consider dengue in childhood strokes in endemic regions. Copyright © 2014 Elsevier Inc. All rights reserved.

  19. Magnetic resonance angiography in suspected cerebral vasculitis

    International Nuclear Information System (INIS)

    Demaerel, Philippe; De Ruyter, Nele; Wilms, Guido; Maes, Frederik; Velghe, Beatrijs

    2004-01-01

    The purpose of this study was to determine the technical capacity and diagnostic accuracy of 3D time-of-flight magnetic resonance angiography (MRA) in suspected cerebral vasculitis in a retrospective analysis of MRA and digital subtraction angiography (DSA) in 14 young patients with clinical and/or radiological suspicion of cerebral vasculitis. A total of nine arteries were evaluated in each patient. Consensus review of DSA by three observers was the reference standard. The sensitivity for detecting a stenosis varied from 62 to 79% for MRA and from 76 to 94% for DSA, depending on the observer. The specificity for detecting a stenosis varied from 83 to 87% for MRA and from 83 to 97% for DSA. Using the criterion ''more than two stenoses in at least two separate vascular distributions'' to consider the examination as being true positive, the false-positive rates for MRA and DSA were comparable. MRA plays a role as the first angiographical examination in the diagnostic work-up of suspected cerebral vasculitis. When more than two stenoses in at least two separate vascular distributions are depicted on MRA, DSA is not expected to add a significant diagnostic contribution in a patient with suspected cerebral vasculitis. DSA remains necessary when MRA is normal or when less than three stenoses are seen. (orig.)

  20. Cerebral vasculitis associated with Schistosoma mansoni infection

    Directory of Open Access Journals (Sweden)

    Camuset Guillaume

    2012-09-01

    Full Text Available Abstract Background Cerebral involvement in schistosomiasis is not rare, but it is underdiagnosed because of the lack of clinical suspicion and the frequency of asymptomatic forms. Neurologic complications are generally supported by granuloma formation around ectopic eggs which have migrated to the brain. Moreover, vascular lesions and cerebral arteritis have been well documented in histopathological studies. Nevertheless, cerebral vasculitis in later stages of the Schistosoma mansoni infection have not yet been described in living subjects. Case presentation A 28-year-old french woman had a stroke linked with cerebral vasculitis, 6 monthes after returning from Burkina-Faso. At the same time, a S. mansoni disseminated infection was diagnosed. She suffered from a new stroke after undertaking praziquantel therapy, which lead us to associate the S. mansoni infection and cerebral vasculitis. Conclusion This is the first report of such association, since cerebral vasculitis has never been described in later stages of the S. mansoni infection. Although the causal link between the two pathologies could not be proved, we suggest that S. mansoni is able to cause severe vascular damage in cerebral vessels. Schistosomiasis must be investigated in the event of a brain infarct in young people, particularly in patients originating or returning from an endemic area.

  1. Perspective on future therapy of vasculitis.

    Science.gov (United States)

    Boumpas, D T; Kritikos, H D; Daskalakis, N G

    2000-10-01

    This article summarizes recent advances in the management of various vasculitic syndromes and discusses potential new therapies based on a better understanding of their pathogenesis and natural history. Current efforts for optimization of testing for antineutrophil cytoplasmic antibodies and improvement of diagnostic criteria will certainly have a significant impact on future therapy. Biologic agents such as interferon-alpha are already in use in various vasculitides, whereas others, such as inhibitors of tumor necrosis factor-alpha, are in phase I clinical trials. Agents that selectively inhibit distinct steps in the pathogenesis of vasculitis are in preclinical or early clinical stages of development. Newer (mycophenolate mofetil, leflunamide) or older (methotrexate, azathioprine) immunosuppresive agents are finding new roles in the management of vasculitides. For patients with severe vasculitis, short-term use of cytotoxic agents, such as cyclophosphamide, alone or in combination with biologic agents, may expedite remission, which could then be better maintained with other, less toxic (and less expensive) immunosuppressive agents, such as methotrexate, azathioprine, mycophenolate mofetil, and leflunamide. For patients with mild or moderately severe vasculitis, these latter agents alone may be adequate. New therapeutic studies in vasculitis should better address the impact of therapy on health-related quality of life and its long-term toxicity.

  2. Magnetic resonance angiography in suspected cerebral vasculitis

    Energy Technology Data Exchange (ETDEWEB)

    Demaerel, Philippe; De Ruyter, Nele; Wilms, Guido [Department of Radiology, Universitair Ziekenhuis, KU Leuven, 3000, Leuven (Belgium); Maes, Frederik [Department of Medical Imaging Computing, Universitair Ziekenhuis, KU Leuven, 3000, Leuven (Belgium); Velghe, Beatrijs [Department of Radiology, Ziekenhuis Oost-Limburg, Schiepse Bos 6, 3600, Genk (Belgium)

    2004-06-01

    The purpose of this study was to determine the technical capacity and diagnostic accuracy of 3D time-of-flight magnetic resonance angiography (MRA) in suspected cerebral vasculitis in a retrospective analysis of MRA and digital subtraction angiography (DSA) in 14 young patients with clinical and/or radiological suspicion of cerebral vasculitis. A total of nine arteries were evaluated in each patient. Consensus review of DSA by three observers was the reference standard. The sensitivity for detecting a stenosis varied from 62 to 79% for MRA and from 76 to 94% for DSA, depending on the observer. The specificity for detecting a stenosis varied from 83 to 87% for MRA and from 83 to 97% for DSA. Using the criterion ''more than two stenoses in at least two separate vascular distributions'' to consider the examination as being true positive, the false-positive rates for MRA and DSA were comparable. MRA plays a role as the first angiographical examination in the diagnostic work-up of suspected cerebral vasculitis. When more than two stenoses in at least two separate vascular distributions are depicted on MRA, DSA is not expected to add a significant diagnostic contribution in a patient with suspected cerebral vasculitis. DSA remains necessary when MRA is normal or when less than three stenoses are seen. (orig.)

  3. Propylthiouracil induced leukocytoclastic vasculitis: A rare manifestation

    Directory of Open Access Journals (Sweden)

    Semra Ayturk

    2013-01-01

    Full Text Available Propylthiouracil (PTU is a common drug used in patients with hyperthyroidism. It may cause perinuclearantineutrophil cytoplasmic antibodies (p-ANCA in few patients with Graves′ disease. This antibody has been associated with different forms of vasculitis. We report a patient who presented with cutaneous manifestations of leukocytoclasticvasculitis with simultaneous development of p-ANCAs during PTU therapy for Graves′ disease.

  4. Dynamics of intraocular IFN-γ, IL-17 and IL-10-producing cell populations during relapsing and monophasic rat experimental autoimmune uveitis.

    Directory of Open Access Journals (Sweden)

    Ulrike Kaufmann

    Full Text Available A major limitation of most animal models of autoimmune diseases is that they do not reproduce the chronic or relapsing-remitting pattern characteristic of many human autoimmune diseases. This problem has been overcome in our rat models of experimentally induced monophasic or relapsing-remitting autoimmune uveitis (EAU, which depend on the inducing antigen peptides from retinal S-Antigen (monophasic EAU or interphotoreceptor retinoid-binding protein (relapsing EAU. These models enable us to compare autoreactive and regulatory T cell populations. Intraocular, but not peripheral T cells differ in their cytokine profiles (IFN-γ, IL-17 and IL-10 at distinct time points during monophasic or relapsing EAU. Only intraocular T cells concomitantly produced IFN-γ, IL-17 and/or IL-10. Monophasic EAU presented rising numbers of cells expressing IFN-γ and IL-17 (Th1/Th17 and cells expressing IL-10 or Foxp3. During relapsing uveitis an increase of intraocular IFN-γ+ cells and a concomitant decrease of IL-17+ cells was detected, while IL-10+ populations remained stable. Foxp3+ cells and cells expressing IL-10, even in combination with IFN-γ or IL-17, increased during the resolution of monophasic EAU, suggesting a regulatory role for these T cells. In general, cells producing multiple cytokines increased in monophasic and decreased in relapsing EAU. The distinct appearance of certain intraocular populations with characteristics of regulatory cells points to a differential influence of the ocular environment on T cells that induce acute and monophasic or relapsing disease. Here we provide evidence that different autoantigens can elicit distinct and differently regulated immune responses. IFN-γ, but not IL-17 seems to be the key player in relapsing-remitting uveitis, as shown by increased, synchronized relapses after intraocular application of IFN-γ. We demonstrated dynamic changes of the cytokine pattern during monophasic and relapsing-remitting disease

  5. Biopsy-proven case of Epstein-Barr virus (EBV)-associated vasculitis of the central nervous system.

    Science.gov (United States)

    Kano, Kohei; Katayama, Takayuki; Takeguchi, Shiori; Asanome, Asuka; Takahashi, Kae; Saito, Tsukasa; Sawada, Jun; Saito, Masato; Anei, Ryogo; Kamada, Kyousuke; Miyokawa, Naoyuki; Nishihara, Hiroshi; Hasebe, Naoyuki

    2017-06-01

    A 75-year-old woman was admitted to our hospital with rapidly deteriorating consciousness disturbance. She had a 7-year history of rheumatoid arthritis (RA), which had been treated with methotrexate (MTX) and prednisolone. Brain T2-weighted MRI showed diffuse high-intensity lesions in the cerebral subcortical and deep white matter, bilateral basal ganglia and thalamus. A cerebrospinal fluid examination revealed elevated protein levels and positive Epstein-Barr virus (EBV) DNA. Human immunodeficiency virus was negative. Brain biopsy showed perivascular lymphocytic infiltration in the parenchyma and meninx with EBV-encoded small RNA (EBER). Since this case did not fulfill the criteria for chronic active EBV infection (CAEBV), she was diagnosed with Epstein-Barr virus (EBV)-associated vasculitis of the central nervous system. High-dose methylprednisolone, acyclovir, ganciclovir and foscarnet were not effective. Although EBV is a causative agent of infectious mononucleosis (IM), lymphomas and nasopharyngeal carcinomas, vasculitic pathology of the central nervous system with EBV reactivation in the elderly is rare. Immunosuppressive drugs such as steroids and MTX are widely used to treat autoimmune disorders, but may exacerbate the reactivation of EBV. This is the first case of biopsy-proven EBV-positive/HIV-negative vasculitis during the treatment of RA with MTX and steroids. This case indicates that EBV-associated vasculitis needs to be considered as a differential diagnosis of CNS vasculitis. © 2016 Japanese Society of Neuropathology.

  6. Autoimmune liver disease panel

    Science.gov (United States)

    Liver disease test panel - autoimmune ... Autoimmune disorders are a possible cause of liver disease. The most common of these diseases are autoimmune hepatitis and primary biliary cholangitis (formerly called primary biliary cirrhosis). This group of tests ...

  7. CD1d(hi)CD5+ B cells expanded by GM-CSF in vivo suppress experimental autoimmune myasthenia gravis.

    Science.gov (United States)

    Sheng, Jian Rong; Quan, Songhua; Soliven, Betty

    2014-09-15

    IL-10-competent subset within CD1d(hi)CD5(+) B cells, also known as B10 cells, has been shown to regulate autoimmune diseases. Whether B10 cells can prevent or suppress the development of experimental autoimmune myasthenia gravis (EAMG) has not been studied. In this study, we investigated whether low-dose GM-CSF, which suppresses EAMG, can expand B10 cells in vivo, and whether adoptive transfer of CD1d(hi)CD5(+) B cells would prevent or suppress EAMG. We found that treatment of EAMG mice with low-dose GM-CSF increased the proportion of CD1d(hi)CD5(+) B cells and B10 cells. In vitro coculture studies revealed that CD1d(hi)CD5(+) B cells altered T cell cytokine profile but did not directly inhibit T cell proliferation. In contrast, CD1d(hi)CD5(+) B cells inhibited B cell proliferation and its autoantibody production in an IL-10-dependent manner. Adoptive transfer of CD1d(hi)CD5(+) B cells to mice could prevent disease, as well as suppress EAMG after disease onset. This was associated with downregulation of mature dendritic cell markers and expansion of regulatory T cells resulting in the suppression of acetylcholine receptor-specific T cell and B cell responses. Thus, our data have provided significant insight into the mechanisms underlying the tolerogenic effects of B10 cells in EAMG. These observations suggest that in vivo or in vitro expansion of CD1d(hi)CD5(+) B cells or B10 cells may represent an effective strategy in the treatment of human myasthenia gravis. Copyright © 2014 by The American Association of Immunologists, Inc.

  8. Dietary Omega-3 Fatty Acids Suppress Experimental Autoimmune Uveitis in Association with Inhibition of Th1 and Th17 Cell Function

    Science.gov (United States)

    Shoda, Hiromi; Yanai, Ryoji; Yoshimura, Takeru; Nagai, Tomohiko; Kimura, Kazuhiro; Sobrin, Lucia; Connor, Kip M.; Sakoda, Yukimi; Tamada, Koji; Ikeda, Tsunehiko; Sonoda, Koh-Hei

    2015-01-01

    Omega (ω)–3 long-chain polyunsaturated fatty acids (LCPUFAs) inhibit the production of inflammatory mediators and thereby contribute to the regulation of inflammation. Experimental autoimmune uveitis (EAU) is a well-established animal model of autoimmune retinal inflammation. To investigate the potential effects of dietary intake of ω-3 LCPUFAs on uveitis, we examined the anti-inflammatory properties of these molecules in comparison with ω-6 LCPUFAs in a mouse EAU model. C57BL/6 mice were fed a diet containing ω-3 LCPUFAs or ω-6 LCPUFAs for 2 weeks before as well as after the induction of EAU by subcutaneous injection of a fragment of human interphotoreceptor retinoid-binding protein emulsified with complete Freund’s adjuvant. Both clinical and histological scores for uveitis were smaller for mice fed ω-3 LCPUFAs than for those fed ω-6 LCPUFAs. The concentrations of the T helper 1 (Th1) cytokine interferon-γ and the Th17 cytokine interleukin-17 in intraocular fluid as well as the production of these cytokines by lymph node cells were reduced for mice fed ω-3 LCPUFAs. Furthermore, the amounts of mRNAs for the Th1- and Th17-related transcription factors T-bet and RORγt, respectively, were reduced both in the retina and in lymph node cells of mice fed ω-3 LCPUFAs. Our results thus show that a diet enriched in ω-3 LCPUFAs suppressed uveitis in mice in association with inhibition of Th1 and Th17 cell function. PMID:26393358

  9. Multivalent Soluble Antigen Arrays Exhibit High Avidity Binding and Modulation of B Cell Receptor-Mediated Signaling to Drive Efficacy against Experimental Autoimmune Encephalomyelitis.

    Science.gov (United States)

    Hartwell, Brittany L; Pickens, Chad J; Leon, Martin; Berkland, Cory

    2017-06-12

    A pressing need exists for antigen-specific immunotherapies (ASIT) that induce selective tolerance in autoimmune disease while avoiding deleterious global immunosuppression. Multivalent soluble antigen arrays (SAgA PLP:LABL ), consisting of a hyaluronic acid (HA) linear polymer backbone cografted with multiple copies of autoantigen (PLP) and cell adhesion inhibitor (LABL) peptides, are designed to induce tolerance to a specific multiple sclerosis (MS) autoantigen. Previous studies established that hydrolyzable SAgA PLP:LABL , employing a degradable linker to codeliver PLP and LABL, was therapeutic in experimental autoimmune encephalomyelitis (EAE) in vivo and exhibited antigen-specific binding with B cells, targeted the B cell receptor (BCR), and dampened BCR-mediated signaling in vitro. Our results pointed to sustained BCR engagement as the SAgA PLP:LABL therapeutic mechanism, so we developed a new version of the SAgA molecule using nonhydrolyzable conjugation chemistry, hypothesizing it would enhance and maintain the molecule's action at the cell surface to improve efficacy. "Click SAgA" (cSAgA PLP:LABL ) uses hydrolytically stable covalent conjugation chemistry (Copper-catalyzed Azide-Alkyne Cycloaddition (CuAAC)) rather than a hydrolyzable oxime bond to attach PLP and LABL to HA. We explored cSAgA PLP:LABL B cell engagement and modulation of BCR-mediated signaling in vitro through flow cytometry binding and calcium flux signaling assays. Indeed, cSAgA PLP:LABL exhibited higher avidity B cell binding and greater dampening of BCR-mediated signaling than hydrolyzable SAgA PLP:LABL . Furthermore, cSAgA PLP:LABL exhibited significantly enhanced in vivo efficacy compared to hydrolyzable SAgA PLP:LABL , achieving equivalent efficacy at one-quarter of the dose. These results indicate that nonhydrolyzable conjugation increased the avidity of cSAgA PLP:LABL to drive in vivo efficacy through modulated BCR-mediated signaling.

  10. Update in Endocrine Autoimmunity

    OpenAIRE

    Anderson, Mark S.

    2008-01-01

    Context: The endocrine system is a common target in pathogenic autoimmune responses, and there has been recent progress in our understanding, diagnosis, and treatment of autoimmune endocrine diseases.

  11. 18F-fluoro-deoxy-glucose positron emission tomography combined with computed tomography can reliably rule-out infection and cancer in patients with anti-neutrophil cytoplasmic antibody-associated vasculitis suspected of disease relapse

    DEFF Research Database (Denmark)

    Frary, Evan C; Hess, Søren; Gerke, Oke

    2017-01-01

    Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a group of autoimmune diseases characterized by systemic inflammation in small- to medium-sized blood vessels. Although immunosuppressive therapy has greatly improved the prognosis for these patients, there are still...

  12. NKT cells can help mediate the protective effects of 1,25-dihydroxyvitamin D3 in experimental autoimmune encephalomyelitis in mice.

    Science.gov (United States)

    Waddell, Amanda; Zhao, Jun; Cantorna, Margherita T

    2015-05-01

    Active vitamin D [1,25-dihydroxyvitamin D3 (1,25D3)] blocks the development of experimental autoimmune diseases. However, the molecular and immunobiological mechanisms underlying 1,25D3's anti-inflammatory properties are not fully understood. We employed a murine model of experimental autoimmune encephalomyelitis (EAE) in order to determine the role of NKT cells in 1,25D3-mediated protection from EAE. Wild-type (WT) mice or mice lacking all NKT cells (CD1d(-/-)) or invariant NKT cells (Jα18(-/-)) were fed control or 1,25D3-supplemented diets. All mice fed with the control diet developed severe EAE. 1,25D3 treatment of WT mice protected them from developing EAE. CD1d(-/-) and Jα18(-/-) mice treated with 1,25D3 were not protected to the same extent as WT mice. Myelin oligodendrocyte glycoprotein-specific IL-17 and IFN-γ production was significantly reduced in 1,25D3 WT mice compared with WT but was not decreased in 1,25D3 CD1d(-/-) mice compared with CD1d(-/-) mice. IL-4(-/-) mice were utilized to determine how IL-4 deficiency affects susceptibility to EAE. IL-4(-/-) mice were not protected from developing EAE by α-galactosylceramide (α-GalCer) or 1,25D3 treatment. Furthermore, 1,25D3 treatment of splenocytes in vitro decreased α-GalCer-induced IL-17 and increased IL-4, IL-5 and IL-10 production. 1,25D3 alters the cytokine profile of invariant NKT cells in vitro. These studies demonstrate that NKT cells are important mediators of 1,25D3-induced protection from EAE in mice and NKT cell-derived IL-4 may be an important factor in providing this protection. © The Japanese Society for Immunology. 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  13. Warfarin-induced leukocytoclastic vasculitis and proteinuria

    Directory of Open Access Journals (Sweden)

    Khalid Jumean

    2016-01-01

    Full Text Available Warfarin is typically prescribed for patients with thromboembolic diseases and atrial fibrillation. In addition to the complications of bleeding, allergic skin reaction is one of its rare adverse effects. We herein report a case of a 79 year old male patient with leukocytoclastic vasculitis and proteinuria secondary to warfarin. The warfarin was discontinued and oral prednisone therapy was initiated. The cutaneous lesions and the proteinuria resolved thereafter.

  14. A clinical approach to the diagnosis of retinal vasculitis.

    Science.gov (United States)

    El-Asrar, Ahmed M Abu; Herbort, Carl P; Tabbara, Khalid F

    2010-04-01

    Retinal vasculitis is a sight-threatening inflammatory eye condition that involves the retinal vessels. Detection of retinal vasculitis is made clinically, and is confirmed with the help of fundus fluorescein angiography. Active vascular disease is characterized by exudates around retinal vessels resulting in white sheathing or cuffing of the affected vessels. In this review, a practical approach to the diagnosis of retinal vasculitis is discussed based on ophthalmoscopic and fundus fluorescein angiographic findings.

  15. Extensive vascular remodeling in the spinal cord of pre-symptomatic experimental autoimmune encephalomyelitis mice; increased vessel expression of fibronectin and the α5β1 integrin

    Science.gov (United States)

    Boroujerdi, Amin; Welser-Alves, Jennifer V.; Milner, Richard

    2013-01-01

    Alterations in vascular structure and function are a central component of demyelinating disease. In addition to blood-brain barrier (BBB) breakdown, which occurs early in the course of disease, recent studies have described angiogenic remodeling, both in multiple sclerosis tissue and in the mouse demyelinating model, experimental autoimmune encephalomyelitis (EAE). As the precise timing of vascular remodeling in demyelinating disease has yet to be fully defined, the purpose of the current study was to define the time-course of these events in the MOG35-55 EAE model. Quantification of endothelial cell proliferation and vessel density revealed that a large part of angiogenic remodeling in cervical spinal cord white matter occurs during the pre-symptomatic phase of EAE. At the height of vascular remodeling, blood vessels in the cervical spinal cord showed strong transient upregulation of fibronectin and the α5β1 integrin. In vitro experiments revealed that α5 integrin inhibition reduced brain endothelial cell proliferation under inflammatory conditions. Interestingly, loss of vascular integrity was evident in all vessels during the first 4–7 days post-immunization, but after 14 days, was localized predominantly to venules. Taken together, our data demonstrate that extensive vascular remodeling occurs during the pre-symptomatic phase of EAE and point to a potential role for the fibronectin-α5β1 integrin interaction in promoting vascular remodeling during demyelinating disease. PMID:24056042

  16. Development and Pre-Clinical Evaluation of Recombinant Human Myelin Basic Protein Nano Therapeutic Vaccine in Experimental Autoimmune Encephalomyelitis Mice Animal Model

    Science.gov (United States)

    Al-Ghobashy, Medhat A.; Elmeshad, Aliaa N.; Abdelsalam, Rania M.; Nooh, Mohammed M.; Al-Shorbagy, Muhammad; Laible, Götz

    2017-04-01

    Recombinant human myelin basic protein (rhMBP) was previously produced in the milk of transgenic cows. Differences in molecular recognition of either hMBP or rhMBP by surface-immobilized anti-hMBP antibodies were demonstrated. This indicated differences in immunological response between rhMBP and hMBP. Here, the activity of free and controlled release rhMBP poly(ɛ-caprolactone) nanoparticles (NPs), as a therapeutic vaccine against multiple sclerosis (MS) was demonstrated in experimental autoimmune encephalomyelitis (EAE) animal model. Following optimization of nanoformulation, discrete spherical, rough-surfaced rhMBP NPs with high entrapment efficiency and controlled release pattern were obtained. Results indicated that rhMBP was loaded into and electrostatically adsorbed onto the surface of NPs. Subcutaneous administration of free or rhMBP NPs before EAE-induction reduced the average behavioral score in EAE mice and showed only mild histological alterations and preservation of myelin sheath, with rhMBP NPs showing increased protection. Moreover, analysis of inflammatory cytokines (IFN-γ and IL-10) in mice brains revealed that pretreatment with free or rhMBP NPs significantly protected against induced inflammation. In conclusion: i) rhMBP ameliorated EAE symptoms in EAE animal model, ii) nanoformulation significantly enhanced efficacy of rhMBP as a therapeutic vaccine and iii) clinical investigations are required to demonstrate the activity of rhMBP NPs as a therapeutic vaccine for MS.

  17. Rational design and synthesis of altered peptide ligands based on human myelin oligodendrocyte glycoprotein 35-55 epitope: inhibition of chronic experimental autoimmune encephalomyelitis in mice.

    Science.gov (United States)

    Tselios, Theodore; Aggelidakis, Mihalis; Tapeinou, Anthi; Tseveleki, Vivian; Kanistras, Ioannis; Gatos, Dimitrios; Matsoukas, John

    2014-11-04

    Experimental autoimmune encephalomyelitis (EAE) is a demyelinating disease of the central nervous system and is an animal model of multiple sclerosis (MS). Although the etiology of MS remains unclear, there is evidence T-cell recognition of immunodominant epitopes of myelin proteins, such as the 35-55 epitope of myelin oligodendrocyte glycoprotein (MOG), plays a pathogenic role in the induction of chronic EAE. Cyclization of peptides is of great interest since the limited stability of linear peptides restricts their potential use as therapeutic agents. Herein, we have designed and synthesized a number of linear and cyclic peptides by mutating crucial T cell receptor (TCR) contact residues of the human MOG35-55 epitope. In particular, we have designed and synthesized cyclic altered peptide ligands (APLs) by mutating Arg41 with Ala or Arg41 and Arg46 with Ala. The peptides were synthesized in solid phase on 2-chlorotrityl chloride resin (CLTR-Cl) using the Fmoc/t-Bu methodology. The purity of final products was verified by RP-HPLC and their identification was achieved by ESI-MS. It was found that the substitutions of Arg at positions 41 and 46 with Ala results in peptide analogues that reduce the severity of MOG-induced EAE clinical symptoms in C57BL/6 mice when co-administered with mouse MOG35-55 peptide at the time of immunization.

  18. Ginger extracts influence the expression of IL-27 and IL-33 in the central nervous system in experimental autoimmune encephalomyelitis and ameliorates the clinical symptoms of disease.

    Science.gov (United States)

    Jafarzadeh, A; Mohammadi-Kordkhayli, M; Ahangar-Parvin, R; Azizi, V; Khoramdel-Azad, H; Shamsizadeh, A; Ayoobi, A; Nemati, M; Hassan, Z M; Moazeni, S M; Khaksari, M

    2014-11-15

    The immunomodulatory effects of the IL-27 and IL-33 and the anti-inflammatory effects of ginger have been reported in some studies. The aim was to evaluate the effects of the ginger extract on the expression of IL-27 and IL-33 in a model of experimental autoimmune encephalomyelitis (EAE). In PBS-treated EAE mice the expression of IL-27 P28 was significantly lower whereas the expression of IL-33 was significantly higher than unimmunized control mice. In 200 and 300 mg/kg ginger-treated EAE groups the expression of IL-27 P28 and IL-27 EBI3 was significantly higher whereas the expression of IL-33 was significantly lower than PBS-treated EAE mice. The EAE clinical symptoms and the pathological scores were significantly lower in ginger-treated EAE groups. These results showed that the ginger extract modulates the expression of the IL-27 and IL-33 in the spinal cord of EAE mice and ameliorates the clinical symptoms of disease. Copyright © 2014 Elsevier B.V. All rights reserved.

  19. Deficits in Endogenous Adenosine Formation by Ecto-5′-Nucleotidase/CD73 Impair Neuromuscular Transmission and Immune Competence in Experimental Autoimmune Myasthenia Gravis

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    Laura Oliveira

    2015-01-01

    Full Text Available AMP dephosphorylation via ecto-5′-nucleotidase/CD73 is the rate limiting step to generate extracellular adenosine (ADO from released adenine nucleotides. ADO, via A2A receptors (A2ARs, is a potent modulator of neuromuscular and immunological responses. The pivotal role of ecto-5′-nucleotidase/CD73, in controlling extracellular ADO formation, prompted us to investigate its role in a rat model of experimental autoimmune myasthenia gravis (EAMG. Results show that CD4+CD25+FoxP3+ regulatory T cells express lower amounts of ecto-5′-nucleotidase/CD73 as compared to controls. Reduction of endogenous ADO formation might explain why proliferation of CD4+ T cells failed upon blocking A2A receptors activation with ZM241385 or adenosine deaminase in EAMG animals. Deficits in ADO also contribute to neuromuscular transmission failure in EAMG rats. Rehabilitation of A2AR-mediated immune suppression and facilitation of transmitter release were observed by incubating the cells with the nucleoside precursor, AMP. These findings, together with the characteristic increase in serum adenosine deaminase activity of MG patients, strengthen our hypothesis that the adenosinergic pathway may be dysfunctional in EAMG. Given that endogenous ADO formation is balanced by ecto-5′-nucleotidase/CD73 activity and that A2ARs exert a dual role to restore use-dependent neurocompetence and immune suppression in myasthenics, we hypothesize that stimulation of the two mechanisms may have therapeutic potential in MG.

  20. Genetic background can result in a marked or minimal effect of gene knockout (GPR55 and CB2 receptor in experimental autoimmune encephalomyelitis models of multiple sclerosis.

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    Sofia Sisay

    Full Text Available Endocannabinoids and some phytocannabinoids bind to CB1 and CB2 cannabinoid receptors, transient receptor potential vanilloid one (TRPV1 receptor and the orphan G protein receptor fifty-five (GPR55. Studies using C57BL/10 and C57BL/6 (Cnr2 (tm1Zim CB2 cannabinoid receptor knockout mice have demonstrated an immune-augmenting effect in experimental autoimmune encephalomyelitis (EAE models of multiple sclerosis. However, other EAE studies in Biozzi ABH mice often failed to show any treatment effect of either CB2 receptor agonism or antagonism on inhibition of T cell autoimmunity. The influence of genetic background on the induction of EAE in endocannabinoid system-related gene knockout mice was examined. It was found that C57BL/6.GPR55 knockout mice developed less severe disease, notably in female mice, following active induction with myelin oligodendrocyte glycoprotein 35-55 peptide. In contrast C57BL/6.CB2 (Cnr2 (Dgen receptor knockout mice developed augmented severity of disease consistent with the genetically and pharmacologically-distinct, Cnr2 (tm1Zim mice. However, when the knockout gene was bred into the ABH mouse background and EAE induced with spinal cord autoantigens the immune-enhancing effect of CB2 receptor deletion was lost. Likewise CB1 receptor and transient receptor potential vanilloid one knockout mice on the ABH background demonstrated no alteration in immune-susceptibility, in terms of disease incidence and severity of EAE, in contrast to that reported in some C57BL/6 mouse studies. Furthermore the immune-modulating influence of GPR55 was marginal on the ABH mouse background. Whilst sedative doses of tetrahydrocannabinol could induce immunosuppression, this was associated with a CB1 receptor rather than a CB2 receptor-mediated effect. These data support the fact that non-psychoactive doses of medicinal cannabis have a marginal influence on the immune response in MS. Importantly, it adds a note of caution for the translational

  1. Prevention and reversal of experimental autoimmune thyroiditis (EAT) in mice by administration of anti-L3T4 monoclonal antibody at different stages of disease development.

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    Stull, S J; Kyriakos, M; Sharp, G C; Braley-Mullen, H

    1988-11-01

    Experimental autoimmune thyroiditis (EAT) can be induced in CBA/J mice following the transfer of spleen cells from mouse thyroglobulin (MTg)-sensitized donors that have been activated in vitro with MTg. Since L3T4+ T cells are required to transfer EAT in this model, the present study was undertaken to assess the effectiveness of the anti-L3T4 monoclonal antibody (mAb) GK1.5 in preventing or arresting the development of EAT. Spleen cells from mice given mAb GK1.5 prior to sensitization with MTg and adjuvant could not transfer EAT to normal recipients and cells from these mice did not proliferate in vitro to MTg. Donor mice given GK1.5 before immunization did not develop anti-MTg autoantibody and recipients of cells from such mice also produced little anti-MTg. GK1.5 could also prevent the proliferation and activation of sensitized effector cell precursors when added to in vitro cultures. When a single injection of mAb GK1.5 was given to recipients of in vitro-activated spleen cells, EAT was reduced whether the mAb was given prior to cell transfer or as late as 19 days after cell transfer. Whereas the incidence and severity of EAT was consistently reduced by injecting recipient mice with GK1.5, the same mice generally had no reduction in anti-MTg autoantibody. Since EAT is consistently induced in control recipients by 14-19 days after cell transfer, the ability of mAb GK1.5 to inhibit EAT when injected 14 or 19 days after cell transfer indicates that a single injection of the mAb GK1.5 can cause reversal of the histopathologic lesions of EAT in mice. These studies further establish the important role of L3T4+ T cells in the pathogenesis of EAT in mice and also suggest that therapy with an appropriate mAb may be an effective treatment for certain autoimmune diseases even when the therapy is initiated late in the course of the disease.

  2. Exacerbation of experimental autoimmune encephalomyelitis in prion protein (PrPc-null mice: evidence for a critical role of the central nervous system

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    Gourdain Pauline

    2012-01-01

    Full Text Available Abstract Background The cellular prion protein (PrPc is a host-encoded glycoprotein whose transconformation into PrP scrapie (PrPSc initiates prion diseases. The role of PrPc in health is still obscure, but many candidate functions have been attributed to the protein, both in the immune and the nervous systems. Recent data show that experimental autoimmune encephalomyelitis (EAE is worsened in mice lacking PrPc. Disease exacerbation has been attributed to T cells that would differentiate into more aggressive effectors when deprived of PrPc. However, alternative interpretations such as reduced resistance of neurons to autoimmune insult and exacerbated gliosis leading to neuronal deficits were not considered. Method To better discriminate the contribution of immune cells versus neural cells, reciprocal bone marrow chimeras with differential expression of PrPc in the lymphoid or in the central nervous system (CNS were generated. Mice were subsequently challenged with MOG35-55 peptide and clinical disease as well as histopathology were compared in both groups. Furthermore, to test directly the T cell hypothesis, we compared the encephalitogenicity of adoptively transferred PrPc-deficient versus PrPc-sufficient, anti-MOG T cells. Results First, EAE exacerbation in PrPc-deficient mice was confirmed. Irradiation exacerbated EAE in all the chimeras and controls, but disease was more severe in mice with a PrPc-deleted CNS and a normal immune system than in the reciprocal construction. Moreover, there was no indication that anti-MOG responses were different in PrPc-sufficient and PrPc-deficient mice. Paradoxically, PrPc-deficient anti-MOG 2D2 T cells were less pathogenic than PrPc-expressing 2D2 T cells. Conclusions In view of the present data, it can be concluded that the origin of EAE exacerbation in PrPc-ablated mice resides in the absence of the prion protein in the CNS. Furthermore, the absence of PrPc on both neural and immune cells does not

  3. Down-regulation of NTPDase2 and ADP-sensitive P2 Purinoceptors Correlate with Severity of Symptoms during Experimental Autoimmune Encephalomyelitis

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    Marija Jakovljevic

    2017-10-01

    Full Text Available The present study explores tissue and cellular distribution of ectonucleoside triphosphate diphosphohydrolase 2 (NTPDase2 and the gene and protein expression in rat spinal cord during the course of experimental autoimmune encephalomyelitis (EAE. Given that NTPDase2 hydrolyzes ATP with a transient accumulation of ADP, the expression of ADP-sensitive P2 purinoceptors was analyzed as well. The autoimmune disease was actively induced in Dark Agouti female rats and the changes were analyzed 10, 15 and 29 days after the induction. These selected time points correspond to the onset (Eo, peak (Ep and recovery (Er from EAE. In control animals, NTPDase2 was confined in the white matter, in most of the glial fibrillary acidic protein (GFAP-immunoreactive (ir astrocytes and in a considerable number of nestin-ir cells, while the other cell types were immunonegative. Immunoreactivity corresponding to NTPDase2 decreased significantly at Eo and Ep and then returned to the baseline levels at Er. The preservation of the proportion of GFAP single-labeled and GFAP/NTPDase2 double-labeled elements along the course of EAE indicated that changes in NTPDase2-ir occurred at fibrous astrocytes that typically express NTPDase2 in normal conditions. Significant downregulation of P2Y1 and P2Y12 receptor proteins at Eo and several-fold induction of P2Y12 and P2Y13 receptor proteins at Ep and/or Er were observed implying that the pathophysiological process in EAE may be linked to ADP signaling. Cell-surface expression of NTPDase2, NTPDase1/CD39 and ecto-5′-nucleotidase (eN/CD73 was analyzed in CD4+ T cells of a draining lymph node by fluorescence-activated cell sorting. The induction of EAE was associated with a transient decrease in a number of CD4+ NTPDase2+ T cells in a draining lymph node, whereas the recovery was characterized by an increase in NTPDase2+ cells in both CD4+ and CD4− cell populations. The opposite was found for NTPDase1/CD39+ and eN/CD73+ cells, which

  4. Experimental autoimmune encephalomyelitis: Association with mutual regulation of RelA (p65)/NF-κB and phospho-IκB in the CNS

    International Nuclear Information System (INIS)

    Hwang, Insun; Ha, Danbee; Ahn, Ginnae; Park, Eunjin; Joo, Haejin; Jee, Youngheun

    2011-01-01

    Highlights: → The phosphorylation of RelA's inhibitory factor IκB and subsequent RelA activation are important to the disease process of EAE. → The expression of RelA and phospho-IκB was markedly increased in the initiation and during the progression of EAE. → TPCK-treated EAE mice showed lower incidence of EAE with less severe symptoms and quicker recovery than vehicle-treated EAE mice. → TPCK significantly suppressed the MOG 35-55 -specific T cell proliferation by reducing the production of IFN-γ and IL-17 cytokines in EAE. → The NF-κB cascade's activity increased gradually with the development of symptoms and brain pathology of EAE. -- Abstract: Recently emerging evidence that the NF-κB family plays an important role in autoimmune disease has produced very broad and sometimes paradoxical conclusions. In the present study, we elucidated that the activation of RelA (p65) of NF-κB and IκB dissociation assumes a distinct role in experimental autoimmune encephalomyelitis (EAE) progression by altering IκB phosphorylation and/or degradation. In the present study of factors that govern EAE, the presence and immunoreactivity of nuclear RelA and phospho-IκB were recorded at the initiation and peak stage, and degradation of IκBα progressed rapidly at an early stage then stabilized during recovery. The immunoreactivity to RelA and phospho-IκB occurred mainly in inflammatory cells and microglial cells but only slightly in astrocytes. Subsequently, the blockade of IκB dissociation from NF-κB reduced the severity of disease by decreasing antigen-specific T cell response and production of IL-17 in EAE. Thus, blocking the dissociation of IκB from NF-κB can be utilized as a strategy to inhibit the NF-κB signal pathway thereby to reduce the initiation, progression, and severity of EAE.

  5. Active induction of experimental autoimmune encephalomyelitis by MOG35-55 peptide immunization is associated with differential responses in separate compartments of the choroid plexus

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    Murugesan Nivetha

    2012-08-01

    Full Text Available Abstract Background There is increasing awareness that, aside from producing cerebrospinal fluid, the choroid plexus (CP might be a key regulator of immune activity in the central nervous system (CNS during neuroinflammation. Specifically, the CP has recently been posited to control entry of sentinel T cells into the uninflamed CNS during the early stages of neuroinflammatory diseases, like multiple sclerosis (MS and its animal model experimental autoimmune encephalomyelitis (EAE. As the CP is compartmentalized into a stromal core containing fenestrated capillaries devoid of typical blood–brain barrier properties, surrounded by a tight junction-expressing choroidal epithelium, each of these compartments might mount unique responses that instigate the neuroinflammatory process. Methods To discern responses of the respective CP stromal capillary and choroidal epithelial tissues during evolving neuroinflammation, we investigated morphology and in situ expression of 93 immune-related genes during early stages of EAE induced by immunization with myelin oligodendrocyte glycoprotein peptide (MOG35-55. Specifically, 3-D immunofluorescent imaging was employed to gauge morphological changes, and laser capture microdissection was coupled to an Immune Panel TaqMan Low Density Array to detail alterations in gene expression patterns at these separate CP sites on days 9 and 15 post-immunization (p.i.. To resolve CP effects due to autoimmunity against MOG peptide, from those due to complete Freund’s adjuvant (CFA and pertussis toxin (PTX included in the immunization, analysis was performed on MOG-CFA/PTX-treated, CFA/PTX-treated, and naïve cohorts. Results The CP became swollen and displayed significant molecular changes in response to MOG-CFA/PTX immunization. Both stromal capillary and choroidal epithelial tissues mounted vigorous, yet different, changes in expression of numerous genes over the time course analyzed - including those encoding adhesion

  6. Rare Case of Vasculitis of the Hepatic Artery.

    Science.gov (United States)

    Mali, Padmavathi; Muduganti, Sudheer R; Goldberg, Jerry

    2015-12-01

    Vasculitis is an accumulation of inflammatory leucocytes in the blood vessels with reactive damage to mural structures. Isolated vasculitis of the gastrointestinal tract without systemic involvement is rare. We report a unique case of a female patient who presented with abdominal pain, and was found, on serology, to have elevated inflammatory markers without autoantibodies. A computed tomography scan of the abdomen and pelvis was suggestive of vasculitis of the hepatic artery. To the best of our knowledge, this is the first case, to date, of vasculitis of hepatic artery. © 2015 Marshfield Clinic.

  7. Endoscopic Findings of Upper Gastrointestinal Involvement in Primary Vasculitis.

    Science.gov (United States)

    Gong, Eun Jeong; Kim, Do Hoon; Chun, Joo Hyun; Ahn, Ji Yong; Choi, Kwi-Sook; Jung, Kee Wook; Lee, Jeong Hoon; Choi, Kee Don; Song, Ho June; Lee, Gin Hyug; Jung, Hwoon-Yong; Kim, Jin Ho; Song, In Hye; Kim, Yong-Gil

    2016-07-15

    Gastrointestinal involvement in vasculitis may result in life-threatening complications. However, its variable clinical presentations and endoscopic features, and the rarity of the disease, often result in delayed diagnosis. Clinical characteristics, endoscopic features, and histopathological findings were reviewed from medical records. Of 6,477 patients with vasculitis, 148 were diagnosed as primary vasculitis with upper gastrointestinal involvement. Of these, 21 cases (14.2%) were classified as large-vessel vasculitis, 17 cases (11.5%) as medium-vessel vasculitis, and 110 cases (74.3%) as small-vessel vasculitis. According to the specific diagnosis, IgA vasculitis (Henoch-Schönlein purpura) was the most common diagnosis (56.8%), followed by Takayasu arteritis (14.1%), microscopic polyangiitis (10.1%), and polyarteritis nodosa (6.8%). Gastrointestinal symptoms were present in 113 subjects (76.4%), with abdominal pain (78.8%) the most common symptom. Erosion and ulcers were striking endoscopic features, and the second portion of the duodenum was the most frequently involved site. Biopsy specimens were obtained from 124 patients, and only eight (5.4%) presented histopathological signs of vasculitis. Diagnosis of vasculitis involving the upper gastrointestinal tract is difficult. Because of the widespread use of endoscopy, combining clinical features with endoscopic findings may facilitate making appropriate diagnoses; however, the diagnostic yield of endoscopic biopsy is low.

  8. Autoimmune Pancreatitis.

    Science.gov (United States)

    Majumder, Shounak; Takahashi, Naoki; Chari, Suresh T

    2017-07-01

    Autoimmune pancreatitis (AIP) is a chronic fibroinflammatory disease of the pancreas that belongs to the spectrum of immunoglobulin G-subclass4-related diseases (IgG4-RD) and typically presents with obstructive jaundice. Idiopathic duct-centric pancreatitis (IDCP) is a closely related but distinct disease that mimics AIP radiologically but manifests clinically most commonly as recurrent acute pancreatitis in young individuals with concurrent inflammatory bowel disease. IgG4 levels are often elevated in AIP and normal in IDCP. Histologically, lymphoplasmacytic acinar inflammation and storiform fibrosis are seen in both. In addition, the histologic hallmark of IDCP is the granulocyte epithelial lesion: intraluminal and intraepithelial neutrophils in medium-sized and small ducts with or without granulocytic acinar inflammation often associated with destruction of ductal architecture. Initial treatment of both AIP and IDCP is with oral corticosteroids for duration of 4 weeks followed by a gradual taper. Relapses are common in AIP and relatively uncommon in IDCP, a relatively rare disease for which the natural history is not well understood. For patients with relapsing AIP, treatment with immunomodulators and more recently rituximab has been recommended. Although rare instances of pancreaticobiliary malignancy has been reported in patients with AIP, overall the lifetime risk of developing pancreatic cancer does not appear to be elevated.

  9. Selective enrichment of Th1 CD45RBlow CD4+ T cells in autoimmune infiltrates in experimental allergic encephalomyelitis

    DEFF Research Database (Denmark)

    Renno, T; Zeine, R; Girard, J M

    1994-01-01

    The cytokine effector status of CD4+ T cells from lymph nodes (LN) and the central nervous system (CNS) of SJL/J mice immunized with autoantigen in adjuvant for the induction of experimental allergic encephalomyelitis (EAE) was compared. CD4+ T cells were FACS sorted based on the levels...... in the sorted populations. CD45RBlow cells constituted a minority of CD4+ cells in the LN and expressed elevated levels of IL-2, IFN-gamma, and IL-4 mRNA, whereas the CD45RBlow CD4+ population did not express detectable message for these cytokines under linear PCR conditions. By contrast to the LN, CD4+ cells...... of expression of the activation marker CD45RB. Low levels of expression of this surface marker are induced by antigen recognition and are associated with 'effector' T cell function. Reverse transcriptase polymerase chain reaction (PCR) was used to analyze the expression of different T cell cytokine genes...

  10. Induction of endogenous Type I interferon within the central nervous system plays a protective role in experimental autoimmune encephalomyelitis

    DEFF Research Database (Denmark)

    Khorooshi, Reza; Mørch, Marlene Thorsen; Holm, Thomas Hellesøe

    2015-01-01

    show elevated levels of Type I IFNs in the central nervous system (CNS), suggesting a role for endogenous Type I IFN during inflammation. However, the therapeutic benefit of Type I IFN produced in the CNS remains to be established. The aim of this study was to examine whether experimentally induced CNS......-endogenous Type I IFN influences EAE. Using IFN-β reporter mice, we showed that direct administration of polyinosinic-polycytidylic acid (poly I:C), a potent inducer of IFN-β, into the cerebrospinal fluid induced increased leukocyte numbers and transient upregulation of IFN-β in CD45/CD11b-positive cells located...... in the meninges and choroid plexus, as well as enhanced IFN-β expression by parenchymal microglial cells. Intrathecal injection of poly I:C to mice showing first symptoms of EAE substantially increased the normal disease-associated expression of IFN-α, IFN-β, interferon regulatory factor-7 and IL-10 in CNS...

  11. Proapoptotic Bak and Bax guard against fatal systemic and organ-specific autoimmune disease

    Science.gov (United States)

    Mason, Kylie D.; Lin, Ann; Robb, Lorraine; Josefsson, Emma C.; Henley, Katya J.; Gray, Daniel H. D.; Kile, Benjamin T.; Roberts, Andrew W.; Strasser, Andreas; Huang, David C. S.; Waring, Paul; O’Reilly, Lorraine A.

    2013-01-01

    Dysregulation of the “intrinsic” apoptotic pathway is associated with the development of cancer and autoimmune disease. Bak and Bax are two proapoptotic members of the Bcl-2 protein family with overlapping, essential roles in the intrinsic apoptotic pathway. Their activity is critical for the control of cell survival during lymphocyte development and homeostasis, best demonstrated by defects in thymic T-cell differentiation and peripheral lymphoid homeostasis caused by their combined loss. Because most bak−/−bax−/− mice die perinatally, the roles of Bax and Bak in immunological tolerance and prevention of autoimmune disease remain unclear. We show that mice reconstituted with a Bak/Bax doubly deficient hematopoietic compartment develop a fatal systemic lupus erythematosus-like autoimmune disease characterized by hypergammaglobulinemia, autoantibodies, lymphadenopathy, glomerulonephritis, and vasculitis. Importantly, these mice also develop a multiorgan autoimmune disease with autoantibodies against most solid glandular structures and evidence of glandular atrophy and necrotizing vasculitis. Interestingly, similar albeit less severe pathology was observed in mice containing a hematopoietic compartment deficient for only Bak, a phenotype reminiscent of the disease seen in patients with point mutations in BAK. These studies demonstrate a critical role for Bak and an ancillary role for Bax in safeguarding immunological tolerance and prevention of autoimmune disease. This suggests that direct activators of the intrinsic apoptotic pathway, such as BH3 mimetics, may be useful for treatment of diverse autoimmune diseases. PMID:23349374

  12. Isolated pulmonary vasculitis: case report and literature review.

    Science.gov (United States)

    Riancho-Zarrabeitia, Leyre; Zurbano, Felipe; Gómez-Román, Javier; Martínez-Meñaca, Amaya; López, Marta; Hernández, Miguel A; Pina, Trinitario; González-Gay, Miguel A

    2015-04-01

    Single-organ vasculitis has been reported to affect the skin, kidneys, central nervous system, peripheral nerves, genitourinary tract, calf muscles, aorta, coronary arteries, retina, or gastrointestinal tract. However, isolated pulmonary vasculitis is a very rare entity. Our aims were to describe a case of localized pulmonary vasculitis affecting medium-sized vessels and review the literature. A patient with localized pulmonary vasculitis affecting medium-sized vessels that presented as pulmonary arterial hypertension is described. A MEDLINE database search of cases with localized pulmonary vasculitis was also conducted. A 30-year-old man presented with pulmonary hypertension due to isolated pulmonary medium-sized vessel vasculitis that was confirmed histologically. Initially he responded to corticosteroids and vasodilator treatment, but therapy eventually lost efficacy. Treatment with rituximab was not effective, and as the clinical situation worsened, lung transplant was performed. Isolated large pulmonary vessel disease, often related to Takayasu disease or giant cell arteritis, may present as pulmonary artery hypertension, thus mimicking chronic thromboembolic disease. Medium- and small-vessel pulmonary vasculitis usually develops in the context of a systemic disease. Some cases of isolated small-vessel vasculitis have been reported presenting as diffuse alveolar hemorrhage. In contrast, our case developed pulmonary artery hypertension secondary to medium-sized vessels vasculitis. To our knowledge, this is the first case of lung transplantation in isolated pulmonary vasculitis. Pulmonary isolated vasculitis is a rare cause of pulmonary hypertension but it must be taken into consideration after more common disorders are excluded. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. Autoimmunity and Gastric Cancer

    Science.gov (United States)

    Bizzaro, Nicola; Antico, Antonio; Villalta, Danilo

    2018-01-01

    Alterations in the immune response of patients with autoimmune diseases may predispose to malignancies, and a link between chronic autoimmune gastritis and gastric cancer has been reported in many studies. Intestinal metaplasia with dysplasia of the gastric corpus-fundus mucosa and hyperplasia of chromaffin cells, which are typical features of late-stage autoimmune gastritis, are considered precursor lesions. Autoimmune gastritis has been associated with the development of two types of gastric neoplasms: intestinal type and type I gastric carcinoid. Here, we review the association of autoimmune gastritis with gastric cancer and other autoimmune features present in gastric neoplasms. PMID:29373557

  14. Free radical theory of autoimmunity

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    Kannan Subburaj

    2006-06-01

    Full Text Available Abstract Background Despite great advances in clinical oncology, the molecular mechanisms underlying the failure of chemotherapeutic intervention in treating lymphoproliferative and related disorders are not well understood. Hypothesis A hypothetical scheme to explain the damage induced by chemotherapy and associated chronic oxidative stress is proposed on the basis of published literature, experimental data and anecdotal observations. Brief accounts of multidrug resistance, lymphoid malignancy, the cellular and molecular basis of autoimmunity and chronic oxidative stress are assembled to form a basis for the hypothesis and to indicate the likelihood that it is valid in vivo. Conclusion The argument set forward in this article suggests a possible mechanism for the development of autoimmunity. According to this view, the various sorts of damage induced by chemotherapy have a role in the pattern of drug resistance, which is associated with the initiation of autoimmunity.

  15. Características generales de 29 pacientes con vasculitis de pequeños vasos General characteristics of 29 patients with small vessel vasculitis

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    Nicolás Di Benedetto

    2010-04-01

    Full Text Available El objetivo de esta serie fue describir las características generales y manifestaciones clínicas de pacientes con vasculitis de pequeños vasos que concurrieron al servicio de autoinmunidad de un hospital de la comunidad y compararlas con la literatura. Se revisaron de manera retrospectiva las historias clínicas archivadas bajo el rótulo de vasculitis en un período de 16 años. Se seleccionaron aquellos pacientes que cumplieran criterios diagnósticos de vasculitis de pequeños vasos. Se extrajeron los datos de interés y se constató la supervivencia mediante contacto telefónico. Posteriormente se realizó una búsqueda bibliográfica y se compararon los resultados. Se incluyeron 13 pacientes con granulomatosis de Wegener, 6 con síndrome de Churg Strauss y 10 con poliangeítis microscópica. El 55% (16 fueron menores de 55 años al diagnóstico y hubo predominio del sexo femenino (2.6:1. La demora diagnóstica fue mayor a un año en el 46% de los casos. Los sistemas más frecuentemente afectados fueron respiratorio y otorrinolaringológico. El 79% presentó anticuerpos anti-citoplasma de neutrófilos (ANCA positivos. La mortalidad fue del 24% (7/29. Al comparar las características de los pacientes incluidos en esta serie con lo descripto en la literatura, se hallaron diferencias en cuanto a la forma de presentación, sistemas comprometidos y porcentaje de pacientes ANCA positivos; además se observó que el resultado negativo de este marcador parece asociarse con mayor demora diagnóstica y en consecuencia peor pronóstico, lo que remarca su importancia como herramienta adicional no invasiva al momento del diagnóstico.The objective of this series was to describe the general characteristics and clinical manifestations of patients with small vessel vasculitis who were assisted in the autoimmunity department of a community public hospital and to compare the results with the literature. Clinical records under the label of vasculitis in a

  16. Systemic Vasculitis During the Course of Systemic Sclerosis

    Science.gov (United States)

    Quéméneur, Thomas; Mouthon, Luc; Cacoub, Patrice; Meyer, Olivier; Michon-Pasturel, Ulrique; Vanhille, Philippe; Hatron, Pierre-Yves; Guillevin, Loïc; Hachulla, Eric

    2013-01-01

    Abstract Although the presence of antineutrophil cytoplasmic antibodies (ANCA) has been reported in patients with systemic sclerosis (SSc), the association of SSc and systemic vasculitis has rarely been described. We obtained information on cases of systemic vasculitis associated with SSc in France from the French Vasculitis Study Group and all members of the French Research Group on Systemic Sclerosis. We identified 12 patients with systemic vasculitis associated with SSc: 9 with ANCA-associated systemic vasculitis (AASV) and 3 with mixed cryoglobulinemia vasculitis (MCV). In all AASV patients, SSc was of the limited type. The main complication of SSc was pulmonary fibrosis. Only 2 patients underwent a D-penicillamine regimen before the occurrence of AASV. The characteristics of AASV were microscopic polyangiitis (n = 7) and renal limited vasculitis (n = 2). Anti-myeloperoxidase antibodies were found in 8 of the 9 patients. The Five Factor Score was above 1 in 3 of the 9 patients. Of the 3 patients with MCV, Sjögren syndrome was confirmed in 2. We compared our findings with the results of a literature review (42 previously reported cases of AASV with SSc). Although rare, vasculitis is a complication of SSc. AASV is the most frequent type, and its diagnosis can be challenging when the kidney is injured. Better awareness of this rare association could facilitate earlier diagnosis and appropriate management to reduce damage. PMID:23263715

  17. Cerebral vasculitis and its simulators. Diagnostic and interventional radiology

    International Nuclear Information System (INIS)

    Ishimaru, Hideki; Nakajima, Kazuaki; Matsuoka, Yohjiro; Sakamoto, Ayami; Sakugawa, Takayuki; Morikawa, Minoru; Inuzuka, Michiko; Kimura, Seigo

    2009-01-01

    Cerebral vasculitis, although rare in general, is an important cause of cerebral ischemia, because the treatment strategy is different from that of usual cerebral infarction. On the other hand, a variety of common and uncommon nonvasculitic disorders may mimic vasculitis angiographically or clinically. It is also important to distinguish these vasculitis simulators from true vasculitis in order to avoid the unnecessary and harmful side effects of corticosteroid and immunosuppressant, the mainstay of drug therapy for vasculitis. The diagnosis is often difficult. Angiography is expected to demonstrate the underlying vascular pathology; however, many vasculitides affect small arteries beyond the spatial resolution of conventional angiography. The most important role of the diagnostic imaging is the identification of brain lesions consistent with cerebral vasculitis. Multiple lesions in more than one vascular territory should raise this suspicion, although no specific pattern for this entity exists. In large and medium-sized vessel vasculitis, MRI can directly demonstrate mural thickening and enhancement, which is considered to specific for active inflammation. We propose here a classification for cerebral vasculitis and simulators according to the size of the affected brain vessels, which would help us to make a differential diagnosis. We also review the endovascular techniques for this entity, and its indications. (author)

  18. A GPBAR1 (TGR5 small molecule agonist shows specific inhibitory effects on myeloid cell activation in vitro and reduces experimental autoimmune encephalitis (EAE in vivo.

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    Nuruddeen D Lewis

    Full Text Available GPBAR1 is a G protein-coupled receptor that is activated by certain bile acids and plays an important role in the regulation of bile acid synthesis, lipid metabolism, and energy homeostasis. Recent evidence suggests that GPBAR1 may also have important effects in reducing the inflammatory response through its expression on monocytes and macrophages. To further understand the role of GPBAR1 in inflammation, we generated a novel, selective, proprietary GPBAR1 agonist and tested its effectiveness at reducing monocyte and macrophage activation in vitro and in vivo. We have used this agonist, together with previously described agonists to study agonism of GPBAR1, and shown that they can all induce cAMP and reduce TLR activation-induced cytokine production in human monocytes and monocyte-derived macrophages in vitro. Additionally, through the usage of RNA sequencing (RNA-Seq, we identified a select set of genes that are regulated by GPBAR1 agonism during LPS activation. To further define the in vivo role of GPBAR1 in inflammation, we assessed GPBAR1 expression and found high levels on circulating mouse monocytes. Agonism of GPBAR1 reduced LPS-induced cytokine production in mouse monocytes ex vivo and serum cytokine levels in vivo. Agonism of GPBAR1 also had profound effects in the experimental autoimmune encephalomyelitis (EAE mouse model of multiple sclerosis, where monocytes play an important role. Mice treated with the GPBAR1 agonist exhibited a significant reduction in the EAE clinical score which correlated with reduced monocyte and microglial activation and reduced trafficking of monocytes and T cells into the CNS. These data confirm the importance of GPBAR1 in controlling monocyte and macrophage activation in vivo and support the rationale for selective agonists of GPBAR1 in the treatment of inflammatory diseases.

  19. Nitric oxide synthase 2 is required for conversion of pro-fibrogenic inflammatory CD133(+) progenitors into F4/80(+) macrophages in experimental autoimmune myocarditis.

    Science.gov (United States)

    Blyszczuk, Przemyslaw; Berthonneche, Corrine; Behnke, Silvia; Glönkler, Marcel; Moch, Holger; Pedrazzini, Thierry; Lüscher, Thomas F; Eriksson, Urs; Kania, Gabriela

    2013-02-01

    Experimental autoimmune myocarditis (EAM) model mirrors important mechanisms of inflammatory dilated cardiomyopathy (iDCM). In EAM, inflammatory CD133(+) progenitors are a major cellular source of cardiac myofibroblasts in the post-inflammatory myocardium. We hypothesized that exogenous delivery of macrophage-colony-stimulating factor (M-CSF) can stimulate macrophage lineage differentiation of inflammatory progenitors and, therefore, prevent their naturally occurring myofibroblast fate in EAM. EAM was induced in wild-type (BALB/c) and nitric oxide synthase 2-deficient (Nos2(-/-)) mice and CD133(+) progenitors were isolated from inflamed hearts. In vitro, M-CSF converted inflammatory CD133(+) progenitors into nitric oxide-producing F4/80(+) macrophages and prevented transforming growth factor-β-mediated myofibroblast differentiation. Importantly, only a subset of heart-infiltrating CD133(+) progenitors expresses macrophage-specific antigen F4/80 in EAM. These CD133(+)/F4/80(hi) cells show impaired myofibrogenic potential compared with CD133(+)/F4/80(-) cells. M-CSF treatment of wild-type mice with EAM at the peak of disease markedly increased CD133(+)/F4/80(hi) cells in the myocardium, and CD133(+) progenitors isolated from M-CSF-treated mice failed to differentiate into myofibroblasts. In contrast, M-CSF was not effective in converting CD133(+) progenitors from inflamed hearts of Nos2(-/-) mice into macrophages, and M-CSF treatment did not result in increased CD133(+)/F4/80(hi) cell population in hearts of Nos2(-/-) mice. Accordingly, M-CSF prevented post-inflammatory fibrosis and left ventricular dysfunction in wild-type but not in Nos2(-/-) mice. Active and NOS2-dependent induction of macrophage lineage differentiation abrogates the myofibrogenic potential of heart-infiltrating CD133(+) progenitors. Modulating the in vivo differentiation fate of specific progenitors might become a novel approach for the treatment of inflammatory heart diseases.

  20. A Cyclic Altered Peptide Analogue Based on Myelin Basic Protein 87-99 Provides Lasting Prophylactic and Therapeutic Protection Against Acute Experimental Autoimmune Encephalomyelitis.

    Science.gov (United States)

    Emmanouil, Mary; Tseveleki, Vivian; Triantafyllakou, Iro; Nteli, Agathi; Tselios, Theodore; Probert, Lesley

    2018-01-31

    In this report, amide-linked cyclic peptide analogues of the 87-99 myelin basic protein (MBP) epitope, a candidate autoantigen in multiple sclerosis (MS), are tested for therapeutic efficacy in experimental autoimmune encephalomyelitis (EAE). Cyclic altered peptide analogues of MBP 87-99 with substitutions at positions 91 and/or 96 were tested for protective effects when administered using prophylactic or early therapeutic protocols in MBP 72-85 -induced EAE in Lewis rats. The Lys 91 and Pro 96 of MBP 87-99 are crucial T-cell receptor (TCR) anchors and participate in the formation of trimolecular complex between the TCR-antigen (peptide)-MHC (major histocompability complex) for the stimulation of encephalitogenic T cells that are necessary for EAE induction and are implicated in MS. The cyclic peptides were synthesized using Solid Phase Peptide Synthesis (SPPS) applied on the 9-fluorenylmethyloxycarboxyl/tert-butyl Fmoc/tBu methodology and combined with the 2-chlorotrityl chloride resin (CLTR-Cl). Cyclo(91-99)[Ala 96 ]MBP 87-99 , cyclo(87-99)[Ala 91,96 ]MBP 87-99 and cyclo(87-99)[Arg 91 , Ala 96 ]MBP 87-99 , but not wild-type linear MBP 87-99 , strongly inhibited MBP 72-85 -induced EAE in Lewis rats when administered using prophylactic and early therapeutic vaccination protocols. In particular, cyclo(87-99)[Arg 91 , Ala 96 ]MBP 87-99 was highly effective in preventing the onset and development of clinical symptoms and spinal cord pathology and providing lasting protection against EAE induction.

  1. Therapy with granulocyte colony-stimulating factor in the chronic stage, but not in the acute stage, improves experimental autoimmune myocarditis in rats via nitric oxide.

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    Shimada, Kana; Okabe, Taka-aki; Mikami, Yu; Hattori, Miki; Fujita, Masatoshi; Kishimoto, Chiharu

    2010-09-01

    We systematically investigated serial efficacy of granulocyte colony-stimulating factor (G-CSF) therapy upon experimental autoimmune myocarditis (EAM) in rats treated with and without the inhibition of nitric oxide (NO) with the analyses of tissue regeneration. G-CSF could mobilize multipotent progenitor cells of bone marrow into the peripheral blood and may improve ventricular function. A rat model of porcine myosin-induced EAM was used. After the immunization of myosin, G-CSF (10 microg/kg/day) or saline was injected intraperitoneally on days 0-21 in experiment 1 and on days 21-42 in experiment 2. Additional myosin-immunized rats were orally given 25 mg/kg/day of N(G)-nitro-L-arginine methylester (L-NAME), an inhibitor of nitric oxide synthase (NOS), in each experiment (each group; n=8-21). Serum cytokines and peripheral blood cell counts were measured in each group. In experiment 1, G-CSF treatment aggravated cardiac pathology associated with increased macrophage inflammatory protein-2 (MIP-2) and interleukin-6 (IL-6) levels and enhanced superoxide production. In experiment 2, G-CSF treatment reduced the severity of myocarditis with increased capillary density and improved left ventricular ejection fraction. In the rats with EAM treated with G-CSF associated with oral L-NAME treatment in experiment 2, the severity of myocarditis was not reduced. Myocardial c-kit(+) cells were demonstrated only in G-CSF-treated group in experiment 2 but not in other groups. G-CSF has differential effects on EAM in rats associated with the modulation of cytokine network. The overwhelming superoxide production by G-CSF administration in the acute stage may worsen the disease. G-CSF therapy improved cardiac function via NO system in a rat model of myocarditis in the chronic stage, but not in the acute stage, possibly through the myocardial regeneration and acceleration of healing process. Copyright 2010 Elsevier Ltd. All rights reserved.

  2. Evaluation of a radiolabelled peripheral benzodiazepine receptor ligand in the central nervous system inflammation of experimental autoimmune encephalomyelitis: a possible probe for imaging multiple sclerosis

    International Nuclear Information System (INIS)

    Mattner, F.; Katsifis, A.; Ballantyne, P.; Staykova, M.; Willenborg, D.O.

    2005-01-01

    Peripheral benzodiazepine receptors (PBRs) are upregulated on macrophages and activated microglia, and radioligands for the PBRs can be used to detect in vivo neuroinflammatory changes in a variety of neurological insults, including multiple sclerosis. Substituted 2-phenyl imidazopyridine-3-acetamides with high affinity and selectivity for PBRs have been prepared that are suitable for radiolabelling with a number of positron emission tomography and single-photon emission computed tomography (SPECT) isotopes. In this investigation, the newly developed high-affinity PBR ligand 6-chloro-2-(4'-iodophenyl)-3-(N,N-diethyl)imidazo [1,2-a]pyridine-3-acetamide, or CLINDE, was radiolabelled with 123 I and its biodistribution in the central nervous system (CNS) of rats with experimental autoimmune encephalomyelitis (EAE) evaluated. EAE was induced in male Lewis rats by injection of an emulsion of myelin basic protein and incomplete Freund's adjuvant containing Mycobacterium butyricum. Biodistribution studies with 123 I-CLINDE were undertaken on EAE rats exhibiting different clinical disease severity and compared with results in controls. Disease severity was confirmed by histopathology in the spinal cord of rats. The relationship between inflammatory lesions and PBR ligand binding was investigated using ex vivo autoradiography and immunohistochemistry on rats with various clinical scores. 123 I-CLINDE uptake was enhanced in the CNS of all rats exhibiting EAE when compared to controls. Binding reflected the ascending nature of EAE inflammation, with lumbar/sacral cord > thoracic cord > cervical cord > medulla. The amount of ligand binding also reflected the clinical severity of disease. Ex vivo autoradiography and immunohistochemistry revealed a good spatial correspondence between radioligand signal and foci of inflammation and in particular ED-1 + cells representing macrophages and microglia. These results demonstrate the ability of 123 I-CLINDE to measure in vivo

  3. Total glucosides of paeony suppresses experimental autoimmune uveitis in association with inhibition of Th1 and Th2 cell function in mice.

    Science.gov (United States)

    Huang, Xue-Tao; Wang, Bin; Zhang, Wen-Hua; Peng, Man-Qiang; Lin, Ding

    2018-01-01

    Total glucosides of paeony (TGP) are active components extracted from the roots of Paeonia lactiflora Pall. In this study, we investigated the role and mechanisms of TGP in experimental autoimmune uveitis (EAU) model of mice. The C57BL/6 mice were randomly divided into three groups: sham group, EAU-control group, and EAU-TGP group. Clinical score of images of the eye fundus were taken on 7, 14, 21, and 28 days after induction of EAU. The concentrations of proinflammatory cytokines in intraocular fluid were measured at 14 days after EAU induction with the use of a multiplex assay system. Flow cytometry was used to analyze the frequency of CD4+, CD8+, interferon-gamma (IFN-γ), and CD4+/CD8+ ratio in spleen and lymph nodes. Western blotting was used to measure expressions of mitogen-activated protein kinase (MAPK) pathway-related proteins in retina. Clinical scores for uveitis were lower in TGP-treated EAU mice than those without TGP treatment. Importantly, the concentrations of cytokines induced by T-helper 1 (Th1) and T-helper 2 (Th2) cells in intraocular fluid were reduced in EAU mice treated with TGP. Furthermore, the frequency of CD4+, IFN-γ, and CD4+/CD8+ ratio was decreased and the frequency of CD8+ was increased in spleen and lymph nodes of mice treated with TGP. The anti-inflammatory effects of TGP were mediated by inhibiting the MAPK signaling pathways. Our results showed that TGP suppressed uveitis in mice via the inhibition of Th1 and Th2 cell function. Thus, TGP may be a promising therapeutic strategy for uveitis, as well as other ocular inflammatory diseases.

  4. Intestinal barrier dysfunction develops at the onset of experimental autoimmune encephalomyelitis, and can be induced by adoptive transfer of auto-reactive T cells.

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    Mehrnaz Nouri

    Full Text Available Multiple sclerosis (MS is a chronic inflammatory demyelinating disease of the central nervous system with a pathogenesis involving a dysfunctional blood-brain barrier and myelin-specific, autoreactive T cells. Although the commensal microbiota seems to affect its pathogenesis, regulation of the interactions between luminal antigens and mucosal immune elements remains unclear. Herein, we investigated whether the intestinal mucosal barrier is also targeted in this disease. Experimental autoimmune encephalomyelitis (EAE, the prototypic animal model of MS, was induced either by active immunization or by adoptive transfer of autoreactive T cells isolated from these mice. We show increased intestinal permeability, overexpression of the tight junction protein zonulin and alterations in intestinal morphology (increased crypt depth and thickness of the submucosa and muscularis layers. These intestinal manifestations were seen at 7 days (i.e., preceding the onset of neurological symptoms and at 14 days (i.e., at the stage of paralysis after immunization. We also demonstrate an increased infiltration of proinflammatory Th1/Th17 cells and a reduced regulatory T cell number in the gut lamina propria, Peyer's patches and mesenteric lymph nodes. Adoptive transfer to healthy mice of encephalitogenic T cells, isolated from EAE-diseased animals, led to intestinal changes similar to those resulting from the immunization procedure. Our findings show that disruption of intestinal homeostasis is an early and immune-mediated event in EAE. We propose that this intestinal dysfunction may act to support disease progression, and thus represent a potential therapeutic target in MS. In particular, an increased understanding of the regulation of tight junctions at the blood-brain barrier and in the intestinal wall may be crucial for design of future innovative therapies.

  5. Loss of the receptor tyrosine kinase Axl leads to enhanced inflammation in the CNS and delayed removal of myelin debris during Experimental Autoimmune Encephalomyelitis

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    Prieto Anne L

    2011-05-01

    Full Text Available Abstract Background Axl, together with Tyro3 and Mer, constitute the TAM family of receptor tyrosine kinases. In the nervous system, Axl and its ligand Growth-arrest-specific protein 6 (Gas6 are expressed on multiple cell types. Axl functions in dampening the immune response, regulating cytokine secretion, clearing apoptotic cells and debris, and maintaining cell survival. Axl is upregulated in various disease states, such as in the cuprizone toxicity-induced model of demyelination and in multiple sclerosis (MS lesions, suggesting that it plays a role in disease pathogenesis. To test for this, we studied the susceptibility of Axl-/- mice to experimental autoimmune encephalomyelitis (EAE, an animal model for multiple sclerosis. Methods WT and Axl-/- mice were immunized with myelin oligodendrocyte glycoprotein (MOG35-55 peptide emulsified in complete Freund's adjuvant and injected with pertussis toxin on day 0 and day 2. Mice were monitored daily for clinical signs of disease and analyzed for pathology during the acute phase of disease. Immunological responses were monitored by flow cytometry, cytokine analysis and proliferation assays. Results Axl-/- mice had a significantly more severe acute phase of EAE than WT mice. Axl-/- mice had more spinal cord lesions with larger inflammatory cuffs, more demyelination, and more axonal damage than WT mice during EAE. Strikingly, lesions in Axl-/- mice had more intense Oil-Red-O staining indicative of inefficient clearance of myelin debris. Fewer activated microglia/macrophages (Iba1+ were found in and/or surrounding lesions in Axl-/- mice relative to WT mice. In contrast, no significant differences were noted in immune cell responses between naïve and sensitized animals. Conclusions These data show that Axl alleviates EAE disease progression and suggests that in EAE Axl functions in the recruitment of microglia/macrophages and in the clearance of debris following demyelination. In addition, these data

  6. ASP4058, a novel agonist for sphingosine 1-phosphate receptors 1 and 5, ameliorates rodent experimental autoimmune encephalomyelitis with a favorable safety profile.

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    Rie Yamamoto

    Full Text Available Sphingosine-1-phosphate (S1P is a biologically active sphingolipid that acts through the members of a family of five G protein-coupled receptors (S1P1-S1P5. S1P1 is a major regulator of lymphocyte trafficking, and fingolimod, whose active metabolite fingolimod phosphate acts as a nonselective S1P receptor agonist, exerts its immunomodulatory effect, at least in part, by regulating the lymphocyte trafficking by inducing down regulation of lymphocyte S1P1. Here, we detail the pharmacological profile of 5-{5-[3-(trifluoromethyl-4-{[(2S-1,1,1-trifluoropropan-2-yl]oxy}phenyl]-1,2,4-oxadiazol-3-yl}-1H-benzimidazole (ASP4058, a novel next-generation S1P receptor agonist selective for S1P1 and S1P5. ASP4058 preferentially activates S1P1 and S1P5 compared with S1P2, 3, 4 in GTPγS binding assays in vitro. Oral administration of ASP4058 reduced the number of peripheral lymphocytes and inhibited the development of experimental autoimmune encephalomyelitis (EAE in Lewis rats. Further, ASP4058 prevented relapse of disease in a mouse model of relapsing-remitting EAE. Although these immunomodulatory effects were comparable to those of fingolimod, ASP4058 showed a wider safety margin than fingolimod for bradycardia and bronchoconstriction in rodents. These observations suggest that ASP4058 represents a new therapeutic option for treating multiple sclerosis that is safer than nonselective S1P receptor agonists such as fingolimod.

  7. Astrocyte matricellular proteins that control excitatory synaptogenesis are regulated by inflammatory cytokines and correlate with paralysis severity during experimental autoimmune encephalomyelitis

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    Pennelope K. Blakely

    2015-10-01

    Full Text Available The matricellular proteins, secreted protein acidic and rich in cysteine (SPARC and SPARC-like 1 (SPARCL1, are produced by astrocytes and control excitatory synaptogenesis in the central nervous system. While SPARCL1 directly promotes excitatory synapse formation in vitro and in the developing nervous system in vivo, SPARC specifically antagonizes the synaptogenic actions of SPARCL1. We hypothesized these proteins also help maintain existing excitatory synapses in adult hosts, and that local inflammation in the spinal cord alters their production in a way that dynamically modulates motor synapses and impacts the severity of paralysis during experimental autoimmune encephalomyelitis (EAE in mice. Using a spontaneously remitting EAE model, paralysis severity correlated inversely with both expression of synaptic proteins and the number of synapses in direct contact with the perikarya of motor neurons in spinal grey matter. In both remitting and non-remitting EAE models, paralysis severity also correlated inversely with sparcl1:sparc transcript and SPARCL1:SPARC protein ratios directly in lumbar spinal cord tissue. In vitro, astrocyte production of both SPARCL1 and SPARC was regulated by T cell-derived cytokines, causing dynamic modulation of the SPARCL1:SPARC expression ratio. Taken together, these data support a model whereby proinflammatory cytokines inhibit SPARCL1 and/or augment SPARC expression by astrocytes in spinal grey matter that, in turn, cause either transient or sustained synaptic retraction from lumbar spinal motor neurons thereby regulating hind limb paralysis during EAE. Ongoing studies seek ways to alter this SPARCL1:SPARC expression ratio in favor of synapse reformation/maintenance and thus help to modulate neurologic deficits during times of inflammation. This could identify new astrocyte-targeted therapies for diseases such as multiple sclerosis.

  8. Microsomal Prostaglandin E Synthase-1 Facilitates an Intercellular Interaction between CD4⁺ T Cells through IL-1β Autocrine Function in Experimental Autoimmune Encephalomyelitis.

    Science.gov (United States)

    Takemiya, Takako; Takeuchi, Chisen; Kawakami, Marumi

    2017-12-19

    Microsomal prostaglandin synthetase-1 (mPGES-1) is an inducible terminal enzyme that produces prostaglandin E₂ (PGE₂). In our previous study, we investigated the role of mPGES-1 in the inflammation and demyelination observed in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis, using mPGES - 1 -deficient ( mPGES-1 -/- ) and wild-type (wt) mice. We found that mPGES-1 facilitated inflammation, demyelination, and paralysis and was induced in vascular endothelial cells and macrophages and microglia around inflammatory foci. Here, we investigated the role of interleukin-1β (IL-1β) in the intercellular mechanism stimulated by mPGES-1 in EAE spinal cords in the presence of inflammation. We found that the area invaded by CD4-positive (CD4⁺) T cells was extensive, and that PGE₂ receptors EP1-4 were more induced in activated CD4⁺ T cells of wt mice than in those of mPGES - 1 -/- mice. Moreover, IL-1β and IL-1 receptor 1 (IL-1r1) were produced by 65% and 48% of CD4⁺ T cells in wt mice and by 44% and 27% of CD4⁺ T cells in mPGES-1 -/- mice. Furthermore, interleukin-17 (IL-17) was released from the activated CD4⁺ T cells. Therefore, mPGES-1 stimulates an intercellular interaction between CD4⁺ T cells by upregulating the autocrine function of IL-1β in activated CD4⁺ T cells, which release IL-17 to facilitate axonal and myelin damage in EAE mice.

  9. The interaction of dendritic cells and γδ T cells promotes the activation of γδ T cells in experimental autoimmune uveitis

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    Beibei Wang

    2017-03-01

    Full Text Available Uveitis is a severe inflammatory disease that can cause visual impairment. Recently, activated γδ T cells were proved to play a central role in the development of experimental autoimmune uveitis (EAU. However, the mechanism underlying γδ T-cell activation in EAU is incompletely known. In this study, we determined the percentage changes in and the phenotypes of γδ T cells and dendritic cells (DCs obtained from the spleens of immunized C57BL/6 (B6 mice, an animal model of EAU. We found that the number of γδ T cells and DCs obviously increased during the inflammation phase of EAU (days 16–20 of our experiment, and that during this time, γδ T cells expressed high levels of CD69 and the integrin lymphocyte function–associated antigen-1 (LFA-1 and secreted high levels of interleukin (IL-17A. Moreover, DCs obtained during this phase expressed high levels of CD80, CD83, CD86, and intracellular cell adhesion molecule-1 (ICAM-1. Furthermore, we studied the interaction between DCs and γδ T cells by using flow cytometry and confocal microscopy in order to determine whether DCs affected γδ T-cell activation in vitro. Co-cultures of the two types of cells showed that DCs induced high levels of CD69, LFA-1, and IL-17A in γδ T cells. Imaging studies revealed contact between the DCs and γδ T cells. This interaction was mediated by the accumulation of ICAM-1 and LFA-1 at the interface of DCs-γδ T cells. Thus, the activation of γδ T cells in EAU was promoted by DCs interacting with γδ T cells.

  10. In Vivo Quantification of Inflammation in Experimental Autoimmune Encephalomyelitis Rats Using Fluorine-19 Magnetic Resonance Imaging Reveals Immune Cell Recruitment outside the Nervous System.

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    Jia Zhong

    Full Text Available Progress in identifying new therapies for multiple sclerosis (MS can be accelerated by using imaging biomarkers of disease progression or abatement in model systems. In this study, we evaluate the ability to noninvasively image and quantitate disease pathology using emerging "hot-spot" 19F MRI methods in an experimental autoimmune encephalomyelitis (EAE rat, a model of MS. Rats with clinical symptoms of EAE were compared to control rats without EAE, as well as to EAE rats that received daily prophylactic treatments with cyclophosphamide. Perfluorocarbon (PFC nanoemulsion was injected intravenously, which labels predominately monocytes and macrophages in situ. Analysis of the spin-density weighted 19F MRI data enabled quantification of the apparent macrophage burden in the central nervous system and other tissues. The in vivo MRI results were confirmed by extremely high-resolution 19F/1H magnetic resonance microscopy in excised tissue samples and histopathologic analyses. Additionally, 19F nuclear magnetic resonance spectroscopy of intact tissue samples was used to assay the PFC biodistribution in EAE and control rats. In vivo hot-spot 19F signals were detected predominantly in the EAE spinal cord, consistent with the presence of inflammatory infiltrates. Surprising, prominent 19F hot-spots were observed in bone-marrow cavities adjacent to spinal cord lesions; these were not observed in control animals. Quantitative evaluation of cohorts receiving cyclophosphamide treatment displayed significant reduction in 19F signal within the spinal cord and bone marrow of EAE rats. Overall, 19F MRI can be used to quantitatively monitored EAE disease burden, discover unexpected sites of inflammatory activity, and may serve as a sensitive biomarker for the discovery and preclinical assessment of novel MS therapeutic interventions.

  11. Intestinal Barrier Dysfunction Develops at the Onset of Experimental Autoimmune Encephalomyelitis, and Can Be Induced by Adoptive Transfer of Auto-Reactive T Cells

    Science.gov (United States)

    Nouri, Mehrnaz; Bredberg, Anders; Weström, Björn; Lavasani, Shahram

    2014-01-01

    Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system with a pathogenesis involving a dysfunctional blood-brain barrier and myelin-specific, autoreactive T cells. Although the commensal microbiota seems to affect its pathogenesis, regulation of the interactions between luminal antigens and mucosal immune elements remains unclear. Herein, we investigated whether the intestinal mucosal barrier is also targeted in this disease. Experimental autoimmune encephalomyelitis (EAE), the prototypic animal model of MS, was induced either by active immunization or by adoptive transfer of autoreactive T cells isolated from these mice. We show increased intestinal permeability, overexpression of the tight junction protein zonulin and alterations in intestinal morphology (increased crypt depth and thickness of the submucosa and muscularis layers). These intestinal manifestations were seen at 7 days (i.e., preceding the onset of neurological symptoms) and at 14 days (i.e., at the stage of paralysis) after immunization. We also demonstrate an increased infiltration of proinflammatory Th1/Th17 cells and a reduced regulatory T cell number in the gut lamina propria, Peyer's patches and mesenteric lymph nodes. Adoptive transfer to healthy mice of encephalitogenic T cells, isolated from EAE-diseased animals, led to intestinal changes similar to those resulting from the immunization procedure. Our findings show that disruption of intestinal homeostasis is an early and immune-mediated event in EAE. We propose that this intestinal dysfunction may act to support disease progression, and thus represent a potential therapeutic target in MS. In particular, an increased understanding of the regulation of tight junctions at the blood-brain barrier and in the intestinal wall may be crucial for design of future innovative therapies. PMID:25184418

  12. Imaging of systemic vasculitis in childhood

    Energy Technology Data Exchange (ETDEWEB)

    Soliman, Magdy [The Hospital for Sick Children, Department of Medical Imaging, Toronto, ON (Canada); Cairo University, Department of Medical Imaging, Cairo (Egypt); Laxer, Ronald; Yeung, Rae [The Hospital for Sick Children, Department of Rheumatology, Toronto, ON (Canada); Manson, David; Doria, Andrea S. [The Hospital for Sick Children, Department of Medical Imaging, Toronto, ON (Canada)

    2015-08-15

    The term ''systemic vasculitis'' encompasses a diverse set of diseases linked by the presence of blood-vessel inflammation that are often associated with critical complications. These diseases are uncommon in childhood and are frequently subjected to a delayed diagnosis. Although the diagnosis and treatment may be similar for adult and childhood systemic vasculitides, the prevalence and classification vary according to the age group under investigation. For example, Kawasaki disease affects children while it is rarely encountered in adults. In 2006, the European League Against Rheumatism (EULAR) and the Pediatric Rheumatology European Society (PReS) proposed a classification system for childhood vasculitis adopting the system devised in the Chapel Hill Consensus Conference in 1993, which categorizes vasculitides according to the predominant size of the involved blood vessels into small, medium and large vessel diseases. Currently, medical imaging has a pivotal role in the diagnosis of vasculitis given recent developments in the imaging of blood vessels. For example, early diagnosis of coronary artery aneurysms, a serious complication of Kawasaki disease, is now possible by magnetic resonance imaging (MRI) of the heart and multidetector computed tomography (MDCT); positron emission tomography/CT (PET/CT) helps to assess active vascular inflammation in Takayasu arteritis. Our review offers a unique approach using the integration of the proposed classification criteria for common systemic childhood vasculitides with their most frequent imaging findings, along with differential diagnoses and an algorithm for diagnosis based on common findings. It should help radiologists and clinicians reach an early diagnosis, therefore facilitating the ultimate goal of proper management of affected children. (orig.)

  13. Imaging of systemic vasculitis in childhood

    International Nuclear Information System (INIS)

    Soliman, Magdy; Laxer, Ronald; Yeung, Rae; Manson, David; Doria, Andrea S.

    2015-01-01

    The term ''systemic vasculitis'' encompasses a diverse set of diseases linked by the presence of blood-vessel inflammation that are often associated with critical complications. These diseases are uncommon in childhood and are frequently subjected to a delayed diagnosis. Although the diagnosis and treatment may be similar for adult and childhood systemic vasculitides, the prevalence and classification vary according to the age group under investigation. For example, Kawasaki disease affects children while it is rarely encountered in adults. In 2006, the European League Against Rheumatism (EULAR) and the Pediatric Rheumatology European Society (PReS) proposed a classification system for childhood vasculitis adopting the system devised in the Chapel Hill Consensus Conference in 1993, which categorizes vasculitides according to the predominant size of the involved blood vessels into small, medium and large vessel diseases. Currently, medical imaging has a pivotal role in the diagnosis of vasculitis given recent developments in the imaging of blood vessels. For example, early diagnosis of coronary artery aneurysms, a serious complication of Kawasaki disease, is now possible by magnetic resonance imaging (MRI) of the heart and multidetector computed tomography (MDCT); positron emission tomography/CT (PET/CT) helps to assess active vascular inflammation in Takayasu arteritis. Our review offers a unique approach using the integration of the proposed classification criteria for common systemic childhood vasculitides with their most frequent imaging findings, along with differential diagnoses and an algorithm for diagnosis based on common findings. It should help radiologists and clinicians reach an early diagnosis, therefore facilitating the ultimate goal of proper management of affected children. (orig.)

  14. Renal paraneoplastic vasculitis complicating lung adenocarcinoma

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    Besma Ben Dhaou

    2014-01-01

    Full Text Available Renal paraneoplastic vasculitis (RNPV is rare. It can be revealed by glomerulonephritis, microaneurysms or renal failure. RPNV may precede the onset of the primary tumor, and treatment and prognosis depend on the etiology (primary tumor. A 54-year-old man who had a primary lung adenocarcinoma was admitted for nephrotic syndrome. The investigations revealed RNPV. The patient was treated with corticosteroids at high dose and cyclophosphamide with improvement of the renal condition; however, the patient died from worsening of his pulmonary neoplasia.

  15. Cryoglobulinemic vasculitis in a patient with CREST syndrome.

    Science.gov (United States)

    Hurst, Rebecca L; Berianu, Florentina; Ginsburg, William W; Klein, Christopher J; Englestad, Janean K; Kennelly, Kathleen D

    2014-10-01

    Cryoglobulinemic vasculitis is a rare entity. Although it has been reported in diffuse systemic sclerosis, it has not been reported in calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly and telangiectasia (CREST) syndrome. We report a patient with cryoglobulinemic vasculitis with CREST syndrome who did not have typical clinical features of vasculitis. This 58-year-old woman presented with mild generalized weakness and a diagnosis of CREST syndrome, which included Raynaud's syndrome, dysphagia and telangiectasias. She was positive for serum cryoglobulins, which led to a sural nerve biopsy. The biopsy results were consistent with cryoglobulinemic vasculitis. Cryoglobulinemic vasculitis has not been previously reported in CREST syndrome to our knowledge. Additionally, the patient also had limited clinical symptoms. Our patient displays the importance of checking for cryoglobulins and obtaining a nerve biopsy when the serum is positive. Both of these diagnostic tests were integral for directing appropriate treatment for this patient. Copyright © 2014 Elsevier Ltd. All rights reserved.

  16. pANCA-vasculitis associated with rectal adenocarcinoma.

    Science.gov (United States)

    Hommel, C; Rihova, Z; Mokaddem, F; Libotte, B

    2014-12-01

    We report the case of a 69-year-old male patient who was admitted for fever, dry cough, recurrent sinusitis with epistaxis, anorexia with weight loss of 20 kg over a 3-month period, myalgia, and mononeuritis multiplex. He was diagnosed with pANCA/anti-MPO associated vasculitis and rectal adenocarcinoma. The tumor was treated by surgical resection. Recurrence of vasculitis occurred during steroid tapering which prompted us to add Mycophenolate mofetyl. A complete remission was achieved. We conclude that in the present case the vasculitis was an independent disease, not a paraneoplastic phenomenon. We discuss the value of different ANCA serologies for diagnostics and follow-up, the epidemiology of vasculitis associated with malignancy, and the concept of vasculitis as a paraneoplastic syndrome.

  17. Vasculitis Associated With Tumor Necrosis Factor-α Inhibitors

    Science.gov (United States)

    Sokumbi, Olayemi; Wetter, David A.; Makol, Ashima; Warrington, Kenneth J.

    2012-01-01

    Objective To describe the clinical characteristics, histopathologic features, and outcomes of patients in whom vasculitis developed in association with use of tumor necrosis factor-α (TNF-α) inhibitors. Patients and Methods This is a retrospective review of patients evaluated at Mayo Clinic, Rochester, Minnesota, from January 1, 1998, through March 31, 2011, with a diagnosis of vasculitis induced by anti–TNF-α therapy. Results Of 8 patients with vasculitis associated with anti–TNF-α therapy (mean age, 48.5 years), 6 (75%) were female. Four (50%) had rheumatoid arthritis, 1 (13%) had Crohn disease, and 3 (38%) had ulcerative colitis. Five (63%) were treated with infliximab, 2 (25%) with etanercept, and 1 (13%) with adalimumab. The mean duration of treatment before development of vasculitis was 34.5 months. The skin was the predominant organ affected (5 patients [63%]), with the most common cutaneous lesion being palpable purpura (4 of 5 [80%]). Two organs involved in systemic vasculitis were the peripheral nervous system (4 patients [50%]) and kidney (1 patient [13%]). All cases of vasculitis were histopathologically confirmed. Seven of 8 patients improved with discontinuation of therapy (mean time to resolution, 6.9 months) and adjuvant treatment (all 8 received prednisone; another agent was also used in 7); rechallenge with anti–TNF-α therapy was not attempted in any patient. At last follow-up, no patients had experienced a recurrence of vasculitis after therapy discontinuation. Conclusion Cutaneous small-vessel vasculitis was the most common finding, but systemic vasculitis, including peripheral nerve and renal vasculitis, was also frequently observed. PMID:22795634

  18. Clinical Spectrum of Medium-Sized Vessel Vasculitis.

    Science.gov (United States)

    Alibaz-Oner, Fatma; Koster, Matthew J; Crowson, Cynthia S; Makol, Ashima; Ytterberg, Steven R; Salvarani, Carlo; Matteson, Eric L; Warrington, Kenneth J

    2017-06-01

    Polyarteritis nodosa (PAN) is a systemic necrotizing vasculitis of medium-sized visceral vessels. However, cutaneous arteritis (CA) and gastrointestinal (GI) vasculitis are forms of single-organ vasculitis having indistinguishable histopathologic findings from PAN. The aim of this study was to evaluate and compare the clinical characteristics, treatment, and outcomes of patients with systemic PAN, CA, and GI vasculitis. Retrospective cohorts were assembled, consisting of patients with PAN, CA, and GI vasculitis between 1980 and 2014. The demographics, clinical characteristics, treatment, and outcomes of patients were abstracted from medical records. We included 48 patients with PAN, 41 patients with CA, and 19 patients with GI vasculitis. The disease of 1 patient evolved from CA to systemic PAN during the disease course. At diagnosis, 94% of patients with PAN, 93% of patients with CA, and 67% of patients with GI vasculitis were treated with glucocorticoids. Additional immunosuppressive agents were used in 67% of PAN, 37% of GI vasculitis, and 32% of CA cases. The 5-year cumulative relapse rate was 45.2% in CA, and only 9.6% in PAN during a followup of approximately 6 years. No deaths were observed in the CA group. The survival rate at 10 years was 66% in the PAN group and 61% in the GI vasculitis group. Systemic PAN, CA, and GI vasculitis take different clinical courses and therefore may be different diseases, rather than existing on a spectrum of the same disease. Progression of CA to systemic PAN is very rare. Relapse risk is low during followup in PAN. Patients with CA have a higher relapse rate than those with systemic PAN, possibly due to less use of immunosuppressive therapy in CA. © 2016, American College of Rheumatology.

  19. Ctla-4 modulates the differentiation of inducible Foxp3+ Treg cells but IL-10 mediates their function in experimental autoimmune encephalomyelitis.

    Directory of Open Access Journals (Sweden)

    Johan Verhagen

    Full Text Available In vitro induced Foxp3+ T regulatory (iTreg cells form a novel and promising target for therapeutic tolerance induction. However, the potential of these cells as a target for the treatment of various immune diseases, as well as the factors involved in their development and function, remain debated. Here, we demonstrate in a myelin basic protein (MBP-specific murine model of CNS autoimmune disease that adoptive transfer of antigen-specific iTreg cells ameliorates disease progression. Moreover, we show that the co-stimulatory molecule CTLA-4 mediates in vitro differentiation of iTreg cells. Finally, we demonstrate that the secreted, immunosuppressive cytokine IL-10 controls the ability of antigen-specific iTreg cells to suppress autoimmune disease. Overall, we conclude that antigen-specific iTreg cells, which depend on various immune regulatory molecules for their differentiation and function, represent a major target for effective immunotherapy of autoimmune disease.

  20. Autoimmunity in Wiskott-Aldrich Syndrome: an unsolved enigma

    Directory of Open Access Journals (Sweden)

    Marco eCatucci

    2012-07-01

    Full Text Available Wiskott-Aldrich Syndrome (WAS is a severe X-linked Primary Immunodeficiency (PID that affects 1 to 10 out of 1 million male individuals. WAS is caused by mutations in the WAS Protein (WASP expressing gene that leads to the absent or reduced expression of the protein. WASP is a cytoplasmic protein that regulates the formation of actin filaments in hematopoietic cells. WASP deficiency causes many immune cell defects both in humans and in the WAS murine model, the Was-/- mouse. Both cellular and humoral immune defects in WAS patients contribute to the onset of severe clinical manifestations, in particular microthrombocytopenia, eczema, recurrent infections and a high susceptibility to develop autoimmunity and malignancies. Autoimmune diseases affect from 22% to 72% of WAS patients and the most common manifestation is autoimmune hemolytic anemia, followed by vasculitis, arthritis, neutropenia, inflammatory bowel disease and IgA nephropathy. Many groups have widely explored immune cell functionality in WAS partially explaining how cellular defects may lead to pathology. However, the mechanisms underlying the occurrence of autoimmune manifestations have not been clearly described yet. In the present review, we report the most recent progresses in the study of immune cell function in WAS that have started to unveil the mechanisms contributing to autoimmune complications in WAS patients.

  1. Plasma exchange for renal vasculitis and idiopathic rapidly progressive glomerulonephritis: a meta-analysis

    DEFF Research Database (Denmark)

    Walsh, Michael; Catapano, Fausta; Szpirt, Wladimir

    2011-01-01

    Plasma exchange may be effective adjunctive treatment for renal vasculitis. We performed a systematic review and meta-analysis of randomized controlled trials of plasma exchange for renal vasculitis.......Plasma exchange may be effective adjunctive treatment for renal vasculitis. We performed a systematic review and meta-analysis of randomized controlled trials of plasma exchange for renal vasculitis....

  2. Identification of brain antigens recognized by autoantibodies in experimental autoimmune encephalomyelitis-induced animals treated with etomoxir or interferon-β

    DEFF Research Database (Denmark)

    Mørkholt, Anne Skøttrup; Kastaniegaard, Kenneth; Trabjerg, Michael Sloth

    2018-01-01

    Multiple sclerosis (MS) is a neurodegenerative autoimmune disease, where chronic inflammation plays an essential role in its pathology. A feature of MS is the production of autoantibodies stimulated by an altered-peptide-ligand response and epitope spreading, resulting in loss of tolerance for self...

  3. Increased severity of experimental autoimmune encephalomyelitis, chronic macrophage/microglial reactivity, and demyelination in transgenic mice producing tumor necrosis factor-alpha in the central nervous system

    DEFF Research Database (Denmark)

    Taupin, V; Renno, T; Bourbonnière, L

    1997-01-01

    are a target of immune attack. TNF-alpha also regulates macrophage activity which could contribute to autoimmune inflammation. We have expressed TNF-alpha at disease-equivalent levels in the central nervous system of transgenic mice, using a myelin basic protein (MBP) promoter. These mice were normal...

  4. Immune modulation by a tolerogenic myelin oligodendrocyte glycoprotein (MOG)10-60 containing fusion protein in the marmoset experimental autoimmune encephalomyelitis model

    NARCIS (Netherlands)

    Y.S. Kap (Yolanda); N. van Driel (Nikki); R. Arends (Roel); G. Rouwendal; M. Verolin; E. Blezer (Erwin); N. Lycke; B.A. 't Hart (Bert)

    2015-01-01

    textabstractSummary: Current therapies for multiple sclerosis (MS), a chronic autoimmune neuroinflammatory disease, mostly target general cell populations or immune molecules, which may lead to a compromised immune system. A more directed strategy would be to re-enforce tolerance of the

  5. Immune modulation by a tolerogenic myelin oligodendrocyte glycoprotein (MOG)10-60 containing fusion protein in the marmoset experimental autoimmune encephalomyelitis model

    NARCIS (Netherlands)

    Kap, Y. S.; van Driel, N.; Arends, R.; Rouwendal, G.; Verolin, M.; Blezer, E.; Lycke, N.; 't Hart, Bert A.

    Current therapies for multiple sclerosis (MS), a chronic autoimmune neuroinflammatory disease, mostly target general cell populations or immune molecules, which may lead to a compromised immune system. A more directed strategy would be to re-enforce tolerance of the autoaggressive T cells that drive

  6. Immune modulation by a tolerogenic myelin oligodendrocyte glycoprotein (MOG)10-60 containing fusion protein in the marmoset experimental autoimmune encephalomyelitis model

    NARCIS (Netherlands)

    Kap, Y. S.; van Driel, N.; Arends, R.; Rouwendal, G.; Verolin, M.; Blezer, E.; Lycke, N.; 't Hart, B. A.

    2015-01-01

    Summary: Current therapies for multiple sclerosis (MS), a chronic autoimmune neuroinflammatory disease, mostly target general cell populations or immune molecules, which may lead to a compromised immune system. A more directed strategy would be to re-enforce tolerance of the autoaggressive T cells

  7. Predictors of medication non-adherence for vasculitis patients

    Science.gov (United States)

    Hogan, Susan L.; DeVellis, Robert F.

    2013-01-01

    The primary purpose of this article is to document whether demographic, clinical, regimen-related, intrapersonal, and interpersonal factors predict medication non-adherence for vasculitis patients. A secondary purpose is to explore whether adherence varies by medication type and whether patients experienced drug-related side effects. Vasculitis patients (n=228) completed online baseline and 3-month follow-up surveys. Demographic (age, gender, education, race, marital status, and insurance status), clinical (perceived vasculitis severity, disease duration, vasculitis type, and relapse/remission status), regimen-related (experience of side effects), intrapersonal (depressive symptoms), and interpersonal (adherence-related support from family and friends) factors were measured at baseline. Medication non-adherence was assessed at follow-up using the Vasculitis Self-Management Survey medication adherence sub-scale (α=0.89). Variables that significantly correlated (pvasculitis medication types, patients who experienced side effects were less adherent than patients who did not experience side effects. Multiple factors are associated with medication non-adherence for vasculitis patients. Providers should discuss medication adherence and drug-related side effects with vasculitis patients. Providers may want to particularly target younger patients and patients with clinical signs of depression. PMID:23314654

  8. The challenge of treating hepatitis C virus-associated cryoglobulinemic vasculitis in the era of anti-CD20 monoclonal antibodies and direct antiviral agents.

    Science.gov (United States)

    Roccatello, Dario; Sciascia, Savino; Rossi, Daniela; Solfietti, Laura; Fenoglio, Roberta; Menegatti, Elisa; Baldovino, Simone

    2017-06-20

    Mixed cryoglobulinemia syndrome (MC) is a systemic vasculitis involving kidneys, joints, skin, and peripheral nerves. While many autoimmune, lymphoproliferative, and neoplastic disorders have been associated with this disorder, hepatitis C virus (HCV) is known to be the etiologic agent in the majority of patients. Therefore, clinical research has focused on anti-viral drugs and, more recently, on the new, highly potent Direct-acting Antiviral Agents (DAAs). These drugs assure sustained virologic response (SVR) rates >90%. Nevertheless, data on their efficacy in patients with HCV-associated cryoglobulinemic vasculitis are disappointing, possibly due to the inability of the drugs to suppress the immune-mediated process once it has been triggered.Despite the potential risk of exacerbation of the infection, immunosuppression has traditionally been regarded as the first-line intervention in cryoglobulinemic vasculitis, especially if renal involvement is severe. Biologic agents have raised hopes for more manageable therapeutic approaches, and Rituximab (RTX), an anti CD20 monoclonal antibody, is the most widely used biologic drug. It has proved to be safer than conventional immunosuppressants, thus substantially changing the natural history of HCV-associated cryoglobulinemic vasculitis by providing long-term remission, especially with intensive regimens.The present review focuses on the new therapeutic opportunities offered by the combination of biological drugs, mainly Rituximab, with DAAs.

  9. Pentraxin-3 levels are associated with vasculitis and disease activity in childhood-onset systemic lupus erythematosus.

    Science.gov (United States)

    Sahin, S; Adrovic, A; Barut, K; Durmus, S; Gelisgen, R; Uzun, H; Kasapcopur, O

    2017-09-01

    Objectives Childhood-onset systemic lupus erythematosus (cSLE) is a multisystemic autoimmune disease characterized by inflammatory organ damage by means of vasculitis. Pentraxin-3 (PTX3) is expressed locally at the sites of inflammatory processes, predominantly from endothelial cells. In adult studies, PTX3 has shown to be an indicator of active vasculitis both in large-vessel and small-vessel vasculitides, as well as in SLE. Moreover, in SLE it has found to be correlated with disease activity, and with some of the clinical manifestations and laboratory parameters. We aimed to ascertain if PTX3 might be a significant mediator in cSLE and if it might indicate active vasculitis during the course of the disease. Methods Serum PTX3 levels were measured in 76 patients with cSLE and 41 healthy subjects. We have investigated its relation with disease activity, damage, clinical features, laboratory parameters and medications. Results Serum levels of PTX3 were found to be increased in cSLE compared to healthy controls (mean ± SD; 10.6 ± 8.2 ng/mL vs 2.7 ± 1.3 ng/mL, p Lupus International Collaborating Clinics/American College of Rheumatology Damage Index), ESR, CRP, procalcitonin levels, anti-ds DNA antibody, anticardiolipin antibodies was not detected. Conclusions Patients with cSLE have increased levels of serum PTX3 compared to healthy controls. Thus, serum PTX-3 level might be a significant mediator in cSLE. Apart from these, the results support that PTX3 reflects active cutaneous vasculitis in cSLE and correlates with disease activity.

  10. IFN-gamma signaling in the central nervous system controls the course of experimental autoimmune encephalomyelitis independently of the localization and composition of inflammatory foci

    Directory of Open Access Journals (Sweden)

    Lee Eunyoung

    2012-01-01

    Full Text Available Abstract Background Murine experimental autoimmune encephalomyelitis (EAE, a model for multiple sclerosis, presents typically as ascending paralysis. However, in mice in which interferon-gamma (IFNγ signaling is disrupted by genetic deletion, limb paralysis is accompanied by atypical deficits, including head tilt, postural imbalance, and circling, consistent with cerebellar/vestibular dysfunction. This was previously attributed to intense cerebellar and brainstem infiltration by peripheral immune cells and formation of neutrophil-rich foci within the CNS. However, the exact mechanism by which IFNγ signaling prohibits the development of vestibular deficits, and whether the distribution and composition of inflammatory foci within the CNS affects the course of atypical EAE remains elusive. Methods We induced EAE in IFNγ-/- mice and bone marrow chimeric mice in which IFNγR is not expressed in the CNS but is intact in the periphery (IFNγRCNSKO and vice versa (IFNγRperiKO. Blood-brain barrier permeability was determined by Evans blue intravenous administration at disease onset. Populations of immune cell subsets in the periphery and the CNS were quantified by flow cytometry. CNS tissues isolated at various time points after EAE induction, were analyzed by immunohistochemistry for composition of inflammatory foci and patterns of axonal degeneration. Results Incidence and severity of atypical EAE were more pronounced in IFNγRCNSKO as compared to IFNγRperiKO mice. Contrary to what we anticipated, cerebella/brainstems of IFNγRCNSKO mice were only minimally infiltrated, while the same areas of IFNγRperiKO mice were extensively populated by peripheral immune cells. Furthermore, the CNS of IFNγRperiKO mice was characterized by persistent neutrophil-rich foci as compared to IFNγRCNSKO. Immunohistochemical analysis of the CNS of IFNγ-/- and IFNγR chimeric mice revealed that IFNγ protective actions are exerted through microglial STAT1

  11. A cross-sectional study of the Birmingham Vasculitis Activity Score version 3 in systemic vasculitis

    DEFF Research Database (Denmark)

    Suppiah, Ravi; Mukhtyar, Chetan; Flossmann, Oliver

    2011-01-01

    and the vasculitis damage index (VDI) to demonstrate that the BVAS v. 3 measures disease activity. Results. WG (63%), Churg-Strauss syndrome (9%) and microscopic polyangiitis (9%) were the most common diagnoses. The BVAS v. 3 showed convergent validity with the VAI [¿¿=¿0.82 (95% CI 0.77, 0.85)], PGA [¿¿=¿0.85 (95...

  12. The Spectrum of Paraneoplastic Cutaneous Vasculitis in a Defined Population

    Science.gov (United States)

    Loricera, Javier; Calvo-Río, Vanesa; Ortiz-Sanjuán, Francisco; González-López, Marcos A.; Fernández-Llaca, Hector; Rueda-Gotor, Javier; Gonzalez-Vela, Maria C.; Alvarez, Lino; Mata, Cristina; González-Lamuño, Domingo; Martínez-Taboada, Victor M.; González-Gay, Miguel A.; Blanco, Ricardo

    2013-01-01

    Abstract Cutaneous vasculitis may be associated with malignancies, and may behave as a paraneoplastic syndrome. This association has been reported in a variable proportion of patients depending on population selection. We conducted the current study to assess the frequency, clinical features, treatment, and outcome of paraneoplastic vasculitis in a large unselected series of 766 patients with cutaneous vasculitis diagnosed at a single university hospital. Sixteen patients (10 men and 6 women; mean age ± standard deviation, 67.94 ± 14.20 yr; range, 40–85 yr) presenting with cutaneous vasculitis were ultimately diagnosed as having an underlying malignancy. They constituted 3.80% of the 421 adult patients. There were 9 hematologic and 7 solid underlying malignancies. Skin lesions were the initial clinical presentation in all of them, and the median interval from the onset of cutaneous vasculitis to the diagnosis of the malignancy was 17 days (range, 8–50 d). The most frequent skin lesions were palpable purpura (15 patients). Other clinical manifestations included constitutional syndrome (10 patients) and arthralgia and/or arthritis (4 cases). Hematologic cytopenias (11 cases) as well as immature peripheral blood cells (6 cases) were frequently observed in the full blood cell count, especially in those with vasculitis associated with hematologic malignancies. Specific treatment for vasculitis was prescribed in 10 patients; nonsteroidal antiinflammatory drugs (4 patients), corticosteroids (3 patients), chloroquine (1 patient), antihistamines (1 patient), and cyclophosphamide (1 patient). Ten patients died due to the malignancy and 6 patients recovered following malignancy therapy. Patients with paraneoplastic vasculitis were older, more frequently had constitutional syndrome, and less frequently had organ damage due to the vasculitis than the remaining patients with cutaneous vasculitis. In summary, cutaneous paraneoplastic vasculitis is an entity not uncommonly

  13. Acute posterior multifocal placoid pigment epitheliopathy associated with cerebral vasculitis.

    Science.gov (United States)

    Weinstein, J M; Bresnick, G H; Bell, C L; Roschmann, R A; Brooks, B R; Strother, C M

    1988-09-01

    Acute multifocal posterior placoid pigment epitheliopathy (APMPPE) is an unusual self-limited retinal disorder that has been associated with various systemic complications. To our knowledge, three prior cases associated with cerebral vasculitis have been described. This article describes a patient with APMPPE and angiographically documented cerebral vasculitis who was notable because of (a) the presence of two different cerebral ischemic events, occurring 1 month apart, and (b) the long latency (3 months) between the onset of ocular symptoms and the second cerebral ischemic event. Recognition of the association between APMPPE and cerebral vasculitis may permit early treatment of CNS involvement and prevention of morbidity.

  14. Vitiligo and Autoimmune Thyroid Disorders

    Directory of Open Access Journals (Sweden)

    Enke Baldini

    2017-10-01

    Full Text Available Vitiligo represents the most common cause of acquired skin, hair, and oral depigmentation, affecting 0.5–1% of the population worldwide. It is clinically characterized by the appearance of disfiguring circumscribed skin macules following melanocyte destruction by autoreactive cytotoxic T lymphocytes. Patients affected by vitiligo usually show a poorer quality of life and are more likely to suffer from depressive symptoms, particularly evident in dark-skinned individuals. Although vitiligo is a non-fatal disease, exposure of affected skin to UV light increases the chance of skin irritation and predisposes to skin cancer. In addition, vitiligo has been associated with other rare systemic disorders due to the presence of melanocytes in other body districts, such as in eyes, auditory, nervous, and cardiac tissues, where melanocytes are thought to have roles different from that played in the skin. Several pathogenetic models have been proposed to explain vitiligo onset and progression, but clinical and experimental findings point mainly to the autoimmune hypothesis as the most qualified one. In this context, it is of relevance the strong association of vitiligo with other autoimmune diseases, in particular with autoimmune thyroid disorders, such as Hashimoto thyroiditis and Graves’ disease. In this review, after a brief overview of vitiligo and its pathogenesis, we will describe the clinical association between vitiligo and autoimmune thyroid disorders and discuss the possible underlying molecular mechanism(s.

  15. Churg-Strauss syndrome and hemorragic vasculitis

    Directory of Open Access Journals (Sweden)

    Rui Moreira Marques

    2011-12-01

    Full Text Available Churg-Strauss syndrome (CSS is a rare syndrome characterized by sinusitis, asthma and peripheral eosinophilia. This vasculitic syndrome affects medium and small-sized vessels, the lung being the most commonly affected organ, followed by the skin. The authors report a case of a 59-year-old male with a past history of asthma and allergic rhinitis. He presented necrohemorragic lesions in the distal phalanx of the 2nd, 3rd and 4th fingers of the lefthand and petechial lesions in the plant of both feet, accompanied by asthenia, anorexia and weight loss. The analytical study revealed leukocytosis with eosinophilia, elevated inflammatory parameters and p-ANCA positive antibodies. The diagnosis of CSS was established based on clinical and histopathological data. Cutaneous manifestations of hemorragic vasculitis are rare in CSS syndrome but can be the first manifestation of the disease. The recognition of this presentation is important for the early diagnosis and treatment of this syndrome.

  16. Churg-Strauss syndrome and hemorrhagic vasculitis

    Science.gov (United States)

    Marques, Rui Moreira; Cabral, Ana Rita; Monteiro, Antonio; Henriques, Pedro

    2011-01-01

    Churg-Strauss syndrome (CSS) is a rare syndrome characterized by sinusitis, asthma and peripheral eosinophilia. This vasculitic syndrome affects medium and small-sized vessels, the lung being the most commonly affected organ, followed by the skin. The authors report a case of a 59-year-old male with a past history of asthma and allergic rhinitis. He presented necrohemorragic lesions in the distal phalanx of the 2nd, 3rd and 4th fingers of the left-hand and petechial lesions in the plant of both feet, accompanied by asthenia, anorexia and weight loss. The analytical study revealed leukocytosis with eosinophilia, elevated inflammatory parameters and p-ANCA positive antibodies. The diagnosis of CSS was established based on clinical and histopathological data. Cutaneous manifestations of hemorragic vasculitis are rare in CSS syndrome but can be the first manifestation of the disease. The recognition of this presentation is important for the early diagnosis and treatment of this syndrome. PMID:25386301

  17. Vasculitis inducida por metimazol: Reporte de caso

    Directory of Open Access Journals (Sweden)

    Miguel Pinto

    2011-07-01

    Full Text Available Se reporta el caso de una paciente con enfermedad de Graves, que presentó vasculitis asociada al uso de metimazol. Mujer de 14 años, que acudió a consulta por presentar intolerancia al calor, tremor distal y palpitaciones. El examen físico mostró bocio difuso, y el perfil tiroideo, TSH suprimida y hormonas tiroideas elevadas. Los anticuerpos antiperoxidasa tiroidea fueron positivos. Se inició tratamiento con metimazol y beta bloqueadores. Después de 20 días, la paciente regresó por presentar malestar general, fiebre, poliartralgia, lesiones cutáneas maculopapulares y edema de miembros inferiores. Los anticuerpos antinucleares fueron negativos y los anticuerpos anticitoplasma de los neutrófilos (ANCA, positivos. Se suspendió el metimazol y se inició prednisona. Después de 10 días de tratamiento, las molestias desaparecieron y la paciente recibió I 131.Las vasculitis asociadas al uso de tionamidas son poco frecuentes, no dependen de la dosis y están asociadas a la presencia de anticuerpos tipo ANCA. Clásicamente, afectan a los vasos pequeños de la piel; sin embargo, también pueden afectar los riñones y pulmones. El cuadro clínico se caracteriza por artralgias y mialgias. En algunos casos puede ocurrir insuficiencia renal de grado variable. En la mayoría de casos, el cuadro remite con la suspensión de la droga; pero, en algunos se requiere el uso de glucocorticoides o inmunosupresores.(Rev Med Hered 2011;22:147-150.

  18. Bioinspired engineering study of Plantae vascules for self-healing composite structures

    Science.gov (United States)

    Trask, R. S.; Bond, I. P.

    2010-01-01

    This paper presents the first conceptual study into creating a Plantae-inspired vascular network within a fibre-reinforced polymer composite laminate, which provides an ongoing self-healing functionality without incurring a mass penalty. Through the application of a ‘lost-wax’ technique, orthogonal hollow vascules, inspired by the ‘ray cell’ structures found in ring porous hardwoods, were successfully introduced within a carbon fibre-reinforced epoxy polymer composite laminate. The influence on fibre architecture and mechanical behaviour of single vascules (located on the laminate centreline) when aligned parallel and transverse to the local host ply was characterized experimentally using a compression-after-impact test methodology. Ultrasonic C-scanning and high-resolution micro-CT X-ray was undertaken to identify the influence of and interaction between the internal vasculature and impact damage. The results clearly show that damage morphology is influenced by vascule orientation and that a 10 J low-velocity impact damage event is sufficient to breach the vasculature; a prerequisite for any subsequent self-healing function. The residual compressive strength after a 10 J impact was found to be dependent upon vascule orientation. In general, residual compressive strength decreased to 70 per cent of undamaged strength when vasculature was aligned parallel to the local host ply and a value of 63 per cent when aligned transverse. This bioinspired engineering study has illustrated the potential that a vasculature concept has to offer in terms of providing a self-healing function with minimum mass penalty, without initiating premature failure within a composite structure. PMID:19955122

  19. Refractory disease in antineutrophil cytoplasmic antibodies associated vasculitis

    NARCIS (Netherlands)

    Rutgers, Abraham; Kallenberg, Cornelis

    Purpose of review Induction treatment of antineutrophil cytoplasmic antibodies (ANCA) associated vasculitis (AAV) is not always successful and nonresponding patients are considered refractory. Recent findings Refractory disease should be subdefined to the treatment that was received.

  20. Genetically distinct subsets within ANCA-associated vasculitis

    DEFF Research Database (Denmark)

    Lyons, Paul A; Rayner, Tim F; Trivedi, Sapna

    2012-01-01

    Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis is a severe condition encompassing two major syndromes: granulomatosis with polyangiitis (formerly known as Wegener's granulomatosis) and microscopic polyangiitis. Its cause is unknown, and there is debate about whether it is a single...

  1. Propylthiouracil-Induced Vasculitis With Antineutrophil Cytoplasmic Antibody.

    Science.gov (United States)

    Criado, Paulo Ricardo; Grizzo Peres Martins, Ana Claudia; Gaviolli, Camila Fatima; Alavi, Afsaneh

    2015-06-01

    Propylthiouracil (PTU)-associated vasculitis is a potentially life-threatening disease with a recent increase in the reported cases in the medical literature. This increase may suggest that some earlier cases have been unrecognized or assigned to an alternative nosology category. Although the skin can be the only organ affected by PTU-associated vasculitis, there are many reports with multiple-system involvement. Classically, the symptoms appear under a tetrad of fever, sore throat, arthralgia, and skin lesions. Cutaneous lesions in reported cases of PTU vasculitis have most commonly consisted of retiform acral, purpuric plaques, or nodules. We report a case of perinuclear antineutrophil cytoplasmic antibody-associated vasculitis developed during treatment with PTU for Grave's disease. © The Author(s) 2014.

  2. Vasculitis and antineutrophil cytoplasmic autoantibodies associated with propylthiouracil therapy

    NARCIS (Netherlands)

    Dolman, K. M.; Gans, R. O.; Vervaat, T. J.; Zevenbergen, G.; Maingay, D.; Nikkels, R. E.; Donker, A. J.; von dem Borne, A. E.; Goldschmeding, R.

    1993-01-01

    Vasculitis is a rare complication of propylthiouracil therapy. Antineutrophil cytoplasmic antibodies (ANCA) have been described in association with several vasculitic disorders. We report detection of ANCA against human neutrophil elastase, proteinase 3, and myeloperoxidase in serum from six

  3. Antineutrophil cytoplasmic autoantibody-associated small-vessel vasculitis

    NARCIS (Netherlands)

    Kallenberg, Cees G. M.

    Purpose of reviews This review focuses on recent advance in the diagnosis pathogenesis and treatment of antineutrophil cytoplasmic autoantibody-associated small-vessel vasculitis. Recent findings Antineutrophil cytoplasmic autoantibodies are closely associated with Wegener's granulomatosis and

  4. A Unique Case of Systemic Lupus Erythematosus Pelvic Vasculitis

    Directory of Open Access Journals (Sweden)

    Pamela Traisak

    2016-01-01

    Full Text Available The clinical presentation of Systemic Lupus Erythematosus (SLE is diverse and vasculitis can be a potential manifestation. Cutaneous lesions involving small vessels are the most frequent presentation. However, medium and large vessel vasculitis may present with life-threatening visceral manifestations. We present a unique case of pelvic vasculitis mimicking a pelvic mass as an initial presentation of SLE. There are case reports of systemic vasculitis involving the female genital tract with giant cell arteritis (GCA, polyarteritis nodosa (PAN, and granulomatous with polyangiitis and microscopic polyangiitis (GPA/MPA, among others, but only a few cases attributed to SLE. Awareness of this condition and a prompt diagnosis are warranted as this is a severe and potentially life-threatening condition.

  5. Therapeutic Potential of Invariant Natural Killer T Cells in Autoimmunity

    Directory of Open Access Journals (Sweden)

    Luc Van Kaer

    2018-03-01

    Full Text Available Tolerance against self-antigens is regulated by a variety of cell types with immunoregulatory properties, such as CD1d-restricted invariant natural killer T (iNKT cells. In many experimental models of autoimmunity, iNKT cells promote self-tolerance and protect against autoimmunity. These findings are supported by studies with patients suffering from autoimmune diseases. Based on these studies, the therapeutic potential of iNKT cells in autoimmunity has been explored. Many of these studies have been performed with the potent iNKT cell agonist KRN7000 or its structural variants. These findings have generated promising results in several autoimmune diseases, although mechanisms by which iNKT cells modulate autoimmunity remain incompletely understood. Here, we will review these preclinical studies and discuss the prospects for translating their findings to patients suffering from autoimmune diseases.

  6. A pragmatic approach to vasculitis in the gastrointestinal tract.

    Science.gov (United States)

    Chetty, Runjan; Serra, Stefano

    2017-06-01

    Although vasculitis involving the gastrointestinal tract (GIT) is an uncommon occurrence, occasionally vasculitis can present as haemorrhagic infarction or ischaemia for which a length of bowel is removed. Invariably, the appropriate clinical history is not forthcoming, or vasculitis is not clinically suspected. The purpose of this overview is to provide the practising gastrointestinal (GI) pathologist with a framework to recognise and diagnose vasculitides within the GIT. The classification may be approached by aetiological agent or size of vessel involved; an international consensus group now favours the latter approach. The symptoms that systemic and/or localised vasculitis may cause in the GIT are protean and non-specific. As a result, pathologists examining resection specimens for unexplained haemorrhagic infarction or ischaemia should be aware that vasculitis may be a potential cause. Several well-known systemic vasculitides such as polyarteritis nodosa, microscopic polyangiitis, eosinophilic granulomatosis with polyangiitis or Churg-Strauss syndrome and granulomatosis with polyangiitis or Wegener's granulomatosis can occur in the GIT. The latter three constitute the antineutrophil cytoplasmic antibody-positive vasculitides. In addition, the so-called solitary organ vasculitis (SOV) can occur in the GIT as the harbinger of later onset systemic vasculitis, and be the cause of the GIT symptoms. In addition, SOV can occur incidentally and coexist with GIT disease such as gallstones or polyps, and there may be no manifestations of systemic vasculitis for years, or not at all. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  7. Testicular lymphocytic vasculitis treated with prednisolone and azathioprine.

    Science.gov (United States)

    Kanzawa, Yohei; Imai, Yukihiro; Mizuno, Yasushi; Nishioka, Hiroaki

    2017-07-01

    Testicular vasculitis is a rare condition and little is known about its morphological features. Herein, we report a case of testicular lymphocytic vasculitis, which is rarely documented, in an elderly man. He presented with left testicular swelling and fever, but without any signs of other organ involvement. He was effectively treated with prednisolone and azathioprine. This case report offers information related to the disease course and the importance of biopsy.

  8. Long-term patient survival in ANCA-associated vasculitis

    DEFF Research Database (Denmark)

    Flossmann, Oliver; Berden, Annelies; de Groot, Kirsten

    2011-01-01

    Wegener's granulomatosis and microscopic polyangiitis are antineutrophil cytoplasm antibodies (ANCA)-associated vasculitides with significant morbidity and mortality. The long-term survival of patients with ANCA associated vasculitis treated with current regimens is uncertain.......Wegener's granulomatosis and microscopic polyangiitis are antineutrophil cytoplasm antibodies (ANCA)-associated vasculitides with significant morbidity and mortality. The long-term survival of patients with ANCA associated vasculitis treated with current regimens is uncertain....

  9. Acrally distributed dermatoses: Vascular dermatoses (purpura and vasculitis).

    Science.gov (United States)

    Kazandjieva, Jana; Antonov, Dimitar; Kamarashev, Jivko; Tsankov, Nikolai

    Purpuric lesions appear in acral distribution in a variety of conditions and often provide clues to the clinical diagnosis. Purpuric means "hemorrhagic"-that is, the lesions do not blanch from pressure. This review focuses on dermatoses that produce hemorrhagic lesions in acral distribution from the large groups of the vasculitic diseases and their mimics. Cutaneous small vessel vasculitis is confined to the skin, involves mainly postcapillary venules, and has the hallmark manifestation of palpable purpura. Henoch-Schönlein purpura is an immune complex-mediated systemic vasculitis of the small vessels with manifestations from the skin, joints, kidneys, and gastrointestinal system. Only cases where the immune complexes contain immunoglobulin A type are classified as Henoch-Schönlein purpura. Cryoglobulinemic vasculitis is induced by the deposition of cold-precipitated immune complexes in the small vessels. Urticarial vasculitis comprises a spectrum of conditions with the characteristic course of chronic urticaria, with wheals that persist longer than 24 hours, leave hyperpigmentation, and have leukocytoclastic vasculitis on histologic examination. Polyarteritis nodosa is a rare multisystem, segmental necrotizing vasculitis of mainly the medium-sized vessels. Pigmented purpuric dermatoses are chronic benign dermatoses characterized by petechiae, purpura, and increased skin pigmentation. The hallmark of pigmented purpuric dermatoses is their orange-brown, speckled, cayenne pepper-like discoloration. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Vasculitis as an adverse event following immunization - Systematic literature review.

    Science.gov (United States)

    Bonetto, Caterina; Trotta, Francesco; Felicetti, Patrizia; Alarcón, Graciela S; Santuccio, Carmela; Bachtiar, Novilia Sjafri; Brauchli Pernus, Yolanda; Chandler, Rebecca; Girolomoni, Giampiero; Hadden, Robert D M; Kucuku, Merita; Ozen, Seza; Pahud, Barbara; Top, Karina; Varricchio, Frederick; Wise, Robert P; Zanoni, Giovanna; Živković, Saša; Bonhoeffer, Jan

    2016-12-12

    Several types of vasculitis have been observed and reported in temporal association with the administration of various vaccines. A systematic review of current evidence is lacking. This systematic literature review aimed to assess available evidence and current reporting practice of vasculitides as adverse events following immunization (AEFI). We reviewed the literature from 1st January 1994 to 30th June 2014. This review comprises randomized controlled trials, observational studies, case series, case reports, reviews and comments regardless of vaccine and target population. The initial search resulted in the identification of 6656 articles. Of these, 157 articles were assessed for eligibility and 75 studies were considered for analysis, including 6 retrospective/observational studies, 2 randomized controlled trials, 7 reviews, 11 case series, 46 case reports and 3 comments. Most of the larger, higher quality studies found no causal association between vaccination and subsequent development of vasculitis, including several studies on Kawasaki disease and Henoch-Schönlein purpura (IgA vasculitis). Smaller case series reported a few cases of vasculitis following BCG and vaccines against influenza and hepatitis. Only 24% of the articles reported using a case definition of vasculitis. Existing literature does not allow establishing a causative link between vaccination and vasculitides. Further investigations were strengthened by the use of standardized case definitions and methods for data collection, analysis and presentation to improve data comparability and interpretation of vasculitis cases following immunization. Published by Elsevier Ltd.

  11. Clinically Apparent Arterial Thrombosis in Persons with Systemic Vasculitis

    Directory of Open Access Journals (Sweden)

    Alexander Tsoukas

    2017-01-01

    Full Text Available Objective. To estimate the incidence rate of clinically apparent arterial thrombotic events and associated comorbidities in patients with primary systemic vasculitis. Methods. Using large cohort administrative data from Quebec, Canada, we identified patients with vasculitis, including polyarteritis nodosa (PAN and granulomatosis with polyangiitis (GPA. Incident acute myocardial infarctions (AMIs and cerebrovascular accidents (CVAs after the diagnosis of vasculitis were ascertained in the PAN and GPA group via billing and hospitalization data. These were compared to rates of a general population comparator group. The incidences of comorbidities (type 2 diabetes mellitus, dyslipidemia, and hypertension were also collected. Results. Among the 626 patients identified with vasculitis, 19.7% had PAN, 2.9% had Kawasaki disease, 23.8% had GPA, 52.4% had GCA, and 1.3% had Takayasu arteritis. The AMI rate was substantially higher in males aged 18–44 with PAN, with rates up to 268.1 events per 10,000 patient years [95% CI 67.1–1070.2], approximately 30 times that in the age- and sex-matched control group. The CVA rate was also substantially higher, particularly in adults aged 45–65. Patients with vasculitis had elevated incidences of diabetes, dyslipidemia, and hypertension versus the general population. Conclusion. Atherothrombotic rates were elevated in patients identified as having primary systemic vasculitis. While incident rates of cardiovascular comorbidities were also increased, the substantial elevation in AMIs seen in young adults suggests a disease-specific component which requires further investigation.

  12. Helicobacter pylori and autoimmune disease: Cause or bystander

    Science.gov (United States)

    Smyk, Daniel S; Koutsoumpas, Andreas L; Mytilinaiou, Maria G; Rigopoulou, Eirini I; Sakkas, Lazaros I; Bogdanos, Dimitrios P

    2014-01-01

    Helicobacter pylori (H. pylori) is the main cause of chronic gastritis and a major risk factor for gastric cancer. This pathogen has also been considered a potential trigger of gastric autoimmunity, and in particular of autoimmune gastritis. However, a considerable number of reports have attempted to link H. pylori infection with the development of extra-gastrointestinal autoimmune disorders, affecting organs not immediately relevant to the stomach. This review discusses the current evidence in support or against the role of H. pylori as a potential trigger of autoimmune rheumatic and skin diseases, as well as organ specific autoimmune diseases. We discuss epidemiological, serological, immunological and experimental evidence associating this pathogen with autoimmune diseases. Although over one hundred autoimmune diseases have been investigated in relation to H. pylori, we discuss a select number of papers with a larger literature base, and include Sjögrens syndrome, rheumatoid arthritis, systemic lupus erythematosus, vasculitides, autoimmune skin conditions, idiopathic thrombocytopenic purpura, autoimmune thyroid disease, multiple sclerosis, neuromyelitis optica and autoimmune liver diseases. Specific mention is given to those studies reporting an association of anti-H. pylori antibodies with the presence of autoimmune disease-specific clinical parameters, as well as those failing to find such associations. We also provide helpful hints for future research. PMID:24574735

  13. Severe Small-Vessel Vasculitis Temporally Associated With Administration of Ustekinumab.

    Science.gov (United States)

    MacArthur, Kelly M; Merkel, Peter A; Van Voorhees, Abby S; Nguyen, Jennifer; Rosenbach, Misha

    2016-03-01

    Vasculitis may be caused by infection, medications, systemic diseases, malignancy, or occur as an idiopathic condition. In cases of drug-induced vasculitis, it is essential to identify and discontinue the culprit medication. As novel agents are approved through clinical trials, some rare events, including vasculitis, may not become apparent until wider use, and rigorous post-marketing surveillance for new medications is important. Physicians should consider drug-induced vasculitis on the differential for all new vasculitis diagnoses, and if the potential triggering medication is a novel medication, it is essential to rigorously investigate the potential for emerging cases of medication-associated vasculitis in all available scientific literature.

  14. The Autoimmune Ecology.

    Science.gov (United States)

    Anaya, Juan-Manuel; Ramirez-Santana, Carolina; Alzate, Maria A; Molano-Gonzalez, Nicolas; Rojas-Villarraga, Adriana

    2016-01-01

    Autoimmune diseases (ADs) represent a heterogeneous group of disorders that affect specific target organs or multiple organ systems. These conditions share common immunopathogenic mechanisms (i.e., the autoimmune tautology), which explain the clinical similarities they have among them as well as their familial clustering (i.e., coaggregation). As part of the autoimmune tautology, the influence of environmental exposure on the risk of developing ADs is paramount (i.e., the autoimmune ecology). In fact, environment, more than genetics, shapes immune system. Autoimmune ecology is akin to exposome, that is all the exposures - internal and external - across the lifespan, interacting with hereditary factors (both genetics and epigenetics) to favor or protect against autoimmunity and its outcomes. Herein, we provide an overview of the autoimmune ecology, focusing on the immune response to environmental agents in general, and microbiota, cigarette smoking, alcohol and coffee consumption, socioeconomic status (SES), gender and sex hormones, vitamin D, organic solvents, and vaccines in particular. Inclusion of the autoimmune ecology in disease etiology and health will improve the way personalized medicine is currently conceived and applied.

  15. Bistability in autoimmune diseases

    DEFF Research Database (Denmark)

    Rapin, Nicolas; Mosekilde, Erik; Lund, Ole

    2011-01-01

    Autoimmune diseases damage host tissue, which, in turn, may trigger a stronger immune response. Systems characterized by such positive feedback loops can display co-existing stable steady states. In a mathematical model of autoimmune disease, one steady state may correspond to the healthy state...

  16. Update in endocrine autoimmunity.

    Science.gov (United States)

    Anderson, Mark S

    2008-10-01

    The endocrine system is a common target in pathogenic autoimmune responses, and there has been recent progress in our understanding, diagnosis, and treatment of autoimmune endocrine diseases. Rapid progress has recently been made in our understanding of the genetic factors involved in endocrine autoimmune diseases. Studies on monogenic autoimmune diseases that include endocrine phenotypes like autoimmune polyglandular syndrome type 1 and immune dysregulation, polyendocrinopathy, enteropathy, X-linked have helped reveal the role of key regulators in the maintenance of immune tolerance. Highly powered genetic studies have found and confirmed many new genes outside of the established role of the human leukocyte antigen locus with these diseases, and indicate an essential role of immune response pathways in these diseases. Progress has also been made in identifying new autoantigens and the development of new animal models for the study of endocrine autoimmunity. Finally, although hormone replacement therapy is still likely to be a mainstay of treatment in these disorders, there are new agents being tested for potentially treating and reversing the underlying autoimmune process. Although autoimmune endocrine disorders are complex in etiology, these recent advances should help contribute to improved outcomes for patients with, or at risk for, these disorders.

  17. THE AUTOIMMUNE ECOLOGY.

    Directory of Open Access Journals (Sweden)

    Juan-Manuel eAnaya

    2016-04-01

    Full Text Available Autoimmune diseases (ADs represent a heterogeneous group of disorders that affect specific target organs or multiple organ systems. These conditions share common immunopathogenic mechanisms (i.e., the autoimmune tautology, which explain the clinical similarities they have among them as well as their familial clustering (i.e., coaggregation. As part of the autoimmune tautology, the influence of environmental exposure on the risk of developing ADs is paramount (i.e., the autoimmune ecology. In fact, environment, more than genetics, shapes immune system. Autoimmune ecology is akin to exposome, that is all the exposures - internal and external - across the lifespan, interacting with hereditary factors (both genetics and epigenetics to favor or protect against autoimmunity and its outcomes. Herein we provide an overview of the autoimmune ecology, focusing on the immune response to environmental agents in general, and microbiota, cigarette smoking, alcohol and coffee consumption, socioeconomic status, gender and sex hormones, vitamin D, organic solvents and vaccines in particular. Inclusion of the autoimmune ecology in disease etiology and health will improve the way personalized medicine is currently conceived and applied.

  18. Cryofibrinogenemia: a marker of severity of cryoglobulinemic vasculitis.

    Science.gov (United States)

    Michaud, Martin; Moulis, Guillaume; Puissant, Bénédicte; Balardy, Laurent; Huart, Antoine; Gaches, Francis; Cougoul, Pierre; Arlet, Philippe; Blancher, Antoine; Pourrat, Jacques; Sailler, Laurent

    2015-08-01

    Cryofibrinogenemia is frequently associated with cryoglobulinemia. The aim of this study was to determine the characteristics associated with the presence of cryofibrinogenemia in patients with cryoglobulinemic vasculitis. This was a single-center retrospective study that included patients with cryoglobulinemic vasculitis who were tested for cryofibrinogen at a tertiary referral center between January 1, 2011 and December 31, 2012. Twenty-nine patients fulfilled the CryoVas (cryoglobulinemic vasculitis) Survey criteria for cryoglobulinemic vasculitis. Eighteen patients had a detectable cryofibrinogen (CF-positive) and 11 had no detectable cryofibrinogen (CF-negative). Median cryoglobulin levels were 89 ± 129 mg/L in the CF-positive group and 68 ± 82 mg/L in the CF-negative group (P = .32). Median cryofibrinogen level was 70 ± 174 mg/L. Clinical manifestations were similar in both groups. Cancers and hematological disorders were more frequent among CF-positive patients (39% vs 0%, P = .026). Levels of alpha-1 and alpha-2 globulinemia were higher in the CF-positive group. Cryofibrinogenemia ≥ 100 mg/L was associated with cryoglobulinemic vasculitis (odds ratio [OR] 2.86; 95% confidence interval [CI], 1.06-7.73) in cryoglobulinemic patients. Presence of cryofibrinogenemia was associated with use of corticosteroids, immunosuppressants, or plasmapheresis in cryoglobulinemic vasculitis patients (OR 22.7; 95% CI, 2.02-256.44). Our results strongly suggest that presence of cryofibrinogenemia is associated with a more severe phenotype among patients with cryoglobulinemic vasculitis. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. CT findings at lupus mesenteric vasculitis

    International Nuclear Information System (INIS)

    Ko, S.F.; Lee, T.Y.; Cheng, T.T.; Ng, S.H.; Lai, H.M.; Cheng, Y.F.; Tsai, C.C.

    1997-01-01

    Purpose: To describe the spectrum of early CT findings of lupus mesenteric vasculitis (LMV) and to assess the utility of CT in the management of this uncommon entity. Methods: Abdominal CT was performed within 1-4 days (average 2.2 days) of the onset of severe abdominal pain and tenderness in 15 women with systemic lupus erythematosus. Prompt high-dose i.v. corticosteroid in 11 patients after the CT diagnosis of LMV was made. CT was performed after abdominal symptoms subsided. Results: Eleven cases revealed CT features suggestive of LMV including conspicuous prominence of mesentric vessels with palisade pattern or comb-like appearance (CT comb sign) supplying focal or diffuse dilated bowel loops (n=11), ascites with slightly increased peritoneal enhancement (n=11), small bowel wall thickening (n=10) with double halo or target sign (n=8). Follow-up CT before high-dose steroid therapy revealed complete or marked resolution of the abnormal CT findings. Conclusion: CT is helpful for confirming the diagnosis of LMV, especially the comb sign which may be an early sign. Bowel ischemia due to LMV is less ominous than previously expected, and the abnormal CT findings were reversible when early diagnosis and prompt i.v. steroid therapy could be achieved. (orig.)

  20. CT findings at lupus mesenteric vasculitis

    Energy Technology Data Exchange (ETDEWEB)

    Ko, S.F. [Chang Gung Medical College and Memorial Hospital, Dept. of Radiology, Kaohsiung Hsien (Taiwan); Lee, T.Y. [Chang Gung Medical College and Memorial Hospital, Dept. of Radiology, Kaohsiung Hsien (Taiwan); Cheng, T.T. [Chang Gung Medical College and Memorial Hospital, Dept. of Rheumatology, Kaohsiung Hsien (Taiwan); Ng, S.H. [Chang Gung Medical College and Memorial Hospital, Dept. of Radiology, Kaohsiung Hsien (Taiwan); Lai, H.M. [Chang Gung Medical College and Memorial Hospital, Dept. of Rheumatology, Kaohsiung Hsien (Taiwan); Cheng, Y.F. [Chang Gung Medical College and Memorial Hospital, Dept. of Radiology, Kaohsiung Hsien (Taiwan); Tsai, C.C. [Chang Gung Medical College and Memorial Hospital, Dept. of Radiology, Kaohsiung Hsien (Taiwan)

    1997-01-01

    Purpose: To describe the spectrum of early CT findings of lupus mesenteric vasculitis (LMV) and to assess the utility of CT in the management of this uncommon entity. Methods: Abdominal CT was performed within 1-4 days (average 2.2 days) of the onset of severe abdominal pain and tenderness in 15 women with systemic lupus erythematosus. Prompt high-dose i.v. corticosteroid in 11 patients after the CT diagnosis of LMV was made. CT was performed after abdominal symptoms subsided. Results: Eleven cases revealed CT features suggestive of LMV including conspicuous prominence of mesentric vessels with palisade pattern or comb-like appearance (CT comb sign) supplying focal or diffuse dilated bowel loops (n=11), ascites with slightly increased peritoneal enhancement (n=11), small bowel wall thickening (n=10) with double halo or target sign (n=8). Follow-up CT before high-dose steroid therapy revealed complete or marked resolution of the abnormal CT findings. Conclusion: CT is helpful for confirming the diagnosis of LMV, especially the comb sign which may be an early sign. Bowel ischemia due to LMV is less ominous than previously expected, and the abnormal CT findings were reversible when early diagnosis and prompt i.v. steroid therapy could be achieved. (orig.).

  1. Thoracic vasculitis presenting as surgical problems.

    LENUS (Irish Health Repository)

    Jansen, Michael

    2010-01-01

    We present four patients with vasculitis manifesting with unusual clinical or pathological features, generating surgical problems. Two cases presented with pulmonary hypertension, with investigations and radiological evidence prompting clinical suspicion of pulmonary thrombo-embolic disease. First case, with an antecedant history of Wegener\\'s granulomatosis (WG), demonstrated following "embolectomy", WG involving the large pulmonary elastic arteries. The second case of inoperable "pulmonary thrombo-embolic disease" was subsequently found at limited post mortem to have giant cell arteritis, which affected widespread small peripheral pulmonary arterial vessels. The other two cases were of aortitis occurring in the background of immune-mediated disease, which had been treated with aggressive immunosuppression regimens. The first of these was a case of Cogan\\'s syndrome complicated by descending aortitis, a rarely reported phenomenon, with co-existent acute endocarditis of the aortic valve leaflets. Most cases of endocarditis in this context occur secondary to and in continuity with ascending aortitis. That this case, and a case of ascending aortitis occurring in the context of relapsing polychondritis occurred in the face of aggressive immunosuppression with an apparent clinical response, underscores the need to not accept a clinical picture at face value. This has implications for clinical management, particularly in the follow-up of surgical prosthetic devices such as grafts which may be used in these cases. All four cases emphasise the continued importance of histology and the post-mortem examination in elucidating previously undetected or unsuspected disease.

  2. PF-1355, a mechanism-based myeloperoxidase inhibitor, prevents immune complex vasculitis and anti-glomerular basement membrane glomerulonephritis.

    Science.gov (United States)

    Zheng, Wei; Warner, Roscoe; Ruggeri, Roger; Su, Chunyan; Cortes, Christian; Skoura, Athanasia; Ward, Jessica; Ahn, Kay; Kalgutkar, Amit; Sun, Dexue; Maurer, Tristan S; Bonin, Paul D; Okerberg, Carlin; Bobrowski, Walter; Kawabe, Thomas; Zhang, Yanwei; Coskran, Timothy; Bell, Sammy; Kapoor, Bhupesh; Johnson, Kent; Buckbinder, Leonard

    2015-05-01

    Small vessel vasculitis is a life-threatening condition and patients typically present with renal and pulmonary injury. Disease pathogenesis is associated with neutrophil accumulation, activation, and oxidative damage, the latter being driven in large part by myeloperoxidase (MPO), which generates hypochlorous acid among other oxidants. MPO has been associated with vasculitis, disseminated vascular inflammation typically involving pulmonary and renal microvasculature and often resulting in critical consequences. MPO contributes to vascular injury by 1) catabolizing nitric oxide, impairing vasomotor function; 2) causing oxidative damage to lipoproteins and endothelial cells, leading to atherosclerosis; and 3) stimulating formation of neutrophil extracellular traps, resulting in vessel occlusion and thrombosis. Here we report a selective 2-thiouracil mechanism-based MPO inhibitor (PF-1355 [2-(6-(2,5-dimethoxyphenyl)-4-oxo-2-thioxo-3,4-dihydropyrimidin-1(2H)-yl)acetamide) and demonstrate that MPO is a critical mediator of vasculitis in mouse disease models. A pharmacokinetic/pharmacodynamic response model of PF-1355 exposure in relation with MPO activity was derived from mouse peritonitis. The contribution of MPO activity to vasculitis was then examined in an immune complex model of pulmonary disease. Oral administration of PF-1355 reduced plasma MPO activity, vascular edema, neutrophil recruitment, and elevated circulating cytokines. In a model of anti-glomerular basement membrane disease, formerly known as Goodpasture disease, albuminuria and chronic renal dysfunction were completely suppressed by PF-1355 treatment. This study shows that MPO activity is critical in driving immune complex vasculitis and provides confidence in testing the hypothesis that MPO inhibition will provide benefit in treating human vasculitic diseases. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.

  3. [Large vessel vasculitis with myelodysplastic syndrome: A rare association].

    Science.gov (United States)

    Galland, J; Kawski, H; Guichard, J-F; Maurier, F

    2017-07-01

    The vasculitis can be the consequence of malignancy: most often hematologic rather than solid tumors. The association between large vessels vasculitis and myelodysplastic syndrome is rare. A 55-year-old man experienced asthenia, fever, polyarthritis and inflammatory syndrome. Haematological investigations found a type 2 refractory anemia with excess blasts (RAEB-2) with discovery of severe anemia (Hb: 7,8g/dl) and thrombopenia (platelets: 40,000/mm 3 ). Radiological examinations found thoracic aortitis and carotid vasculitis. Treatment in the form of steroids and azacitidine was instituted. The lack of control of both RAEB-2 and vasculitis was responsible for the death of the patient. Myelodysplastic syndrome and large vessels vasculitis is a rare but serious association disease. The lack of efficiency of corticosteroids seems to be common. Prognosis depends on the haematological treatment effectiveness. Copyright © 2016 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier SAS. All rights reserved.

  4. Radiologic studies in two outbreaks of isolated vasculitis in the central nervous system

    International Nuclear Information System (INIS)

    Robertson, H.J.; Perez, M.; Tilton, A.H.; Garcia, C.; McGarry, P.

    1989-01-01

    Cerebral vasculitis is only occasionally diagnosed with angiography. Two outbreaks of isolated central nervous system vasculitis permitted a comparison of the accuracy of diagnostic radiologic studies. Two new radiologic features and methods of diagnosis are discussed

  5. Elevated Expression of Fractalkine (CX3CL1 and Fractalkine Receptor (CX3CR1 in the Dorsal Root Ganglia and Spinal Cord in Experimental Autoimmune Encephalomyelitis: Implications in Multiple Sclerosis-Induced Neuropathic Pain

    Directory of Open Access Journals (Sweden)

    Wenjun Zhu

    2013-01-01

    Full Text Available Multiple sclerosis (MS is a central nervous system (CNS disease resulting from a targeted autoimmune-mediated attack on myelin proteins in the CNS. The release of Th1 inflammatory mediators in the CNS activates macrophages, antibodies, and microglia resulting in myelin damage and the induction of neuropathic pain (NPP. Molecular signaling through fractalkine (CX3CL1, a nociceptive chemokine, via its receptor (CX3CR1 is thought to be associated with MS-induced NPP. An experimental autoimmune encephalomyelitis (EAE model of MS was utilized to assess time dependent gene and protein expression changes of CX3CL1 and CX3CR1. Results revealed significant increases in mRNA and the protein expression of CX3CL1 and CX3CR1 in the dorsal root ganglia (DRG and spinal cord (SC 12 days after EAE induction compared to controls. This increased expression correlated with behavioural thermal sensory abnormalities consistent with NPP. Furthermore, this increased expression correlated with the peak neurological disability caused by EAE induction. This is the first study to identify CX3CL1 signaling through CX3CR1 via the DRG /SC anatomical connection that represents a critical pathway involved in NPP induction in an EAE model of MS.

  6. [Non-autoimmune thyroiditis].

    Science.gov (United States)

    Rizzo, Leonardo F L; Mana, Daniela L; Bruno, Oscar D

    2014-01-01

    The term thyroiditis comprises a group of thyroid diseases characterized by the presence of inflammation, including autoimmune and non-autoimmune entities. It may manifest as an acute illness with severe thyroid pain (subacute thyroiditis and infectious thyroiditis), and conditions in which the inflammation is not clinically evident evolving without pain and presenting primarily thyroid dysfunction and/or goiter (drug-induced thyroiditis and Riedel thyroiditis). The aim of this review is to provide an updated approach on non-autoimmune thyroiditis and its clinical, diagnostic and therapeutic aspects.

  7. Stress proteins, autoimmunity, and autoimmune disease.

    Science.gov (United States)

    Winfield, J B; Jarjour, W N

    1991-01-01

    At birth, the immune system is biased toward recognition of microbial antigens in order to protect the host from infection. Recent data suggest that an important initial line of defense in this regard involves autologous stress proteins, especially conserved peptides of hsp60, which are presented to T cells bearing gamma delta receptors by relatively nonpolymorphic class lb molecules. Natural antibodies may represent a parallel B cell mechanism. Through an evolving process of "physiological" autoreactivity and selection by immunodominant stress proteins common to all prokaryotes, B and T cell repertoires expand during life to meet the continuing challenge of infection. Because stress proteins of bacteria are homologous with stress proteins of the host, there exists in genetically susceptible individuals a constant risk of autoimmune disease due to failure of mechanisms for self-nonself discrimination. That stress proteins actually play a role in autoimmune processes is supported by a growing body of evidence which, collectively, suggests that autoreactivity in chronic inflammatory arthritis involves, at least initially, gamma delta cells which recognize epitopes of the stress protein hsp60. Alternate mechanisms for T cell stimulation by stress proteins undoubtedly also exist, e.g., molecular mimicry of the DR beta third hypervariable region susceptibility locus for rheumatoid arthritis by a DnaJ stress protein epitope in gram-negative bacteria. While there still is confusion with respect to the most relevant stress protein epitopes, a central role for stress proteins in the etiology of arthritis appears likely. Furthermore, insight derived from the work thus far in adjuvant-induced arthritis already is stimulating analyses of related phenomena in autoimmune diseases other than those involving joints. Only limited data are available in the area of humoral autoimmunity to stress proteins. Autoantibodies to a number of stress proteins have been identified in SLE and

  8. Hypertrophic cardiomyopathy secondary to hepatitis C virus-related vasculitis.

    Science.gov (United States)

    Cavalli, Giulio; Berti, Alvise; Fragasso, Gabriele; De Cobelli, Francesco

    2016-12-01

    : Almost invariably associated with chronic HCV infection, cryoglobulinemic vasculitis is a small-vessel vasculitis commonly affecting the skin, kidneys, and peripheral nervous system. Cardiac involvement, possibly due to cardiac microcirculation involvement, is an utterly rare and severe complication. We describe a case of hypertrophic cardiomyopathy secondary to cryoglobulinemic vasculitis. Evaluation with transthoracic cardiac ultrasound and cardiac MRI evidenced severe left ventricular hypertrophy and diffuse hypokinesia, a marked decrease in left ventricular ejection fraction, and a subtle late enhancement of inferior and lateral left ventricular walls. Upon clinical stabilization, the patient received treatment with anti-CD20 monoclonal antibody rituximab. Clinical and radiological follow-up with cardiac ultrasound and cardiac MRI documented a dramatic and sustained clinical improvement, with marked reduction of left ventricular hypertrophy, resolution of late enhancement, recovery of left ventricular contractility and function.

  9. Does vasculitis alone cause AVN? A review of literature.

    Science.gov (United States)

    Abraham, Rtika R; Meyerhoff, John O

    2013-10-01

    AVN is caused by a disease, or severe trauma that affects the blood supply to the bone or in many cases may be idiopathic, with no known cause. AVN pathophysiology is most closely linked to SLE literature, and there is a strong cause and effect relationship between corticosteroid intake and AVN development in SLE patients, and AVN is extremely rare in the absence of steroid use. Apart from few anecdotal reports, there is no data on exact pathophysiologic mechanisms responsible for AVN in the setting of vasculitis. We saw a 69-year-old man with femoral AVN and a possibility of vasculitis as the underlying cause was raised by the radiologist, and hence we present this literature search on vasculitis per se causing AVN of the bone.

  10. Cutaneous polyarteritis nodosa: A rare isolated cutaneous vasculitis

    Directory of Open Access Journals (Sweden)

    Praveen Kumar A Subbanna

    2012-01-01

    Full Text Available Cutaneous polyarteritis nodosa (CPAN is a rare form of cutaneous vasculitis that involves small and medium sized arteries of the dermis and subcutaneous tissue without systemic involvement. It presents with tender subcutaneous nodules, digital gangrene, livedo reticularis and subcutaneous ulcerations. The diagnosis is by skin biopsy and characteristic pathologic feature is a leukocytoclastic vasculitis in the small to medium-sized arterioles of the dermis. We report a rare case of benign cutaneous PAN in a 14-year-old girl who presented with history of fever, subcutaneous nodules with cutaneous ulcer and digital gangrene. The skin biopsy showed leukocytoclastic vasculitis with fibrinoid necrosis in the dermal vessels. She received treatment with steroids and lesions resolved completely over a period of month.

  11. Present and future management of anti-neutrophil cytoplasmic antibody associated vasculitis: how therapy changed the prognosis

    Directory of Open Access Journals (Sweden)

    Massimo L’Andolina

    2013-03-01

    Full Text Available Anti-neutrophil cytoplasmic antibody associated vasculitis is part of a multi-systemic idiopathic, small vessel pouci-immune vasculitis. Given the heterogeneous spectrum of the disease, and the need to update therapeutic protocols, the aim of this review was to evaluate clinical-diagnostic approaches. We examined statistical data available in the literature, in particular the 2010 review of St. Hamour et al. Management of Anca-associated Vasculitis, published in Therapeutics and Clinical Risk Management. Acute immunosuppressive therapy and long-term maintenance, with the use of prednisolone, have significantly changed the prognosis of this disease, particularly compared with the 1970s before the introductions of steroids and cyclophosphamide. New drugs such as rituximab, monoclonal antibodies and other modulating immune system molecules are entering clinical use, and experience will confirm whether or not therapeutic guidelines are appropriate. The current diagnostic tools, ranging from laboratory and autoimmune tests, chest X-ray, broncho-alveolar lavage to capillaroscopy, allow prompt diagnosis and early treatment through a first phase of induction-remission, and a second phase of maintenance. There are, however, recurrent and refractory forms of the disease that require long-term immunosuppression and further research into this is merited. These issues have continued to drive the search for safer and more effective modulation of the immune system using targeted immunotherapy. However, the treatment limitations of incomplete efficacy, infection, and cumulative toxicity persist. Modifications to traditional treatment protocols by the use of azathioprine or methotrexate rather than cyclophosphamide, and the introduction of newer agents, such as rituximab, have meant that outcomes have been maintained while toxicity has been reduced.

  12. Autoantibodies in Autoimmune Hepatitis.

    Science.gov (United States)

    Muratori, Luigi; Deleonardi, Gaia; Lalanne, Claudine; Barbato, Erica; Tovoli, Alessandra; Libra, Alessia; Lenzi, Marco; Cassani, Fabio; Muratori, Paolo

    2015-01-01

    The detection of diagnostic autoantibodies such as antinuclear antibodies (ANA), anti-smooth muscle antibodies (SMA), anti-liver/kidney microsomal type 1 (anti-LKM1), anti-liver cytosol type 1 (anti-LC1) and anti-soluble liver antigen (anti-SLA) is historically associated with the diagnosis of autoimmune hepatitis. When autoimmune hepatitis is suspected, the detection of one or any combination of diagnostic autoantibodies, by indirect immunofluorescence or immuno-enzymatic techniques with recombinant antigens, is a pivotal step to reach a diagnostic score of probable or definite autoimmune hepatitis. Diagnostic autoantibodies (ANA, SMA, anti-LKM1, anti-LC1, anti-SLA) are a cornerstone in the diagnosis of autoimmune hepatitis. Other ancillary autoantibodies, associated with peculiar clinical correlations, appear to be assay-dependent and institution-specific, and validation studies are needed. © 2015 S. Karger AG, Basel.

  13. Treatment of renal manifestations of ANCA-associated vasculitis.

    Science.gov (United States)

    Galesic, Kresimir; Ljubanovic, Danica; Horvatic, Ivica

    2013-01-01

    Vasculitis is a clinicopathological entity characterized by inflammation and necrosis of blood vessels. Directory of Open Access Journals (DOAJ), Google Scholar, Pubmed (NLM), LISTA (EBSCO) and Web of Science have been searched. Two major autoantigens for ANCA are myeloperoxidase (MPO) and proteinase 3 (PR3), which are proteins in the primary granules of neutrophils and in the lysosomes of monocytes. They are expressed in mature neutrophils of patients with ANCA, while absent in healthy subjects. The kidney is the most commonly affected vital organ in ANCA-associated vasculitis, and patient outcomes are largely determined by the severity of renal disease at diagnosis and by its response to treatment.

  14. Inhibition of myeloperoxidase by N-acetyl lysyltyrosylcysteine amide reduces experimental autoimmune encephalomyelitis-induced injury and promotes oligodendrocyte regeneration and neurogenesis in a murine model of progressive multiple sclerosis.

    Science.gov (United States)

    Yu, Guoliang; Zheng, Shikan; Zhang, Hao

    2018-02-07

    It is known that oxidative stress produced by proinflammatory myeloid cells plays an important role in demyelination and neuronal injury in progressive multiple sclerosis (MS). Myeloperoxidase (MPO) is a pro-oxidative enzyme released from myeloid cells during inflammation. It has been shown that MPO-dependent oxidative stress plays important roles in inducing tissue injury in many inflammatory diseases. In this report, we treated NOD experimental autoimmune encephalomyelitis (EAE) mice, a murine model of progressive MS, with N-acetyl lysyltyrosylcysteine amide (KYC), a novel specific MPO inhibitor. Our data showed that KYC treatment not only attenuated MPO-mediated oxidative stress but also reduced demyelination and axonal injury in NOD EAE mice. More importantly, we found that KYC treatment increased oligodendrocyte regeneration and neurogenesis in NOD EAE mice. Taken together, our data suggests that targeting MPO should be a good therapeutic approach for reducing oxidative injury and preserving neuronal function in progressive MS patients.

  15. Small vessel vasculitis History, classification, etiology, histopathology, clinic, diagnosis and treatment; Vasculitis de pequenos vasos. Historia, clasificacion, etiologia, histopatologia, clinica, diagnostico y tratamiento

    Energy Technology Data Exchange (ETDEWEB)

    Iglesias Gamarra, Antonio; Matteson, Eric L; Restrepo, Jose Felix

    2007-07-01

    Small-vessel vasculitis is a convenient descriptor for a wide range of diseases characterized by vascular inflammation of the venules, capillaries, and/or arterioles with pleomorphic clinical manifestations. The classical clinical phenotype is leucocytoclastic vasculitis with palpable purpura, but manifestations vary widely depending upon the organs involved. Histopathologic examination in leucocytoclastic vasculitis reveals angiocentric segmental inflammation, fibrinoid necrosis, and a neutrophilic infiltrate around the blood vessel walls with erythrocyte extravasation. The etiology of small-vessel vasculitis is unknown in many cases, but in others, drugs, post viral syndromes, malignancy, primary vasculitis such as microscopic polyarteritis, and connective tissue disorders are associated, The diagnosis of small- vessel vasculitis relies on a thorough history and physical examination, as well as relevant antibody testing including antinuclear antibody and anti neutrophil cytoplasmic antibody, hepatitis B and C serologies, assessment of complement, immunoglobulins, blood count, serum creatinine liver function tests, urinalysis, radiographic imaging and biopsy. The treatment is based primarily on corticosteroid and immunosuppressive agents.

  16. Allogeneic Adipose-Derived Mesenchymal Stromal Cells Ameliorate Experimental Autoimmune Encephalomyelitis by Regulating Self-Reactive T Cell Responses and Dendritic Cell Function

    Directory of Open Access Journals (Sweden)

    Per Anderson

    2017-01-01

    Full Text Available Multipotent mesenchymal stromal cells (MSCs have emerged as a promising therapy for autoimmune diseases, including multiple sclerosis (MS. Administration of MSCs to MS patients has proven safe with signs of immunomodulation but their therapeutic efficacy remains low. The aim of the current study has been to further characterize the immunomodulatory mechanisms of adipose tissue-derived MSCs (ASCs in vitro and in vivo using the EAE model of chronic brain inflammation in mice. We found that murine ASCs (mASCs suppress T cell proliferation in vitro via inducible nitric oxide synthase (iNOS and cyclooxygenase- (COX- 1/2 activities. mASCs also prevented the lipopolysaccharide- (LPS- induced maturation of dendritic cells (DCs in vitro. The addition of the COX-1/2 inhibitor indomethacin, but not the iNOS inhibitor L-NAME, reversed the block in DC maturation implicating prostaglandin (PG E2 in this process. In vivo, early administration of murine and human ASCs (hASCs ameliorated myelin oligodendrocyte protein- (MOG35-55- induced EAE in C57Bl/6 mice. Mechanistic studies showed that mASCs suppressed the function of autoantigen-specific T cells and also decreased the frequency of activated (CD11c+CD40high and CD11c+TNF-α+ DCs in draining lymph nodes (DLNs. In summary, these data suggest that mASCs reduce EAE severity, in part, through the impairment of DC and T cell function.

  17. Assessment of disease activity in large-vessel vasculitis

    DEFF Research Database (Denmark)

    Aydin, Sibel Z.; Direskeneli, Haner; Merkel, Peter A.

    2017-01-01

    Objective. To arrive at consensus for candidate outcomes for disease activity assessment in largevessel vasculitis (LVV) in clinical trials. Methods.A Delphi survey including 99 items was circulated among international experts for 3 rounds. Results. Fifty-seven items were accepted for both giant ...

  18. Anca associated vasculitis : occurrence, prediction, prevention, and outcome of relapses

    NARCIS (Netherlands)

    Boomsma, Maarten Michiel

    2001-01-01

    During follow-up, relapses of disease activity occur in the majority of patients with ANCA associated vasculitis. The general objective brought together in this thesis was to further elucidate the characteristics and consequences of these relapses. Investigated items are the occurrence, the

  19. Prednisone and vardenafil hydrochloride for refractory levamisole-induced vasculitis.

    Science.gov (United States)

    Mandrell, Joshua; Kranc, Christina L

    2016-08-01

    Levamisole is an immunomodulatory drug that was previously used to treat various medical conditions, including parasitic infections, nephrotic syndrome, and colorectal cancer. Over the last few years, increasing amounts of levamisole have been used as an adulterant in cocaine. Levamisole-cut cocaine has become a concern because it is known to cause a necrotizing purpuric rash, autoantibody production, and life-threatening leukopenia. Mixed histologic findings of vasculitis and thrombosis are characteristic of levamisole-induced purpura. The recommended management of levamisole-induced vasculitis currently involves withdrawal of the culprit along with supportive treatment. We describe a patient with levamisole-induced vasculitis who continued to develop skin lesions despite self-reported cocaine cessation. Complete resolution of cutaneous disease occurred with the addition of oral prednisone and vardenafil hydrochloride, suggesting the possibility of a new treatment option in patients with refractory disease. In addition, we review the clinical presentation, disease course, diagnostic approach, laboratory findings, histology, and management of levamisole-induced vasculitis. The harmful effects of levamisole-cut cocaine are serious enough that public alerts have been issued to increase awareness. Clinicians should consider the possibility of levamisole exposure in cocaine users presenting with any combination of fever, neutropenia, and necrotic skin lesions, especially in acral areas including the ears.

  20. [Necrotic leg ulcer revealing vasculitis induced by vitamin K antagonists].

    Science.gov (United States)

    Chabli, H; Hocar, O; Akhdari, N; Amal, S; Hakkou, M; Hamdaoui, A

    2015-12-01

    Vitamin K antagonists are widely used in thromboembolic diseases. Hemorrhagic complications related to drug overdose represent their main side effect. We report a rare side effect, a severe and unexpected type of skin vasculitis - necrotic leg ulcer - induced by vitamin K antagonist. A 63-year-old female with a history of diabetes developed hyperalgesic necrotic ulcerations on the lower limbs one month after starting an acenocoumarol-based treatment for ischemic heart disease. Histological examination revealed lymphocytic vasculitis with fibrinoid necrosis. Etiological explorations searching for vasculitis were negative. In the absence of a precise etiology, drug-induced ulcer was suspected. Low molecular weight heparin was prescribed to replace acenocoumarol. The lesions slowly resolved with topical treatment. The chronological criteria and the negativity of etiological explorations allowed the diagnosis of vitamin K antagonist-induced necrotic skin ulcer. Clinicians should be aware of this rare complication induced by oral anticoagulants because of its practical therapeutic implications. This is the first case of necrotic leg ulcer induced by acenocoumarol corresponding histologically to necrotising lymphocytic vasculitis. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  1. Vasculitis related to viral and other microbial agents.

    Science.gov (United States)

    Teng, Gim Gee; Chatham, W Winn

    2015-04-01

    Vasculitis due to infection may occur as a consequence of the inflammation of vessel walls due to direct or contiguous infection, type II or immune complex-mediated reaction, cell-mediated hypersensitivity, or inflammation due to immune dysregulation triggered by bacterial toxin and/or superantigen production. As immunosuppressive therapy administered in the absence of antimicrobial therapy may increase morbidity and fail to effect the resolution of infection-associated vascular inflammation, it is important to consider infectious entities as potential inciting factors in vasculitis syndromes. The causality between infection and vasculitis has been established in hepatitis B-associated polyarteritis nodosa (HBV-PAN) and hepatitis C-associated (cryoglobulinemic) vasculitis (HCV-CV). The review summarizes the recent literature on the pathophysiological mechanisms and the approaches to the management of HBV-PAN and HCV-CV. Roles of other viral and microbial infections, which either manifest as vasculitic syndromes or are implicated in the pathogenesis of primary vasculitides, are also discussed. Copyright © 2015. Published by Elsevier Ltd.

  2. Acute type II cryoglobulinaemic vasculitis mimicking atherosclerotic peripheral vascular disease.

    LENUS (Irish Health Repository)

    Saeed, A

    2012-01-31

    Atherosclerotic peripheral vascular disease is a common presenting cause for digital ischaemia in life long smokers. Acute severe Type II Cryoglobulinaemic vasculitis is a rare yet important cause, which may present with similar clinical features and which if undiagnosed may be rapidly fatal. Following the instigation of therapy with intravenous methylprednisolone and cyclophosphamide this patient made an excellent recovery.

  3. Genetically distinct subsets within ANCA-associated vasculitis.

    LENUS (Irish Health Repository)

    Lyons, Paul A

    2012-07-19

    Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis is a severe condition encompassing two major syndromes: granulomatosis with polyangiitis (formerly known as Wegener\\'s granulomatosis) and microscopic polyangiitis. Its cause is unknown, and there is debate about whether it is a single disease entity and what role ANCA plays in its pathogenesis. We investigated its genetic basis.

  4. Autoimmune gastritis: Pathologist's viewpoint.

    Science.gov (United States)

    Coati, Irene; Fassan, Matteo; Farinati, Fabio; Graham, David Y; Genta, Robert M; Rugge, Massimo

    2015-11-14

    Western countries are seeing a constant decline in the incidence of Helicobacter pylori-associated gastritis, coupled with a rising epidemiological and clinical impact of autoimmune gastritis. This latter gastropathy is due to autoimmune aggression targeting parietal cells through a complex interaction of auto-antibodies against the parietal cell proton pump and intrinsic factor, and sensitized T cells. Given the specific target of this aggression, autoimmune gastritis is typically restricted to the gastric corpus-fundus mucosa. In advanced cases, the oxyntic epithelia are replaced by atrophic (and metaplastic) mucosa, creating the phenotypic background in which both gastric neuroendocrine tumors and (intestinal-type) adenocarcinomas may develop. Despite improvements in our understanding of the phenotypic changes or cascades occurring in this autoimmune setting, no reliable biomarkers are available for identifying patients at higher risk of developing a gastric neoplasm. The standardization of autoimmune gastritis histology reports and classifications in diagnostic practice is a prerequisite for implementing definitive secondary prevention strategies based on multidisciplinary diagnostic approaches integrating endoscopy, serology, histology and molecular profiling.

  5. Curcumin and autoimmune disease.

    Science.gov (United States)

    Bright, John J

    2007-01-01

    The immune system has evolved to protect the host from microbial infection; nevertheless, a breakdown in the immune system often results in infection, cancer, and autoimmune diseases. Multiple sclerosis, rheumatoid arthritis, type 1 diabetes, inflammatory bowel disease, myocarditis, thyroiditis, uveitis, systemic lupus erythromatosis, and myasthenia gravis are organ-specific autoimmune diseases that afflict more than 5% of the population worldwide. Although the etiology is not known and a cure is still wanting, the use of herbal and dietary supplements is on the rise in patients with autoimmune diseases, mainly because they are effective, inexpensive, and relatively safe. Curcumin is a polyphenolic compound isolated from the rhizome of the plant Curcuma longa that has traditionally been used for pain and wound-healing. Recent studies have shown that curcumin ameliorates multiple sclerosis, rheumatoid arthritis, psoriasis, and inflammatory bowel disease in human or animal models. Curcumin inhibits these autoimmune diseases by regulating inflammatory cytokines such as IL-1beta, IL-6, IL-12, TNF-alpha and IFN-gamma and associated JAK-STAT, AP-1, and NF-kappaB signaling pathways in immune cells. Although the beneficial effects of nutraceuticals are traditionally achieved through dietary consumption at low levels for long periods of time, the use of purified active compounds such as curcumin at higher doses for therapeutic purposes needs extreme caution. A precise understanding of effective dose, safe regiment, and mechanism of action is required for the use of curcumin in the treatment of human autoimmune diseases.

  6. Outcome of Renal Transplant in Recipients With Vasculitis.

    Science.gov (United States)

    Barbouch, Samia; Hajji, Meriam; Aoudia, Raja; Ounissi, Monther; Zammouri, Asma; Goucha, Rym; Ben Hamida, Fathi; Bacha, Mohammed Mongi; Abderrahim, Ezzedine; Ben Abdallah, Taieb

    2017-02-01

    End-stage renal disease develops in a high percentage of patients with vasculitis, in whom kidney transplant has become a therapeutic option. However, limited data are available on the prognosis and outcomes after kidney transplant in these patients. We aimed to compare the long-term graft survival and graft function in 8 renal transplant recipients with vasculitis (granulomatosis with polyangiitis, microscopic polyangiitis, Goodpasture syndrome, and Henoch-Schonlein purpura) with the other kidney recipients at a single center. We conducted a retrospective study of patients followed for chronic renal failure associated with vasculitis before renal transplant. We excluded patients with no biopsy-proven nephropathy. There was no difference in the occurrence of metabolic and cardiovascular complications in our case group compared with the other graft recipients. Infections were frequent and included cytomegalovirus and urinary tract infection. The rates of bacterial and viral infection were equivalent in our population. The incidence of allograft loss was estimated at 1.8%, less than that seen in our entire transplant population. The presence of vasculitis was not significantly related to renal failure (P = .07). Extrarenal relapse occurred in 1 patient with microscopic polyangiitis. Antineutrophil cytoplasmic antibody levels in patients with granulomatosis with polyangiitis and microscopic polyangiitis did not seem to influence the renal outcome (P = .08). Circulating antineutrophil cytoplasmic antibodies were associated with the development of vascular lesions in the graft but were not significantly correlated with graft survival (P = .07). This study supports the theory that renal transplant is an effective treatment option for patients with end-stage renal disease secondary to vasculitis. These patients fare similarly to, if not better than, other patients.

  7. Mechanism of action and efficacy of RX-111, a thieno[2,3-c]pyridine derivative and small molecule inhibitor of protein interaction with glycosaminoglycans (SMIGs), in delayed-type hypersensitivity, TNBS-induced colitis and experimental autoimmune encephalomyelitis.

    Science.gov (United States)

    Harris, Nicholas; Koppel, Juraj; Zsila, Ferenc; Juhas, Stefan; Il'kova, Gabriela; Kogan, Faina Yurgenzon; Lahmy, Orly; Wildbaum, Gizi; Karin, Nathan; Zhuk, Regina; Gregor, Paul

    2016-04-01

    Elucidate the mechanism of action of the small molecule inhibitor of protein binding to glycosaminoglycans, RX-111 and assay its anti-inflammatory activity in animal models of inflammatory disease. The glycosaminoglycan, heparin, was used in the mechanism of action study of RX-111. Human T lymphocytes and umbilical vein endothelial cells were used to assay the in vitro activity of RX-111. Mouse and rat models of disease were used to assay the anti-inflammatory activity of RX-111 in vivo. Circular dichroism and UV/Vis absorption spectroscopy were used to study the binding of RX-111 to the glycosaminoglycan, heparin. T lymphocyte rolling on endothelial cells under shear flow was used to assay RX-111 activity in vitro. Delayed-type hypersensitivity (DTH) and tri-nitrobenzene sulfonic acid (TNBS)-induced colitis in mice and experimental autoimmune encephalomyelitis (EAE) in rats were used to assay anti-inflammatory activity of RX-111 in vivo. RX-111 was shown to bind directly to heparin. It inhibited leukocyte rolling on endothelial cells under shear flow and reduced inflammation in the mouse model of DTH. RX-111 was efficacious in the mouse model of inflammatory bowel disease, TNBS-induced colitis and the rat model of multiple sclerosis, EAE. RX-111 exercises its broad spectrum anti-inflammatory activity by a singular mechanism of action, inhibition of protein binding to the cell surface GAG, heparan sulfate. RX-111 and related thieno[2,3-c]pyridine derivatives are potential therapeutics for the treatment of inflammatory and autoimmune diseases.

  8. [Autoimmune thyroid disease and other non-endocrine autoimmune diseases].

    Science.gov (United States)

    Dilas, Ljiljana Todorović; Icin, Tijana; Paro, Jovanka Novaković; Bajkin, Ivana

    2011-01-01

    Autoimmune diseases are chronic conditions initiated by the loss of immunological tolerance to self-antigens. They constitute heterogeneous group of disorders, in which multiple alterations in the immune system result in a spectrum of syndromes that either target specific organs or affect the body systematically. Recent epidemiological studies have shown a possible shift of one autoimmune disease to another or the fact that more than one autoimmune disease may coexist in a single patient or in the same family. Numerous autoimmune diseases have been shown to coexist frequently with thyroid autoimmune diseases. AUTOIMMNUNE THYROID DISEASE AND OTHER ORGAN SPECIFIC NON-ENDOCRINE AUTOIMMUNE DISEASES: This part of the study reviews the prevalence of autoimmune thyroid disease coexisting with: pernicious anaemia, vitiligo, celiac disease, autoimmune liver disease, miastenia gravis, alopecia areata and sclerosis multiplex, and several recommendations for screening have been given. AUTOIMMUNE THYROID DISEASE AND OTHER ORGAN NON-SPECIFIC NON-ENDOCRINE AUTOIMMUNE DISEASES: Special attention is given to the correlation between autoimmune thyroid disease and rheumatoid arthritis, systemic lupus erythematosus, syndrome Sjögren, systemic sclerosis and mixed connective tissue disease. Screening for autoimmune thyroid diseases should be recommended in everyday clinical practice, in patients with primary organ-specific or organ non-specific autoimmune disease. Otherwise, in patients with primary thyroid autoimmune disease, there is no good reason of seeking for all other autoimmune diseases, although these patients have a greater risk of developing other autoimmune disease. Economic aspects of medicine require further analyzing of these data, from cost/benefit point of view to justified either mandatory screening or medical practitioner judgment.

  9. Determinants of Vessel Targeting in Vasculitis

    Directory of Open Access Journals (Sweden)

    Gary S. Hoffman

    2004-01-01

    Full Text Available Studies of autoimmune diseases have not yet elucidated why certain organs or vessels become the objects of injury while others are spared. This paper will explore the hypothesis that important differences exist in regions of the aorta that determine vulnerability to diseases, such as atherosclerosis, aortitis, giant cell arteritis and Takayasu's disease. The reader is invited to reassess; (1 whether the aorta is indeed a single homogeneous structure, and (2 whether the initial stage of aortitis (and indeed other diseases considered “autoimmune” may be primarily due to acquired alterations of substrate, that influence unique immune profiles, which by themselves may not be pathogenic. Disease susceptibility and patterns are influenced by many factors that are inborn and acquired. Examples include genetic background, gender, ethnicity, aging, prior and concomitant illnesses, habits, diet, toxin and environmental exposures. Studies of vascular diseases must assess how such variables may affect regional differences in endothelial cells, subendothelial matrix, vascular smooth muscle and the response of each to a variety of stimuli.

  10. [Glomerulonephritis and vasculitis as causes of arterial hypertension].

    Science.gov (United States)

    Eicken, Sibylle; Gugger, Mathias; Marti, Hans-Peter

    2012-05-01

    The various types of glomerulonephritis, including many forms of vasculitis, are responsible for about 15% of cases of end-stage renal disease (ESRD). Arterial hypertension represents a frequent finding in patients suffering from glomerulonephritis or vasculitis and hypertension also serves as an indicator for these severe types of diseases. In addition, there are symptoms and signs like hematuria, proteinuria and renal failure. Especially, rapidly progressive glomerulonephritis (RPGN) constitutes a medical emergency and must not be missed by treating physicians. This disease can either occur limited to the kidneys or in the context of a systemic inflammatory disorder, like a vasculitis. If left untreated, RPGN can lead to a necrotizing destruction of glomeruli causing irreversible kidney damage within several months or even weeks. With respect to the immunologically caused vasculitis, there are - depending upon the severity and type of organ involved - many clinical warning signs to be recognized, such as arterial hypertension, hemoptysis, arthalgias, muscle pain, palpable purpura, hematuria, proteinuria and renal failure. In addition, constitutional signs, such as fever and loss of body weight may occur concurrently. Investigations of glomerulonephritis or vasculitis must contain a careful and complete examination of family history and medications used by the respective patient. Thereafter, a thorough clinical examination must follow, including skin, joints and measurement of arterial blood pressure. In addition, a spectrum of laboratory analyses is required in blood, such as full blood screen, erythrocyte sedimentation rate, CRP, creatinine, urea and glucose, and in urine, including urinalysis looking for hematuria, red cell casts and proteinuria. Importantly, proteinuria needs to be quantified by the utilization of a random urine sample. Proteinuria > 3g/d is diagnostic for a glomerular damage. These basic tests are usually followed by more specialized analyses

  11. High salt intake does not exacerbate murine autoimmune thyroiditis

    Science.gov (United States)

    Kolypetri, P; Randell, E; Van Vliet, B N; Carayanniotis, G

    2014-01-01

    Recent studies have shown that high salt (HS) intake exacerbates experimental autoimmune encephalomyelitis and have raised the possibility that a HS diet may comprise a risk factor for autoimmune diseases in general. In this report, we have examined whether a HS diet regimen could exacerbate murine autoimmune thyroiditis, including spontaneous autoimmune thyroiditis (SAT) in non-obese diabetic (NOD.H2h4) mice, experimental autoimmune thyroiditis (EAT) in C57BL/6J mice challenged with thyroglobulin (Tg) and EAT in CBA/J mice challenged with the Tg peptide (2549–2560). The physiological impact of HS intake was confirmed by enhanced water consumption and suppressed aldosterone levels in all strains. However, the HS treatment failed to significantly affect the incidence and severity of SAT or EAT or Tg-specific immunoglobulin (Ig)G levels, relative to control mice maintained on a normal salt diet. In three experimental models, these data demonstrate that HS intake does not exacerbate autoimmune thyroiditis, indicating that a HS diet is not a risk factor for all autoimmune diseases. PMID:24528002

  12. The thyroid and autoimmunity

    International Nuclear Information System (INIS)

    Drexhage, H.A.; Wiersinga, W.M.

    1986-01-01

    These proceedings give an almost complete picture of what is presently known on the autoimmune aspects of both functional and growth disturbances of the thyroid gland. It comprises 12 reviews on main areas of present research, each followed by shorter communications of work in progress relevant to the topic. (Auth.)

  13. Paraneoplastic autoimmune movement disorders.

    Science.gov (United States)

    Lim, Thien Thien

    2017-11-01

    To provide an overview of paraneoplastic autoimmune disorders presenting with various movement disorders. The spectrum of paraneoplastic autoimmune disorders has been expanding with the discovery of new antibodies against cell surface and intracellular antigens. Many of these paraneoplastic autoimmune disorders manifest as a form of movement disorder. With the discovery of new neuronal antibodies, an increasing number of idiopathic or neurodegenerative movement disorders are now being reclassified as immune-mediated movement disorders. These include anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis which may present with orolingual facial dyskinesia and stereotyped movements, CRMP-5 IgG presenting with chorea, anti-Yo paraneoplastic cerebellar degeneration presenting with ataxia, anti-VGKC complex (Caspr2 antibodies) neuromyotonia, opsoclonus-myoclonus-ataxia syndrome, and muscle rigidity and episodic spasms (amphiphysin, glutamic acid decarboxylase, glycine receptor, GABA(A)-receptor associated protein antibodies) in stiff-person syndrome. Movement disorders may be a presentation for paraneoplastic autoimmune disorders. Recognition of these disorders and their common phenomenology is important because it may lead to the discovery of an occult malignancy. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. [Autoimmune hepatitis: Immunological diagnosis].

    Science.gov (United States)

    Brahim, Imane; Brahim, Ikram; Hazime, Raja; Admou, Brahim

    2017-11-01

    Autoimmune hepatopathies (AIHT) including autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC) and autoimmune cholangitis (AIC), represent an impressive entities in clinical practice. Their pathogenesis is not perfectly elucidated. Several factors are involved in the initiation of hepatic autoimmune and inflammatory phenomena such as genetic predisposition, molecular mimicry and/or abnormalities of T-regulatory lymphocytes. AIHT have a wide spectrum of presentation, ranging from asymptomatic forms to severe acute liver failure. The diagnosis of AIHT is based on the presence of hyperglobulinemia, cytolysis, cholestasis, typical even specific circulating auto-antibodies, distinctive of AIH or PBC, and histological abnormalities as well as necrosis and inflammation. Anti-F actin, anti-LKM1, anti-LC1 antibodies permit to distinguish between AIH type 1 and AIH type 2. Anti-SLA/LP antibodies are rather associated to more severe hepatitis, and particularly useful for the diagnosis of seronegative AIH for other the antibodies. Due to the relevant diagnostic value of anti-M2, anti-Sp100, and anti-gp210 antibodies, the diagnosis of PBC is more affordable than that of PSC and AIC. Based on clinical data, the immunological diagnosis of AIHT takes advantage of the various specialized laboratory techniques including immunofluorescence, immunodot or blot, and the Elisa systems, provided of a closer collaboration between the biologist and the physician. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  15. Cocaine-induced vasculitis: is this a new trend?

    Directory of Open Access Journals (Sweden)

    García Pérez MR

    2013-10-01

    Full Text Available Miraida Reneé García Pérez,1 Vanessa L Ortiz-González,1 Maria Betancourt,1 Rogelio Mercado21Department of Internal Medicine, San Juan City Hospital, 2Department of Dermatology, University of Puerto Rico School of Medicine, San Juan, Puerto RicoAbstract: Cocaine-induced vasculitis is a rare complication found in drug abusers. It occurs due to cocaine adulterated with levamisole. Levamisole was once used as a chemotherapy and immunomodulator for different conditions. One of the side effects of this medication is necrotizing vasculitis which has been reported in the US and Puerto Rico. Here we present another case of cocaine induced vasculitis in Puerto Rico. We describe a 43-year-old female with past medical history of bronchial asthma, migraine, and crack smoking who presented to the emergency room due to blood in her urine for 5 days. She also reported fever, chills, and fatigue. At the physical exam she had a right knee ulcer with swelling erythema, warmth, and pain. Also, she had retiform purpuric plaque lesions in her ears, bilaterally. Eroded plaques with elevated borders at left foot and finger dorsum were also present. Laboratory workup was positive for cocaine. The patient showed leucopenia and microcytic anemia with a normal absolute neutrophil count in her cell blood count. Blood cultures, urine cultures, and ulcer cultures were negative. Urinalysis was positive for proteinuria and hematuria. Also, the patient had positive perinuclear anti-neutrophil cytoplasmic antibody, cytoplasmic anti-neutrophil cytoplasmic antibody, and antinuclear antibody tests and elastase specificity. She showed negative anticardiolipin and lupus anticoagulant antibodies. Her complement levels were decreased. The punch biopsy of her ear showed superficial thrombosis of superficial vascular plexus with perivascular lymphocytic infiltrates and deeper sections showed epidermal necrosis and necrotizing vasculitis. She was started on a high dose of steroids, but

  16. Autoimmune paediatric liver disease.

    Science.gov (United States)

    Mieli-Vergani, Giorgina; Vergani, Diego

    2008-06-07

    Liver disorders with a likely autoimmune pathogenesis in childhood include autoimmune hepatitis (AIH), autoimmune sclerosing cholangitis (ASC), and de novo AIH after liver transplantation. AIH is divided into two subtypes according to seropositivity for smooth muscle and/or antinuclear antibody (SMA/ANA, type 1) or liver kidney microsomal antibody (LKM1, type 2). There is a female predominance in both. LKM1 positive patients tend to present more acutely, at a younger age, and commonly have partial IgA deficiency, while duration of symptoms before diagnosis, clinical signs, family history of autoimmunity, presence of associated autoimmune disorders, response to treatment, and long-term prognosis are similar in both groups. The most common type of paediatric sclerosing cholangitis is ASC. The clinical, biochemical, immunological, and histological presentation of ASC is often indistinguishable from that of AIH type 1. In both, there are high IgG, non-organ specific autoantibodies, and interface hepatitis. Diagnosis is made by cholangiography. Children with ASC respond to immunosuppression satisfactorily and similarly to AIH in respect to remission and relapse rates, times to normalization of biochemical parameters, and decreased inflammatory activity on follow up liver biopsies. However, the cholangiopathy can progress. There may be evolution from AIH to ASC over the years, despite treatment. De novo AIH after liver transplantation affects patients not transplanted for autoimmune disorders and is strikingly reminiscent of classical AIH, including elevated titres of serum antibodies, hypergammaglobulinaemia, and histological findings of interface hepatitis, bridging fibrosis, and collapse. Like classical AIH, it responds to treatment with prednisolone and azathioprine. De novo AIH post liver transplantation may derive from interference by calcineurin inhibitors with the intrathymic physiological mechanisms of T-cell maturation and selection. Whether this condition is a

  17. Nonsegmental Vitiligo and Autoimmune Mechanism

    Directory of Open Access Journals (Sweden)

    Naoki Oiso

    2011-01-01

    Full Text Available Nonsegmental vitiligo is a depigmented skin disorder showing acquired, progressive, and depigmented lesions of the skin, mucosa, and hair. It is believed to be caused mainly by the autoimmune loss of melanocytes from the involved areas. It is frequently associated with other autoimmune diseases, particularly autoimmune thyroid diseases including Hashimoto's thyroiditis and Graves' disease, rheumatoid arthritis, type 1 diabetes, psoriasis, pernicious anemia, systemic lupus erythematosus, Addison's disease, and alopecia areata. This indicates the presence of genetically determined susceptibility to not only vitiligo but also to other autoimmune disorders. Here, we summarize current understanding of autoimmune pathogenesis in non-segmental vitiligo.

  18. Correlation of angiography and MR imaging in cerebral vasculitis

    International Nuclear Information System (INIS)

    Cloft, H.J.; Phillips, C.D.; Dix, J.E.; McNulty, B.C.; Kallmes, D.F.; Zagardo, M.T.

    1999-01-01

    Purpose: MR imaging and cerebral angiography were correlated in patients with primary angiitis of the central nervous system (PACNS) to assess the relative roles of these imaging modalities in the diagnosis. Material and Methods: In 9 patients, MR imaging and angiography were compared with regard to the relative involvement of each major vascular territory. Vascular territories assessed were the anterior, middle, and posterior cerebral arteries, and the posterior fossa. Results: All patients had angiographic findings consistent with vasculitis in multiple vascular territories. MR findings ranged from normal to diffusely abnormal. One patient had a completely normal MR investigation. Of 50 territories affected by vasculitis on angiography, 17 (34%) were normal on MR. Conclusion: Relative to cerebral angiography, MR imaging is a poor indicator of the presence or absence of PACNS. Angiography is indicated when clinical suspicion of PACNS is strong, regardless of the findings on MR. (orig.)

  19. Urticarial vasculitis induced by OTC diet pills: a case report.

    Science.gov (United States)

    Chérrez Ojeda, Iván; Loayza, Enrique; Greiding, Leonardo; Calderón, Juan Carlos; Cherrez, Annia; Adum, Farid

    2015-01-01

    Urticarial Vasculitis (UV) is in most of the cases idiopathic; however it has been associated with several conditions and drugs. Over the counter (OTC) diet pills are widely available, even on-line, but they are rarely regulated by pharmaceutical control. We present the case of a 35-year-old female patient suffering of pruriginous and painful wheals more than 1 cm in diameter, with a burning sensation. The eruption lasted more than 24 hours and was accompanied by angioedema, headache and myalgia. No remarkable medical history was found, except for previous intake of OTC diet pills. UV diagnosis was confirmed by the skin biopsy of a lesion. OTC diet pills are widely available worldwide, and due to its widespread use, allergologists and dermatologist should be able to recognize symptoms and lesions of cutaneous vasculitis, which may be under reported.

  20. Ongoing Cerebral Vasculitis During Treatment of Rocky Mountain Spotted Fever.

    Science.gov (United States)

    Sun, Lisa R; Huisman, Thierry A G M; Yeshokumar, Anusha K; Johnston, Michael V

    2015-11-01

    Rocky Mountain spotted fever is a tickborne infection that produces a systemic small-vessel vasculitis; its prognosis is excellent if appropriate treatment is initiated early. Because the advent of effective antirickettsial therapies predates the widespread use of brain magnetic resonance imaging, there are limited data on the effect of untreated Rocky Mountain spotted fever infection on neuroimaging studies. We describe a 7-year-old girl with delayed treatment of Rocky Mountain spotted fever who suffered severe neurological impairment. Serial brain magnetic resonance images revealed a progressive "starry sky appearance," which is proposed to result from the same small vessel vasculitis that causes the characteristic skin rash of this infection. Neurological injury can continue to occur despite specific antirickettsial therapy in Rocky Mountain spotted fever. This child's clinical features raise questions about the optimal management of this infection, particularly the utility of immune modulating therapies in cases of delayed treatment and neurological involvement. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Small vessel vasculitis History, classification, etiology, histopathology, clinic, diagnosis and treatment

    International Nuclear Information System (INIS)

    Iglesias Gamarra, Antonio; Matteson, Eric L; Restrepo, Jose Felix

    2007-01-01

    Small-vessel vasculitis is a convenient descriptor for a wide range of diseases characterized by vascular inflammation of the venules, capillaries, and/or arterioles with pleomorphic clinical manifestations. The classical clinical phenotype is leucocytoclastic vasculitis with palpable purpura, but manifestations vary widely depending upon the organs involved. Histopathologic examination in leucocytoclastic vasculitis reveals angiocentric segmental inflammation, fibrinoid necrosis, and a neutrophilic infiltrate around the blood vessel walls with erythrocyte extravasation. The etiology of small-vessel vasculitis is unknown in many cases, but in others, drugs, post viral syndromes, malignancy, primary vasculitis such as microscopic polyarteritis, and connective tissue disorders are associated, The diagnosis of small- vessel vasculitis relies on a thorough history and physical examination, as well as relevant antibody testing including antinuclear antibody and anti neutrophil cytoplasmic antibody, hepatitis B and C serologies, assessment of complement, immunoglobulins, blood count, serum creatinine liver function tests, urinalysis, radiographic imaging and biopsy. The treatment is based primarily on corticosteroid and immunosuppressive agents

  2. Central Nervous System Vasculitis: Still More Questions than Answers

    Science.gov (United States)

    Alba, Marco A; Espígol-Frigolé, Georgina; Prieto-González, Sergio; Tavera-Bahillo, Itziar; García-Martínez, Ana; Butjosa, Montserrat; Hernández-Rodríguez, José; Cid, Maria C

    2011-01-01

    The central nervous system (CNS) may be involved by a variety of inflammatory diseases of blood vessels. These include primary angiitis of the central nervous system (PACNS), a rare disorder specifically targeting the CNS vasculature, and the systemic vasculitides which may affect the CNS among other organs and systems. Both situations are severe and convey a guarded prognosis. PACNS usually presents with headache and cognitive impairment. Focal symptoms are infrequent at disease onset but are common in more advanced stages. The diagnosis of PACNS is difficult because, although magnetic resonance imaging is almost invariably abnormal, findings are non specific. Angiography has limited sensitivity and specificity. Brain and leptomeningeal biopsy may provide a definitive diagnosis when disclosing blood vessel inflammation and are also useful to exclude other conditions presenting with similar findings. However, since lesions are segmental, a normal biopsy does not completely exclude PACNS. Secondary CNS involvement by systemic vasculitis occurs in less than one fifth of patients but may be devastating. A prompt recognition and aggressive treatment is crucial to avoid permanent damage and dysfunction. Glucocorticoids and cyclophosphamide are recommended for patients with PACNS and for patients with secondary CNS involvement by small-medium-sized systemic vasculitis. CNS involvement in large-vessel vasculitis is usually managed with high-dose glucocorticoids (giant-cell arteritis) or glucocorticoids and immunosuppressive agents (Takayasu’s disease). However, in large vessel vasculitis, where CNS symptoms are usually due to involvement of extracranial arteries (Takayasu’s disease) or proximal portions of intracranial arteries (giant-cell arteritis), revascularization procedures may also have an important role. PMID:22379458

  3. Pulmonary Vasculitis and a Horseshoe Kidney in Noonan Syndrome

    OpenAIRE

    Surasak Puvabanditsin; Rosanna Abellar; Adaora Madubuko; Rajeev Mehta; Lauren Walzer

    2018-01-01

    We report a term male neonate with congenital myeloproliferative disorder, thrombocytopenia, a horseshoe kidney, feeding difficulty secondary to dysphagia/foregut dysmotility, and respiratory failure. Prenatal molecular genetic analysis revealed a fetus carrying c.184T>G (p.Tyr62Asp) pathogenic variant in PTPN11. The infant eventually succumbed to respiratory failure. Bacterial and viral cultures/studies were all no growth/negative. Pulmonary capillaritis and vasculitis were noted at autopsy....

  4. Ulcerative colitis presenting as leukocytoclastic vasculitis of skin.

    Science.gov (United States)

    Akbulut, Sabiye; Ozaslan, Ersan; Topal, Firdevs; Albayrak, Levent; Kayhan, Burcak; Efe, Cumali

    2008-04-21

    A number of cutaneous changes are known to occur in the course of inflammatory bowel diseases (IBD), including pyoderma gangrenosum, erythema nodosum, perianal disease, erythematous eruptions, urticaria, and purpura. However, occurrence of skin manifestations prior to the development of ulcerative colitis is a rare occasion. Here, we report a case of ulcerative colitis associated with leukocytoclastic vasculitis in which the intestinal symptoms became overt 8 mo after the development of skin lesions.

  5. Ulcerative colitis presenting as leukocytoclastic vasculitis of skin

    OpenAIRE

    Akbulut, Sabiye; Ozaslan, Ersan; Topal, Firdevs; Albayrak, Levent; Kayhan, Burcak; Efe, Cumali

    2008-01-01

    A number of cutaneous changes are known to occur in the course of inflammatory bowel diseases (IBD), including pyoderma gangrenosum, erythema nodosum, perianal disease, erythematous eruptions, urticaria, and purpura. However, occurrence of skin manifestations prior to the development of ulcerative colitis is a rare occasion. Here, we report a case of ulcerative colitis associated with leukocytoclastic vasculitis in which the intestinal symptoms became overt 8 mo after the development of skin ...

  6. Clinical features and outcomes of ANCA-associated renal vasculitis

    Directory of Open Access Journals (Sweden)

    Sidy Mohamed Seck

    2012-01-01

    Full Text Available To determine the patterns and outcomes of the pauci-immune vasculitis in the nephrology department at hospital La Conception in Marseille, we conducted a retrospective study including all patients with diagnosis of pauci-immune renal vasculitis between January 1, 2000 and December 31, 2007. Among 33 cases, 25 were diagnosed as Wegener granulomatosis (WG, seven as microscopic polyangitis (MPA and one as Churg-Strauss syndrome (SCS. The median age of the patients was 57.7 years and the sex-ratio (M/F was 1.6. The visceral mani-festations included kidneys (100% of patients, lungs (75%, ENT (52% of WG, and nervous system (57% of MPA. The mean serum creatinine at admission was 3.3 mg/dL. Renal biopsies revealed a pauci-immune crescentic gromerulonephritis in 96% of the cases. Two patients with WG received plasmapheresis and seven patients required emergency hemodialysis. Induction therapy comprised cyclophosphamide IV and corticosteroids, while maintenance therapy included azathioprine for the majority of patients. Eighty four percent of the patients experienced complete remission after induction therapy. During maintenance therapy relapses were more frequent among patients with MPA (28% compared to WG cases (12%. After 35 months of follow-up, eight patients ended on chronic hemodialysis, and five patients died. ANCA associated vasculitis are frequent in our patients. Long-term outcomes are relatively good despite a mortality rate of 15% and 25% of the patients entering dialysis after three years of follow-up.

  7. Etiology of cutaneous vasculitis: utility of a systemic approach

    Science.gov (United States)

    Chanussot-Deprez, Caroline; Vega-Memije, María Elisa; Flores-Suárez, Luis; Ríos-Romero, Celia; Cabiedes-Contreras, Javier; Reyes, Edgardo; Rangel-Gamboa, Lucia

    2018-01-01

    Cutaneous vasculities (CV) represents a diagnostic challenge, occurs as primary cutaneous disorder or as a manifestation of other entities. To search the cause of CV. Methods: Patients with CV were prospectively evaluated. In all patients, skin biopsies were drawn, and direct immunofluorescence was done in most of the patients. American College of Rheumatology (ACR) and Chapel Hill Consensus Conference Criteria (CHCC) were used for classification. 32 patients were studied. There was female predominance (71.8%). Children presented drug-associated CV or Schönlein-Henoch púrpura (SHP). Adults presented more frequently SHP, systemic lupus erythematosus or paraneoplastic vasculitis, other diagnosis as polyarteritis nodosa, microscopic polyangiitis, thrombotic vasculitis (post-puerperal), antiphospholipid syndrome, Churg-Strauss syndrome, and drug-associated CV were presented. Using the ACR and CHCC criteria, 50% of cases were classified. In our institution, during this work the etiologic diagnostic of CV increased more than twice. However, in the case of HSV or LA and SHP none of the proposed criteria had high specificity; other parameters were used to discern between both. Six patients remained as not classified. In our view, cryoglobulins and hepatitis serology do not seem useful unless patient’s history supports they need to be done. Unclassified patients were followed-up closely for 2 years. Copyright: © 2018 SecretarÍa de Salud

  8. Neonatal cerebral oxygenation is not linked to foetal vasculitis and predicts intraventricular haemorrhage in preterm infants

    DEFF Research Database (Denmark)

    Sørensen, Line Carøe; Maroun, Lisa Leth; Borch, K.

    2008-01-01

    AIM: The aim of the study was to compare the cerebral tissue oxygenation index (c-TOI) measured by near infrared spectroscopy (NIRS) in infants with and without foetal vasculitis. METHODS: Twenty-four infants with placental signs of a foetal inflammatory response (FIR), foetal vasculitis, were.......002). CONCLUSION: Cerebral oxygenation was not affected in the first day of life in preterm infants born with foetal vasculitis, while cerebral oxygenation in infants that later developed intraventricular haemorrhage was impaired Udgivelsesdato: 2008/11...

  9. Neonatal cerebral oxygenation is not linked to foetal vasculitis and predicts intraventricular haemorrhage in preterm infants

    DEFF Research Database (Denmark)

    Sorensen, Line C; Maroun, Lisa L; Borch, Klaus

    2008-01-01

    Aim: The aim of the study was to compare the cerebral tissue oxygenation index (c-TOI) measured by near infrared spectroscopy (NIRS) in infants with and without foetal vasculitis. Methods: Twenty-four infants with placental signs of a foetal inflammatory response (FIR), foetal vasculitis, were.......002). Conclusion: Cerebral oxygenation was not affected in the first day of life in preterm infants born with foetal vasculitis, while cerebral oxygenation in infants that later developed intraventricular haemorrhage was impaired....

  10. Preclinical Validation of 99mTc–Annexin A5–128 in Experimental Autoimmune Myocarditis and Infective Endocarditis: Comparison with 99mTc–HYNIC–Annexin A5

    Directory of Open Access Journals (Sweden)

    Khadija Benali

    2015-01-01

    Full Text Available Hydrazinonicotinamide–annexin A5 (HYNIC-Anx, a 99m technetium (99mTc-labeled agent targeting phosphatidylserine, proved to be sensitive for the detection of apoptosis and thrombosis but is no longer available for clinical use. A mutant of human annexin designed for direct 99mTc labeling (referred to as Anx A5–128 showed improved binding affinity to phosphatidylserine and is expected to be used in humans. We compared both radiotracers with regard to pharmacokinetics and diagnostic ability in animal models. Biodistribution studies were performed in normal rats. Radiolabeled Anx A5–128 and HYNIC-Anx were compared in cardiovascular settings involving phosphatidylserine expression: experimental autoimmune myocarditis and infective endocarditis. Initial blood clearance was faster for Anx A5–128 than for HYNIC-Anx, and tissue biodistribution was similar overall for both tracers. The diagnostic sensitivity of Anx A5–128 was excellent and comparable to that of HYNIC-Anx. Anx A5–128 showed biodistribution and diagnostic ability similar to those of the HYNIC-Anx derivative, supporting its translation to clinical use.

  11. Peptides Against Autoimmune Neurodegeneration.

    Science.gov (United States)

    Stepanov, Alexey; Lomakin, Yakov; Gabibov, Alexander; Belogurov, Alexey

    2017-01-01

    The mammalian immune system is a nearly perfect defensive system polished by a hundred million years of evolution. Unique flexibility and adaptivity have created a virtually impenetrable barrier to numerous exogenous pathogens that are assaulting us every moment. Unfortunately, triggers that remain mostly enigmatic will sometimes persuade the immune system to retarget against self-antigens. This civil war remains underway, showing no mercy and taking no captives, eventually leading to irreversible pathological changes in the human body. Research that has emerged during the last two decades has given us hope that we may have a chance to overcome autoimmune diseases using a variety of techniques to "reset" the immune system. In this report, we summarize recent advances in utilizing short polypeptides - mostly fragments of autoantigens - in the treatment of autoimmune neurodegeneration. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  12. Sarcoidosis and Thyroid Autoimmunity

    Directory of Open Access Journals (Sweden)

    Piera Fazzi

    2017-08-01

    Full Text Available Most of the studies have shown a higher risk for subclinical and clinical hypothyroidism, antithyroid autoantibodies [overall antithyroid peroxidase antibodies (TPOAb], and in general, thyroid autoimmunity, overall in the female gender in patients with sarcoidosis (S. A significantly higher prevalence of clinical hypothyroidism and Graves’ disease was also described in female S patients with respect to controls. Gallium-67 (Ga-67 scyntigraphy in S patients, in the case of thyroid uptake, suggests the presence of aggressive autoimmune thyroiditis and hypothyroidism. For this reason, ultrasonography and thyroid function should be done in the case of Ga-67 thyroid uptake. In conclusion, thyroid function, TPOAb measurement, and ultrasonography should be done to assess the clinical profile in female S patients, and the ones at high risk (female individuals, with TPOAb positivity, and hypoechoic and small thyroid should have periodically thyroid function evaluations and suitable treatments.

  13. Elevated Adiponectin Serum Levels in Women with Systemic Autoimmune Diseases

    Directory of Open Access Journals (Sweden)

    Éric Toussirot

    2010-01-01

    Full Text Available Adipose tissue produces a wide range of proteins that may influence the immune system. In this study, we assessed the serum levels of leptin, adiponectin, and ghrelin, in association with the measurements of body composition, in 15 female patients with various autoimmune diseases (systemic lupus erythematosus, primary Sjögren's syndrome, sarcoidosis, mixed connective tissue disease, vasculitis, CREST syndrome, and polymyositis and in 15 healthy female controls. There were no statistically significant differences between the patients and controls with regard to serum leptin, serum ghrelin, global fat mass, adiposity, and fat mass in the android or gynoid regions, whereas serum adiponectin levels were higher in patients than controls (16.3±1.6 μg/mL versus 9.7±0.6 μg/mL; =.01. As adiponectin is known to exhibit potent anti-inflammatory properties, a high adiponectinemia in patients with systemic autoimmune disease may mitigate the inflammatory response. However, the precise consequences of these elevated serum adiponectin levels on the metabolic syndrome development and atherosclerotic cardiovascular risk in this patient population still needs to be determined.

  14. Autoimmune Addison's disease.

    Science.gov (United States)

    Napier, Catherine; Pearce, Simon H S

    2012-12-01

    Addison's disease is a rare autoimmune disorder. In the developed world, autoimmune adrenalitis is the commonest cause of primary adrenal insufficiency, where the majority of patients have circulating antibodies against the key steroidogenic enzyme 21-hydroxylase. A complex interplay of genetic, immunological and environmental factors culminates in symptomatic adrenocortical insufficiency, with symptoms typically developing over months to years. Biochemical evaluation and further targeted investigations must confirm primary adrenal failure and establish the underlying aetiology. The diagnosis of adrenocortical insufficiency will necessitate lifelong glucocorticoid and mineralocorticoid replacement therapy, aiming to emulate physiological patterns of hormone secretion to achieve well-being and good quality of life. Education of patients and healthcare professionals is essential to minimise the risk of a life-threatening adrenal crisis, which must be promptly recognised and aggressively managed when it does occur. This article provides an overview of our current understanding of the natural history and underlying genetic and immunological basis of this condition. Future research may reveal novel therapeutic strategies for patient management. Until then, optimisation of pharmacological intervention and continued emphasis on education and empowerment of patients should underpin the management of individuals with autoimmune Addison's disease. Copyright © 2012. Published by Elsevier Masson SAS.

  15. Autoimmune thyrotoxicosis: diagnostic challenges.

    Science.gov (United States)

    Ponto, Katharina A; Kahaly, George J

    2012-09-01

    Autoimmune thyrotoxicosis or Graves' disease (GD) is the most common cause of hyperthyroidism in the United States (full text available online: http://education.amjmed.com/pp1/249). GD occurs more often in women (ratio 5:1) and has a population prevalence of 1-2%. A genetic determinant to the susceptibility to GD is suspected because of familial clustering of the disease, a high sibling recurrence risk, and the familial occurrence of thyroid autoantibodies. GD is a systemic autoimmune thyroid disorder characterized by the infiltration of immune effector cells and thyroid-antigen-specific T cells into the thyroid and thyroid stimulating hormone receptor (TSHR) expressing tissues, i.e. orbit, skin, with the production of autoantibodies to well-defined thyroidal antigens. Stimulatory autoantibodies in GD activate the TSHR leading to thyroid hyperplasia and unregulated thyroid hormone production and secretion. Diagnosis of GD is straightforward in a patient with a diffusely enlarged, heterogeneous, hypervascular (increased Doppler flow on neck ultrasound) thyroid gland, associated orbitopathy, biochemically confirmed thyrotoxicosis, positive TSHR autoantibodies, and often a family history of autoimmune disorders. Copyright © 2012. Published by Elsevier Inc.

  16. Autoimmune liver disease 2007.

    Science.gov (United States)

    Muratori, Paolo; Granito, Alessandro; Pappas, Georgios; Muratori, Luigi; Lenzi, Marco; Bianchi, Francesco B

    2008-01-01

    Autoimmune liver disease (ALD) includes a spectrum of diseases which comprises both cholestatic and hepatitic forms: autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC) and the so called "overlap" syndromes where hepatitic and cholestatic damage coexists. All these diseases are characterized by an extremely high heterogeneity of presentation, varying from asymptomatic, acute (as in a subset of AIH) or chronic (with aspecific symptoms such as fatigue and myalgia in AIH or fatigue and pruritus in PBC and PSC). The detection and characterization of non organ specific autoantibodies plays a major role in the diagnostic approach of autoimmune liver disease; anti nuclear reactivities (ANA) and anti smooth muscle antibodies (SMA) mark type 1 AIH, liver kidney microsomal antibody type 1 (LKM1) and liver cytosol type 1 (LC1) are the serological markers of type 2 AIH; antimitochondrial antibodies (AMA) are associated with PBC, while no specific marker is found in PSC, since anticytoplasmic neutrophil antibodies with perinuclear pattern (atypical p-ANCA or p-ANNA) are also detected in a substantial proportion of type 1 AIH cases. Treatment options rely on immunosoppressive therapy (steroids and azathioprine) in AIH and on ursodeoxycholic acid in cholestatic conditions; in all these diseases liver transplantation remains the only therapeutical approach for the end stage of liver disease.

  17. Autoimmune liver disease and therapy in childhood

    Directory of Open Access Journals (Sweden)

    Matjaž Homan

    2013-10-01

    Full Text Available Autoimmune hepatitis is a chronic immune-mediated disease of the liver. In childhood, autoimmune liver disorders include autoimmune hepatitis type I and II, autoimmune sclerosing cholangitis, Coombs-positive giant cell hepatitis, and de novo autoimmune hepatitis after liver transplantation. Autoimmune liver disease has a more aggressive course in children, especially autoimmune hepatitis type II. Standard therapy is a combination of corticosteroids and azathioprine. Around 80 % of children with autoimmune liver disease show a rapid response to combination therapy. The non-responders are treated with more potent drugs, otherwise autoimmune disease progresses to cirrhosis of the liver and the child needs liver transplantation as rescue therapy.

  18. [Treatment of autoimmune hepatic diseases].

    Science.gov (United States)

    Bueverov, A O

    2004-01-01

    The immunosuppresive drugs, primarily glucocorticosteroids, serve as the basis for the pathogenetic treatment of autoimmune diseases of the liver. In autoimmune hepatitis, immunosuppressive therapy induces and maintains persistent remission in most patients while in primary biliary cirrhosis and primary sclerosing cholangitis, its capacities are substantially limited. Ursodeoxycholic acid is used as the basic drug in predominantly occurring intrahepatic cholestasis. The treatment of cross autoimmune syndromes generally requires the choice of a combination of drugs.

  19. A case of propylthiouracil-induced antineutrophilic cytoplasmic antibody-positive vasculitis successfully treated with radioactive iodine

    Directory of Open Access Journals (Sweden)

    C. Bes

    2013-07-01

    Full Text Available Antineutrophilic cytoplasmic antibody (ANCA associated vasculitis is one of the rare complications of propylthiouracil treatment. Having a variable clinical spectrum, it may be presented with both skin limited vasculitis and life-threatening systemic vasculitis. In this study, we present a case that developed ANCA-positive vasculitis with skin and kidney involvement (hematuria and proteinuria six months after propylthiouracil treatment was initiated for toxic nodular goiter. Proteinuria recovered dramatically subsequent to radioactive iodine treatment following ceasing the drug.

  20. Autoimmune hepatitis vs. pregnancy

    Directory of Open Access Journals (Sweden)

    Olga Adamczyk-Gruszka

    2017-07-01

    Full Text Available Introduction Autoimmune hepatitis (AIH is a disease of unknown etiology. In pregnancy, it may have mild clinical course as well as can lead to liver failure, or exacerbation of clinical symptoms. In pregnant women the severity of symptoms is often observed between the second and third trimester, and in the puerperium. The disease is marked by enhanced activity of Th lymphocytes, which hepatocytes recognize as foreign antigens. This results in interleukin production activating B lymphocytes, and the production of specific antibodies attacking and destroying the hepatocytes. Case report A 35-year old patient, CII PII, 7 Hbd, with autoimmune hepatitis reported for a check-up. Her first pregnancy was 18 years ago, without history of underlying disease, carried to term without complications. The woman gave birth to a baby-son weighing 3,280g, 10 points Apgar. The delivery was spontaneous and uneventful. The patient got pregnant after an 18-year break. When she twice-tested positively for pregnancy, the treatment with azathioprine was switched to prednisolone. Over the pregnancy the patient was hospitalized 4 times, in 25, 29, 35, and 37 week of gestation due to a threat of preterm delivery, and pregnancy-related cholestasis associated with AIH. In 37 week of gestation, delivery was induced, and she gave birth to a healthy male, weighing 2,650 g, body height of 49 cm, 10 points Apgar scale. The liver function improved and stabilized after the delivery. Treatment with prednisolone has been continued, and the patient’s condition is still controlled. Pregnant patients with autoimmune hepatitis often experience exacerbation of the disease, especially in the third trimester, and in the postpartum period. This case shows that with proper care it is possible to continue and terminate pregnancy safely for the mother and her newly born baby.

  1. Pulmonary vasculitis may obscure large cell lung carcinoma. A case report

    NARCIS (Netherlands)

    Kreeftenberg, HG; Ligtenberg, JJM; van der Werf, TS; Timens, W; Tervaert, JWC

    2001-01-01

    Several vasculitic syndromes are recognized as paraneoplastic symdromes of an underlying malignant disease. Most frequently small vessel vasculitis of the skin has been reported. We describe the case of a 62-year-old man with a pulmonary mass due to pulmonary vasculitis. After resection of the

  2. A sphingosine 1-phosphate receptor agonist ameliorates animal model of vasculitis.

    Science.gov (United States)

    Miyabe, Chie; Miyabe, Yoshishige; Komiya, Takaki; Shioya, Hiroki; Miura, Noriko N; Takahashi, Kei; Ohno, Naohito; Tsuboi, Ryoji; Luster, Andrew D; Kawai, Shinichi; Miyasaka, Nobuyuki; Nanki, Toshihiro

    2017-04-01

    Sphingosine 1-phosphate (S1P) is a bioactive lipid that binds to cell surface receptors (S1P 1-5 ). In this study, we examined the effect of S1P 1 agonist, ONO-W061, on murine Candida albicans water-soluble fraction (CAWS)-induced vasculitis. Mice were administered ONO-W061, and the number of peripheral blood cells was counted. Vasculitis was induced by an intraperitoneal injection of CAWS. Expression of S1P receptors and CXCL1 was analyzed by quantitative RT-PCR. ONO-W061 was orally administered, and vasculitis was evaluated histologically. Number of neutrophils, macrophages and T cells in the vasculitis tissue was counted using flow cytometry. Production of chemokines from S1P-stimulated human umbilical vein endothelial cells (HUVECs) was measured by ELISA. Number of peripheral blood lymphocytes was decreased by ONO-W061. Expression of CXCL1 and S1P 1 was enhanced in CAWS-induced vasculitis tissue. Vasculitis score, CXCL1 and number of neutrophils in the vasculitis tissue were lower in ONO-W061-treated mice. Treatment of HUVECs with S1P upregulated the production of CXCL1 and IL-8 in vitro, and this was inhibited by ONO-W061. ONO-W061 significantly improved CAWS-induced vasculitis. This effect may be partly exerted through the inhibited production of chemokines by endothelial cells, which in turn could induce neutrophil recruitment into inflamed vessels.

  3. Complete remission of coronary vasculitis in Churg-Strauss Syndrome by prednisone and cyclophosphamide.

    Science.gov (United States)

    Riksen, Niels P; Gehlmann, Helmut; Brouwer, Annemarie E; van Deuren, Marcel

    2013-03-01

    The heart is involved in up to 50% of all patients with Churg-Strauss syndrome, but vasculitis of the coronary arteries has only been rarely documented. We present a young patient with severe coronary aneurysms and stenotic lesions due to a Churg-Strauss vasculitis. Prompt therapy with prednisone and cyclophosphamide resulted in the complete resolution of all lesions.

  4. Complete remission of coronary vasculitis in Churg-Strauss Syndrome by prednisone and cyclophosphamide

    NARCIS (Netherlands)

    Riksen, N.P.; Gehlmann, H.R.; Brouwer, A.E.; Deuren, M. van

    2013-01-01

    The heart is involved in up to 50% of all patients with Churg-Strauss syndrome, but vasculitis of the coronary arteries has only been rarely documented. We present a young patient with severe coronary aneurysms and stenotic lesions due to a Churg-Strauss vasculitis. Prompt therapy with prednisone

  5. Zuo-Gui and You-Gui pills, two traditional Chinese herbal formulas, downregulated the expression of NogoA, NgR, and RhoA in rats with experimental autoimmune encephalomyelitis.

    Science.gov (United States)

    Kou, Shuang; Zheng, Qi; Wang, Yizhou; Zhao, Hui; Zhang, Qiuxia; Li, Ming; Qi, Fang; Fang, Ling; Liu, Lei; Ouyang, Junyao; Zhao, Haiyu; Wang, Lei

    2014-12-02

    Zuo-Gui pills (ZGPs) and You-Gui pills (YGPs) are 2 traditional Chinese herbal formulas used for treating multiple sclerosis (MS) in the clinical setting and have been shown to have neuroprotective effects in experimental autoimmune encephalomyelitis (EAE), an animal model of MS. The aim of this study was to explore the mechanisms underlying the neuroprotective functions of ZGPs and YGPs. Female Lewis rats were randomly divided into normal control, EAE model, 2g/kg ZGP-treated EAE, 3g/kg YGP-treated EAE, and prednisone acetate-treated groups. EAE model was induced by subcutaneous injection of MBP68-86 antigen. The neurological function scores were estimated. Histological structures of the brains and spinal cords were observed, and myelinated and axons imaged. NogoA, Nogo receptor (NgR), and RhoA transcript and protein levels were measured by real-time quantitative RT-PCR and western blotting on postimmunization (PI) days 14 (acute stage) and 28 (remission stage). ZGPs and YGPs significantly reduced neurological functions scores and abrogated inflammatory infiltrates, demyelination, and axonal damage. Furthermore, treatment with ZGPs and YGPs inhibited NogoA, NgR, and RhoA mRNA and protein expression in rats at both the acute and remission stages. ZGPs exhibited stronger effects on NogoA and RhoA expressions, as well as neurological function, during the acute stage of EAE, while YGPs caused greater reductions in NogoA expression during the remission stage. Our findings suggested that ZGPs and YGPs exerted neuroprotective effects by downregulation of NogoA, NgR, and RhoA pathways, with differences in response times and targets observed between ZGPs and YGPs. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  6. Pulmonary Vasculitis and a Horseshoe Kidney in Noonan Syndrome

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    Surasak Puvabanditsin

    2018-01-01

    Full Text Available We report a term male neonate with congenital myeloproliferative disorder, thrombocytopenia, a horseshoe kidney, feeding difficulty secondary to dysphagia/foregut dysmotility, and respiratory failure. Prenatal molecular genetic analysis revealed a fetus carrying c.184T>G (p.Tyr62Asp pathogenic variant in PTPN11. The infant eventually succumbed to respiratory failure. Bacterial and viral cultures/studies were all no growth/negative. Pulmonary capillaritis and vasculitis were noted at autopsy. This report presents a new case of Noonan syndrome with unusual associated disorders and a review of the literature.

  7. Pulmonary Vasculitis and a Horseshoe Kidney in Noonan Syndrome.

    Science.gov (United States)

    Puvabanditsin, Surasak; Abellar, Rosanna; Madubuko, Adaora; Mehta, Rajeev; Walzer, Lauren

    2018-01-01

    We report a term male neonate with congenital myeloproliferative disorder, thrombocytopenia, a horseshoe kidney, feeding difficulty secondary to dysphagia/foregut dysmotility, and respiratory failure. Prenatal molecular genetic analysis revealed a fetus carrying c.184T>G (p.Tyr62Asp) pathogenic variant in PTPN11 . The infant eventually succumbed to respiratory failure. Bacterial and viral cultures/studies were all no growth/negative. Pulmonary capillaritis and vasculitis were noted at autopsy. This report presents a new case of Noonan syndrome with unusual associated disorders and a review of the literature.

  8. A general rehabilitation inpatient with exercise-induced vasculitis.

    Science.gov (United States)

    Cushman, Dan; Rydberg, Leslie

    2013-10-01

    While on our general inpatient rehabilitation floor, a 58-year-old man with no hematologic or dermatologic history developed an erythematous patch on his medial ankle that turned more purpuric, with a slight orange tint, and was associated with mild pruritus. The diagnosis of exercise-induced vasculitis was made after initially being mistaken for cellulitis. This common exanthem is often misdiagnosed. Due to its association with exercise, the physiatrist should be aware of its presence in both the inpatient and outpatient settings. Copyright © 2013 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.

  9. Central nervous system vasculitis caused by propylthiouracil therapy: a case report and literature review.

    Science.gov (United States)

    Vanek, C; Samuels, M H

    2005-01-01

    Antineutrophil cytoplasmic antibodies (ANCA) are associated with vasculitis, including vasculitis induced by drugs such as the thionamides. The affected organ systems in thionamide-induced vasculitis have been primarily renal, musculoskeletal, and dermatologic. We describe the first case of thionamide-induced central nervous system vasculitis presenting as confusion, with complete resolution after discontinuation of propylthiouracil. We review the literature and summarize 42 additional cases of thionamide-induced ANCA-positive vasculitis since 1992. Propylthiouracil was responsible in 93% of cases and the predominant ANCA pattern on immunofluorescent staining was perinuclear (p-ANCA). Clinical improvement occurred after drug discontinuation in 93%, steroid therapy was used in some cases. The mean duration of treatment with thionamides was 35 months prior to presentation. Long-term medical treatment with thionamides for hyperthyroidism may increase the risk of this severe side effect.

  10. Steroids and Autoimmunity.

    Science.gov (United States)

    Trombetta, Amelia Chiara; Meroni, Marianna; Cutolo, Maurizio

    2017-01-01

    From the middle of the 19th century, it is known that endocrine and immune systems interact bi-directionally in different processes that ensure organism homeostasis. Endocrine and nervous systems have a pivotal role in the balancing of pro- and anti-inflammatory functions of immune system, and constitute a complex circadian neuroendocrine network. Autoimmune diseases have in fact a complex pathogenic origin in which the importance of endocrine system was demonstrated. In this chapter, we will mention the structure and function of steroidal hormones involved in the neuroendocrine immune network and we will address the ways in which endocrine and immune systems influence each other, in a bi-directional fashion. Adrenal hormones, sex hormones, vitamin D, and melatonin and prolactin importantly all contribute to the homeostasis of the immune system. Indeed, some of the steroidal hormone activities determine inhibition or stimulation of immune system components, in both physiological (i.e. suppression of an unwanted response in pregnancy, or stimulation of a protective response in infections) and pathological conditions. We will finally mention the rationale for optimization of exogenous administration of glucocorticoids in chronic autoimmune diseases, and the latest developments concerning these drugs. © 2017 S. Karger AG, Basel.

  11. Current topics in autoimmune hepatitis.

    Science.gov (United States)

    Muratori, Luigi; Muratori, Paolo; Granito, Alessandro; Pappas, Giorgios; Cassani, Fabio; Lenzi, Marco

    2010-11-01

    Autoimmune hepatitis is a chronic liver disease of unknown aetiology characterized by interface hepatitis, hypergammaglobulinaemia and circulating autoantibodies. In the last decade a number of advancements have been made in the field of clinical and basic research: the simplified diagnostic criteria, the complete response defined as normalization of transaminase levels, the molecular identification of the antigenic targets of anti-liver cytosol antibody type 1 and anti-soluble liver antigen, the detection of anti-actin antibodies, the description of de novo autoimmune hepatitis after liver transplantation for non-autoimmune liver diseases, the characterization of autoimmune hepatitis with overlapping features of primary biliary cirrhosis or primary sclerosing cholangitis, the preliminary experience with novel treatment strategies based on cyclosporine, mycophenolate mofetil and budesonide, the role played by "impaired" regulatory T cells and the development of novel animal models of autoimmune hepatitis. Copyright © 2010 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

  12. Cocaine-Levamisole-Induced Vasculitis/Vasculopathy Syndrome.

    Science.gov (United States)

    Marquez, Javier; Aguirre, Lina; Muñoz, Carolina; Echeverri, Andres; Restrepo, Mauricio; Pinto, Luis F

    2017-06-01

    To understand the clinical spectrum of cocaine-levamisole-induced vasculitis. Worldwide recreational drug consumption is high among the adult population from various social strata. The use of cocaine with levamisole, a frequently added antiparasitic diluent, favors the manifestations of vasculitic lesions, especially in the skin. New insights into immunological mechanisms involved in the pathogenesis of the disease. There are still many unknown aspects in the pathogenesis of this disease, such as the immune system interaction with p-ANCAs and the release of inflammatory NETs (neutrophil extracellular traps), which are the origin of auto-antigens and tissue damage, manifesting as vasculitic purpura on the skin. The clinical presentation constitutes a challenge for the clinician to be able to distinguish it from small-vessel vasculitides. This paper intends to improve the understanding of this condition, exhibiting the broad clinical spectrum of local and systemic manifestations of cocaine-levamisole-induced vasculitis, to facilitate a timely diagnosis, in order to take corrective measures and avoid sequelae, along with tissue damage and the consequent deformities and permanent scars.

  13. Monitoring Vasculitis with 18F-FDG PET

    International Nuclear Information System (INIS)

    Jan BUCERIUS, Jan

    2016-01-01

    Whereas in the past the term “vasculitis” was most frequently used in context with systemic vasculitides, such as the large vessel vasculitides (LVV) Takayasa arteritis and giant cell arteritis, characterized by inflammation of blood vessel walls, it nowadays comprises also inflammatory changes of the vessel wall as a substantial part of the atherosclerotic disease process. Implementing non-invasive imaging techniques, such as computed tomography angiography (CTA), magnetic resonance angiography (MRA) as well as positron emission tomography (PET) in the diagnostic algorithm of atherosclerosis and LVV, depicts a promising step towards an earlier detection with a, consecutively, improved therapeutic approach and potentially prognostic benefit in patients suffering from vasculitis. Mainly molecular imaging with 18F-fluorodeoxyglucose (FDG) PET seems to be promising in offering an early and sensitive identification of inflammatory changes in both, atherosclerosis and LVV. This review will therefore provide an overview on the diagnostic performance and clinical relevance of FDG-PET in monitoring vasculitis in atherosclerosis and LVV, with a focus on LVV.

  14. Eosinophils in vasculitis: characteristics and roles in pathogenesis

    Science.gov (United States)

    Khoury, Paneez; Grayson, Peter C.; Klion, Amy D.

    2016-01-01

    Eosinophils are multifunctional granular leukocytes that are implicated in the pathogenesis of a wide variety of disorders, including asthma, helminth infection, and rare hypereosinophilic syndromes. Although peripheral and tissue eosinophilia can be a feature of many types of small-vessel and medium-vessel vasculitis, the role of eosinophils has been best studied in eosinophilic granulomatosis with polyangiitis (EGPA), where eosinophils are a characteristic finding in all three clinical stages of the disorder. Whereas numerous studies have demonstrated an association between the presence of eosinophils and markers of eosinophil activation in the blood and tissues of patients with EGPA, the precise role of eosinophils in disease pathogenesis has been difficult to ascertain owing to the complexity of the disease process. In this regard, results of clinical trials using novel agents that specifically target eosinophils are providing the first direct evidence of a central role of eosinophils in EGPA. This Review focuses on the aspects of eosinophil biology most relevant to the pathogenesis of vasculitis and provides an update of current knowledge regarding the role of eosinophils in EGPA and other vasculitides. PMID:25003763

  15. Leukocytoclastic Vasculitis in a Patient with Ankylosing Spondylitis

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    Senol Kobak

    2014-01-01

    Full Text Available A 26-year-old male patient presented to our rheumatology clinic with pain, swelling and limitation of movement in his right ankle, and also purpuric skin lesions in the lower extremity pretibial region. He was asked questions, and he said that he had been having chronic low back pain and morning stiffness for the last few years. His physical examination revealed that he had arthritis in his right ankle, purpuric skin lesions in pretibial regions of both legs, and bilateral FABERE/FADIR positivity. The sacroiliac joint imaging and MRI revealed bilateral sacroiliitis findings, and the lateral heel imaging revealed enthesitis. HLA-B27 was positive. Skin biopsy from lower skin lesions was reported to be consistent with leukocytoclastic vasculitis. Based on clinical, laboratory, radiological, and pathological examinations, the patient was diagnosed with ankylosing spondylitis and leukocytoclastic vasculitis. Administration of corticosteroid, salazopyrin, and nonsteroid anti-inflammatory medications was started. Notable clinical and laboratory regression was observed during his checks 3 months later.

  16. MRI in human immunodeficiency virus-associated cerebral vasculitis

    International Nuclear Information System (INIS)

    Berkefeld, J.; Lanfermann, H.

    2000-01-01

    Cerebral ischaemia caused by inflammatory vasculopathies has been described as complication of human immunodeficiency virus (HIV) infection. Imaging studies have shown ischaemic lesions and changes of the vascular lumen, but did not allow demonstration of abnormalities within the vessel wall itself. Two HIV-infected men presented with symptoms of a transient ischaemic attack. Initial MRI of the first showed no infarct; in the second two small lacunar lesions were detected. In both cases, multiplanar 3-mm slice contrast-enhanced T1-weighted images showed aneurysmal dilatation, with thickening and contrast enhancement of the wall of the internal carotid and middle cerebral (MCA) arteries. These findings were interpreted as indicating cerebral vasculitis. In the first patient the vasculopathy progressed to carotid artery occlusion, and he developed an infarct in the MCA territory, but then remained neurologically stable. In the second patient varicella zoster virus (VZV) infection was the probable cause of vasculitis. The clinical deficits and vasculitic MRI changes regressed with antiviral and immunosuppressive therapy. (orig.)

  17. MRI in human immunodeficiency virus-associated cerebral vasculitis

    Energy Technology Data Exchange (ETDEWEB)

    Berkefeld, J.; Lanfermann, H. [Frankfurt Univ. (Germany). Abt. fuer Neuroradiologie; Enzensberger, W. [Klinik fuer Neurologie, Klinikum der Johann Wolfgang Goethe-Univ. Frankfurt am Main (Germany)

    2000-07-01

    Cerebral ischaemia caused by inflammatory vasculopathies has been described as complication of human immunodeficiency virus (HIV) infection. Imaging studies have shown ischaemic lesions and changes of the vascular lumen, but did not allow demonstration of abnormalities within the vessel wall itself. Two HIV-infected men presented with symptoms of a transient ischaemic attack. Initial MRI of the first showed no infarct; in the second two small lacunar lesions were detected. In both cases, multiplanar 3-mm slice contrast-enhanced T1-weighted images showed aneurysmal dilatation, with thickening and contrast enhancement of the wall of the internal carotid and middle cerebral (MCA) arteries. These findings were interpreted as indicating cerebral vasculitis. In the first patient the vasculopathy progressed to carotid artery occlusion, and he developed an infarct in the MCA territory, but then remained neurologically stable. In the second patient varicella zoster virus (VZV) infection was the probable cause of vasculitis. The clinical deficits and vasculitic MRI changes regressed with antiviral and immunosuppressive therapy. (orig.)

  18. Multiple evanescent white dot syndrome associated with retinal vasculitis

    Directory of Open Access Journals (Sweden)

    Takahashi A

    2015-09-01

    Full Text Available Akihiro Takahashi, Wataru Saito, Yuki Hashimoto, Susumu Ishida Department of Ophthalmology, Hokkaido University Graduate School of Medicine, Sapporo, Japan Purpose: A recent study revealed thickening of the inner retinal layers in acute stage of multiple evanescent white dot syndrome (MEWDS; however, the pathogenesis is still unknown. We report two cases with MEWDS whose funduscopy showed obvious retinal vasculitis. Methods: Case reports. Results: Healthy myopic 16- and 27-year-old women were the cases under study. In both cases, funduscopic examination revealed multiple, faint, small, subretinal white dots at the posterior pole to the midperiphery and macular granularity oculus dexter. Retinal vascular sheathing was also observed at midperiphery. Late-phase fluorescein angiography revealed leakages corresponding to the vascular sheathing. Enhanced depth imaging optical coherence tomography revealed the discontinuity of the ellipsoid zone corresponding to the white dots and increased macular choroidal thickness. One month later, these white dots and retinal sheathing spontaneously resolved in both cases. Three months later, impairments of the outer retinal morphology and the visual acuity were restored. Conclusion: These results suggest that retinal vasculitis possibly plays a role in the pathogenesis of thickened inner retinal layers in acute stage of MEWDS. Keywords: enhanced depth imaging optical coherence tomography, choroidal thickness, inner retinal layer, retinal vascular sheathing

  19. Autoimmune premature ovarian failure

    Directory of Open Access Journals (Sweden)

    Beata Komorowska

    2017-02-01

    Full Text Available Premature ovarian failure (POF, also termed as primary ovarian insufficiency (POI, is a highly heterogenous condition affecting 0.5-3.0% of women in childbearing age. These young women comprise quite a formidable group with unique physical and psychological needs that require special attention. Premature ovarian senescence (POS in all of its forms evolves insidiously as a basically asymptomatic process, leading to complete loss of ovarian function, and POI/POF diagnoses are currently made at relatively late stages. Well-known and well-documented risk factors exist, and the presence or suspicion of autoimmune disorder should be regarded as an important one. Premature ovarian failure is to some degree predictable in its occurrence and should be considered while encountering young women with loss of menstrual regularity, especially when there is a concomitant dysfunction in the immune system.

  20. Psychoneuroimmunology - psyche and autoimmunity.

    Science.gov (United States)

    Ziemssen, Tjalf

    2012-01-01

    Psychoneuroimmunology is a relatively young field of research that investigates interactions between central nervous and immune system. The brain modulates the immune system by the endocrine and autonomic nervous system. Vice versa, the immune system modulates brain activity including sleep and body temperature. Based on a close functional and anatomical link, the immune and nervous systems act in a highly reciprocal manner. From fever to stress, the influence of one system on the other has evolved in an intricate manner to help sense danger and to mount an appropriate adaptive response. Over recent decades, reasonable evidence has emerged that these brain-to-immune interactions are highly modulated by psychological factors which influence immunity and autoimmune disease. For several diseases, the relevance of psychoneuroimmunological findings has already been demonstrated.

  1. Autoimmune hepatitis in children.

    Science.gov (United States)

    Mieli-Vergani, Giorgina; Vergani, Diego

    2002-08-01

    AIH, ASC, and de novo AIH after liver transplantation are childhood liver diseases of an autoimmune nature. The mode of presentation of AIH in childhood is variable, and the disease should be suspected and excluded in all children presenting with symptoms and signs of prolonged or severe acute liver disease. Although corticosteroids are effective in all types of childhood AIH, patients with LKM1 have a higher frequency of acute hepatic failure and relapse after corticosteroid withdrawal than do patients with ANA/SMA. ASC occurs commonly in the absence of inflammatory bowel disease, requires cholangiography for diagnosis, and improves during corticosteroid therapy. The development of AIH de novo in children who undergo liver transplantation for nonautoimmune liver disease may reflect interference with the maturation of T cells by immunosuppressive drugs.

  2. MR-angiography in vasculitis and benign angiopathy of the central nervous system

    International Nuclear Information System (INIS)

    Schlueter, A.; Hirsch, W.; Jassoy, A.; Behrmann, C.; Spielmann, R.P.; Kornhuber, M.; Keysser, G.

    2001-01-01

    To evaluate TOF 3D magnetic resonance angiography (MRA) of the intracranial arteries in patients with vasculitis or vasculitis-like benign angiopathy of the central nervous system (CNS). Method: The results of MRA in 20 patients with clinically and radiographically proven vasculitis (17/20) or vasculitis-like benign angiopathy (3/20) of the CNS were retrospectively analysed. Patients with hyperintense lesions of more than 3 mm on T 2 -weighted MRI images were included in this trial. An inflammatory, embolic, neurodegenerative or metastatic origin of these lesions was excluded by extensive clinical studies. For the MR-examination a TOF 3D FISP sequence was used on a 1.5 T imager. Results: MRA showed characteristic changes for vasculitis or angiopathy in 15 of 20 patients (75%). Conclusions: In patients suspected of having a vasculitis or vasculitis-like angiopathy, MRA is recommended as a non-invasive modality. If the results of MRI and extensive clinical studies are carefully correlated, MRA may substitute conventional angiography in cases with typical vascular changes. (orig.) [de

  3. Red Blood Cell Distribution Width and Neutrophil-to-Lymphocyte Ratio in Patients with Cutaneous Vasculitis.

    Science.gov (United States)

    Emiroglu, Nazan; Cengiz, Fatma Pelin; Bahalı, Anıl Gulsel; Ozkaya, Dilek Biyik; Su, Ozlem; Onsun, Nahide

    2017-03-01

    Vasculitis represents a specific pattern of inflammation of the blood vessel wall that can occur in any organ system of the body. The neutrophil to lymphocyte ratio (NLR) and red blood cell distribution width (RDW) are currently used as markers of inflammation in several diseases. This study analyzed C-reactive protein level (CRP), erythrocyte sedimentation rate (ESR), white blood cell (WBC), NLR, and RDW in patients who had cutaneous vasculitis, or cutaneous vasculitis with systemic involvement, and in healthy controls. A total of 85 individuals were included in our study: 45 with vasculitis and 40 healthy controls. Patients who had complete blood count (CBC) analysis, CRP, and ESR at the time of skin biopsy were included in the study. NLR was calculated from these parameters. NLR, CRP, ESR, and WBC were significantly higher in patients with vasculitis than in healthy controls (p≤0.05), but RDW did not significantly differ between the two groups. This study suggests that blood NLR may be used for predicting vasculitis, especially cutaneous vasculitis with systemic involvement. © 2017 by the Association of Clinical Scientists, Inc.

  4. Eosinophilic leukocytoclastic vasculitis - a spectrum ranging from Wells' syndrome to Churg-Strauss syndrome?

    Science.gov (United States)

    Ratzinger, Gudrun; Zankl, Julia; Eisendle, Klaus; Zelger, Bernhard

    2014-01-01

    Wells' syndrome is defined as an inflammatory disorder with the histopathological presence of eosinophilic infiltrates and flame figures in the absence of vasculitis. Eosinophilic leukocytoclastic vasculitis shows eosinophilic infiltrates in combination with vasculitic changes. And Churg Strauss Syndrome comprises all three characteristics - eosinophilic infiltrates, vasculitis and flame figures. To determine whether these three diseases are distinct entities or different manifestations of a similar clinicopathologic process. Histopathological samples and clinical courses of 17 patients with eosinophilic infiltrates, flame figures and clinical features of Wells' syndrome were re-evaluated. Histopathologically, we focused on the presence or absence of vasculitic features. Clinically, we included only patients who were diagnosed with Wells' syndrome at least once in the course of their disease. 4 patients were finally diagnosed with Wells' syndrome, 5 with eosinophilic leukocytoclastic vasculitis and 6 with Churg Strauss syndrome. Further, we had one case of an overlap between Wells' syndrome and eosinophilic vasculitis and one case of Wegener granulomatosis. Vasculitic features were found in the samples of all patients. Histologically, we find vasculitic features in typical presentations of Wells' syndrome. Clinically, we find typical features of Wells' syndrome in patients finally diagnosed with eosinophilic leukocytoclastic vasculitis or Churg Strauss syndrome. Furthermore, we have observed and formerly reported 3 patients with progression from Wells' syndrome to Churg Strauss syndrome. Thus, we assume that eosinophilic leukocytoclastic vasculitis might form a bridge between Wells' syndrome and Churg Strauss syndrome.

  5. Mechanism of action and efficacy of RX-111, a thieno[2,3-c]pyridine derivative and small molecule inhibitor of protein interaction with glycosaminoglycans (SMIGs), in delayed-type hypersensitivity, TNBS-induced colitis and experimental autoimmune encephalomyelitis

    Czech Academy of Sciences Publication Activity Database

    Harris, N.; Koppel, J.; Zsila, F.; Juhás, Štefan; Ilková, G.; Kogan, F. Y.; Lahmy, O.; Wildbaum, G.; Karin, N.; Zhuk, R.; Gregor, P.

    2016-01-01

    Roč. 65, č. 4 (2016), s. 285-294 ISSN 1023-3830 Institutional support: RVO:67985904 Keywords : small molecule drug * glycosaminoglycan * heparin binding protein * heparan sulfate * inflammation * autoimmune disease Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.659, year: 2016

  6. Recurrence and graft loss after renal transplantation in adults with IgA vasculitis.

    Science.gov (United States)

    Kawabe, Mayuko; Yamamoto, Izumi; Komatsuzaki, Yo; Yamakawa, Takafumi; Katsumata, Haruki; Katsuma, Ai; Mafune, Aki; Nakada, Yasuyuki; Kobayashi, Akimitsu; Tanno, Yudo; Ohkido, Ichiro; Tsuboi, Nobuo; Yokoyama, Keitaro; Horita, Shigeru; Okumi, Masayoshi; Ishida, Hideki; Yamamoto, Hiroyasu; Yokoo, Takashi; Tanabe, Kazunari

    2017-08-01

    IgA vasculitis, a rare condition resulting in end-stage renal disease, is a small-vessel vasculitis that affects the kidney in 49-83 % of adults. The reported recurrence rate of IgA vasculitis in renal transplant recipients is 11.5-60 %, leading to graft loss in 0-50 % of these patients. However, limited data are available on recurrence and graft loss after renal transplantation. We evaluated renal transplant recipients seen from 1987 to 2015 at the Jikei University School of Medicine and the Department of Urology, Tokyo Women's Medical University. Using a 1:2 match, 21 patients with IgA vasculitis and 42 controls were selected. The mean post-transplant follow-up was 121 ± 69 months for IgA vasculitis and 147 ± 66 months for the controls. The 15-year patient survival was 100 % in IgA vasculitis and 97.6 % in the controls (p = 0.22). The 5-, 10-, and 15-year graft survival rates were 95.2, 90.5, and 81 % in IgA vasculitis and 100, 90.5, and 88.1 % in the controls, respectively (p = 0.63). The recurrence rate was 28.6 % (6 of 21 cases) and half of them (3 of 6 cases) showed histological activity (ISKDC III). We treated them with methylprednisolone pulse therapy and/or tonsillectomy. None of the recurrence cases lost the allograft. The long-term patient and graft survival of IgA vasculitis in renal transplantation were comparable with the previous reports. The recurrence rate was 28.6 %, but none of the recurrent cases showed allograft loss in this study. We speculate that methylprednisolone pulse therapy and/or tonsillectomy prevent the progression of recurrent IgA vasculitis.

  7. Causal Attributions about Disease-Onset and Relapse in Patients with Systemic Vasculitis

    Science.gov (United States)

    Grayson, Peter C.; Amudala, Naomi A.; McAlear, Carol A.; Leduc, Renée L.; Shereff, Denise; Richesson, Rachel; Fraenkel, Liana; Merkel, Peter A.

    2014-01-01

    Objectives Patients vary in their beliefs related to the cause of serious illness. The impact of these beliefs among patients with systemic vasculitis is not known. This study aimed to describe causal attributions about disease-onset and relapse in systemic vasculitis and to examine whether causal beliefs a) differ by type of vasculitis; and b) are associated with negative health outcomes. Methods Patients with vasculitis were recruited to complete an online questionnaire. Categories of causal beliefs were assessed with the Revised Illness Perception Questionnaire (IPQ-R). Differences in beliefs about disease-onset versus relapse were compared across different forms of vasculitis. Causal beliefs were assessed in association with several health outcomes including fatigue, functional impairments, and personal understanding of the condition. Results 692 patients representing 9 forms of vasculitis completed the questionnaire. The majority (90%) of patients had beliefs about the cause of their illness. Causal attributions were highly variable, but altered immunity and stress were the most commonly agreed upon causal beliefs. Frequencies of causal beliefs were strikingly similar across different forms of vasculitis, with few notable exceptions primarily in Behçet’s disease. Beliefs differed about causes of disease-onset versus relapse. Specific beliefs about disease-onset and relapse were weakly associated with fatigue, functional impairments, and understanding of the condition. Conclusion Patient beliefs related to the cause of systemic vasculitis are highly variable. Patterns of causal beliefs are associated with important negative health outcomes. Clinicians who care for patients with vasculitis should be mindful of these associations and consider asking about patients’ causal beliefs. PMID:24634202

  8. A project by the SIDeMaST Immunopathology Group on cutaneous vasculitis.

    Science.gov (United States)

    Papini, M; Quaglino, P; La Placa, M; Marzano, A V

    2015-04-01

    Vasculitides are a challenge to the clinician, in terms of both diagnosis and therapy. Multiple classification systems have been implemented and the numerous classification schemes reflect the complexity of establishing a simple classification that could be functional for daily care. Although vasculitis classification has become increasingly elaborated, some areas remain ill defined. Some forms of vasculitis are still difficult to assign to a specific disease entity. Generally accepted operational criteria are available for many vasculitides, but for some entities there are no effective criteria. Moreover, diagnostic criteria for vasculitis with sufficient strength and/or confidence that can be universally accepted are not yet available. The need for diagnostic criteria validated and agreed upon is particularly relevant in the context of cutaneous vasculitis. The project of the SIDeMaST Italian Group of Immunopathology on cutaneous vasculitis is a national prospective observational study designed to develop and validate diagnostic criteria and to improve and validate classification criteria for cutaneous small vessel vasculitis also known as leukocytoclastic vasculitis (CLV). Primary objective of the study will also be that of developing the CUtaneous VAsculitis Severity Index (CUVASI). Secondary objectives of the project will be: 1) definition of the etiological agents that are most frequently associated with CLV; 2) search for possible correlations between causative agent and peculiar clinical and/or histopathological aspects; 3) evaluation of immunofluorescence pattern observed in this specific group of primitive cutaneous vasculitis in order to characterize the diagnostic sensitivity and specificity of this technique; 4) identification of a set of clinical investigations and laboratory tests to be performed for a correct CLV assessment. Actually 15 Italian dermatological clinics are contributing to the project and anticipated recruiting >100 patients with CLV

  9. ANCA-associated vasculitis in scleroderma: a case series of fourteen patients

    Directory of Open Access Journals (Sweden)

    Kimberly P. Liang

    2011-01-01

    Full Text Available Antimyeloperoxidase (MPO, perinuclear antineutrophil cytoplasmic antibodies (pANCA, and/or clinically evident vasculitis in patients with scleroderma have been reported only rarely. The clinical significance and prognosis of ANCA-associated vasculitis in systemic sclerosis is uncertain. To report a case and identify the clinical characteristics of scleroderma patients with ANCA-associated vasculitis. Patients with both vasculitis and scleroderma occurring between 1976 to 2006 were identified using an electronic diagnostic index. These diagnoses were confirmed by retrospective review of complete medical records. Clinical features and outcomes recorded included age at vasculitis diagnosis, connective tissue disease (CTD features, type of scleroderma (limited or diffuse; ANCA serology, vasculitic organ system manifestations; and death. Fourteen cases of scleroderma patients with ANCA-associated and/or small vessel vasculitis were identified. The majority (71% were female, with mean age at vasculitis diagnosis 53 years. Seven patients (50% had overlap CTD features, and the majority (79% had limited variant of scleroderma. All of the 10 patients tested were MPO and pANCA positive. Seven patients (50% had glomerulonephritis, 11 (79% pulmonary involvement including 3 with pulmonary-renal syndrome, 6 skin purpura, and 5 mononeuritis multiplex and/or peripheral neuropathy. Six patients (43% died during followup to 2008. The presence of pANCA-associated small vessel vasculitis is a rarely reported complication of scleroderma. It occurs most commonly in women with limited scleroderma and most commonly includes pulmonary and/or renal involvement, including severe organ-threatening manifestations and death. Further studies are needed to clarify the role and clinical impact of ANCA in scleroderma patients with and without vasculitis.

  10. Oral Tolerance: Therapeutic Implications for Autoimmune Diseases

    Directory of Open Access Journals (Sweden)

    Ana M. C. Faria

    2006-01-01

    Full Text Available Oral tolerance is classically defined as the suppression of immune responses to antigens (Ag that have been administered previously by the oral route. Multiple mechanisms of tolerance are induced by oral Ag. Low doses favor active suppression, whereas higher doses favor clonal anergy/deletion. Oral Ag induces Th2 (IL-4/IL-10 and Th3 (TGF-β regulatory T cells (Tregs plus CD4+CD25+ regulatory cells and LAP+T cells. Induction of oral tolerance is enhanced by IL-4, IL-10, anti-IL-12, TGF-β, cholera toxin B subunit (CTB, Flt-3 ligand, anti-CD40 ligand and continuous feeding of Ag. In addition to oral tolerance, nasal tolerance has also been shown to be effective in suppressing inflammatory conditions with the advantage of a lower dose requirement. Oral and nasal tolerance suppress several animal models of autoimmune diseases including experimental allergic encephalomyelitis (EAE, uveitis, thyroiditis, myasthenia, arthritis and diabetes in the nonobese diabetic (NOD mouse, plus non-autoimmune diseases such as asthma, atherosclerosis, colitis and stroke. Oral tolerance has been tested in human autoimmune diseases including MS, arthritis, uveitis and diabetes and in allergy, contact sensitivity to DNCB, nickel allergy. Positive results have been observed in phase II trials and new trials for arthritis, MS and diabetes are underway. Mucosal tolerance is an attractive approach for treatment of autoimmune and inflammatory diseases because of lack of toxicity, ease of administration over time and Ag-specific mechanism of action. The successful application of oral tolerance for the treatment of human diseases will depend on dose, developing immune markers to assess immunologic effects, route (nasal versus oral, formulation, mucosal adjuvants, combination therapy and early therapy.

  11. Imaging micro-glial/macrophage activation in spinal cords of experimental autoimmune encephalomyelitis rats by Positron Emission Tomography using the mitochondrial 18 kDa translocator protein radioligand [18F]DPA-714

    International Nuclear Information System (INIS)

    Abourbeh, Galith; Theze, Benoit; Dubois, Albertine; Tavitian, Bertrand; Boisgard, Raphael; Maroy, Renaud; Brulon, Vincent; Fontyn, Yoann; Dolle, Frederic

    2012-01-01

    Multiple sclerosis (MS) is an inflammatory demyelinating disease of the CNS. Activated micro-glia/macrophages play a key role in the immuno-pathogenesis of MS and its corresponding animal models, experimental autoimmune encephalomyelitis (EAE). Micro-glia activation begins at early stages of the disease and is associated with elevated expression of the 18 kDa mitochondrial translocator protein (TSPO). Thus, positron emission tomography (PET) imaging of micro-glial activation using TSPO-specific radioligands could be valuable for monitoring disease-associated neuro-inflammatory processes. EAE was induced in rats using a fragment of myelin basic protein, yielding acute clinical disease that reflects extensive spinal cord inflammation. Enhanced TSPO expression in spinal cords of EAE rats versus those of controls was confirmed by Western blot and immunohistochemistry. Biodistribution studies in control and EAE rats were performed using the TSPO radioligand [ 18 F]DPA-714 [N,N-diethyl-2-(2-(4-(2-fluoroethoxy)phenyl)-5,7-dimethylpyrazolo[1,5- a]pyrimidin-3-yl)acetamide]. At 1 h after injection, almost fivefold higher levels of [ 18 F]DPA-714 were measured in spinal cords of EAE rats versus controls. The specific binding of [ 18 F]DPA-714 to TSPO in spinal cords was confirmed in competition studies, using unlabeled (R,S)-PK11195 [(R,S)-N-methyl-N-(1-methylpropyl)-1-(2-chlorophenyl) - isoquinoline-3-carboxamide)] or DPA-714 in excess. MicroPET studies affirm that this differential radioactivity uptake in spinal cords of EAE versus control rats could be detected and quantified. Using [ 18 F]DPA-714, neuro-inflammation in spinal cords of EAE-induced rats could be visualized by PET, offering a sensitive technique for monitoring neuro-inflammatory lesions in the CNS and particularly in the spinal cord. In addition to current MRI protocols, this approach could provide molecular images of neuro-inflammation for detection, monitoring, and research in MS. (authors)

  12. Recent advances in understanding autoimmune thyroid disease

    DEFF Research Database (Denmark)

    Bliddal, Sofie; Nielsen, Claus Henrik; Feldt-Rasmussen, Ulla

    2017-01-01

    Autoimmune thyroid disease (AITD) is often observed together with other autoimmune diseases. The coexistence of two or more autoimmune diseases in the same patient is referred to as polyautoimmunity, and AITD is the autoimmune disease most frequently involved. The occurrence of polyautoimmunity h...

  13. Focal cerebral vasculitis associated with circulating immune complexes and brain irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Groothuis, D.R.; Mikhael, M.A.

    1986-06-01

    In this report we describe a patient with a benign glioma treated with surgery and radiation. After a period of stability he developed subacute bacterial endocarditis, and deteriorated neurologically. Computed tomographic scans did not show recurrent tumor. An angiogram showed vasculitis restricted to the previously irradiated area. Secondary to subacute bacterial endocarditis was the presence of high levels of circulating immune complexes. His neurological status was unchanged after antibiotics, but improved after treatment with dexamethasone. We interpret the clinical course as an immune-complex-mediated vasculitis superimposed on a subclinical radiation vasculitis. This case supports the hypothesis that immune mechanisms may be involved in delayed radiation injury to the nervous system.

  14. Omalizumab for Urticarial Vasculitis: Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Misbah Nasheela Ghazanfar

    2015-01-01

    Full Text Available Urticarial vasculitis is characterised by inflamed itching or burning red patches or wheals that resemble urticaria but persist for greater than 24 hours. It is often idiopathic but is sometimes associated with collagen-vascular disease, particularly systemic lupus erythematosus. Treatment options include oral antihistamines, oral corticosteroids, dapsone, colchicine or hydroxychloroquine. We describe a male patient with urticarial vasculitis who was treated with omalizumab (anti-IgE with convincing results and provide a review of previous reports of patients with urticarial vasculitis treated with omalizumab.

  15. Focal cerebral vasculitis associated with circulating immune complexes and brain irradiation

    International Nuclear Information System (INIS)

    Groothuis, D.R.; Mikhael, M.A.

    1986-01-01

    In this report we describe a patient with a benign glioma treated with surgery and radiation. After a period of stability he developed subacute bacterial endocarditis, and deteriorated neurologically. Computed tomographic scans did not show recurrent tumor. An angiogram showed vasculitis restricted to the previously irradiated area. Secondary to subacute bacterial endocarditis was the presence of high levels of circulating immune complexes. His neurological status was unchanged after antibiotics, but improved after treatment with dexamethasone. We interpret the clinical course as an immune-complex-mediated vasculitis superimposed on a subclinical radiation vasculitis. This case supports the hypothesis that immune mechanisms may be involved in delayed radiation injury to the nervous system

  16. The hygiene hypothesis in autoimmunity: the role of pathogens and commensals.

    Science.gov (United States)

    Bach, Jean-François

    2018-02-01

    The incidence of autoimmune diseases has been steadily rising. Concomitantly, the incidence of most infectious diseases has declined. This observation gave rise to the hygiene hypothesis, which postulates that a reduction in the frequency of infections contributes directly to the increase in the frequency of autoimmune and allergic diseases. This hypothesis is supported by robust epidemiological data, but the underlying mechanisms are unclear. Pathogens are known to be important, as autoimmune disease is prevented in various experimental models by infection with different bacteria, viruses and parasites. Gut commensal bacteria also play an important role: dysbiosis of the gut flora is observed in patients with autoimmune diseases, although the causal relationship with the occurrence of autoimmune diseases has not been established. Both pathogens and commensals act by stimulating immunoregulatory pathways. Here, I discuss the importance of innate immune receptors, in particular Toll-like receptors, in mediating the protective effect of pathogens and commensals on autoimmunity.

  17. [Stress and auto-immunity].

    Science.gov (United States)

    Delévaux, I; Chamoux, A; Aumaître, O

    2013-08-01

    The etiology of auto-immune disorders is multifactorial. Stress is probably a participating factor. Indeed, a high proportion of patients with auto-immune diseases report uncommon stress before disease onset or disease flare. The biological consequences of stress are increasingly well understood. Glucocorticoids and catecholamines re