Sample records for subepidermal autoimmune blistering



    Ana Maria Abreu Velez; Daniel Alberto Vasquez-Hincapie; Howard, Michael S.


    Autoimmune mucocutaneous blistering diseases (ABDs) represent a group of conditions that manifest with blisters on the skin and/or mucous membranes. Bullous pemphigoid (BP) is the most common autoimmune mucocutaneous blistering disease. In BP, the location of the blisters is subepidermal and the oral involvement is rare. Variants of BP have been described, including pemphigoid vegetans; however, this disease is not completely characterized. The majority of ABDs have blisters and/or vesicles, ...


    Directory of Open Access Journals (Sweden)

    Ana Maria Abreu Velez


    Full Text Available Autoimmune mucocutaneous blistering diseases (ABDs represent a group of conditions that manifest with blisters on the skin and/or mucous membranes. Bullous pemphigoid (BP is the most common autoimmune mucocutaneous blistering disease. In BP, the location of the blisters is subepidermal and the oral involvement is rare. Variants of BP have been described, including pemphigoid vegetans; however, this disease is not completely characterized. The majority of ABDs have blisters and/or vesicles, that are often pruritic, and manifest autoantibodies to diverse proteins. These proteins include 1 hemidesmosomal plaque proteins(ie, BP230, plectins, 2 transmembrane proteins such as BP180 and α6β4-integrin, which are connected via laminin 332 to type VII collagen and 3 currently uncharacterized 105 kDa and 200 kDa molecules. Other ABDs include drug-induced linear IgA disease, bullous systemic lupus erythematosus (BSLE, dermatitis herpetiformis (DH, cicatricial pemphigoid (CP; also termed mucous membrane pemphigoid, lichen planus pemphigoides (LPP, pemphigoid gestationis (PG, herpes gestationis(HG, chronic bullous dermatosis of childhood (CBDC and the localized forms of CP, such as Brunsting-Perry pemphigoid. The diagnosis of ABDs requires clinical data; skin biopsies (in 10% buffered formalin for hematoxylin and eosin (H&E examination and skin biopsies(in Michel’s transport medium for direct immunofluorescence (DIF. In many ABDs, the histopathologic findings demonstrate a subepidermal vesicle or bulla with a luminal inflammatory infiltrate of neutrophils, eosinophils and/or lymphocytes. In many ABDs, an extensive perivascular and interstitial inflammatory infiltrate is also noted subjacent to the blister in the upper dermis. Normal skin adjacent to an ABD plaque is often excellent for DIF results. Many ABD biopsies reveal autoantibody deposition at the lesional basement membrane zone (BMZ; IgG, IgM, IgA, other immunoglobulins, complement components and

  3. Association between the subepidermal autoimmune blistering diseases linear IgA disease and the pemphigoid group and inflammatory bowel disease: two case reports and literature review. (United States)

    Shipman, A R; Reddy, H; Wojnarowska, F


    We report two patients with subepidermal autoimmune blistering diseases and inflammatory bowel disease (IBD) [one with linear IgA disease (LAD) and ulcerative colitis (UC), and the other with mucous membrane pemphigoid (MMP) and Crohn disease (CD)], and present a review of all previously reported cases. We reviewed the literature, and found 48 cases of patients with autoimmune blistering diseases and IBD. The blistering diseases were LAD (25 patients), bullous pemphigoid (BP) (21), MMP (1) and pemphigoid gestationis (1), while the IBD types comprised UC (40) and CD (8). We describe the clinical and immunopathological features and demographic characteristics of the patients. In all but one case, the diagnosis of IBD predated the development of the skin condition. The association was more common with LAD than BP. The immunopathogenesis of IBD and autoimmune blistering diseases is discussed and a link between them hypothesized, namely, that the presentation of multiple antigens to the immune system during the unregulated inflammation in the bowel wall results in excitation of the immune system and recognition of autologous antigens. © The Author(s). CED © 2012 British Association of Dermatologists.

  4. Steroid-sparing effect of mycophenolate mofetil in the treatment of a subepidermal blistering autoimmune disease in a dog : clinical communication

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    P.J. Ginel


    Full Text Available A 7-year-old female Cocker spaniel-cross was referred with an 8-month history of mucocutaneous erosive dermatitis. On physical examination, skin lesions affected the eyelids and periocular area, lips and vulva. Lesions were symmetrical with small diffuse superficial ulcers, haemorrhagic crusts, adherent purulent exudation in haired skin, and alopecia with hyperpigmentation and scarring. Histopathologic evaluation showed multiple, non-intact dermoepidermal junction vesicles and ulceration associated with a dermal lichenoid infiltrate. Immunohistochemistry showed strong to moderate reactivity in the dermoepidermal junction for the antibodies directed against canine IgG, human IgG lambda light chains and C3, respectively. A diagnosis of autoimmune subepidermal blistering dermatosis was made. Treatment with oral prednisone at 2 mg/kg and mycophenolate mofetil (MMF at 20 mg/kg twice daily was initiated and after 4 weeks the ulcers and erosions were cured. During the rest of treatment, MMF was maintained at 10 mg/kg twice daily and prednisone could be tapered to 0.25 mg/kg once every other day without recurrences. In conclusion, this case report shows that MMF was well tolerated and might be effective as steroid-sparing agent in the long-term treatment of this autoimmune subepidermal blistering disease.



    Ana Maria Abreu Velez; Juliana Calle; Howard, Michael S.


    Autoimmune bullous skin diseases (ABDs) are uncommon, potentially fatal diseases of skin and mucous membranes which are associated with deposits of autoantibodies and complement against distinct molecules of the epidermis and dermal/epidermal basement membrane zone (BMZ). These autoantibodies lead to a loss in skin molecular integrity, which manifests clinically as formation of blisters or erosions. In pemphigus vulgaris, loss of adhesion occurs within the epidermis. The pioneering work of Er...

  6. [Autoimmune blistering diseases]. (United States)

    Duvert-Lehembre, S; Joly, P


    Autoimmune blistering diseases are characterized by the production of pathogenic autoantibodies that are responsible for the formation of epidermal blisters. Major advances in the understanding of the pathogenesis of these disorders have allowed the development of new therapeutic agents. Recent epidemiologic data showed that bullous pemphigoid mainly affects elderly patients. Bullous pemphigoid is often associated with degenerative neurologic disorders. A major increase in the incidence of bullous pemphigoid has been observed in France. Treatment of bullous pemphigoid is mainly based on superpotent topical corticosteroids. The role of desmosomal proteins has been demonstrated in the initiation, propagation and persistence of the autoimmune response in pemphigus. Several studies have shown a correlation between anti-desmoglein antibody titers and disease activity. Pemphigus susceptibility genes have been identified. Oral corticosteroids remain the mainstay of pemphigus treatment. Dramatic and long-lasting improvement has been recently obtained with rituximab in recalcitrant types of pemphigus. Other autoimmune junctional blistering diseases are rare entities, whose prognosis can be severe. Their diagnosis has been improved by the use of new immunological assays and immunoelectronic microscopy. Immunosupressants are widely used in severe types in order to prevent mucosal sequelae. Copyright © 2013 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.

  7. Autoimmune Subepidermal Bullous Diseases of the Skin and Mucosae: Clinical Features, Diagnosis, and Management. (United States)

    Amber, Kyle T; Murrell, Dedee F; Schmidt, Enno; Joly, Pascal; Borradori, Luca


    Autoimmune subepidermal blistering diseases of the skin and mucosae constitute a large group of sometimes devastating diseases, encompassing bullous pemphigoid, gestational pemphigoid, mucous membrane pemphigoid, epidermolysis bullosa acquisita, and anti-p200 pemphigoid. Their clinical presentation is polymorphic. These autoimmune blistering diseases are associated with autoantibodies that target distinct components of the basement membrane zone of stratified epithelia. These autoantigens represent structural proteins important for maintenance of dermo-epidermal integrity. Bullous pemphigoid (BP) is the most common subepidermal autoimmune blistering disease of the skin and mucosae. Although the disease typically presents with a generalized blistering eruption associated with itch, atypical variants with either localized bullous lesions or "non-bullous" presentations are observed in approximately 20% of patients. A peculiar form of BP typically associated with pregnancy is pemphigoid gestationis. In anti-p200 pemphigoid, patients present with tense blisters on erythematosus or normal skin resembling BP, with a predilection for acral surfaces. These patients have antibodies targeting the 200-kDa basement membrane protein. Epidermolysis bullosa is a rare autoimmune blistering disease associated with autoantibodies against type VII collagen that can have several phenotypes including a classical form mimicking dystrophic epidermolysis bullosa, an inflammatory presentation mimicking BP, or mucous membrane pemphigoid-like lesions. Mucous membrane pemphigoid (MMP) is the term agreed upon by international consensus for an autoimmune blistering disorder, which affects one or more mucous membrane and may involve the skin. The condition involves a number of different autoantigens in the basement membrane zone. It may result in severe complications from scarring, such as blindness and strictures. Diagnosis of these diseases relies on direct immunofluorescence microscopy studies


    Directory of Open Access Journals (Sweden)

    Ana Maria Abreu Velez


    Full Text Available Autoimmune bullous skin diseases (ABDs are uncommon, potentially fatal diseases of skin and mucous membranes which are associated with deposits of autoantibodies and complement against distinct molecules of the epidermis and dermal/epidermal basement membrane zone (BMZ. These autoantibodies lead to a loss in skin molecular integrity, which manifests clinically as formation of blisters or erosions. In pemphigus vulgaris, loss of adhesion occurs within the epidermis. The pioneering work of Ernst H. Beutner, Ph.D. and Robert E. Jordon, M.D. confirmed the autoimmune nature of these diseases. Walter F. Lever, M.D. contributed significantly to our understanding of the histopathologic features of these diseases. Walter Lever, M.D. and Ken Hashimoto, M.D. contributed electron microscopic studies of these diseases, especially in pemphigus vulgaris and bullous pemphigoid. In bullous pemphigoid (BP, linear IgA bullous dermatosis, epidermolysis bullosa acquisita (EBA and dermatitis herpetiformis (DH, loss of adhesion takes place within or underneath the BMZ. Classic EBA demonstrates extensive skin fragility; DH is commonly associated with gluten-sensitive enteropathy, and manifests clinically with pruritic papulovesicles on the extensor surfaces of the extremities and the lumbosacral area. The clinical spectrum of bullous pemphigoid includes tense blisters, urticarial plaques, and prurigo-like eczematous lesions. Pemphigoid gestationis mostly occurs during the last trimester of pregnancy, and mucous membrane pemphigoid primarily involves the oral mucosa and conjunctivae and leads to scarring. Linear IgA bullous dermatosis manifests with tense blisters in a „cluster of jewels”-like pattern in childhood (chronic bullous disease of childhood and is more clinically heterogeneous in adulthood. Many of the autoantigens in these disorders are known and have been well characterized. ABDs may be influenced by both genetic and exogenous factors. The diagnoses of

  9. Subepidermal blistering induced by human autoantibodies to BP180 requires innate immune players in a humanized bullous pemphigoid mouse model. (United States)

    Liu, Zhi; Sui, Wen; Zhao, Minglang; Li, Zhuowei; Li, Ning; Thresher, Randy; Giudice, George J; Fairley, Janet A; Sitaru, Cassian; Zillikens, Detlef; Ning, Gang; Marinkovich, M Peter; Diaz, Luis A


    Bullous pemphigoid (BP) is a cutaneous autoimmune inflammatory disease associated with subepidermal blistering and autoantibodies against BP180, a transmembrane collagen and major component of the hemidesmosome. Numerous inflammatory cells infiltrate the upper dermis in BP. IgG autoantibodies in BP fix complement and target multiple BP180 epitopes that are highly clustered within a non-collagen linker domain, termed NC16A. Anti-BP180 antibodies induce BP in mice. In this study, we generated a humanized mouse strain, in which the murine BP180NC14A is replaced with the homologous human BP180NC16A epitope cluster region. We show that the humanized NC16A (NC16A+/+) mice injected with anti-BP180NC16A autoantibodies develop BP-like subepidermal blisters. The F(ab')(2) fragments of pathogenic IgG fail to activate the complement cascade and are no longer pathogenic. The NC16A+/+ mice pretreated with mast cell activation blocker or depleted of complement or neutrophils become resistant to BP. These findings suggest that the humoral response in BP critically depends on innate immune system players.

  10. Crescentic glomerulonephritis and subepidermal blisters with autoantibodies to alpha5 and alpha6 chains of type IV collagen. (United States)

    Ghohestani, Reza F; Rotunda, Sherry L; Hudson, Billy; Gaughan, William J; Farber, John L; Webster, Guy; Uitto, Jouni


    We describe a novel autoimmune disease characterized by severe subepidermal bullous eruption and crescentic glomerulonephritis with autoantibodies directed against the noncollagenous domain of the alpha5 and alpha6 chains of type IV collagen. Biopsy of perilesional skin revealed a subepidermal blister with marked polymorphonuclear infiltrate with linear deposits of IgA and C3. Light microscopy of a kidney biopsy specimen revealed a crescentic glomerulonephritis, and immunofluorescence microscopy showed linear basement membrane staining for IgA (3+), C3 (1+), and IgG (1+). No electron-dense deposits were observed by transmission electron microscopy. The patient's autoantibodies reacted with normal human skin and kidney: IgA (3+) and IgG (1+) antibodies stained the basement membrane zones of skin, renal glomerulus, and some tubules. The identity of the target antigen was determined by immunochemical analyses of candidate antigens using the patient's autoantibodies. The patient's IgA and IgG autoantibodies reacted with a 185- to 190-kDa antigen from a human dermal extract that was distinguished from the other dermal or epidermal antigens, including the 145- to 290-kDa (type VII collagen) epidermolysis bullosa acquisita antigen, the 165- to 200-kDa alpha3 laminin mucous membrane cicatricial pemphigoid antigen, and the 230-kDa and the 180-kDa bullous pemphigoid antigens. Patient's IgA and IgG autoantibodies further reacted with the alpha5(IV) and weakly with the alpha6(IV) chains of type IV collagen by Western blot and ELISA. This report expands the repertoire of bullous skin disorders and provides an explanation for the association of anti-type IV collagen autoantibodies and glomerulonephritis with subepidermal blisters.

  11. Serological Diagnosis of Autoimmune Blistering Diseases

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    Birgül Özkesici


    Full Text Available Autoimmune blistering diseases are a rare diseases, characterized by development of autoantibodies against the structural proteins of the epidermis or dermoepidermal junction, and blisters and erosions on skin and/or mucous membranes clinically. Clinical features are important guiding findings for suspicious of this group of diseases. The diagnosis is achieved by the evaluation together of clinical features, histological and immunological findings. The gold standard in the diagnosis of this group diseases are demonstration of tissue bound and/or circulating autoantibodies. Methods for this purpose are; direct and indirect immunofluorescence, Enzyme Linked Immunosorbent Assay (ELISA, immunoprecipitation and immunoblotting. The aim of this paper is to review serological diagnostic methods in the diagnosis of autoimmune bullous diseases and to present developments in recent years.

  12. The use of skin substrates deficient in basement membrane molecules for the diagnosis of subepidermal autoimmune bullous disease

    NARCIS (Netherlands)

    Vodegel, RM; Kiss, M; De Jong, MCJM; Pas, HH; Altmayer, A; Molnar, K; Husz, S; Van der Meer, JB; Jonkman, MF

    A case is presented of subepidermal, autoimmune bullous disease in which the initial examinations suggested the combination of epidermolysis bullosa acquisita and bullous pemphigoid. The diagnosis of epidermolysis bullosa acquisita was made by indirect immunofluorescence microscopy: the patient's

  13. A subepidermal blistering disorder

    African Journals Online (AJOL)

    Y Moolla. Dr Yusuf Moolla is a specialist physician in the Department of Internal Medicine at Addington Hospital, Durban, South Africa. He recently obtained an MMed from the University of KwaZulu-Natal for his work on HIV infection. Corresponding author: Y Moolla ( A young woman presented ...

  14. Paraneoplastic Pemphigus and Autoimmune Blistering Diseases Associated with Neoplasm: Characteristics, Diagnosis, Associated Neoplasms, Proposed Pathogenesis, Treatment. (United States)

    Kartan, Saritha; Shi, Vivian Y; Clark, Ashley K; Chan, Lawrence S


    Autoimmune paraneoplastic and neoplasm-associated skin syndromes are characterized by autoimmune-mediated cutaneous lesions in the presence of a neoplasm. The identification of these syndromes provides information about the underlying tumor, systemic symptoms, and debilitating complications. The recognition of these syndromes is particularly helpful in cases of skin lesions presenting as the first sign of the malignancy, and the underlying malignancy can be treated in a timely manner. Autoimmune paraneoplastic and neoplasm-associated bullous skin syndromes are characterized by blister formation due to an autoimmune response to components of the epidermis or basement membrane in the context of a neoplasm. The clinical manifestations, histopathology and immunopathology findings, target antigens, associated neoplasm, current diagnostic criteria, current understanding of pathogenesis, and treatment options for a selection of four diseases are reviewed. Paraneoplastic pemphigus manifests with clinically distinct painful mucosal erosions and polymorphic cutaneous lesions, and is often associated with lymphoproliferative neoplasm. In contrast, bullous pemphigoid associated with neoplasm presents with large tense subepidermal bullae of the skin, and mild mucosal involvement, but without unique clinical features. Mucous membrane pemphigoid associated with neoplasm is a disorder of chronic subepithelial blisters that evolve into erosions and ulcerations that heal with scarring, and involves stratified squamous mucosal surfaces. Linear IgA dermatosis associated with neoplasm is characterized by annularly grouped pruritic papules, vesicles, and bullae along the extensor surfaces of elbows, knees, and buttocks. Physicians should be aware that these autoimmune paraneoplastic and neoplasm-associated syndromes can manifest distinct or similar clinical features as compared with the non-neoplastic counterparts.

  15. Psychosocial impact of inherited and autoimmune blistering diseases

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    Swaranjali V. Jain, B Med Sci (Hons MD


    Full Text Available Inherited and autoimmune blistering diseases are rare, chronic, and often severe disorders that have the potential to significantly affect patients’ quality of life. The effective management of these conditions requires consideration of the physical, emotional, and social aspects of the disease. Self-esteem is integral to patients’ ability to cope with their illness, participate in treatment, and function in society. This article discusses quality-of-life studies of patients with blistering diseases with a particular focus on self-esteem issues that patients may face.

  16. Modern diagnosis of autoimmune blistering skin diseases. (United States)

    Schmidt, Enno; Zillikens, Detlef


    The diagnostic gold standard of autoimmune bullous diseases is the detection of autoantibodies in skin or mucous membranes by direct immunofluorescence microscopy of a perilesional biopsy. The molecular characterisation of several target antigens within the last 10 years has, however, fostered the development of sensitive and specific diagnostic tools that allow the serological diagnosis in about 90% of patients. Based on the recombinant immunodominant portions of the target antigens, ELISA systems are commercially available for the detection of circulating antibodies against desmoglein 1, desmoglein 3, envoplakin, BP180, and BP230. Autoantibodies against the soluble ectodomain of BP180 (LAD-1), laminin 332, type VII collagen, and most recently, laminin γ1 can be detected by Western blotting with recombinant or cell-derived forms of these proteins. The definite differentiation between the various immunobullous disorders that comprise about a dozen entities is increasingly important since more diverse treatment options are employed. Exact diagnosis is also pivotal for the prognosis, since some autoimmune bullous diseases may indicate an underlying tumor. Association with a malignancy has been shown in paraneoplastic pemphigus (in 100%) and anti-laminin 332 mucous pemphigoid (in 25%) In pemphigus vulgaris, pemphigus foliaceus, and bullous pemphigoid, autoantibodies to desmoglein 3, desmoglein 1, and BP180, respectively, have been shown to correlate with the disease activity. The detection of serum autoantibodies during the course of the disease may thus be helpful in guiding treatment decisions in these patients. Copyright © 2010 Elsevier B.V. All rights reserved.

  17. Paraneoplastic Pemphigus. A Life-Threatening Autoimmune Blistering Disease. (United States)

    Tirado-Sánchez, A; Bonifaz, A


    Paraneoplastic pemphigus (PNP), a subset of pemphigus, is a unique autoimmune blistering condition that can affect multiple organs other than the skin. It is a life-threatening disease associated with an underlying malignancy, most commonly of lymphoproliferative origin. The clinical picture may resemble pemphigus, pemphigoid, erythema multiforme, graft-versus-host disease, or lichen planus. The earliest and most consistent finding is a painful, severe, chronic and often recalcitrant stomatitis. Treatment of PNP is difficult. Immunosuppressive agents are required to decrease blistering, and treating the underlying tumor may control autoantibody production. In this review, we included essential diagnostic aspects of PNP and the most useful treatment options in the dermatologist practice. Copyright © 2017 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.

  18. Reduced Skin Blistering in Experimental Epidermolysis Bullosa Acquisita After Anti-TNF Treatment

    NARCIS (Netherlands)

    Hirose, Misa; Kasprick, Anika; Beltsiou, Foteini; Dieckhoff, Katharina Schulze; Schulze, Franziska Sophie; Samavedam, Unni K. J. S. R. L.; Hundt, Jennifer E.; Pas, Hendri H.; Jonkman, Marcel F.; Schmidt, Enno; Kalies, Kathrin; Zillikens, Detlef; Ludwig, Ralf J.; Bieber, Katja


    Epidermolysis bullosa acquisita (EBA) is a difficult-to-treat subepidermal autoimmune blistering skin disease (AIBD) with circulating and tissue-bound anti-type VII collagen antibodies. Different reports have indicated increased concentration of tumor necrosis factor a (TNF) in the serum and blister

  19. Coma blisters in two postoperative patients. (United States)

    Chacon, Anna H; Farooq, Uzma; Choudhary, Sonal; Yin, Natalie; Nolan, Bridgit; Shiman, Michael; Milikowski, Clara; Izakovic, Jan; Elgart, George W


    Coma blisters are self-limited cutaneous bullae that occur in the setting of loss of consciousness because of a drug, illness, or accident, with the most common settings being barbiturate overdose and neurological disorders. The etiology behind coma blisters is poorly understood and is not related to underlying infections or autoimmune conditions. The clinical presentation consists of bullae, erosions, and violaceous plaques usually involving sites of pressure. The skin lesions usually occur within 48-72 hours of the start of a coma and resolve within 2-4 weeks. We present one case of a 5-month-old infant with severe valvular disease who required surgical repair. He was placed on extra corporeal membrane oxygenation and developed multiple tense coma blisters during the course of therapy. Skin biopsy revealed a noninflammatory subepidermal blister with necrosis of the overlying epidermis and necrosis of the eccrine ducts. We also present a second case of an 18-year-old female patient who underwent surgical resection of a benign mandibular tumor. She subsequently developed bullae on both arms 4 days after surgery. The skin biopsy showed a necrotic epidermis, a subepidermal blister, and diffuse necrosis of the eccrine coils.

  20. Prothrombotic state and impaired fibrinolysis in bullous pemphigoid, the most frequent autoimmune blistering disease. (United States)

    Marzano, A V; Tedeschi, A; Polloni, I; Crosti, C; Cugno, M


    Bullous pemphigoid (BP) is a potentially life-threatening autoimmune blistering disease that is burdened with an increased risk of cardiovascular events. In BP, there is an interplay between inflammation and coagulation both locally, which contributes to skin damage, and systemically, which leads to a prothrombotic state. Fibrinolysis is an important defence mechanism against thrombosis, but has only been studied locally in BP and no systemic data are available. The aim of this observational study was to evaluate systemic fibrinolysis and coagulation activation in patients with BP. We measured parameters of fibrinolysis and coagulation by immunoenzymatic methods in plasma from 20 patients with BP in an active phase and during remission after corticosteroid treatment. The controls were 20 age- and sex-matched healthy subjects. Plasma levels of plasminogen activator inhibitor type 1 (PAI-1) antigen, PAI-1 activity and tissue plasminogen activator (t-PA) antigen were significantly higher in the BP patients with active disease than in healthy controls (P = 0·0001 for all), as were the plasma levels of the fibrin fragment d-dimer and prothrombin fragment F1+2 (P = 0·0001 for both). During remission after treatment, levels of PAI-1 antigen and PAI-1 activity decreased significantly (P = 0·008 and P = 0·006, respectively), and there was also a significant decrease in plasma levels of d-dimer (P = 0·0001) and F1+2 (P = 0·0001). Fibrinolysis is inhibited in patients with active BP, due mainly to an increase in plasma levels of PAI-1. Corticosteroids not only induce the regression of BP lesions, but also reduce the inhibition of fibrinolysis, which may contribute to decreasing thrombotic risk. © 2012 British Society for Immunology.

  1. CD1a, HAM56, CD68 and S-100 are present in lesional skin biopsies from patients affected by autoimmune blistering diseases

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    Ana Maria Abreu Velez


    Full Text Available Introduction: Previous research on autoimmune skin blistering diseases (ABD has primarily focused on the humoral immune response; moreover, little attention has been given to the potential role of the antigen presenting cells (APCs in lesional skin. Aim: The purpose of our study was to immunophenotype selected APC in the lesional skin of ABDs, utilizing immunohistochemistry (IHC stains. Materials and Methods: We utilized IHC to stain for dendritic cells (DC, staining with CD1a, CD68, HAM56, and S-100 in lesional skin from 30 patients with endemic pemphigus foliaceus (EPF, 15 controls from the EPF endemic area, and 15 healthy controls from the USA. We also tested archival biopsies from patients with selected ABD, including 30 patients with bullous pemphigoid (BP, 20 with pemphigus vulgaris (PV, 8 with pemphigus foliaceus (PF and 14 with dermatitis herpetiformis (DH and 2 with epidermolysis bullosa acquisita (EBA. Results: Cells stained by CD68, HAM56 and S-100 were present in the majority of the ABD skin biopsies; these cells were located primarily in perivascular infiltrates surrounding dermal vessels subjacent to the blisters. However, these cells were also noted within the blisters, in vessels supplying dermal eccrine glands and ducts, and in areas of dermal endothelial-mesenchymal cell junction-like structures, especially in BP cases. In our CD1a staining, the number and location of positive staining cells varied with each disease, being abundant in most ABD in the epidermis suprajacent to the blisters, or in the epidermis surrounding the blister site if the blister site epidermis was missing. In the control biopsies, most did not display positive IHC staining, with the exception of a few CD1a positive cells in the epidermis Conclusion: Our findings confirm positive IHC staining for APCs in areas of the skin besides the disease blisters. Our findings suggest that the antigen presentation in ABD proceeds in areas distant from the blister site

  2. Salt split technique: A useful tool in the diagnosis of subepidermal bullous disorders

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    De Abhishek


    Full Text Available Background: Direct immunofluorescence (DIF is the gold standard in the diagnosis of immunobullous diseases. However, it cannot reliably differentiate various subtypes of subepidermal immune- bullous diseases (SIBD. Salt split technique (SST could be used under such circumstances to differentiate them. There is paucity of reports in the Indian literature regarding the SST. Aim: This study was designed to evaluate the utility of direct SST in subepidermal blistering diseases. Materials and Methods: Fourteen clinically diagnosed cases of subepidermal blistering diseases were included in the study. Two perilesional punch biopsies were taken one each for DIF and salt split study. Results: Linear basement membrane zone band with IgG and/or C 3 was seen in 14 cases of patients BP. Salt split study showed epidermal or mixed pattern of deposits in 12 patients and exclusive floor pattern in two patients. The diagnosis was revised in these two patients to epidermolysis bullosa acquisita. Conclusion: SST is a simple, inexpensive procedure and should be routinely employed in the diagnosis of subepidermal bullous diseases.

  3. Fracture Blisters

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    Uebbing, Claire M


    Full Text Available Fracture blisters are a relatively uncommon complication of fractures in locations of the body, such as the ankle, wrist elbow and foot, where skin adheres tightly to bone with little subcutaneous fat cushioning. The blister that results resembles that of a second degree burn.These blisters significantly alter treatment, making it difficult to splint or cast and often overlying ideal surgical incision sites. Review of the literature reveals no consensus on management; however, most authors agree on early treatment prior to blister formation or delay until blister resolution before attempting surgical correction or stabilization. [West J Emerg Med. 2011;12(1;131-133.


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    Ana Maria Abreu Velez


    Full Text Available Introduction: Autoimmune bullous skin diseases (ABDs represent a heterogeneous group of disorders of the skin and mucosa; these disorders are commonly associated with deposits of immunoglobulins, complement, and fibrinogen, usually directed against distinct adhesion molecules. Methods: We utilized hematoxylin and eosin (H & E stained tissues sections to evaluate for the presence of rouleaux in lesional skin biopsies of patients affected by ABDs including patients with endemic and nonendemic pemphigus foliaceus, bullous pemphigoid (BP, pemphigus vulgaris (PV, dermatitis herpetiformis (DH, and a group of controls taken from routine biopsies seen in our practice. Results: Most autoimmune bullous skin diseases biopsies showed rouleaux formation within and around post-capillary venules in the superficial vascular plexus in association with a pinkish brush-like material that resembles fibrin or other amorphous eosinophilic material. Discussion: We document that rouleaux and the pinkish aggregates are present in within biopsies taken from lesional skin in the majority of patients with ABDs and speculate that this maybe as result of the exocytosis of inflammatory cells, antibodies that form when exposed to the extracellular matrix which is already edematous in most ABDs. In addition red blood cells in the presence of plasma proteins or other macromolecules may form aggregates. Further studies are needed.

  5. Clinical evaluation of a multiparametric ELISA as a rapid tool for routinely diagnosing IgG-mediated autoimmune blistering dermatoses in ethnic Slavs. (United States)

    Gornowicz-Porowska, Justyna; Seraszek-Jaros, Agnieszka; Bowszyc-Dmochowska, Monika; Bartkiewicz, Paweł; Kaczmarek, Elżbieta; Dmochowski, Marian


    Technical innovation of autoimmune blistering dermatoses (ABDs) diagnosis aimed at multiplex approach. Two multiparametric ELISA tests are commercially available for ABDs serology. The aim was to compare diagnostic accuracy of multiparametric and monospecific ELISAs and to examine the diagnostic value/agreement of multivariant ELISA in compliance with traditional diagnostic setup for ABDs. In total, 128 sera from suspected ABDs patients were studied (27 sera in order to compare ELISAs). Multivariant ELISA (detection of IgG against desmoglein 1 and 3 - DSG1/3; BP180, BP230, envoplakin, type VII collagen), monovariant ELISA, and statistical analysis were performed. With the use of sera from patients with suspected ABDs, the multiparametric ELISA yield an agreement of 84% with traditional stepwise diagnostics. Multivariant ELISA with BP180 and BP230 showed 87.5% and 80% sensitivity, 87.5% and 91% specificity, 87.5% reliability as well as 87.5% and 80% positive predictive value, 87.5% and 91% negative predictive value, respectively, in relation to monospecific ELISA. Multivariant ELISA with DSG1 and DSG3 showed 50% and 80% sensitivity, 100% and 80% specificity, 85% and 80% reliability as well as 100% and 57% positive predictive value, 82% and 92% negative predictive value, respectively, in relation to monospecific ELISA. A better rate of agreement was observed among ELISA systems with BP180 and BP230, than with ELISA systems with DSG1 and DSG3. Multivariant ELISA test combined with clinical examinations and DIF is recommended as a minimal approach to diagnosing ABDs in ethnic Slavs. © 2017 Wiley Periodicals, Inc.

  6. Epidermolysis bullosa acquisita in a 17-year-old boy with Crohn's disease

    National Research Council Canada - National Science Library

    Russo, Irene; Ferrazzi, Anna; Zanetti, Irene; Alaibac, Mauro


    Epidermolysis bullosa acquisita is a rare, acquired, autoimmune subepidermal blistering disease of the skin, characterised by blisters and erosions, especially in trauma-prone sites and extensor skin...

  7. Decontamination Data - Blister Agents (United States)

    U.S. Environmental Protection Agency — Decontamination efficacy data for blister agents on various building materials using various decontamination solutions. This dataset is associated with the following...

  8. Origin of the subepidermal tissue in Piper L. leaves. (United States)

    Nakamura, A T; Simão, E; Silva, L; Torres, G A


    Studies on the anatomy of Piper leaves demonstrate the presence of a subepidermal tissue distinct from the adjacent epidermis, which cells show thin walls and hyaline contents. Some authors consider such cells a hypodermal tissue, while others refer to them as components of a multiple epidermis. In this study, the nature of this subepidermal tissue was investigated through the analysis of leaf ontogeny in three Piper species. The analysis showed that the referred tissue originates from the ground meristem and, thus, should be considered a hypodermis. The studied species suggests that the role of the hypodermis would be to protect the photosynthetic apparatus from excess light, regulating the intensity of light reaching the chlorophyll parenchyma.

  9. Dermatoses bolhosas auto-imunes Autoimmune bullous dermatoses

    Directory of Open Access Journals (Sweden)

    Paulo R. Cunha


    Full Text Available Dermatoses bolhosas autoimunes são doenças cuja manifestação cutânea primária e fundamental consiste em vesículas e bolhas. Classificam-se conforme a localização da bolha, em intraepidérmica e subepidérmica. Os pacientes produzem autoanticorpos contra estruturas específicas da pele detectáveis por técnicas de imunofluorescência, immunobloting e Elisa. Os recentes avanços da biologia molecular e celular têm permitido conhecer esses autoantígenos, contra os quais os pacientes se sensibilizam e que estão localizados na epiderme ou na junção dermoepidérmica. São doenças de baixa incidência, porém de elevada morbidade e por vezes letais. O objetivo deste trabalho é revisar e descrever os progressos nos conhecimentos de quatro doenças vésico-bolhosas autoimunes: pênfigo foliáceo endêmico (fogo selvagem, pênfigo vulgar, penfigóide bolhoso e dermatite herpetiforme.Autoimmune bullous dermatoses are diseases in which blisters and vesicles are the primary and fundamental types of skin lesion. Their classification is based on the location of the blister: intraepidermal and subepidermal. Patients produce autoantibodies against self-specific structures of the skin detectable by immunofluorescence techniques, immunoblotting and ELISA. Recent advances in molecular and cellular biology have brought to knowledge these self-antigens, against which patients are sensitized, and which are found in epidermis or in the dermo-epidermal junction. These are low incidence, but high morbidity diseases that may be fatal. The aim of this article is to review and describe the progress of four autoimmune vesiculobullous disorders: endemic pemphigus foliaceous (wild fire, pemphigus vulgaris, bullous pemphigoid and dermatitis herpetiformis.

  10. Blisters: First Aid (United States)

    ... 5, 2014. Brennan FH. Treatment and prevention of foot friction blisters. ACSM's Health & Fitness Journal. 2013;17:45. Khodaee M, et al. Common ultramarathon injuries and illnesses: Race day management. Current Sports Medicine Reports. 2012;11: ...

  11. [Application of blistering cupping]. (United States)

    Gu, Xingui; Chen, Zelin; Chen, Bo; Fan, Yihua; Chen, Xianghong


    Blistering cupping is special as eliminating wind and dampness as well as removing phlegm and blood stasis, and it achieves effects through suction. In this paper we reviewed relevant literature combined with clinical experience so as to summarize its operation attention through exploring the origin, mechanism and application. We divide the progress into the blistering period, the phlegm-stasis-eliminating period, and the escharosis period according to the changes of bubble and the things pulled out. Blistering cupping creates ways to eliminate concrete unhealthy influences through smoothing meridians and collaterals, such as phlegm and retained fluid, dampness and blood stasis. Thus chronic diseases are relieved. Also,we propose the rules of "blistering acupoints being related to disease location as well as the nature of acupoints and diseases". The therapy has been used to treat diseases of respiratory system, osteoarticular, skin and subcutaneous tissue, mental and behavioral disorders, and tumor, among which the effects of intractable diseases of respiratory and osteoarticular systems are definite. It deserves to be further explored and promoted.

  12. Meeting Report of the Pathogenesis of Pemphigus and Pemphigoid Meeting in Munich, September 2016

    NARCIS (Netherlands)

    Schmidt, Enno; Spindler, Volker; Eming, Ruediger; Amagai, Masayuki; Antonicelli, Frank; Baines, John F.; Belheouane, Meriem; Bernard, Philippe; Borradori, Luca; Caproni, Marzia; Di Zenzo, Giovanni; Grando, Sergei; Harman, Karen; Jonkman, Marcel F.; Koga, Hiroshi; Ludwig, Ralf J.; Kowalczyk, Andrew P.; Mueller, Eliane J.; Nishie, Wataru; Pas, Hendri; Payne, Aimee S.; Sadik, Christian D.; Seppanen, Allan; Setterfield, Jane; Shimizu, Hiroshi; Sinha, Animesh A.; Sprecher, Eli; Sticherling, Michael; Ujiie, Hideyuki; Zillikens, Detlef; Hertl, Michael; Waschke, Jens

    Autoimmune blistering diseases are a heterogeneous group of about a dozen complex disorders that are characterized by intraepidermal (pemphigus) and subepidermal blistering (pemphigoid diseases and dermatitis herpetiformis). The Pathogenesis of Pemphigus and Pemphigoid Meeting, organized by the

  13. Passive transfer of collagen XVII-specific antibodies induces sustained blistering disease in adult mice

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    Chiriac Mircea Teodor


    Full Text Available Abstract Background Bullous pemphigoid is a subepidermal blistering disorder associated with tissue-bound and circulating autoantibodies directed mainly to the hemidesmosomal component collagen XVII. While recapitulating the main immunopathological features of the human disease, frank skin blistering does not develop in the absence of skin rubbing in experimental pemphigoid models that have been established in neonatal mice. Moreover, due to their experimental design they only allow for short-term disease observation. In the present study we aimed to establish a model that reproduces the frank skin blistering seen in patients and allows for longer observation times. Methods Rabbit and sheep antibodies specific to several fragments of collagen XVII were generated and the purified antibodies were passively transferred into adult mice. Results Collagen XVII-specific IgG bound to the basal membrane of the skin and mucous membranes activating murine complement in vivo. Mice injected with collagen XVII-specific antibodies, in contrast to mice receiving control antibodies, developed frank skin blistering disease, reproducing human bullous pemphigoid at the clinical, histological and immunopathological levels. Titres of circulating IgG in the serum of mice correlated with the extent of the clinical disease. Mice receiving sheep antibodies specific to murine collagen XVII showed an early onset and a more active disease when compared to litter mates receiving specific rabbit antibodies. Conclusion This novel animal model for bullous pemphigoid should facilitate further investigations of the pathogenesis of bullous pemphigoid and the development of innovative therapies for this disease.

  14. Changes of human skin in subepidermal wound healing process. (United States)

    Sugata, Keiichi; Kitahara, Takashi; Takema, Yoshinori


    The wound healing process involves unexplained mechanisms. An aberration in this process is known to cause dermal disorders such as keloid or hypertrophic scars, but the mechanism by which these scars are formed remains to be elucidated. Here we examined the usefulness of a non-invasive optical imaging device to clarify mechanisms of wound healing and of scar formation. An 8 mm experimental wound was made in the forearms of six subjects by a suction blister method. To observe chronological changes associated with wound healing, horizontal cross-sectional images were non-invasively obtained of the wounded area from the skin surface down to 129 microm below at 21.5 microm intervals using in vivo laser confocal scanning microscopy (LCSM). The wounds were covered with a new epidermis by week 2, at which time the dermal papilla count decreased while the thickness from the skin surface to the apex of the dermal papilla increased. The count and the thickness returned to the initial levels when the wound was healed. In two out of six subjects, fibrous tissues were observed in the upper dermis, whereas in one other subject, melanocyte-like dendritic cells were observed in the epidermis-dermis border in later phases of wound healing. This non-invasive method using in vivo LCSM revealed chronological changes in the dermis and epidermis during wound healing. In addition, although a scar was not formed in any of study subjects, this microscopy revealed aspects similar to the fibrous tissue overgrowth or to melanocyte migration, both of which may relate to wound healing. These results indicate the usefulness of this non-invasive method in studies of wound healing and of scar formation.

  15. Early Description of Diet-Induced Blistering Skin Diseases in Medieval Persia: Avicenna's Point of View. (United States)

    Atarzadeh, Fatemeh; Daneshfard, Babak; Dastgheib, Ladan; Jaladat, Amir-Mohammad; Amin, Gholamreza


    Pemphigus is an autoimmune blistering skin disease that is strongly associated with different environmental factors. Among these, nutritional factors are considered to trigger pemphigus; however, their role may be underestimated. Investigated more recently in conventional medicine, this causative bond between dietary factors and blistering skin diseases was mentioned by Persian scholars such as Avicenna a thousand years ago. Avicenna, a well-known Persian physician and philosopher, who could be considered a pioneer in dermatology, discussed skin diseases in a chapter in The Canon of Medicine. He accounted for some nutritional triggers for skin blisters (mentioned as "hot swellings"), such as onion, garlic, leek, pepper, and wine. His precise description of causative factors based on principles of traditional Persian medicine (TPM) is appreciable and might well lead us to find more efficient ways for the prevention and treatment of blistering skin diseases.

  16. False-negative results in immunoblot assay of serum IgA antibodies reactive with the 180-kDa bullous pemphigoid antigen : the importance of primary incubation temperature

    NARCIS (Netherlands)

    Pas, HH; Kloosterhuis, GJ; De Jong, MCJM; Jonkman, MF


    Background Different subepidermal autoimmune blistering skin disorders are characterized by linear deposition of IgA, sometimes accompanied by linear IgG, along the epidermal basement membrane zone. Identification of the targeted autoantigen is usually attempted by immunoblotting. Although

  17. Radiation blistering in metals and alloys

    Energy Technology Data Exchange (ETDEWEB)

    Das, S.K.; Kaminsky, M.


    Radiation blistering in solids has been identified as a process leading to damage and erosion of irradiated surfaces. Some of the major parameters governing the blistering process in metals and some metallic alloys are the type of projectile and its energy, total dose, dose rate, target temperature, channeling condition of the projectile, orientation of the irradiated surface plane, and target material and its microstructure. Experimental results and models proposed for blister formation and rupture are reviewed. The blistering phenomenon is important as an erosion process in applications such as fusion reactor technology (plasma-wall interactions) and accelerator technology (erosion of components and targets). A description of methods for the reduction of surface erosion caused by blistering is included.

  18. [Ruptured cerebral artery blister aneurysm]. (United States)

    Vega Valdés, Pedro; Murias Quintana, Eduardo; Meilán Martínez, Angela; Gutiérrez Morales, Julio; Lopez Garcia, Antonio


    We report the case of a young patient with subarachnoid haemorrhage secondary to a ruptured blister-like aneurysm. Since this kind of aneurysms have fragile walls without a well-defined neck, their treatment is difficult. We initially planned the deployment of a flow-diverter stent, but an angiogram obtained after 10 days revealed a morphological change of the aneurysm. Therefore, we finally deployed a conventional stent and introduced 2 micro coils into the point of rupture, obtaining a good morphological result without rebleeding. Follow-up at 1 and 6 months did not observe regrowth of the aneurysm. We offer a brief introduction and discussion of this pathology and its treatment. Copyright © 2010 Sociedad Española de Neurocirugía. Published by Elsevier España. All rights reserved.

  19. Bullous skin diseases: classical types of autoimmune diseases. (United States)

    Damoiseaux, Jan


    The prototypic bullous skin diseases, pemphigus vulgaris, pemphigus foliaceus, and bullous pemphigoid, are characterized by the blister formation in the skin and/or oral mucosa in combination with circulating and deposited autoantibodies reactive with (hemi)desmosomes. Koch's postulates, adapted for autoimmune diseases, were applied on these skin diseases. It appears that all adapted Koch's postulates are fulfilled, and, therefore, these bullous skin diseases are to be considered classical autoimmune diseases within the wide and expanding spectrum of autoimmune diseases.

  20. The shape of telephone cord blisters (United States)

    Ni, Yong; Yu, Senjiang; Jiang, Hongyuan; He, Linghui


    Formation of telephone cord blisters as a result of buckling delamination is widely observed in many compressed film-substrate systems. Here we report a universal morphological feature of such blisters characterized by their sequential sectional profiles exhibiting a butterfly shape using atomic force microscopy. Two kinds of buckle morphologies, light and heavy telephone cord blisters, are observed and differentiated by measurable geometrical parameters. Based on the Föppl-von Kármán plate theory, the observed three-dimensional features of the telephone cord blister are predicted by the proposed approximate analytical model and simulation. The latter further replicates growth and coalescence of the telephone cord into complex buckling delamination patterns observed in the experiment.

  1. How To Prevent and Treat Blisters (United States)

    ... occur anywhere on the body where body parts rub together or rub against clothing. Fortunately, blisters can be prevented by ... areas: This helps reduce friction when your skin rubs together or rubs against clothing. Stop your activity ...


    Directory of Open Access Journals (Sweden)

    Karolina Vrandečić


    Full Text Available The obligate fungi inside the family Albuginaceae are widespread world wide and cause white rust or white blister disease. Mycopopulation of weeds has been researched within the project „The role of weeds in epidemiology of row-crop diseases“. The aim of this research was to identify white blister species occurring on weeds in Eastern Croatia. Weed plants with disease symptoms characteristic for white blister species have been collected since 2001 on location Slavonia and Baranja country. Determination of white blister species was based on morphological characters of pathogen and the host. Wilsoniana bliti was determined on Amaranthus retroflexus and Amaranthus hybridus leaves. Capsella bursa pastoris is a host for Albugo candida. Ambrosia artemisiifolia is a host for Pustula sp. and Cirsium arvense was found to be host for Pustula spinulosa. Wilsoniana portulaceae was determined on Portulaca oleracea.

  3. Accuracy of ultrasound, thermography and subepidermal moisture in predicting pressure ulcers: a systematic review. (United States)

    Oliveira, A L; Moore, Z; O Connor, T; Patton, D


    Our aims were to: establish the clinical significance of ultrasound, thermography, photography and subepidermal moisture (SEM) measurement; determine the accuracy of ultrasound, thermography, photography and SEM measurement in detecting skin/tissue damage; determine the relative accuracy of one of these assessment methods over another; make recommendations for practice pertaining to assessment of early skin/tissue damage. The following databases, Cochrane Wounds Group Specialised Register, The Cochrane Central Register of Controlled Trials, Ovid MEDLINE, Ovid EMBASE, Elsevier version, EBSCO CINAHL, , WHO International Clinical Trials Registry (ICTR) and The EU Clinical Trials Register were searched for terms including; thermography, ultrasound, subepidermal moisture, photograph and pressure ulcer. We identified four SEM, one thermography and five ultrasound studies for inclusion in this review. Data analysis indicated that photography was not a method which allowed for the early prediction of PU presence. SEM values increased with increasing tissue damage, with the sacrum and the heels being the most common anatomical locations for the development of erythema and stage I PUs. Thermography identified temperature changes in tissues and skin that may give an indication of early PU development; however the data were not sufficiently robust. Ultrasound detected pockets of fluid/oedema at different levels of the skin that were comparable with tissue damage. Thus, SEM and ultrasound were the best methods for allowing a more accurate assessment of early skin/tissue damage. Using the EBL Critical Appraisal Tool the overall validities of the studies varied between 33.3-55.6%, meaning that there is potential for bias within all the included studies. All of the studies were situated at level IV, V and VII of the evidence pyramid. Although the methodological quality of the studies warrants consideration, these studies showed the potential that SEM and

  4. Failure analysis of blistered organic coatings on gray iron castings (United States)

    Tianen, Matthew N.

    This study investigates the blistering failure of a two part coating consisting of talc-filled polyester resin and polyurethane primer on large gray iron castings. Surface metallography was performed and failed coating was characterized by scanning electron microscopy. Corrosion products were found inside of coating blisters. The proposed blistering mechanism is osmosis as a result of soluble species produced by the corrosion. It was believed that excessively thin primer layers resulted in a poor barrier to permeation of water, leading to blisters, and that a basecoat containing a corrosion inhibitor like zinc phosphate would reduce blistering. These hypotheses were tested with designed experiments using environmental testing in humidity and submersion environments. Thicker primer layers resulted in significant reductions in blistering and prolonged the time required before blister formation. A basecoat containing zinc phosphate was not found to be effective at reducing blistering in this coating system.

  5. Blistering behavior in Mo/Si multilayers

    NARCIS (Netherlands)

    Kuznetsov, Alexey; Gleeson, Michael; van de Kruijs, Robbert Wilhelmus Elisabeth; Bijkerk, Frederik; Kuznetsov, A.S.


    This paper is concerned with mapping the characteristics of blistering induced on Mo/Si multilayers as a result of irradiation by hydrogen species generated in a thermal capillary cracker. The nature and extent of the damage observed is dependent on exposure conditions such as the sample

  6. Paraneoplastic Pemphigus: A Paraneoplastic Autoimmune Multiorgan Syndrome or Autoimmune Multiorganopathy?

    Directory of Open Access Journals (Sweden)

    Vikram K. Mahajan


    Full Text Available Paraneoplastic pemphigus (PNP, a clinically and immunopathologically distinct mucocutaneous blistering dermatosis, is a severe form of autoimmune multiorgan syndrome generally associated with poor therapeutic outcome and high mortality. This IgG-mediated disease is initiated by an obvious or occult lymphoproliferative disorder in most cases. Clinically severe mucositis, and polymorphic blistering skin eruptions, and histologically acantholysis, keratinocyte necrosis and interface dermatitis are its hallmark features. A 58-year-old female presented with recurrent, severe, recalcitrant stomatitis and widespread erosions/blistering lesions of one-year duration. Treatment with repeated courses of systemic corticosteroids at a peripheral center would provide temporary relief. She also had fever, productive cough, odynophagia and poor oral intake, herpes zoster ophthalmicus, pain in the abdomen, and watery diarrhea. An array of investigations revealed chronic lymphocytic leukemia (CLL, mediastinal and para-aortic lymphadenopathy, bronchiolitis obliterans, and vertebral osteoporosis/fractures. With the diagnosis of CLL-associated PNP she was managed with dexamethasone-cyclophosphamide pulse (DCP therapy for 3 cycles initially, followed by COP regimen (cyclophosphamide, vincristine, and prednisolone for 5 cycles. Remission is being maintained with chlorambucil and prednisolone pulse therapy once in 3 weeks with complete resolution of skin lesions and adequate control of CLL.

  7. Autoimmune Diseases (United States)

    ... autoimmune diseases are rare, while others, such as Hashimoto's disease, affect many people. Who gets autoimmune diseases? ... often occur on both sides of the body. Hashimoto's (hah-shee-MOH-tohz) disease (underactive thyroid) A ...

  8. Suction blistering the lesional skin of vitiligo patients reveals useful biomarkers of disease activity. (United States)

    Strassner, James P; Rashighi, Mehdi; Ahmed Refat, Maggi; Richmond, Jillian M; Harris, John E


    Vitiligo is an autoimmune disease of the skin with limited treatment options; there is an urgent need to identify and validate biomarkers of disease activity to support vitiligo clinical studies. To investigate potential biomarkers of disease activity directly in the skin of vitiligo subjects and healthy subjects. Patient skin was sampled via a modified suction-blister technique, allowing for minimally invasive, objective assessment of cytokines and T-cell infiltrates in the interstitial skin fluid. Potential biomarkers were first defined and later validated in separate study groups. In screening and validation, CD8+ T-cell number and C-X-C motif chemokine ligand (CXCL) 9 protein concentration were significantly elevated in active lesional compared to nonlesional skin. CXCL9 protein concentration achieved greater sensitivity and specificity by receiver operating characteristic analysis. Suction blistering also allowed for phenotyping of the T-cell infiltrate, which overwhelmingly expresses C-X-C motif chemokine receptor 3. A small number of patients were enrolled for the study, and only a single patient was used to define the treatment response. Measuring CXCL9 directly in the skin might be effective in clinical trials as an early marker of treatment response. Additionally, use of the modified suction-blister technique supports investigation of inflammatory skin diseases using powerful tools like flow cytometry and protein quantification. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  9. Bullous Skin Diseases: Classical Types of Autoimmune Diseases

    Directory of Open Access Journals (Sweden)

    Jan Damoiseaux


    Full Text Available The prototypic bullous skin diseases, pemphigus vulgaris, pemphigus foliaceus, and bullous pemphigoid, are characterized by the blister formation in the skin and/or oral mucosa in combination with circulating and deposited autoantibodies reactive with (hemidesmosomes. Koch’s postulates, adapted for autoimmune diseases, were applied on these skin diseases. It appears that all adapted Koch’s postulates are fulfilled, and, therefore, these bullous skin diseases are to be considered classical autoimmune diseases within the wide and expanding spectrum of autoimmune diseases.

  10. Oral mucosal manifestations of autoimmune skin diseases. (United States)

    Mustafa, Mayson B; Porter, Stephen R; Smoller, Bruce R; Sitaru, Cassian


    A group of autoimmune diseases is characterised by autoantibodies against epithelial adhesion structures and/or tissue-tropic lymphocytes driving inflammatory processes resulting in specific pathology at the mucosal surfaces and the skin. The most frequent site of mucosal involvement in autoimmune diseases is the oral cavity. Broadly, these diseases include conditions affecting the cell-cell adhesion causing intra-epithelial blistering and those where autoantibodies or infiltration lymphocytes cause a loss of cell-matrix adhesion or interface inflammation. Clinically, patients present with blistering, erosions and ulcers that may affect the skin as well as further mucosal surfaces of the eyes, nose and genitalia. While the autoimmune disease may be suspected based on clinical manifestations, demonstration of tissue-bound and circulating autoantibodies, or lymphocytic infiltrates, by various methods including histological examination, direct and indirect immunofluorescence microscopy, immunoblotting and quantitative immunoassay is a prerequisite for definitive diagnosis. Given the frequency of oral involvement and the fact that oral mucosa is the initially affected site in many cases, the informed practitioner should be well acquainted with diagnostic and therapeutic aspects of autoimmune dermatosis with oral involvement. This paper reviews the pathogenesis and clinical presentation of these conditions in the oral cavity with a specific emphasis on their differential diagnosis and current management approaches. Copyright © 2015 Elsevier B.V. All rights reserved.

  11. Ion implantation induced blistering of rutile single crystals

    Energy Technology Data Exchange (ETDEWEB)

    Xiang, Bing-Xi [School of Physics, Shandong University, Jinan, Shandong 250100 (China); Jiao, Yang [College of Physics and Electronics, Shandong Normal University, Jinan, Shandong 250100 (China); Guan, Jing [School of Physics, Shandong University, Jinan, Shandong 250100 (China); Wang, Lei [School of Physics, Shandong University, Jinan, Shandong 250100 (China); Key Laboratory of Nanodevices and Applications, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences (China)


    The rutile single crystals were implanted by 200 keV He{sup +} ions with a series fluence and annealed at different temperatures to investigate the blistering behavior. The Rutherford backscattering spectrometry, optical microscope and X-ray diffraction were employed to characterize the implantation induced lattice damage and blistering. It was found that the blistering on rutile surface region can be realized by He{sup +} ion implantation with appropriate fluence and the following thermal annealing.

  12. Reliable site for suction blister induction and harvesting

    Directory of Open Access Journals (Sweden)

    Laxmisha Chandrashekar


    Full Text Available Background: Suction blister grafting is a useful modality of treatment of patients with resistant and stable vitiligo. However, there have been no detailed studies to find out the best donor site for blister formation. Methods: The study was conducted between the period of October 2004 and February 2005 in the dermatology department at a tertiary care center. Nine patients with vitiligo (focal vitiligo, 3; mucosal vitiligo, 2; acrofacial vitiligo, 2; vitiligo vulgaris, 1; and segmental vitiligo, 1 were selected for blister harvesting and grafting. The blisters were raised using the method described by Gupta et al. Results: Suction blisters were attempted to be raised at 52 sites, but only 38 blisters could be raised, 24 complete and 14 incomplete. Blisters were raised in all the three cases on the flexor aspect of the arm (100%, 15 of 17 cases (88.2% on the flexor aspect of the forearm, 4 of 5 cases (80% on the abdomen, 11 of 16 cases (68.7% on the anterolateral thigh, and less frequently over leg or foot. Complete blisters were formed in 13/15 cases (86.6% on the flexor aspect of the forearm, 6/11 cases (54.5% on the anterolateral thigh, and in all cases over leg. Conclusion: The flexor aspect of the forearm is a good site for suction blister harvesting.

  13. Autoimmune gastritis. (United States)

    Kulnigg-Dabsch, Stefanie


    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.

  14. Evaluation of microbial quality of selected blister-packed ...

    African Journals Online (AJOL)

    Ten brands of blister-packed paracetamol tablet and twenty brands of paracetamol syrup marketed in Nigeria were evaluated for their microbial quality. While no microbial contaminant was isolated from all blistered-packed paracetamol tablets, ten of syrups were contaminated with organisms such as Escherichia coli, ...

  15. Autoimmune disorders (United States)

    ... at the same time. Common autoimmune disorders include: Addison disease Celiac disease - sprue (gluten-sensitive enteropathy) Dermatomyositis Graves ... In: McPherson RA, Pincus MR, eds. Henry's Clinical Diagnosis and Management by Laboratory Methods . 22nd ed. Philadelphia, ...

  16. Autoimmune Hepatitis (United States)

    ... person usually needs blood tests for an exact diagnosis because a person with autoimmune hepatitis can have the same symptoms as those of other liver diseases or metabolic disorders. Blood tests. A blood test involves drawing ...

  17. General mechanism for helium blistering involving displaced atom transport

    Energy Technology Data Exchange (ETDEWEB)

    McDonell, W.R.


    A mechanism developed to account for formation of vertically elongated blisters in high displacement environments produced by /sup 252/Cf alpha particles and fission fragments has been extended to formation of done-shaped blisters in the low displacement environments produced by simple helium ion beams. In this mechanism, transport of displaced atoms to relieve compressive stresses in the helium-implanted layer allows interconnections of small, subsurface bubbles to form the blister cavity. The same transport may cause thickening of the blister caps at low implantation energies. The transition from dome-shaped to vertically elongated blistering occurs between the 300 and 3000 displacements per helium atom produced by simple helium ions and /sup 252/Cf radiations respectively.

  18. Autoimmune pancreatitis

    Directory of Open Access Journals (Sweden)

    Davorin Dajčman


    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

  19. The flavonoid luteolin inhibits Fcγ-dependent respiratory burst in granulocytes, but not skin blistering in a new model of pemphigoid in adult mice.

    Directory of Open Access Journals (Sweden)

    Eva Oswald

    Full Text Available Bullous pemphigoid is an autoimmune blistering skin disease associated with autoantibodies against the dermal-epidermal junction. Passive transfer of antibodies against BP180/collagen (C XVII, a major hemidesmosomal pemphigoid antigen, into neonatal mice results in dermal-epidermal separation upon applying gentle pressure to their skin, but not in spontaneous skin blistering. In addition, this neonatal mouse model precludes treatment and observation of diseased animals beyond 2-3 days. Therefore, in the present study we have developed a new disease model in mice reproducing the spontaneous blistering and the chronic course characteristic of the human condition. Adult mice were pre-immunized with rabbit IgG followed by injection of BP180/CXVII rabbit IgG. Mice pre-immunized against rabbit IgG and injected 6 times every second day with the BP180/CXVII-specific antibodies (n = 35 developed spontaneous sustained blistering of the skin, while mice pre-immunized and then treated with normal rabbit IgG (n = 5 did not. Blistering was associated with IgG and complement C3 deposits at the epidermal basement membrane and recruitment of inflammatory cells, and was partly dependent on Ly-6G-positive cells. We further used this new experimental model to investigate the therapeutic potential of luteolin, a plant flavonoid with potent anti-inflammatory and anti-oxidative properties and good safety profile, in experimental BP. Luteolin inhibited the Fcγ-dependent respiratory burst in immune complex-stimulated granulocytes and the autoantibody-induced dermal-epidermal separation in skin cryosections, but was not effective in suppressing the skin blistering in vivo. These studies establish a robust animal model that will be a useful tool for dissecting the mechanisms of blister formation and will facilitate the development of more effective therapeutic strategies for managing pemphigoid diseases.

  20. Autoimmune encephalopathies (United States)

    Leypoldt, Frank; Armangue, Thaís; Dalmau, Josep


    Over the last 10 years the continual discovery of novel forms of encephalitis associated with antibodies to cell-surface or synaptic proteins has changed the paradigms for diagnosing and treating disorders that were previously unknown or mischaracterized. We review here the process of discovery, the symptoms, and the target antigens of twelve autoimmune encephatilic disorders, grouped by syndromes and approached from a clinical perspective. Anti-NMDAR encephalitis, several subtypes of limbic encephalitis, stiff-person spectrum disorders, and other autoimmune encephalitides that result in psychosis, seizures, or abnormal movements are described in detail. We include a novel encephalopathy with prominent sleep dysfunction that provides an intriguing link between chronic neurodegeneration and cell-surface autoimmunity (IgLON5). Some of the caveats of limited serum testing are outlined. In addition, we review the underlying cellular and synaptic mechanisms that for some disorders confirm the antibody pathogenicity. The multidisciplinary impact of autoimmune encephalitis has been expanded recently by the discovery that herpes simplex encephalitis is a robust trigger of synaptic autoimmunity, and that some patients may develop overlapping syndromes, including anti-NMDAR encephalitis and neuromyelitis optica or other demyelinating diseases. PMID:25315420

  1. The role of neutrophils in autoimmune diseases. (United States)

    Németh, Tamás; Mócsai, Attila


    Though chronic autoimmune disorders such as rheumatoid arthritis or systemic lupus erythematosus affect a significant percentage of the human population and strongly diminish the quality of life and life expectancy in Western societies, the molecular pathomechanisms of those diseases are still poorly understood, hindering the development of novel treatment strategies. Autoimmune diseases are thought to be caused by disturbed recognition of foreign and self antigens, leading to the emergence of autoreactive T-cells (so-called immunization phase). Those autoreactive T-cells then trigger the second (so-called effector) phase of the disease which is characterized by immune-mediated damage to host tissues. For a long time, neutrophils have mainly been neglected as potential players of the development of autoimmune diseases. However, a significant amount of new experimental data now indicates that neutrophils likely play an important role in both the immunization and the effector phase of autoimmune diseases. Here we review the current literature on the role of neutrophils in autoimmune diseases with special emphasis on rheumatoid arthritis, systemic lupus erythematosus, autoimmune vasculitides and blistering skin diseases. We also discuss the role of neutrophil cell surface receptors (e.g. integrins, Fc-receptors or chemokine receptors) and intracellular signal transduction pathways (e.g. Syk and other tyrosine kinases) in the pathogenesis of autoimmune inflammation. Though many of the results discussed in this review were obtained using animal models, additional data indicate that those mechanisms likely also contribute to human pathology. Taken together, neutrophils should be considered as one of the important cell types in autoimmune disease pathogenesis and they may also prove to be suitable targets of the pharmacological control of those diseases in the future. Copyright © 2012 Elsevier B.V. All rights reserved.

  2. Blister formation in Mo/Si multilayered structures induced by hydrogen ions

    NARCIS (Netherlands)

    Van Den Bos, R. A.J.M.; Lee, C. J.; Benschop, J. P.H.; Bijkerk, F.


    We report on blister formation in nanometer thick Mo/Si multilayer structures due to exposure to hydrogen ion fluxes. The influence of hydrogen flux and ion energy for blister formation have been measured and compared to a blister model. The blister number density increases significantly around 100

  3. Autoimmune sialadenitis

    NARCIS (Netherlands)

    Guntinas-Lichius, O.; Vissink, A.; Ihrler, S.

    Using the European-American classification criteria the diagnosis of autoimmune sialadenitis in Sjogren's syndrome can generally be easily established or excluded. In addition, sonography performed by the ENT physician is helpful in diagnosing and especially in follow-up screening for MALT

  4. Autoimmun hypophysitis

    DEFF Research Database (Denmark)

    Krarup, Therese; Hagen, Claus


    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...

  5. Suction blister grafting - Modifications for easy harvesting and grafting

    Directory of Open Access Journals (Sweden)


    Full Text Available Suction blister grafting is a simple modality of treatment of patients with resistant and stable vitiligo. But raising the blisters may be time consuming and transferring to the recipient site may be difficult as the graft is ultrathin. By doing some modifications we can make the technique simpler and easier. We can decrease the blister induction time by intradermal injection of saline, exposure to Wood′s lamp, intrablister injection of saline. By these methods we can decrease the blister induction time from 2-3 hrs to 45-90 minutes. After harvesting the graft, it can be transferred to the recipient area by taking the graft on a sterile glass slide, on the gloved finger, rolling the graft over a sterile syringe and then spreading on the recipient area, or taking on the sterile wrapper of paraffin dressing and then placing over the recipient area.

  6. The Causes of Blistering in Boat Building Materials (United States)


    polymerization was initiated using methyl ethyl kcetone peroxide according to manufacturer’s instructions. One set of samples was Initiated with BPO ...advertising or sales promotion purposes. Citation of trade names and manufacturers does not constitute endorsement or approval of such products. TABLE OF...and severity of blisters on boats does not exist. While we have seen over 100 cases of coat blisters, there Is no statistically established correlation

  7. Autoimmun pankreatitis

    DEFF Research Database (Denmark)

    Fjordside, Eva; Novovic, Srdan; Schmidt, Palle Nordblad


    Autoimmune pancreatitis (AIP) is a rare inflammatory disease. AIP has characteristic histology, serology and imaging findings. Two types of AIP exist, type 1, which is a part of the systemic immunoglobulin G4-related disease, and type 2, which is only localized to the pancreas. Patients with type 1...... are predominantly older men, have involvement of other organs and more often experience relapse than patients with type 2. Both types respond well to steroid treatment. The most important differential diagnose is pancreatic cancer....


    Directory of Open Access Journals (Sweden)

    Yusri Dianne Jurnalis


    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

  9. Autoimmune liver disease panel (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 ...

  10. Study on thickness distribution of thermoformed medical PVC blister (United States)

    Li, Yiping


    Vacuum forming has many advantages over other plastic forming processes due to its cost effectiveness, time efficiency, higher product precision, and more design flexibility. Nevertheless, when pressures greater than the atmospheric value are required to force the thermo-plastic into more intimate contact with the mold surface, pressure forming is a better choice. This paper studies the process of air-pressure thermoforming of plastic sheet, and focuses on medical blister PVC products. ANSYS POLYFLOW tool is used to simulate the process and analyze the wall thickness distribution of the blister. The influence of mold parameters on the wall thickness distribution of thermoformed part is thus obtained through simulation. Increasing radius between mold and side wall at the bottom of blister and draft prove to improve the wall thickness distribution.

  11. The ‘Sticky Elastica’: delamination blisters beyond small deformations

    KAUST Repository

    Wagner, Till J. W.


    We consider the form of an elastic loop adhered to a rigid substrate: the \\'Sticky Elastica\\'. In contrast to previous studies of the shape of delamination \\'blisters\\', the theory developed accounts for deflections with large slope (i.e. geometrically nonlinear). Starting from the classical Euler Elastica we provide numerical results for the dimensions of such blisters for a variety of end-end confinements and develop asymptotic expressions that reproduce these results well, even up to the point of self-contact. Interestingly, we find that the width of such blisters does not grow monotonically with increased confinement. Our theoretical predictions are confirmed by simple desktop experiments and suggest a new method for the measurement of the elastocapillary length for deformations that cannot be considered small. We discuss the implications of our results for applications such as flexible electronics. © 2013 The Royal Society of Chemistry.

  12. [Autoimmune pancreatitis]. (United States)

    Beyer, G; Menzel, J; Krüger, P-C; Ribback, S; Lerch, M M; Mayerle, J


    Autoimmune pancreatitis is a relatively rare form of chronic pancreatitis which is characterized by a lymphoplasmatic infiltrate with a storiform fibrosis and often goes along with painless jaundice and discrete discomfort of the upper abdomen. Clinically we distinguish between two subtypes, which differ in terms of their histology, clinical picture and prognosis. Type 1 autoimmune pancreatitis is the pancreatic manifestation of the IgG4-associated syndrome which also involves other organs. About one third of the patients can only be diagnosed after either histological prove or a successful steroid trail. Type 2 is IgG4-negative with the histological picture of an idiopathic duct centric pancreatitis and is to higher degree associated with inflammatory bowel disease. A definitive diagnosis can only be made using biopsy. Usually both forms show response to steroid treatment, but in type 1 up to 50 % of the patients might develop a relapse. The biggest challenge and most important differential diagnosis remains the discrimination of AIP from pancreatic cancer, because also AIP can cause mass of the pancreatic head, lymphadenopathy and ductal obstruction. This article summarizes recent advances on epidemiology, clinical presentation, diagnostic strategy, therapy and differential diagnosis in this relatively unknown disease. © Georg Thieme Verlag KG Stuttgart · New York.

  13. Autoimmune bullous skin diseases. Part 1: Clinical manifestations. (United States)

    Kneisel, Andrea; Hertl, Michael


    Autoimmune bullous skin diseases are characterized by autoantibodies against adhesion molecules of the skin. Pemphigus is a disorder with an intraepidermal loss of adhesion and is characterized by fragile blisters and erosions. Pemphigus vulgaris often shows extensive lesions of the oral mucosa, while pemphigus foliaceus is commonly restricted to cutaneous involvement with puff pastry-like scale formation. Paraneoplastic pemphigus is obligatorily associated with malignancies and often presents as hemorrhagic stomatitis with multiforme-like exanthems. IgA pemphigus typically presents with pustules and annular plaques but not with mucosal involvement. The clinical spectrum of the pemphigoids includes tense blisters, urticarial plaques, and prurigo- like eczematous lesions. Pemphigoid gestationis mostly occurs during the last trimester of pregnancy and mucous membrane pemphigoid primarily involves the oral mucosa and conjunctivae and leads to scarring. Linear IgA bullous dermatosis manifests with tense blisters in a "cluster of jewels"-like pattern in childhood and is more heterogeneous in adulthood. Classical epidermolysis bullosa acquisita shows extensive skin fragility. Dermatitis herpetiformis is associated with gluten-sensitive enteropathy and manifests clinically with severe itching and papulovesicles on the extensor surfaces of the extremities and the lumbosacral area. The intention of the review is to demonstrate the heterogeneous clinical spectrum of autoimmune bullous disorders. © The Authors • Journal compilation © Blackwell Verlag GmbH, Berlin.

  14. Update in Endocrine Autoimmunity


    Anderson, Mark S.


    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.

  15. Exposure to a First World War blistering agent. (United States)

    Le, H Q; Knudsen, S J


    Sulfur mustards act as vesicants and alkylating agents. They have been used as chemical warfare since 1917 during the first world war. This brief report illustrates the progression of injury on a primary exposed patient to a first world war blistering agent. This case documents the rapid timeline and progression of symptoms. It emphasises the importance of appropriate personal protective equipment and immediate medical response plan with rapid decontamination and proper action from military and civilian medical treatment facilities. This case reports the first US active duty military exposure to a blistering agent in the age of global terrorism.

  16. Sensitive and specific assays for routine serological diagnosis of epidermolysis bullosa acquisita

    NARCIS (Netherlands)

    Komorowski, Lars; Mueller, Ralf; Vorobyev, Artem; Probst, Christian; Recke, Andreas; Jonkman, Marcel F.; Hashimoto, Takashi; Kim, Soo-Chan; Groves, Richard; Ludwig, Ralf J.; Zillikens, Detlef; Stoecker, Winfried; Schmidt, Enno

    Background: Epidermolysis bullosa acquisita (EBA) is a severe autoimmune subepidermal blistering disease characterized by autoantibodies against the N-terminal collagenous domain (NC1) of type VII collagen (Col VII). Objective: Development of reliable assays for the detection of anti-Col VII-NC1

  17. Management of bullous pemphigoid : the European Dermatology Forum consensus in collaboration with the European Academy of Dermatology and Venereology

    NARCIS (Netherlands)

    Feliciani, C.; Joly, P.; Jonkman, M. F.; Zambruno, G.; Zillikens, D.; Ioannides, D.; Kowalewski, C.; Jedlickova, H.; Karpati, S.; Marinovic, B.; Mimouni, D.; Uzun, S.; Yayli, S.; Hertl, M.; Borradori, L.

    Bullous pemphigoid is the most common autoimmune subepidermal blistering disease of the skin and mucous membranes. This disease typically affects the elderly and presents with itch and localized or generalized bullous lesions. In up to 20% of affected patients, bullae may be completely absent, and

  18. Epidermolysis bullosa acquisita in a 17-year-old boy with Crohn's disease


    Russo, Irene; Ferrazzi, Anna; Zanetti, Irene; Alaibac, Mauro


    Epidermolysis bullosa acquisita is a rare, acquired, autoimmune subepidermal blistering disease of the skin, characterised by blisters and erosions, especially in trauma-prone sites and extensor skin surface, scarring with formation of milia, skin fragility and nail dystrophy. Epidermolysis bullosa acquisita is extremely rare in childhood and it has been reported to be frequently associated with Crohn's disease. Furthermore, autoantibodies against type VII collagen have been found in a large ...

  19. White pines, Ribes, and blister rust: a review and synthesis (United States)

    Brian W. Geils; Kim E. Hummer; Richard S. Hunt


    For over a century, white pine blister rust (Cronartium ribicola) has linked white pines (Strobus) with currants and gooseberries (Ribes) in a complex and serious disease epidemic in Asia, Europe, and North America. Because of ongoing changes in climate, societal demands for forests and their amenities, and scientific advances in genetics and proteomics, our current...

  20. Resistance of three interspecific white pine hybrids to blister rust (United States)

    R. Z. Callaham


    Three white pine hybrids exposed to infection by white pine blister rust (Cronartium ribicola Fischer) since 1946 have inherited the relative resistance of their parental species. The hybrids were produced from controlled pollinations in 1940 and 1941 at the Institute of Forest Genetics, Placerville, Calif. Twelve seedlings of each hybrid were...

  1. Microbiological Quality of Blister Pack Tablets in Community ...

    African Journals Online (AJOL)

    Purpose: To investigate the microbiological quality of blister-packed tablets manufactured and marketed in Jordan in order to assess Good Manufacturing ... Six of the products with the highest stratified bacterial count were manufactured by one company and were also found to be contaminated with Aeromonas species.

  2. Blister rust control in the management of western white pine (United States)

    Kenneth P. Davis; Virgil D. Moss


    The forest industry of the western white pine region depends on the production of white pine as a major species on about 2,670,000 acres of commercial forest land. Continued production of this species and maintenance of the forest industry at anything approaching its present level is impossible unless the white pine blister rust is controlled. Existing merchantable...

  3. White pines, Ribes, and blister rust: integration and action (United States)

    R. S. Hunt; B. W. Geils; K. E. Hummer


    The preceding articles in this series review the history, biology and management of white pine blister rust in North America, Europe and eastern Asia. In this integration, we connect and discuss seven recurring themes important for understanding and managing epidemics of Cronartium ribicola in the white pines (five-needle pines in subgenus Strobus). Information and...

  4. Computer simulation of white pine blister rust epidemics (United States)

    Geral I. McDonald; Raymond J. Hoff; William R. Wykoff


    A simulation of white pine blister rust is described in both word and mathematical models. The objective of this first generation simulation was to organize and analyze the available epidemiological knowledge to produce a foundation for integrated management of this destructive rust of 5-needle pines. Verification procedures and additional research needs are also...

  5. White pine blister rust in the interior Mountain West (United States)

    Kelly Burns; Jim Blodgett; Dave Conklin; Brian Geils; Jim Hoffman; Marcus Jackson; William Jacobi; Holly Kearns; Anna Schoettle


    White pine blister rust is an exotic, invasive disease of white, stone, and foxtail pines (also referred to as white pines or five-needle pines) in the genus Pinus and subgenus Strobus (Price and others 1998). Cronartium ribicola, the fungus that causes WPBR, requires an alternate host - currants and gooseberries in the genus Ribes and species of Pedicularis...

  6. White pine blister rust resistance research in Minnesota and Wisconsin (United States)

    Andrew David; Paul Berrang; Carrie Pike


    The exotic fungus Cronartium ribicola causes the disease white pine blister rust on five-needled pines throughout North America. Although the effects of this disease are perhaps better known on pines in the western portion of the continent, the disease has also impacted regeneration and growth of eastern white pine (Pinus strobus L. ...

  7. Seronegative autoimmune diseases. (United States)

    Alessandri, Cristiano; Conti, Fabrizio; Conigliaro, Paola; Mancini, Riccardo; Massaro, Laura; Valesini, Guido


    A close relationship exists between autoimmunity and autoantibodies; despite this, some patients are persistently negative for disease-specific autoantibodies. These conditions have been defined as seronegative autoimmune diseases. Although the prevalence of seronegative autoimmune diseases is low, they may represent a practical problem because they are often difficult cases. There are also situations in which autoantibodies are positive in healthy subjects. In particular, three different conditions can be described: latent autoimmunity, preclinical autoimmunity, and postclinical autoimmunity. Here, we analyze briefly the meaning of autoantibody negativity in the seronegative autoimmune diseases, focusing in particular on the specificities associated with systemic lupus erythematosus, antiphospholipid syndrome, and rheumatoid arthritis.

  8. Autoimmune Pancreatitis. (United States)

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


    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. Autoimmune pancreatitis. (United States)

    Pannala, Rahul; Chari, Suresh T


    Autoimmune pancreatitis (AIP) is an increasingly recognized clinical condition. Our objective is to provide a concise review of the advances in the past year in our understanding of AIP. In a hospital survey from Japan, the prevalence of AIP was estimated at 0.82 per 100,000 individuals. The pathogenesis of AIP remains unclear but a recent report noted that T helper type 2 and T regulatory cells predominantly mediate the immune reaction in AIP. Genetic associations that may predispose to relapse of AIP were reported. Multiple case series further described the clinical profile of AIP and its extrapancreatic manifestations. A large series on immunoglobulin G4 (IgG4)-associated cholangitis noted that patients with IgG4-associated cholangitis presented with obstructive jaundice and had increased serum IgG4 levels and IgG4-positive cells in bile duct biopsy specimens. Tissue IgG4 staining is likely to be a useful adjunct to serological diagnosis. AIP is steroid-responsive but maintaining remission continues to remain challenging. Presently low-dose steroids or immunomodulators are being used but efficacy of these medications remains to be determined. There has been significant progress in understanding the clinical profile of AIP but knowledge of pathogenesis remains limited. Treatment practices vary widely and management of refractory disease continues to be challenging.


    Directory of Open Access Journals (Sweden)

    Ana Maria Abreu Velez


    Full Text Available Introduction: The in situ immune response within skin biopsies from patients affected by autoimmune skin blistering diseases (ABDs is not well characterized. Aim: Based on the fact that the ABD immune response is considered an adaptive immune response, both an innate immune response and inflammation would be expected in these diseases. Our investigation investigates the presence of cyclo-oxygenase-2 (COX-2, since this enzyme is commonly involved in innate immune responses. Methods: We utilized immunohistochemistry (IHC to evaluate the presence of COX-2 in lesional skin biopsies of patients affected by ABDs. We tested 30 patients with endemic pemphigus foliaceus (EPF, 15 controls from the endemic area, and 15 biopsies from healthy controls from the USA. We also tested archival biopsies from patients with selected ABDs, including 20 patients with bullous pemphigoid, 20 with pemphigus vulgaris, 8 with pemphigus foliaceus and 12 with dermatitis herpetiformis. Results: Most ABD biopsies stained positive for COX-2 in the lesional blister and/or the dermal inflammatory infiltrate, accentuated in the upper neurovascular plexus. In BP and EPF, the COX-2 staining was also seen in the sweat glands. All controls were negative. Conclusions: We document that COX-2 is expressed in lesional skin of patients with ABDs.

  11. Autoimmunity and Gastric Cancer

    Directory of Open Access Journals (Sweden)

    Nicola Bizzaro


    Full Text Available 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.

  12. Absent skin at birth with blistering: Bart's Syndrome?

    Directory of Open Access Journals (Sweden)

    Amina Asfiya M Iqbal


    Full Text Available Bart's Syndrome is a disorder characterised by aplasia cutis congenita and epidermolysis bullosa. We report a case of a 4-day-old baby who had absent skin over the legs along with blistering and nail dystrophy. The diagnosis of Bart's Syndrome was made based on history and clinical examination. However, detailed investigations and histopathological confirmation is needed for final diagnosis. The management is conservative and needs multidisciplinary support.

  13. Blister-Like Malformations an Tea Seedlings 307

    Indian Academy of Sciences (India)

    Shaw, Dorothy, E. .. “Condition resembling blister blight of tea on tea seedlings . in quarantine in New Guinea,” RAD. Plant Prat. Haiti,. 1965, 13, 56~64. Venkata Ram, C. S. “Report of the plant pathologist,” AR. UPASI Sci. Dept. Tea Sect. for 1964~65, 1965, 18-28. Venkataxamani, K. S. . . “Report of the botanist? A.R. UPASI ...

  14. Blister growth in zirconium alloys: experimentation and modeling

    Energy Technology Data Exchange (ETDEWEB)

    Domizzi, G. [Comision Nacional de Energia Atomica, Buenos Aires (Argentina). Dept. de Materiales; Enrique, R.A. [Instituto Balseiro, Universidad Nacional de Cuyo and Comision Nacional de Energia Atomica, 8400 San Carlos de Bariloche (Argentina); Ovejero-Garcia, J. [Comision Nacional de Energia Atomica, Buenos Aires (Argentina). Dept. de Materiales; Buscaglia, G.C. [Instituto Balseiro, Universidad Nacional de Cuyo and Comision Nacional de Energia Atomica, 8400 San Carlos de Bariloche (Argentina)]|[Centro Atomico Bariloche, Comision Nacional de Energia Atomica, 8400 San Carlos de Bariloche (Argentina)


    Hydrogen redistribution in the presence of a cold spot is considered, with hydrogen concentrations above the solid-solubility limit and thus with hydrogen flowing through a hydride-matrix mixture. Fully-hydrided regions (frequently called blisters) grow in the samples, beginning at the cold spot. Under equivalent conditions, the experiment is carried out on several Zr-2.5% Nb samples, allowing for the hydrogen migration times to vary from 1.10{sup 5} to 6.10{sup 5} s, so as to construct a blister-growth curve. Metallographic examination of the samples is performed before and after the imposition of the thermal gradient. A mathematical model is then presented, and the corresponding equations are numerically solved by means of a finite element method, refining the discretization so as to render approximation errors unimportant. Agreement between model and experiment is shown to be quite good for migration times greater than 3.10{sup 5} s. For shorter times, implying small blisters around the cold spot, discrepancies arise between model and experiment, which are attributed to errors in estimating the local temperature field near the sample surface. (orig.).

  15. Prevalence of collagen VII-specific autoantibodies in patients with autoimmune and inflammatory diseases


    Licarete Emilia; Ganz Susanne; Recknagel Martin J; Di Zenzo Giovanni; Hashimoto Takashi; Hertl Michael; Zambruno Giovanna; Hundorfean Gheorghe; Mudter Jonas; Neurath Markus F; Bruckner-Tuderman Leena; Sitaru Cassian


    Abstract Background Autoimmunity to collagen VII is typically associated with the skin blistering disease epidermolysis bullosa acquisita (EBA), but also occurs occasionally in patients with systemic lupus erythematosus or inflammatory bowel disease. The aim of our present study was to develop an accurate immunoassay for assessing the presence of autoantibodies against collagen VII in large cohorts of patients and healthy donors. Methods Based on in silico antigenic analysis and previous wetl...

  16. American Autoimmune Related Diseases Association (United States)

    ... Help Patients ARNet Research Survey AD Knowledge Base Autoimmune Disease List Common Thread Women & Autoimmunity Diagnosis Tips Coping ... Caregiver Relationship The Male Caregiver AD Knowledge Base Autoimmune Disease List Common Thread Women & Autoimmunity Diagnosis Tips Published ...

  17. Pharmacokinetic Profile of Meropenem, Administered at 500 Milligrams Every 8 Hours, in Plasma and Cantharidin-Induced Skin Blister Fluid (United States)

    Maglio, Dana; Teng, Renli; Thyrum, Per T.; Nightingale, Charles H.; Nicolau, David P.


    The pharmacokinetic disposition of meropenem, administered at 500 mg every 8 h, in plasma and cantharidin-induced blister fluid is described. Peak meropenem concentrations in blister fluid lagged behind peak meropenem concentrations in plasma, while a lower elimination rate from blister fluid was also noted. The mean penetration of meropenem into blister fluid was 67%. The pharmacokinetic profile of meropenem in blister fluid supports the utility of this dose in the management of skin and soft tissue infections. PMID:12709358

  18. Autoimmunity and Gastric Cancer


    Nicola Bizzaro; Antonio Antico; Danilo Villalta


    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 gastri...

  19. Autoimmune Thyroid Disorders


    B. N. Macharia; Iddah, M. A.


    Purpose of Review. Studies have been published in the field of autoimmune thyroid diseases since January 2005. The review is organized into areas of etiology, autoimmune features, autoantibodies, mechanism of thyroid cell injury, B-cell responses, and T-cell responses. Also it reviews the diagnosis and the relationship between autoimmune thyroid disease, neoplasm, and kidney disorders. Recent Findings. Autoimmune thyroid diseases have been reported in people living in different parts of the w...

  20. Langerhans Cells Prevent Autoimmunity via Expansion of Keratinocyte Antigen-Specific Regulatory T Cells

    Directory of Open Access Journals (Sweden)

    Daniela Y. Kitashima


    Full Text Available Langerhans cells (LCs are antigen-presenting cells in the epidermis whose roles in antigen-specific immune regulation remain incompletely understood. Desmoglein 3 (Dsg3 is a keratinocyte cell-cell adhesion molecule critical for epidermal integrity and an autoantigen in the autoimmune blistering disease pemphigus. Although antibody-mediated disease mechanisms in pemphigus are extensively characterized, the T cell aspect of this autoimmune disease still remains poorly understood. Herein, we utilized a mouse model of CD4+ T cell-mediated autoimmunity against Dsg3 to show that acquisition of Dsg3 and subsequent presentation to T cells by LCs depended on the C-type lectin langerin. The lack of LCs led to enhanced autoimmunity with impaired Dsg3-specific regulatory T cell expansion. LCs expressed the IL-2 receptor complex and the disruption of IL-2 signaling in LCs attenuated LC-mediated regulatory T cell expansion in vitro, demonstrating that direct IL-2 signaling shapes LC function. These data establish that LCs mediate peripheral tolerance against an epidermal autoantigen and point to langerin and IL-2 signaling pathways as attractive targets for achieving tolerogenic responses particularly in autoimmune blistering diseases such as pemphigus.

  1. Spectrum of autoimmune bullous diseases in Kuwait. (United States)

    Nanda, Arti; Dvorak, Richard; Al-Saeed, Khloud; Al-Sabah, Humoud; Alsaleh, Qasem A


    Autoimmune bullous diseases (ABDs) are a rare but significant group of dermatoses that pose great challenges to the treating dermatologist. Most epidemiological studies have focused on a single ABD. Few surveys have been carried out to describe the whole spectrum of ABDs in a region, and no such studies are available from the Arabian Peninsula. To determine the clinico-epidemiological features of various ABDs in Kuwait, and to compare the results with those reported elsewhere. A total of 128 cases of ABDs were studied over a span of 11.5 years. The diagnosis in all cases was confirmed by histopathology, and direct and indirect immunofluorescence (IMF). The diagnosis of various subepidermal ABDs was further confirmed by indirect IMF on salt-split skin (SSS) and that of pemphigus by desmoglein 1 and 3 enzyme-linked immunosorbent assay (ELISA). Eighty seven per cent of patients were of Arab ethnicity. Pemphigus was observed to be the commonest ABD (47%), followed by pemphigoid (22%), pemphigoid gestationis (PG) (19%), linear IgA bullous disease (LABD) (7%), lichen planus pemphigoides (LPP) (3%), and epidermolysis bullosa acquisita (EBA) (2.3%). The minimum estimated incidence in the local population was 4.6, 2.14, 1.83, 0.69, 0.30, and 0.23 cases per million per year, respectively. Pemphigus patients were observed to have a younger age of onset (36.50 +/- 11.36 years) than reported elsewhere. BP, although the second commonest ABD, was less prevalent than in Europe and Singapore, and BP patients were observed to have a striking female predominance (85%). The prevalence of PG was much higher than that reported elsewhere. LABD was the fourth commonest ABD, and 89% of patients were children. The study suggests that similar surveys from different regions would expand our understanding of ABD.

  2. Boat Hull Blisters: Repair Techniques and Long Term Effects on Hull Degradation (United States)


    blistering of boat hulls is a serious problem which affects many fiber- glass polyester boats. It can range from a surficial cosmetic problem to a deep...something present in the resin itself. We have reported blistering vhen sorbitol is added to the resin. Pritchard has reported on the role of excess glycol...Is blistering and water absorption only a cosmetic and surficial problem or does deep seated damage occur after prolonged water exposure? The

  3. Real-time imaging of suction blistering in human skin using optical coherence tomography (United States)

    Carvalho, Joana C.O.; Palero, Jonathan A.; Jurna, Martin


    Separation of skin epidermis from the dermis by suction blistering has been used with high success rate for autologous skin epidermal grafting in burns, chronic wounds and vitiligo transplantation treatment. Although commercial products that achieve epidermal grafting by suction blistering are presently available, there is still limited knowledge and understanding on the dynamic process of epidermal-dermal separation during suction blistering. In this report we integrated a suction system to an Optical Coherence Tomography (OCT) which allowed for the first time, real-time imaging of the suction blistering process in human skin. We describe in this report the evolution of a suction blister where the growth is modeled with a Boltzmann sigmoid function. We further investigated the relationship between onset and steady-state blister times, blister growth rate, applied suction pressure and applied local skin temperature. Our results show that while the blister time is inversely proportional to the applied suction pressure, the relationship between the blister time and the applied temperature is described by an exponential decay. PMID:26713194

  4. Polyglandular autoimmune syndromes. (United States)

    Kahaly, G J; Frommer, L


    In recent years, scientific knowledge pertaining to the rare ORPHAN polyglandular autoimmune syndrome (registered code ORPHA 282196) has accumulated. To offer current demographic, clinical, serological and immunogenic data on PAS. Review of the pertinent and current literature. Polyglandular autoimmune syndromes (PAS) are multifactorial diseases with at least two coexisting autoimmune-mediated endocrinopathies. PAS show a great heterogeneity of syndromes and manifest sequentially with a large time interval between the occurrence of the first and second glandular autoimmune disease. PAS cluster with several non-endocrine autoimmune diseases. In most endocrinopathies of PAS, the autoimmune process causes an irreversible loss of function, while chronic autoimmune aggressions can simultaneously modify physiological processes in the affected tissue and lead to altered organ function. The rare juvenile PAS type I is inherited in a monogenetic manner, whereas several susceptibility gene polymorphisms have been reported for the more prevalent adult types. Relevant for a timely diagnosis at an early stage is the screening for polyglandular autoimmunity in patients with monoglandular autoimmune disease and/or first degree relatives of patients with PAS. The most prevalent adult PAS type is the combination of type 1 diabetes with autoimmune thyroid disease. Early detection of specific autoantibodies and latent organ-specific dysfunction is advocated to alert physicians to take appropriate action in order to prevent full-blown PAS disease.

  5. Non-pathogenic pemphigus foliaceus (PF) IgG acts synergistically with a directly pathogenic PF IgG to increase blistering by p38MAPK-dependent desmoglein 1 clustering✩ (United States)

    Yoshida, Kenji; Ishii, Ken; Shimizu, Atsushi; Yokouchi, Mariko; Amagai, Masayuki; Shiraishi, Ken; Shirakata, Yuji; Stanley, John R.; Ishiko, Akira


    Background Pemphigus foliaceus (PF) is an autoimmune blistering disease caused by autoantibodies (Abs) against desmoglein 1 (Dsg1). PF sera contain polyclonal Abs which are heterogeneous mixture of both pathogenic and non-pathogenic Abs, as shown by isolation of monoclonal Abs (mAbs). Objective To investigate how pathogenic and non-pathogenic anti-Dsg1 Abs contribute to blister formation in PF. Methods Using organ-cultured human skin, we compared the effect of a single pathogenic anti-Dsg1 IgG mAb, a single non-pathogenic anti-Dsg1 IgG mAb, and their mixture on blister formation as analyzed by histology, subcellular localization of IgG deposits and desmosomal proteins by confocal microscopy, and desmosomal structure by electron microscopy. In addition, we measured keratinocyte adhesion by an in vitro dissociation assay. Results 24 h after injection, a single pathogenic anti-Dsg1 IgG caused a subcorneal blister with IgG and Dsg1 localized linearly on the cell surface of keratinocytes. A single non-pathogenic anti-Dsg1 IgG bound linearly on the keratinocytes but did not induce blisters. A pathogenic and a non-pathogenic IgG mAb injected together caused an aberrant granular pattern of IgG and Dsg1 in the lower epidermis with blister formation in the superficial epidermis. Electron microscopy demonstrated that the mixture of mAbs shortened desmosomal lengths more than a single mAb in the basal and spinous layers. Furthermore, although Dsg1 clustering required both cross-linking of Dsg1 molecules by the non-pathogenic IgG plus a pathogenic antibody, the latter could be in the form of a monovalent single chain variable fragment, suggesting that loss of trans-interaction of Dsg1 is required for clustering. Finally, a p38MAPK inhibitor blocked Dsg1 clustering. When pathogenic strength was measured by the dissociation assay, a mixture of pathogenic and non-pathogenic IgG mAbs disrupted keratinocyte adhesion more than a single pathogenic mAb. This pathogenic effect was only

  6. Non-pathogenic pemphigus foliaceus (PF) IgG acts synergistically with a directly pathogenic PF IgG to increase blistering by p38MAPK-dependent desmoglein 1 clustering. (United States)

    Yoshida, Kenji; Ishii, Ken; Shimizu, Atsushi; Yokouchi, Mariko; Amagai, Masayuki; Shiraishi, Ken; Shirakata, Yuji; Stanley, John R; Ishiko, Akira


    Pemphigus foliaceus (PF) is an autoimmune blistering disease caused by autoantibodies (Abs) against desmoglein 1 (Dsg1). PF sera contain polyclonal Abs which are heterogeneous mixture of both pathogenic and non-pathogenic Abs, as shown by isolation of monoclonal Abs (mAbs). To investigate how pathogenic and non-pathogenic anti-Dsg1 Abs contribute to blister formation in PF. Using organ-cultured human skin, we compared the effect of a single pathogenic anti-Dsg1 IgG mAb, a single non-pathogenic anti-Dsg1 IgG mAb, and their mixture on blister formation as analyzed by histology, subcellular localization of IgG deposits and desmosomal proteins by confocal microscopy, and desmosomal structure by electron microscopy. In addition, we measured keratinocyte adhesion by an in vitro dissociation assay. 24h after injection, a single pathogenic anti-Dsg1 IgG caused a subcorneal blister with IgG and Dsg1 localized linearly on the cell surface of keratinocytes. A single non-pathogenic anti-Dsg1 IgG bound linearly on the keratinocytes but did not induce blisters. A pathogenic and a non-pathogenic IgG mAb injected together caused an aberrant granular pattern of IgG and Dsg1 in the lower epidermis with blister formation in the superficial epidermis. Electron microscopy demonstrated that the mixture of mAbs shortened desmosomal lengths more than a single mAb in the basal and spinous layers. Furthermore, although Dsg1 clustering required both cross-linking of Dsg1 molecules by the non-pathogenic IgG plus a pathogenic antibody, the latter could be in the form of a monovalent single chain variable fragment, suggesting that loss of trans-interaction of Dsg1 is required for clustering. Finally, a p38MAPK inhibitor blocked Dsg1 clustering. When pathogenic strength was measured by the dissociation assay, a mixture of pathogenic and non-pathogenic IgG mAbs disrupted keratinocyte adhesion more than a single pathogenic mAb. This pathogenic effect was only partially suppressed by the p38MAPK

  7. Galectin-3 in autoimmunity and autoimmune diseases. (United States)

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


    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.

  8. Sirolimus for Autoimmune Disease of Blood Cells (United States)


    Autoimmune Pancytopenia; Autoimmune Lymphoproliferative Syndrome (ALPS); Evans Syndrome; Idiopathic Thrombocytopenic Purpura; Anemia, Hemolytic, Autoimmune; Autoimmune Neutropenia; Lupus Erythematosus, Systemic; Inflammatory Bowel Disease; Rheumatoid Arthritis

  9. Assessment of imperfect detection of blister rust in whitebark pine within the Greater Yellowstone Ecosystem (United States)

    Wright, Wilson J.; Irvine, Kathryn M.


    We examined data on white pine blister rust (blister rust) collected during the monitoring of whitebark pine trees in the Greater Yellowstone Ecosystem (from 2004-2015). Summaries of repeat observations performed by multiple independent observers are reviewed and discussed. These summaries show variability among observers and the potential for errors being made in blister rust status. Based on this assessment, we utilized occupancy models to analyze blister rust prevalence while explicitly accounting for imperfect detection. Available covariates were used to model both the probability of a tree being infected with blister rust and the probability of an observer detecting the infection. The fitted model provided strong evidence that the probability of blister rust infection increases as tree diameter increases and decreases as site elevation increases. Most importantly, we found evidence of heterogeneity in detection probabilities related to tree size and average slope of a transect. These results suggested that detecting the presence of blister rust was more difficult in larger trees. Also, there was evidence that blister rust was easier to detect on transects located on steeper slopes. Our model accounted for potential impacts of observer experience on blister rust detection probabilities and also showed moderate variability among the different observers in their ability to detect blister rust. Based on these model results, we suggest that multiple observer sampling continue in future field seasons in order to allow blister rust prevalence estimates to be corrected for imperfect detection. We suggest that the multiple observer effort be spread out across many transects (instead of concentrated at a few each field season) while retaining the overall proportion of trees with multiple observers around 5-20%. Estimates of prevalence are confounded with detection unless it is explicitly accounted for in an analysis and we demonstrate how an occupancy model can be used

  10. Metals and kidney autoimmunity.


    Bigazzi, P. E.


    The causes of autoimmune responses leading to human kidney pathology remain unknown. However, environmental agents such as microorganisms and/or xenobiotics are good candidates for that role. Metals, either present in the environment or administered for therapeutic reasons, are prototypical xenobiotics that cause decreases or enhancements of immune responses. In particular, exposure to gold and mercury may result in autoimmune responses to various self-antigens as well as autoimmune disease o...

  11. Autoimmune liver diseases


    Invernizzi, Pietro; Mackay, Ian R


    The liver was one of the earliest recognized sites among autoimmune diseases yet autoimmune hepatitis, primary biliary cirrhosis, primary sclerosing cholangitis, and their overlap forms, are still problematic in diagnosis and causation. The contributions herein comprise 'pairs of articles' on clinical characteristics, and concepts of etiopathogenesis, for each of the above diseases, together with childhood autoimmune liver disease, overlaps, interpretations of diagnostic serology, and liver t...

  12. Autoimmune pancreatitis: a review. (United States)

    Zandieh, Iman; Byrne, Michael-F


    Autoimmune pancreatitis has emerged over the last 40 years from a proposed concept to a well established and recognized entity. As an efficient mimicker of pancreatic carcinoma, its early and appropriate recognition are crucial. With mounting understanding of its pathogenesis and natural history, significant advances have been made in the diagnosis of autoimmune pancreatitis. The characteristic laboratory features and imaging seen in autoimmune pancreatitis are reviewed along with some of the proposed diagnostic criteria and treatment algorithms.

  13. Autoimmune pancreatitis: A review


    Zandieh, Iman; Michael F Byrne


    Autoimmune pancreatitis has emerged over the last 40 years from a proposed concept to a well established and recognized entity. As an efficient mimicker of pancreatic carcinoma, its early and appropriate recognition are crucial. With mounting understanding of its pathogenesis and natural history, significant advances have been made in the diagnosis of autoimmune pancreatitis. The characteristic laboratory features and imaging seen in autoimmune pancreatitis are reviewed along with some of the...

  14. [Thymoma and autoimmune diseases]. (United States)

    Jamilloux, Y; Frih, H; Bernard, C; Broussolle, C; Petiot, P; Girard, N; Sève, P


    The association between thymoma and autoimmunity is well known. Besides myasthenia gravis, which is found in 15 to 20% of patients with thymoma, other autoimmune diseases have been reported: erythroblastopenia, systemic lupus erythematosus, inflammatory myopathies, thyroid disorders, Isaac's syndrome or Good's syndrome. More anecdotally, Morvan's syndrome, limbic encephalitis, other autoimmune cytopenias, autoimmune hepatitis, and bullous skin diseases (pemphigus, lichen) have been reported. Autoimmune diseases occur most often before thymectomy, but they can be discovered at the time of surgery or later. Two situations require the systematic investigation of a thymoma: the occurrence of myasthenia gravis or autoimmune erythroblastopenia. Nevertheless, the late onset of systemic lupus erythematosus or the association of several autoimmune manifestations should lead to look for a thymoma. Neither the characteristics of the patients nor the pathological data can predict the occurrence of an autoimmune disease after thymectomy. Thus, thymectomy usefulness in the course of the autoimmune disease, except myasthenia gravis, has not been demonstrated. This seems to indicate the preponderant role of self-reactive T lymphocytes distributed in the peripheral immune system prior to surgery. Given the high infectious morbidity in patients with thymoma, immunoglobulin replacement therapy should be considered in patients with hypogammaglobulinemia who receive immunosuppressive therapy, even in the absence of prior infection. Copyright © 2017 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier SAS. All rights reserved.

  15. Ion effects in hydrogen-induced blistering of Mo/Si multilayers

    NARCIS (Netherlands)

    Kuznetsov, Alexey; Gleeson, M.A.; Bijkerk, Frederik


    The role that energetic (>800 eV) hydrogen ions play in inducing and modifying the formation of blisters in nanoscale Mo/Si multilayer samples is investigated. Such samples are confirmed to be susceptible to blistering by two separate mechanisms. The first is attributed to the segregation of H atoms

  16. Ion effects in hydrogen-induced blistering of Mo/Si multilayers

    NARCIS (Netherlands)

    Kuznetsov, A. S.; Gleeson, M. A.; F. Bijkerk,


    The role that energetic (>800 eV) hydrogen ions play in inducing and modifying the formation of blisters in nanoscale Mo/Si multilayer samples is investigated. Such samples are confirmed to be susceptible to blistering by two separate mechanisms. The first is attributed to the segregation of

  17. Screening conventional fungicides...control of blister rust on sugar pine in California (United States)

    Clarence R. Quick


    After 5 years, 4 of 14 fungicides tested showed varying pr of development into satisfactory direct control of blister rust. Little promise of systemic control was found. Trees treated were second-growth sugar pine in a mixed conifer forest in eastern Shasta County, California, where blister rust has been intensifying for many years. Most trees received basal-stem...

  18. Biology and pathology of Ribes and their implications for management of white pine blister rust (United States)

    P. J. Zambino


    Ribes (currants and gooseberries) are telial hosts for the introduced and invasive white pine blister rust fungus, Cronartium ribicola. Knowledge of wild and introduced Ribes helps us understand the epidemiology of blister rust on its aecial hosts, white pines, and develop disease control and management strategies. Ribes differ by species in their contribution to...

  19. Autoimmune liver disease, autoimmunity and liver transplantation. (United States)

    Carbone, Marco; Neuberger, James M


    Primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC) and autoimmune hepatitis (AIH) represent the three major autoimmune liver diseases (AILD). PBC, PSC, and AIH are all complex disorders in that they result from the effects of multiple genes in combination with as yet unidentified environmental factors. Recent genome-wide association studies have identified numerous risk loci for PBC and PSC that host genes involved in innate or acquired immune responses. These loci may provide a clue as to the immune-based pathogenesis of AILD. Moreover, many significant risk loci for PBC and PSC are also risk loci for other autoimmune disorders, such type I diabetes, multiple sclerosis and rheumatoid arthritis, suggesting a shared genetic basis and possibly similar molecular pathways for diverse autoimmune conditions. There is no curative treatment for all three disorders, and a significant number of patients eventually progress to end-stage liver disease requiring liver transplantation (LT). LT in this context has a favourable overall outcome with current patient and graft survival exceeding 80% at 5years. Indications are as for other chronic liver disease although recent data suggest that while lethargy improves after transplantation, the effect is modest and variable so lethargy alone is not an indication. In contrast, pruritus rapidly responds. Cholangiocarcinoma, except under rigorous selection criteria, excludes LT because of the high risk of recurrence. All three conditions may recur after transplantation and are associated with a greater risk of both acute cellular and chronic ductopenic rejection. It is possible that a crosstalk between alloimmune and autoimmune response perpetuate each other. An immunological response toward self- or allo-antigens is well recognised after LT in patients transplanted for non-autoimmune indications and sometimes termed "de novo autoimmune hepatitis". Whether this is part of the spectrum of rejection or an autoimmune

  20. Sock systems to prevent foot blisters and the impact on overuse injuries of the knee joint. (United States)

    Van Tiggelen, Damien; Wickes, Simon; Coorevits, Pascal; Dumalin, Mich; Witvrouw, Erik


    The incidence of foot blisters and other overuse injuries of the lower limb is very high during basic military training (BMT). One hundred and eighty-nine subjects were divided into two intervention groups wearing alternative sock systems and one control group. Overall, 57% of the 173 recruits who completed the training, developed foot blisters. Binary logistic regression revealed the type of sock, race, previous hiking or military experience, and known orthopedic foot conditions to be predictive variables for foot blisters. Fifty-three percent of the 173 recruits also developed another overuse injury of the lower limb (25.4% related to the knee joint). Previous military or hiking experience and the association of foot blisters revealed to be predictive for the overuse injuries of the knee joint. The results of the present study suggest associated foot blisters are also an important factor in the development of overuse injuries of the knee joint during BMT.

  1. Blister formation on rough and technical tungsten surfaces exposed to deuterium plasma (United States)

    Manhard, Armin; Balden, Martin; von Toussaint, Udo


    Up to now, blister formation on rough or technical tungsten surfaces exposed to hydrogen isotope plasma was believed to be completely suppressed. The few dedicated experiments on this issue that can be found in literature appear to support that claim. Using a novel technique of 3D difference imaging of tungsten surfaces, we now demonstrate that roughness introduced by chemical etching, i.e. without the associated mechanical deformation layer introduced by grinding, only moderately reduces blistering. A technical surface with comparable roughness produced by precision grinding (R a  ⩽  1.6 µm) led to a strong reduction in blister size and density, but blisters were found nevertheless. In this article we give a detailed description of the investigated rough W surfaces and present a statistical evaluation of blistering on these surfaces after exposure to a low-temperature deuterium plasma.

  2. Metals and kidney autoimmunity. (United States)

    Bigazzi, P E


    The causes of autoimmune responses leading to human kidney pathology remain unknown. However, environmental agents such as microorganisms and/or xenobiotics are good candidates for that role. Metals, either present in the environment or administered for therapeutic reasons, are prototypical xenobiotics that cause decreases or enhancements of immune responses. In particular, exposure to gold and mercury may result in autoimmune responses to various self-antigens as well as autoimmune disease of the kidney and other tissues. Gold compounds, currently used in the treatment of patients with progressive polyarticular rheumatoid arthritis, can cause a nephrotic syndrome. Similarly, an immune-mediated membranous nephropathy frequently occurred when drugs containing mercury were commonly used. Recent epidemiologic studies have shown that occupational exposure to mercury does not usually result in autoimmunity. However, mercury induces antinuclear antibodies, sclerodermalike disease, lichen planus, or membranous nephropathy in some individuals. Laboratory investigations have confirmed that the administration of gold or mercury to experimental animals leads to autoimmune disease quite similar to that observed in human subjects exposed to these metals. In addition, studies of inbred mice and rats have revealed that a few strains are susceptible to the autoimmune effects of gold and mercury, whereas the majority of inbred strains are resistant. These findings have emphasized the importance of genetic (immunogenetic and pharmacogenetic) factors in the induction of metal-associated autoimmunity. (italic)In vitro(/italic) and (italic)in vivo(/italic) research of autoimmune disease caused by mercury and gold has already yielded valuable information and answered a number of important questions. At the same time it has raised new issues about possible immunostimulatory or immunosuppressive mechanisms of xenobiotic activity. Thus it is evident that investigations of metal

  3. Mesotherapy for skin rejuvenation: assessment of the subepidermal low-echogenic band by ultrasound evaluation with cross-sectional B-mode scanning. (United States)

    Lacarrubba, Francesco; Tedeschi, Aurora; Nardone, Beatrice; Micali, Giuseppe


    Skin-targeted ultrasound is a noninvasive technique that has been extensively used to evaluate age-related dermal changes, and the presence of a subepidermal low-echogenic band (SLEB) has been related to chronic UVR exposure in several studies. Since SLEB echogenicity is photoage-related, the aim of this study was to evaluate, through ultrasound imaging, the effects on skin photoaging of mesotherapy, a treatment approach currently used in cosmetic dermatology for skin rejuvenation. Twenty women (mean age: 46.7 range 40-60 years) with physical signs of moderate photoaging on the dorsum of the hands were enrolled and treated with multiple microinjections of hyaluronic acid (HA) salts of biotechnological origin (1.000 Kd) every week for 4 weeks. In all subjects, ultrasound evaluation was performed at each visit and 1 week after the last treatment to evaluate SLEB echogenicity changes during treatment. At the end of study, a statistically significant (p mesotherapy with HA may be an effective treatment for skin photoaging, as confirmed by ultrasound. Follow-up investigations on larger series of patients are necessary to further evaluate the safety, effectiveness, and duration of effect of this possible therapeutic approach to skin photoaging.

  4. Autoimmune bullous skin diseases. Part 2: diagnosis and therapy. (United States)

    Kneisel, Andrea; Hertl, Michael


    Autoimmune bullous skin diseases represent a heterogenous group of disorders of skin and mucosa which are commonly associated with IgG or IgA autoantibodies against distinct adhesion molecules of the skin. The antibodyinduced loss of adhesion between epidermis and dermis results in blister formation and extensive erosions. There is a great need for rapidly establishing the diagnosis of these disorders since they may run a severe and potentially life-threatening course. In addition, because of their rarity and heterogeneous symptoms, autoimmune bullous skin diseases often pose a major diagnostic challenge. While histopathological examinations provide evidence for the level of blister formation, immunofluorescence microscopy has been established to identify tissue-bound and circulating autoantibodies. Direct immunofluorescence microscopy represents the gold standard for detecting tissue-bound autoantibodies. Indirect immunofluorescence microscopy with defined tissue substrates is considered the first step in detecting circulating autoantibodies. Confirmatory tests such as ELISA, immunoblot or immunoprecipitation analyses are performed utilizing recombinant proteins or keratinocyte extracts. The later assays can be used for primary diagnosis as well as for immunoserological follow-up. Systemic immunosuppressive drugs usually represent the main therapeutic regimen. Initially, systemic corticosteroids are commonly administered in combination with steroid-sparing, immunosuppressive agents. Novel targeted treatments such as immunoadsorption, rituximab or high-dose intravenous immunoglobulins have proven to be highly effective in severe and refractory pemphigus. This review presents a state-of-the-art algorithm for making the diagnosis of autoimmune bullous disorders and provides an overview on currently available therapeutic options. © The Authors • Journal compilation © Blackwell Verlag GmbH, Berlin.


    Directory of Open Access Journals (Sweden)

    Juan-Manuel eAnaya


    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.

  6. Bistability in autoimmune diseases

    DEFF Research Database (Denmark)

    Rapin, Nicolas; Mosekilde, Erik; Lund, Ole


    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...

  7. Cancer and autoimmune diseases. (United States)

    Giat, Eitan; Ehrenfeld, Michael; Shoenfeld, Yehuda


    The association between autoimmunity and cancer is well established. Cancer has been implicated in some autoimmune disorders (AID), such as scleroderma and myositis. On the other hand, many autoimmune disorders and immunosuppressive therapy, have been linked to an increased risk for cancer. We reviewed the accumulating data on the association between autoimmunity and cancer during the past three years, with an emphasis on large cohorts, as well as concept changing discoveries in the association of cancer and auto-immunity. Recent published data from large registries and databases have changed our perspective on the association of AID and cancer, as well as the presumed association between anti-tumor necrosis factor (anti -TNF) therapy and certain malignancies, suggesting a small to no increase in almost all types of cancers. Similarly, the increased risk of malignancies in some AID, such as Sjogren's syndrome (SS) and lupus, may be different from previous estimations. New associations with malignancies were discovered, such as IgG4 related disease, Behcet's and sarcoidosis, which were not clearly associated with cancer in the past. These newly described associations may have clinical implications and contribute to our understanding of both autoimmunity and cancer. Similarly, we reviewed studies of autoimmunity secondary to malignancy, and the concomitant appearance of cancer with autoimmune disease, such as the discovery of a specific mutation in scleroderma (SS) patients that developed cancer, which establishes the association between these disorders and sheds light on the pathology behind this association. Copyright © 2017. Published by Elsevier B.V.

  8. Bullous pemphigoid associated with acquired hemophilia a: a rare association of autoimmune disease. (United States)

    Aljasser, Mohammed I; Sladden, Chris; Crawford, Richard I; Au, Sheila


    Acquired hemophilia (AH) is a rare autoimmune disease with an annual incidence of one per million and has a mortality rate of up to 22%. It is caused by the development of autoantibodies against factor VIII. Approximately half of the reported cases are associated with autoimmune disorders, pregnancy, malignancies, and adverse drug reactions. Autoimmune diseases are the most frequently associated disorders and include rheumatoid arthritis, systemic lupus erythematosus, cryoglobulinemia, pemphigus vulgaris, and bullous pemphigoid. There are a few reports of acquired hemophilia and bullous pemphigoid in the literature. We report a 73-year-old male who presented with cutaneous blistering, upper gastrointestinal bleeding, and hemoptysis. He later developed right flank pain secondary to a retroperitoneal hematoma. He had a prolonged partial thromboplastin time, a low factor VIII level, and a high factor VIII inhibitor level, all consistent with acquired hemophilia. Skin biopsies were diagnostic for bullous pemphigoid. He was treated successfully with prednisone, cyclophosphamide, rituximab, and intravenous immunoglobulin.

  9. Development of a disease registry for autoimmune bullous diseases: initial analysis of the pemphigus vulgaris subset. (United States)

    Shah, Amit Aakash; Seiffert-Sinha, Kristina; Sirois, David; Werth, Victoria P; Rengarajan, Badri; Zrnchik, William; Attwood, Kristopher; Sinha, Animesh A


    Pemphigus vulgaris (PV) is a rare, potentially life threatening, autoimmune blistering skin disease. The International Pemphigus and Pemphigoid Foundation (IPPF) has recently developed a disease registry with the aim to enhance our understanding of autoimmune bullous diseases with the long-term goal of acquiring information to improve patient care. Patients were recruited to the IPPF disease registry through direct mail, e-mail, advertisements, and articles in the IPPF-quarterly, -website, -Facebook webpage, and IPPF Peer Health Coaches to complete a 38-question survey. We present here the initial analysis of detailed clinical information collected on 393 PV patients. We report previously unrecognized gender differences in terms of lesion location, autoimmune comorbidity, and delay in diagnosis. The IPPF disease registry serves as a useful resource and guide for future clinical investigation.

  10. Leptin and autoimmune disease. (United States)

    Fujita, Yoshimasa


    Leptin is secreted from adipocytes and acts mainly on the hypothalamus causing weight loss due to suppression of appetite and increased energy expenditure. On the other hand, the leptin receptor is also expressed in hematopoietic cells and its action on the immune system has become known, and the significance of leptin in autoimmune diseases has gradually become clear. It has been shown that leptin acts as an exacerbating factor in many autoimmune diseases and it is suggested that inhibition of leptin signal may be a novel therapeutic method for autoimmune diseases. In this article, we will outline the significance of leptin in the immune system based on the current reports.

  11. Silica, Silicosis and Autoimmunity.

    Directory of Open Access Journals (Sweden)

    Kenneth Michael Pollard


    Full Text Available Inhalation of dust containing crystalline silica is associated with a number of acute and chronic diseases including systemic autoimmune diseases. Evidence for the link with autoimmune disease comes from epidemiological studies linking occupational exposure to crystalline silica dust with the systemic autoimmune diseases SLE, SSc and RA. Although little is known regarding the mechanism by which silica exposure leads to systemic autoimmune disease, there is a voluminous literature on silica exposure and silicosis that may help identify immune processes that precede development of autoimmunity. The pathophysiology of silicosis consists of deposition of silica particles in the alveoli of the lung. Ingestion of these particles by macrophages initiates an inflammatory response which stimulates fibroblasts to proliferate and produce collagen. Silica particles are encased by collagen leading to fibrosis and the nodular lesions characteristic of the disease. The steps in the development of silicosis, including acute and chronic inflammation and fibrosis, have different molecular and cellular requirements suggesting that silica-induced inflammation and fibrosis may be mechanistically separate. Significantly, it is unclear whether silica-induced inflammation and fibrosis contribute similarly to the development of autoimmunity. Nonetheless, the findings from human and animal model studies are consistent with an autoimmune pathogenesis that begins with activation of the innate immune system leading to proinflammatory cytokine production, pulmonary inflammation leading to activation of adaptive immunity, breaking of tolerance, autoantibodies and tissue damage. The variable frequency of these immunological features following silica exposure suggests substantial genetic involvement and gene/environment interaction in silica-induced autoimmunity. However numerous questions remain unanswered.

  12. Vaccines, adjuvants and autoimmunity. (United States)

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


    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.

  13. Eosinophils in Autoimmune Diseases

    Directory of Open Access Journals (Sweden)

    Daniela Čiháková


    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.

  14. Eosinophils in Autoimmune Diseases. (United States)

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


    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.

  15. Blistering mechanisms of atomic-layer-deposited AlN and Al2O3 films (United States)

    Broas, Mikael; Jiang, Hua; Graff, Andreas; Sajavaara, Timo; Vuorinen, Vesa; Paulasto-Kröckel, Mervi


    Blistering of protective, structural, and functional coatings is a reliability risk pestering films ranging from elemental to ceramic ones. The driving force behind blistering comes from either excess hydrogen at the film-substrate interface or stress-driven buckling. Contrary to the stress-driven mechanism, the hydrogen-initiated one is poorly understood. Recently, it was shown that in the bulk Al-Al2O3 system, the blistering is preceded by the formation of nano-sized cavities on the substrate. The stress- and hydrogen-driven mechanisms in atomic-layer-deposited (ALD) films are explored here. We clarify issues in the hydrogen-related mechanism via high-resolution microscopy and show that at least two distinct mechanisms can cause blistering in ALD films.

  16. Epidermolysis bullosa acquisita: current diagnosis and therapy

    Directory of Open Access Journals (Sweden)

    Christine R. Mehren


    Full Text Available Epidermolysis bullosa acquisita (EBA is an acquired, autoimmune subepidermal blistering disease with an approximate prevalence of 0,2/million people. The hallmark of EBA is the presence of autoantibodies (mainly IgG class to anchoring fibril collagen (type VII collagen located at the dermal-epidermal junction. Clinically EBA is subdivided into the inflammatory and the non-inflammatory phenotypes, depending on the level of the cleavage in the basal membrane. A recent addition to the diagnostic techniques is the analysis of the serration pattern of the autoantibody deposits at the basal membrane in the direct immunofluorescence. EBA and the closely related bullous systemic lupus erythematosus are the only diseases presenting with the so-called u-serration pattern which distinguishes them from many other autoimmune subepidermal blistering diseases. We also discuss the recent advances in therapy, including the experience with Rituximab.

  17. Synergistic helium and deuterium blistering in tungsten–tantalum composites

    Energy Technology Data Exchange (ETDEWEB)

    Dias, M., E-mail: [Associação Euratom/IST, Instituto de Plasmas e Fusão Nuclear, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa (Portugal); Mateus, R.; Catarino, N.; Franco, N. [Associação Euratom/IST, Instituto de Plasmas e Fusão Nuclear, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa (Portugal); Nunes, D. [CENIMAT-I3N, Departamento de Ciência dos Materiais, Faculdade de Ciências e Tecnologia, FCT, Universidade Nova de Lisboa, 2829-516 Caparica (Portugal); Correia, J.B. [LNEG, Laboratório Nacional de Energia e Geologia, Estrada do Paço do Lumiar, 1649-038 Lisboa (Portugal); Carvalho, P.A. [Associação Euratom/IST, Instituto de Plasmas e Fusão Nuclear, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa (Portugal); ICEMS, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa (Portugal); Hanada, K. [AIST, National Institute of Advanced Industrial Science and Technology, 1-2-1 Namiki, Tsukuba, 305-8564 Ibaraki (Japan); Sârbu, C. [National Institute of Materials and Physics, 105bis Atomistilor street, 077125 Magurele-Ilfov (Romania); and others


    Abstruct: Tungsten–tantalum composites with 10 and 20 at.% Ta were prepared by ball milling W powder with Ta fibers and by consolidating the milled materials with spark plasma sintering. The composites were implanted at room temperature with He{sup +} (30 keV with a fluence 5 × 10{sup 21} at/m{sup 2}) and/or D{sup +} (15 keV with a fluence 5 × 10{sup 21} at/m{sup 2}) ion beams. The materials were studied by scanning and high-resolution transmission electron microscopy, both coupled with energy dispersive X-ray spectroscopy, and by X-ray diffraction, Rutherford backscattering spectrometry and nuclear reaction analysis. The microstructure observations revealed that the milling operation resulted in severe fragmentation of the Ta fibers. Furthermore, during the consolidation process the Ta phase acted as oxygen getter and reduced the W oxide present in the original material. The surface of the tungsten–tantalum composites implanted with D{sup +} remained essentially unaltered, while the materials implanted with He{sup +} evidenced blisters on the Ta-rich regions. D retention in the composites increased with He{sup +} pre-implantation.

  18. Hand Blisters in Major League Baseball Pitchers: Current Concepts and Management. (United States)

    McNamara, Andrew R; Ensell, Scott; Farley, Timothy D


    Friction blisters are a common sequela of many athletic activities. Their significance can range from minor annoyance to major performance disruptions. The latter is particularly true in baseball pitchers, who sustain repeated trauma between the baseball seams and the fingers of the pitching hand, predominately at the tips of the index and long fingers. Since 2010, 6 Major League Baseball (MLB) players accounted for 7 stints on the disabled list (DL) due to blisters. These injuries resulted in a total of 151 days spent on the DL. Since 2012, 8 minor league players spent time on the DL due to blisters. Moreover, there have been several documented and publicized instances of professional baseball pitchers suffering blisters that did not require placement on the DL but did result in injury time and missed starts. The purpose of this article is to review the etiology and pathophysiology of friction blisters with particular reference to baseball pitchers; provide an overview of past and current prevention methods; and discuss our experience in treating friction blisters in MLB pitchers.

  19. 2D simulation of hydride blister cracking during a RIA transient with the fuel code ALCYONE

    Directory of Open Access Journals (Sweden)

    Sercombe Jérôme


    Full Text Available This paper presents 2D generalized plain strain simulations of the thermo-mechanical response of a pellet fragment and overlying cladding during a RIA transient. A fictitious hydride blister of increasing depth (25 to 90% of the clad thickness is introduced at the beginning of the calculation. When a pre-determined hoop stress is exceeded at the clad outer surface, radial cracking of the blister is taken into account in the simulation by a modification of the mechanical boundary conditions. The hoop stress criterion is based on Finite Element simulations of laboratory hoop tensile tests performed on highly irradiated samples with a through-wall hydride blister. The response of the remaining clad ligament (beneath the cracked blister to the pellet thermal expansion is then studied. The simulations show that plastic strains localize in a band orientated at ∼45° to the radial direction, starting from the blister crack tip and ending at the clad inner wall. This result is in good agreement with the ductile shear failures of the clad ligaments observed post-RIA transients. Based on a local plastic strain failure criterion in the shear band, ALCYONE simulations are then used to define the enthalpy at failure in function of the blister depth.

  20. Bullous Pemphigoid Induced by Vildagliptin


    Bengür Taşkıran Bahattin; Erdoğan Canan Solak; Şişman Güven; Barış Cansu


    Bullous pemphigoid (BP) is an uncommon chronic, autoimmune, and subepidermal disease. Tense blisters occur on normal or erythematous skin. It can be induced by medications. There is a number of reports on BP induced by dipeptidyl peptidase 4 (DPP-4) inhibitors (vildagliptin, sitagliptin, saxagliptin). DPP-4 (CD26), present as a cell surface molecule on immune cells, also plays an important costimulatory role in immune activation. BP more commonly affects elderly men. We present a case of BP i...

  1. Autoimmune gastritis: Pathologist's viewpoint. (United States)

    Coati, Irene; Fassan, Matteo; Farinati, Fabio; Graham, David Y; Genta, Robert M; Rugge, Massimo


    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.

  2. Autoimmunity and Asbestos Exposure

    Directory of Open Access Journals (Sweden)

    Jean C. Pfau


    Full Text Available Despite a body of evidence supporting an association between asbestos exposure and autoantibodies indicative of systemic autoimmunity, such as antinuclear antibodies (ANA, a strong epidemiological link has never been made to specific autoimmune diseases. This is in contrast with another silicate dust, crystalline silica, for which there is considerable evidence linking exposure to diseases such as systemic lupus erythematosus, systemic sclerosis, and rheumatoid arthritis. Instead, the asbestos literature is heavily focused on cancer, including mesothelioma and pulmonary carcinoma. Possible contributing factors to the absence of a stronger epidemiological association between asbestos and autoimmune disease include (a a lack of statistical power due to relatively small or diffuse exposure cohorts, (b exposure misclassification, (c latency of clinical disease, (d mild or subclinical entities that remain undetected or masked by other pathologies, or (e effects that are specific to certain fiber types, so that analyses on mixed exposures do not reach statistical significance. This review summarizes epidemiological, animal model, and in vitro data related to asbestos exposures and autoimmunity. These combined data help build toward a better understanding of the fiber-associated factors contributing to immune dysfunction that may raise the risk of autoimmunity and the possible contribution to asbestos-related pulmonary disease.

  3. A suction blister model reliably assesses skin barrier restoration and immune response. (United States)

    Smith, Tracey J; Wilson, Marques A; Young, Andrew J; Montain, Scott J


    Skin wound healing models can be used to detect changes in immune function in response to interventions. This study used a test-retest format to assess the reliability of a skin suction blister procedure for quantitatively evaluating human immune function in repeated measures type studies. Up to eight suction blisters (~30 mm(2)) were induced via suction on each participant's left and right forearm (randomized order; blister session 1 and 2), separated by approximately one week. Fluid was sampled from each blister, and the top layer of each blister was removed to reveal up to eight skin wounds. Fluid from each wound was collected 4, 7 and 24h after blisters were induced, and proinflammatory cytokines were measured. Transepidermal water loss (TEWL), to assess skin barrier recovery, was measured daily at each wound site until values were within 90% of baseline values (i.e., unbroken skin). Sleep, stress and inflammation (i.e., factors that affect wound healing and immune function), preceding the blister induction, were assessed via activity monitors (Actical, Philips Respironics, Murrysville, Pennsylvania), the Perceived Stress Scale (PSS) and C-reactive protein (CRP), respectively. Area-under-the-curve and TEWL, between blister session 1 and 2, were compared using Pearson correlations and partial correlations (controlling for average nightly sleep, PSS scores and CRP). The suction blister method was considered reliable for assessing immune response and skin barrier recovery if correlation coefficients reached 0.7. Volunteers (n=16; 12 M; 4F) were 23 ± 5 years [mean ± SD]. Time to skin barrier restoration was 4.9 ± 0.8 and 4.8 ± 0.9 days for sessions 1 and 2, respectively. Correlation coefficients for skin barrier restoration, IL-6, IL-8 and MIP-1α were 0.9 (Psuction blister method is sufficiently reliable for assessing skin barrier restoration and immune responsiveness. This data can be used to determine sample sizes for cross-sectional or repeated

  4. Epigenetics and Autoimmune Diseases (United States)

    Quintero-Ronderos, Paula; Montoya-Ortiz, Gladis


    Epigenetics is defined as the study of all inheritable and potentially reversible changes in genome function that do not alter the nucleotide sequence within the DNA. Epigenetic mechanisms such as DNA methylation, histone modification, nucleosome positioning, and microRNAs (miRNAs) are essential to carry out key functions in the regulation of gene expression. Therefore, the epigenetic mechanisms are a window to understanding the possible mechanisms involved in the pathogenesis of complex diseases such as autoimmune diseases. It is noteworthy that autoimmune diseases do not have the same epidemiology, pathology, or symptoms but do have a common origin that can be explained by the sharing of immunogenetic mechanisms. Currently, epigenetic research is looking for disruption in one or more epigenetic mechanisms to provide new insights into autoimmune diseases. The identification of cell-specific targets of epigenetic deregulation will serve us as clinical markers for diagnosis, disease progression, and therapy approaches. PMID:22536485

  5. [Autoimmune thyroid disease and other non-endocrine autoimmune diseases]. (United States)

    Dilas, Ljiljana Todorović; Icin, Tijana; Paro, Jovanka Novaković; Bajkin, Ivana


    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.

  6. Epigenomics of autoimmune diseases. (United States)

    Gupta, Bhawna; Hawkins, R David


    Autoimmune diseases are complex disorders of largely unknown etiology. Genetic studies have identified a limited number of causal genes from a marginal number of individuals, and demonstrated a high degree of discordance in monozygotic twins. Studies have begun to reveal epigenetic contributions to these diseases, primarily through the study of DNA methylation, but chromatin and non-coding RNA changes are also emerging. Moving forward an integrative analysis of genomic, transcriptomic and epigenomic data, with the latter two coming from specific cell types, will provide an understanding that has been missed from genetics alone. We provide an overview of the current state of the field and vision for deriving the epigenomics of autoimmunity.

  7. Autoimmune basis of glaucoma. (United States)

    Shazly, Tarek A; Aljajeh, Mouhab; Latina, Mark A


    Glaucoma is one of the leading causes of blindness worldwide. The current view of glaucoma is that it is a multifactorial disease. Elevated IOP is a recognized etiologic factor which can trigger initial damage through biomechanical and ischemic injury to the retinal ganglion cells. However, elevated intraocular pressure cannot be entirely responsible for the development of glaucoma. Accumulating evidence suggests that abnormal immunity may be contributing to the glaucomatous optic neuropathy. Autoimmunity may be responsible for initiating or exacerbating glaucoma. This review provides an evaluation of the potential role of autoimmunity in some patients with glaucoma.

  8. Association of severe myoclonic epilepsy of infancy (SMEI with probable autoimmune lymphoproliferative syndrome-variant

    Directory of Open Access Journals (Sweden)

    A. Berio


    Full Text Available The paper reported on a case of severe myoclonic epilepsy of infancy (SMEI associated with a probable autoimmune lymphoproliferative syndrome variant (Dianzani autoimmune lymphoproliferative disease (DALD. A male patient with typical features of SMEI and a SCN1A gene variant presented in the first year of life with multiple lymph nodes, palpable liver at 2 cm from the costal margin, neutropenia, dysgammaglobulinemia, relative and sometimes absolute lymphocytosis. Subsequently the patient presented with constantly raised IgA in serum and positive antinuclear and thyroid antimicrosomal antibodies. The diagnosis of probable autoimmune lymphoproliferative syndrome was made; arthritis, skin and throat blisters, which appeared subsequently led to the diagnosis of linear IgA disease. On the basis of these unique associations, the Authors hypothesized that autoimmunity may be partly responsible of the severe epileptic symptomatology, perhaps mediated by autoantibodies against sodium channels or by accompanying cytotoxic T-lymphocytes. Corticosteroid treatment ameliorated the epilepsy and laboratory tests. Future studies will be necessary to evaluate the relevance of autoimmunity in SMEI.

  9. Autoimmunity and Turner's syndrome. (United States)

    Lleo, Ana; Moroni, Luca; Caliari, Lisa; Invernizzi, Pietro


    Turner Syndrome (TS) is a common genetic disorder, affecting female individuals, resulting from the partial or complete absence of one sex chromosome, and occurring in approximately 50 per 100,000 liveborn girls. TS is associated with reduced adult height and with gonadal dysgenesis, leading to insufficient circulating levels of female sex steroids and to infertility. Morbidity and mortality are increased in TS but average intellectual performance is within the normal range. TS is closely associated to the presence of autoantibodies and autoimmune diseases (AID), especially autoimmune thyroiditis and inflammatory bowel disease. Despite the fact that the strong association between TS and AID is well known and has been widely studied, the underlying immunopathogenic mechanism remains partially unexplained. Recent studies have displayed how TS patients do not show an excess of immunogenic risk markers. This is evocative for a higher responsibility of X-chromosome abnormalities in the development of AID, and particularly of X-genes involved in immune response. For instance, the long arm of the X chromosome hosts a MHC-locus, so the loss of that region may lead to a deficiency in immune regulation. Currently no firm guidelines for diagnosis exist. In conclusion, TS is a condition associated with a number of autoimmune manifestations. Individuals with TS need life-long medical attention. As a consequence of these findings, early diagnosis and regular screening for potential associated autoimmune conditions are essential in the medical follow-up of TS patients. Copyright © 2011 Elsevier B.V. All rights reserved.

  10. Selenium and thyroid autoimmunity

    Directory of Open Access Journals (Sweden)

    Roberto Negro


    Full Text Available Roberto NegroDepartment of Endocrinology, “V. Fazzi” Hospital, Lecce, ItalyAbstract: The trace element selenium (Se occurs in the form of the amino acid selenocysteine in selenoproteins. Selenoproteins exerts multiple physiological effects in human health, many of which are related with regulation of reduction-oxidation processes. In fact, the selenoenzyme families of glutathione peroxidase (GPx and thioredoxin reductase (TRx display the ability to act as antioxidants, protecting cells from oxidative damage. Furthermore, another class of selenoproteins are the iodothyronine deiodinase enzymes (DIO, which catalyze the conversion of thyroxine (T4 in triiodothyronine (T3, then exerting a fine tuned control on thyroid hormones metabolism. Several studies have investigated the potential positive effects of Se supplementation in thyroid diseases, characterized by increased levels of hydrogen peroxide and free radicals, like autoimmune chronic thyroiditis. These studies have supplied evidences indicating that Se supplementation, maximizing the antioxidant enzymes activity, may reduce the thyroid inflammatory status. Then, it may be postulated that Se could play a therapeutical role in thyroid autoimmune diseases. Despite the fact that recent studies seem to be concordant about Se beneficial effects in decreasing thyroid peroxidase antibodies (TPOAb titers and ameliorating the ultrasound echogenicity pattern, several doubts have to be still clarified, before advising Se supplementation in chronic autoimmune thyroiditis.Keywords: selenium, thyroid, autoimmunity

  11. Psychosis: an autoimmune disease? (United States)

    Al-Diwani, Adam A J; Pollak, Thomas A; Irani, Sarosh R; Lennox, Belinda R


    Psychotic disorders are common and disabling. Overlaps in clinical course in addition to epidemiological and genetic associations raise the possibility that autoimmune mechanisms may underlie some psychoses, potentially offering novel therapeutic approaches. Several immune loci including the major histocompatibility complex and B-cell markers CD19 and CD20 achieve genome-wide significance in schizophrenia. Emerging evidence suggests a potential role via neurodevelopment in addition to classical immune pathways. Additionally, lymphocyte biology is increasingly investigated. Some reports note raised peripheral CD19(+) and reduced CD3(+) lymphocyte counts, with altered CD4 : CD8 ratios in acute psychosis. Also, post-mortem studies have found CD3(+) and CD20(+) lymphocyte infiltration in brain regions that are of functional relevance to psychosis. More specifically, the recent paradigm of neuronal surface antibody-mediated (NSAb) central nervous system disease provides an antigen-specific model linking adaptive autoimmunity to psychopathology. NSAbs bind extracellular epitopes of signalling molecules that are classically implicated in psychosis such as NMDA and GABA receptors. This interaction may cause circuit dysfunction leading to psychosis among other neurological features in patients with autoimmune encephalitis. The detection of these cases is crucial as autoimmune encephalitis is ameliorated by commonly available immunotherapies. Meanwhile, the prevalence and relevance of these antibodies in people with isolated psychotic disorders is an area of emerging scientific and clinical interest. Collaborative efforts to achieve larger sample sizes, comparison of assay platforms, and placebo-controlled randomized clinical trials are now needed to establish an autoimmune contribution to psychosis. © 2017 John Wiley & Sons Ltd.

  12. Autoimmune bullous disease and Hashimoto's disease complicated by acquired hemophilia A. (United States)

    Nishiura, Nobuko; Ujimoto, Daisuke; Fujita, Jiro; Maeda, Tetsuo; Nakagawa, Yukinobu; Kashiwagi, Hirokazu; Oritani, Kenji; Tomiyama, Yoshiaki; Kanakura, Yuzuru


    A 67-year-old man was admitted with a 1-month history of spontaneous hematoma in his right back and severe anemia. He had suffered from rashes with blisters involving both legs for 10 years, which had shown worsening and extended to his entire body concurrently with the hematoma. APTT was markedly prolonged to 119 seconds, and Factor VIII:C and FVIII inhibitor levels were less than 1% and 153.1 BU/ml, respectively, confirming the diagnosis of acquired hemophilia A (AHA). Skin biopsy revealed his rashes to be caused by autoimmune bullous disease (ABD), and laboratory and physical findings showed that he also had autoimmune hypothyroidism (Hashimoto's disease). Recombinant FVIIa was effective for management of his bleeding; in addition, FVIII inhibitor reduction and FVIII:C recovery, in parallel with improvement of the skin lesions, were achieved by administering prednisolone and cyclophosphamide. To our knowledge, this is the first report of AHA associated with ABD and Hashimoto's disease.

  13. Epidermolysis bullosa acquisita and anti-p200 pemphigoid as major subepidermal autoimmune bullous diseases diagnosed by floor binding on indirect immunofluorescence microscopy using human salt-split skin

    Directory of Open Access Journals (Sweden)

    Nupur Goyal


    Conclusion: In this study, we report three cases of anti-p200 pemphigoid from India. These cases, though indistinguishable clinically from bullous pemphigoid, revealed a floor-binding pattern on indirect immunofluorescence using salt-split skin.

  14. Comparison of blistering of W bulk and film deposited by magnetron sputtering under helium irradiation

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    Jiangang Yu


    Full Text Available In this work, the W bulk prepared by powder sintering and W film deposited by magnetron sputtering were simultaneously exposed to the helium ions with the energy of 60keV and fluence of 1.0 × 1022 m−2 at room temperature. The surface modifications induced by the helium irradiation were studied by scanning electron microscopy. After helium ion irradiation, numerous blisters were observed on the surface of both samples, some of which burst in various degrees. The formation of blisters is attributed to the high gas pressure in the helium bubbles. In addition, the different structures between W bulk and W film lead to the differences in density and size of blisters.

  15. p38 MAPK Signaling in Pemphigus: Implications for Skin Autoimmunity

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    Athanasios Mavropoulos


    Full Text Available p38 mitogen activated protein kinase (p38 MAPK signaling plays a major role in the modulation of immune-mediated inflammatory responses and therefore has been linked with several autoimmune diseases. The extent of the involvement of p38 MAPK in the pathogenesis of autoimmune blistering diseases has started to emerge, but whether it pays a critical role is a matter of debate. The activity of p38 MAPK has been studied in great detail during the loss of keratinocyte cell-cell adhesions and the development of pemphigus vulgaris (PV and pemphigus foliaceus (PF. These diseases are characterised by autoantibodies targeting desmogleins (Dsg. Whether autoantibody-antigen interactions can trigger signaling pathways (such as p38 MAPK that are tightly linked to the secretion of inflammatory mediators which may perpetuate inflammation and tissue damage in pemphigus remains unclear. Yet, the ability of p38 MAPK inhibitors to block activation of the proapoptotic proteinase caspase-3 suggests that the induction of apoptosis may be a consequence of p38 MAPK activation during acantholysis in PV. This review discusses the current evidence for the role of p38 MAPK in the pathogenesis of pemphigus. We will also present data relating to the targeting of these cascades as a means of therapeutic intervention.

  16. Bullous pemphigoid associated with prostate adenocarcinoma

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    Öztürkcan Serap


    Full Text Available Bullous pemphigoid is a common autoimmune skin disease characterized by the presence of subepidermal blisters. It has been associated with underlying neoplasia in isolated reports. A 78-year-old man with generalized blisters was diagnosed as bullous pemphigoid on clinical, histopathological and direct immunofluorescence grounds. His free and total prostate specific antigen (PSA levels were high and histopathological examination of a prostate specimen revealed prostate adenocarcinoma. We present this rare case to discuss the possible association between bullous pemphigoid and prostate adenocarcinoma.

  17. Diagnosis and clinical features of epidermolysis bullosa acquisita. (United States)

    Caux, Frédéric


    Epidermolysis bullosa acquisita (EBA) is a rare autoimmune subepidermal blistering disease characterized by immune deposits on anchoring fibrils of cutaneous and mucosal basement membrane zones. It is due to circulating antibodies directed to type VII collagen. Clinical manifestations include a classical form with skin fragility, blisters and scars on trauma-prone surfaces, an inflammatory form, and a cicatricial pemphigoid-like form. Specialized tests available in only certain laboratories are necessary to confirm a diagnosis of EBA, such as immunoelectron microscopy, immunoblotting, or ELISA using recombinant proteins. A frequent association between EBA and Crohn disease has been observed. Copyright © 2011 Elsevier Inc. All rights reserved.

  18. Comparative morphological analysis of apple blister mite, Eriophyes mali Nal., a new pest in Serbia

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    Biljana Vidović


    Full Text Available The apple blister mite, Eriophyes mali Nalepa, 1926 (Acari: Prostigmata: Eriophyoidea, has been recently found in Serbia as a new pest of apple. The history of its research, the results of a morphological analysis and degree of infestation are presented. A comparison of the main morphological features of mites from different populations of remote geographical origin has shown that the apple blister mite from Serbia is most similar to another European population (Bulgarian [or Austrian?] while it differs from E. mali originating from the USA and New Zealand. The percentage of infestation varied from 1.6% to 87.6%, with an average of 22.4%.

  19. Sarcoidosis and Thyroid Autoimmunity

    Directory of Open Access Journals (Sweden)

    Piera Fazzi


    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.

  20. Thymoma and autoimmunity


    Shelly, Shahar; Agmon-Levin, Nancy; Altman, Arie; Shoenfeld, Yehuda


    The thymus is a central lymphatic organ that is responsible for many immunological functions, including the production of mature, functional T cells and the induction of self-tolerance. Benign or malignant tumors may originate from the thymus gland, with thymoma being the most common and accounting for 50% of anterior mediastinal tumors. Malignancies linked to thymoma include the loss of self-tolerance and the presence of autoimmunity. In this review, we compiled the current scientific eviden...

  1. Depression in autoimmune diseases


    Pryce, Christopher R.; Fontana, Adriano


    Up to 50% of patients with autoimmune diseases show an impairment of health-related quality of life and exhibit depression-like symptoms. The immune system not only leads to inflammation in affected organs, but also mediates behavior abnormalities including fatigue and depression-like symptoms. This review focuses on the different pathways involved in the communication of the immune system with the neuronal network and the body's timing system. The latter is built up by a hierarchically organ...

  2. Autoimmunity in 2016. (United States)

    Selmi, Carlo


    The number of peer-reviewed articles published during the 2016 solar year and retrieved using the "autoimmunity" key word remained stable while gaining a minimal edge among the immunology articles. Nonetheless, the quality of the publications has been rising significantly and, importantly, acquisitions have become available through scientific journals dedicated to immunology or autoimmunity. Major discoveries have been made in the fields of systemic lupus erythematosus, rheumatoid arthritis, autoimmunity of the central nervous system, vasculitis, and seronegative spondyloarthrithritides. Selected examples include the role of IL17-related genes and long noncoding RNAs in systemic lupus erythematosus or the effects of anti-pentraxin 3 (PTX3) in the treatment of this paradigmatic autoimmune condition. In the case of rheumatoid arthritis, there have been reports of the role of induced regulatory T cells (iTregs) or fibrocytes and T cell interactions with exciting implications. The large number of studies dealing with neuroimmunology pointed to Th17 cells, CD56(bright) NK cells, and low-level TLR2 ligands as involved in multiple sclerosis, along with a high salt intake or the micriobiome-derived Lipid 654. Lastly, we focused on the rare vasculitides to which numerous studies were devoted and suggested that unsuspected cell populations, including monocytes, mucosal-associated invariant T cells, and innate lymphoid cells, may be crucial to ANCA-associated manifestations. This brief and arbitrary discussion of the findings published in 2016 is representative of a promising background for developments that will enormously impact the work of laboratory scientists and physicians at an exponential rate.

  3. Prolactin and autoimmunity. (United States)

    De Bellis, Annamaria; Bizzarro, Antonio; Pivonello, Rosario; Lombardi, Gaetano; Bellastella, Antonio


    The interrelationship between prolactin (PRL) and the immune system have been elucitaded in the last decade, opening new important horizons in the field of the immunoendocrinology. PRL is secreted not only by anterior pituitary gland but also by many extrapituitary sites including the immune cells. The endocrine/paracrine PRL has been shown to stimulate the immune cells by binding to PRL receptors. Increased PRL levels, frequently described in autoimmune diseases, could depend on the enhancement of coordinated bi-directional communications between PRL and the immune system observed in these diseases. Hyperprolactinemia has been described in the active phase of some non organ-specific autoimmune diseases, as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) and organ-specific autoimmune diseases, as celiac disease, type 1 diabetes mellitus, Addison's disease, autoimmune thyroid diseases. In these diseases PRL increases the syntesis of IFNgamma and IL-2 by Th1 lymphocytes. Moreover, PRL activates Th2 lymphocytes with autoantibody production. Of particular interest is the association between hyperprolactinemia and levels of anti DNA antibodies, islet cell antibodies (ICA), thyreoglobulin antibodies (TgAb), thyroperoxidase antibodies (TPOAb), adrenocortical antibodies (ACA), transglutaminase antibodies (tTGAb) in SLE, in type 1 diabetes mellitus, in Hashimoto's thyroiditis, in Addison's disease and in celiac disease, respectively. High levels of PRL have been also frequently detected in patients with lymphocytic hypophysitis (LYH). Several mechanisms have been invoked to explain the hyperprolactinemia in LYH. The PRL increase could be secondary to the inflammatory process of the pituitary gland but, on the other hand, this increase could have a role in enhancing the activity of the immune process in LYH. Moreover, the detection of antipituitary antibodies targeting PRL-secreting cells in some patients with idiopathic hyperprolactinemia suggests the

  4. White pine blister rust in Korea, Japan and other Asian regions: comparisons and implications for North America (United States)

    M.-S. Kim; N. B. Klopfenstein; Y. Ota; S. K. Lee; K.-S. Woo; S. Kaneko


    This article briefly reviews the history of white pine blister rust, attributed to Cronartium ribicola, and addresses current research and management issues in South Korea, Japan and other regions of eastern Asia (China, Russia and Himalaya). For each region, the distribution, damage, aecial hosts, telial hosts and management of C. ribicola and other blister rust fungi...

  5. White pine blister rust resistance of 12 western white pine families at three field sites in the Pacific Northwest (United States)

    Richard A. Sniezko; Robert Danchok; Jim Hamlin; Angelia Kegley; Sally Long; James Mayo


    Western white pine (Pinus monticola Douglas ex D. Don) is highly susceptible to the non-native, invasive pathogen Cronartium ribicola, the causative agent of white pine blister rust. The susceptibility of western white pine to blister rust has limited its use in restoration and reforestation throughout much of western North...

  6. Autoantibodies in Autoimmune Pancreatitis

    Directory of Open Access Journals (Sweden)

    Daniel S. Smyk


    Full Text Available Autoimmune pancreatitis (AIP was first used to describe cases of pancreatitis with narrowing of the pancreatic duct, enlargement of the pancreas, hyper-γ-globulinaemia, and antinuclear antibody (ANA positivity serologically. The main differential diagnosis, is pancreatic cancer, which can be ruled out through radiological, serological, and histological investigations. The targets of ANA in patients with autoimmune pancreatitis do not appear to be similar to those found in other rheumatological diseases, as dsDNA, SS-A, and SS-B are not frequently recognized by AIP-related ANA. Other disease-specific autoantibodies, such as, antimitochondrial, antineutrophil cytoplasmic antibodies or diabetes-specific autoantibodies are virtually absent. Further studies have focused on the identification of pancreas-specific autoantigens and reported significant reactivity to lactoferrin, carbonic anhydrase, pancreas secretory trypsin inhibitor, amylase-alpha, heat-shock protein, and plasminogen-binding protein. This paper discusses the findings of these investigations and their relevance to the diagnosis, management, and pathogenesis of autoimmune pancreatitis.

  7. Paediatric Autoimmune Liver Disease. (United States)

    Liberal, Rodrigo; Vergani, Diego; Mieli-Vergani, Giorgina


    In paediatrics, there are 2 liver disorders in which liver damage most likely stems from an autoimmune attack: 'classical' autoimmune hepatitis (AIH) and the AIH/sclerosing cholangitis overlap syndrome (also known as autoimmune sclerosing cholangitis, ASC). The presentation of childhood autoimmune liver disease (AILD) is non-specific and can mimic most other liver disorders. AIH is exquisitely responsive to immunosuppressive treatment, which should be instituted promptly to prevent rapid deterioration and promote remission and long-term survival. Difficult-to-treat or non-responsive patients should be treated with mycophenolate mofetil; if this fails then calcineurin inhibitors can be tried. Persistent failure to respond or lack of adherence to treatment result in end-stage liver disease. These patients, and those with fulminant liver failure at diagnosis, will require liver transplantation. ASC responds to the same immunosuppressive treatment used for AIH when treatment is initiated early. Abnormal liver function tests often resolve within a few months of treatment, although medium- to long-term prognosis is worse than that of AIH because bile duct disease continues to progress despite treatment in approximately 50% of patients. Ursodeoxycholic acid is usually added to conventional treatment regimen in ASC, but whether this actually helps arrest the progression of bile duct disease remains to be established. The pathogenesis of paediatric-onset AILD is not fully understood, although there is mounting evidence that genetic susceptibility, molecular mimicry and impaired immunoregulatory networks contribute to the initiation and perpetuation of the autoimmune attack. Liver damage is thought to be mediated primarily by CD4pos T-cells. While Th1 effector cells are associated with hepatocyte damage in both AIH and ASC, Th17 immune responses predominate in the latter where they correlate with biochemical indices of cholestasis, indicating that IL-17 is involved in the

  8. Imaging of autoimmune biliary disease. (United States)

    Yeh, Melinda J; Kim, So Yeon; Jhaveri, Kartik S; Behr, Spencer C; Seo, Nieun; Yeh, Benjamin M


    Autoimmune biliary diseases are poorly understood but important to recognize. Initially, autoimmune biliary diseases are asymptomatic but may lead to progressive cholestasis with associated ductopenia, portal hypertension, cirrhosis, and eventually liver failure. The three main forms of autoimmune biliary disease are primary biliary cirrhosis, primary sclerosing cholangitis, and IgG4-associated cholangitis. Although some overlap may occur between the three main autoimmune diseases of the bile ducts, each disease typically affects a distinct demographic group and requires a disease-specific diagnostic workup. For all the autoimmune biliary diseases, imaging provides a means to monitor disease progression, assess for complications, and screen for the development of hepatobiliary malignancies that are known to affect patients with these diseases. Imaging is also useful to suggest or corroborate the diagnosis of primary sclerosing cholangitis and IgG4-associated cholangitis. We review the current literature and emphasize radiological findings and considerations for these autoimmune diseases of the bile ducts.

  9. B Cells in Autoimmune Diseases


    Hampe, Christiane S.


    The role of B cells in autoimmune diseases involves different cellular functions, including the well-established secretion of autoantibodies, autoantigen presentation and ensuing reciprocal interactions with T cells, secretion of inflammatory cytokines, and the generation of ectopic germinal centers. Through these mechanisms B cells are involved both in autoimmune diseases that are traditionally viewed as antibody mediated and also in autoimmune diseases that are commonly classified as T cell...

  10. Polymerase Chain Reaction (PCR) applications in white pine blister rust resistance screening (United States)

    Sam Hendricks; Wendy Sutton; Jeffrey Stone; Richard Sniezko; Angelia Kegley; Anna Schoettle


    A goal of breeding programs for resistance to white pine blister rust is the development of multigenic resistance, even if the genetics and mechanisms of resistance may be imperfectly understood. The goal of multigenic resistance has prompted efforts to categorize host resistance reactions at increasingly finer scales, to identify heritable traits that may confer...

  11. Study of hydrogen implantation-induced blistering in GaSb for potential layer transfer applications (United States)

    Pathak, Ravi; Dadwal, U.; Singh, R.


    GaSb samples were implanted by 100 keV hydrogen ions (H+) at room temperature with fluence values of 1  ×  1017 and 2  ×  1017 ions cm-2. Post-implantation annealing studies revealed that the samples implanted with a fluence of 2  ×  1017 ions cm-2 did not show blistering/exfoliation. For the lower fluence, the samples showed the formation of surface blisters/craters along with the large area exfoliation of the top H-implanted surface. Topographical investigations of the samples were carried out using Nomarski optical microscopy, atomic force microscopy and stylus surface profilometry. The lateral sizes and heights of the blisters varied between 2-5 µm and 5-20 nm respectively. The root mean square roughness of the exfoliated region was about 12 nm while the exfoliation depth was found to be 730 nm. The exfoliation depth in the H-implanted GaSb is close to the damage concentration peak as found from SRIM calculations. The Föppl-von Karman theory of thin plates has been used to understand the effect of internal pressure and stress on the surface blistering. Using the above mentioned implantation and annealing parameters, potential layer transfer of GaSb could be enabled.

  12. Strong partial resistance to white pine blister rust in sugar pine (United States)

    Bohun B. Kinloch, Jr.; Deems Burton; Dean A. Davis; Robert D. Westfall; Joan Dunlap; Detlev Vogler


    Quantitative resistance to white pine blister rust in 128 controlled- and open-pollinated sugar pine families was evaluated in a “disease garden”, where alternate host Ribes bushes were interplanted among test progenies. Overall infection was severe (88%), but with great variation among and within families: a 30-fold range in numbers of infections...

  13. Options for the management of white pine blister rust in the Rocky Mountain Region (United States)

    Kelly S. Burns; Anna W. Schoettle; William R. Jacobi; Mary F. Mahalovich


    This publication synthesizes current information on the biology, distribution, and management of white pine blister rust (WPBR) in the Rocky Mountain Region. In this Region, WPBR occurs within the range of Rocky Mountain bristlecone pine (Pinus aristata), limber pine (P. flexilis), and whitebark pine (P. albicaulis...

  14. Monitoring white pine blister rust infection and mortality in whitebark pine in the Greater Yellowstone ecosystem (United States)

    Cathie Jean; Erin Shanahan; Rob Daley; Gregg DeNitto; Dan Reinhart; Chuck Schwartz


    There is a critical need for information on the status and trend of whitebark pine (Pinus albicaulis) in the Greater Yellowstone Ecosystem (GYE). Concerns over the combined effects of white pine blister rust (WPBR, Cronartium ribicola), mountain pine beetle (MPB, Dendroctonus ponderosae), and climate change prompted an interagency working group to design and implement...

  15. Distribution of Ribes, an alternate host of white pine blister rust, in Colorado and Wyoming (United States)

    Holly S. J. Kearns; William R. Jacobi; Kelly S. Burns; Brian W. Geils


    Ribes (currants and gooseberries) are alternate hosts for Cronartium ribicola, the invasive fungus that causes blister rust of white pines (Pinus, subgenus Strobus) in the Rocky Mountain region of Colorado and Wyoming. The location, species, and density of Ribes can affect...

  16. Resistance to white pine blister rust in Pinus flexilis and P (United States)

    Anna W. Schoettle; Richard A. Sniezko; Angelia Kegley; Jerry Hill; Kelly S. Burns


    The non-native fungus Cronartium ribicola, that causes white pine blister rust (WPBR), is impacting or threatening limber pine, Pinus flexilis, and Rocky Mountain bristlecone pine, Pinus aristata. In the Southern Rockies, where the rust invasion is still expanding, we have the opportunity to be proactive and prepare the landscape for invasion. Genetic...

  17. Histology of white pine blister rust in needles of resistant and susceptible eastern white pine (United States)

    Joel A. Jurgens; Robert A. Blanchette; Paul J. Zambino; Andrew David


    White pine blister rust, Cronartium ribicola, has plagued the forests of North America for almost a century. Over past decades, eastern white pine (Pinus strobus) that appear to tolerate the disease have been selected and incorporated into breeding programs. Seeds from P. strobus with putative resistance were...

  18. The influence of white pine blister rust on seed dispersal in whitebark pine (United States)

    Shawn T. McKinney; Diana F. Tomback


    We tested the hypotheses that white pine blister rust (Cronartium ribicola J.C. Fisch.) damage in whitebark pine (Pinus albicaulis Engelm.) stands leads to reduced (1) seed cone density, (2) predispersal seed survival, and (3) likelihood of Clark's Nutcracker (Nucifraga columbiana (Wilson, 1811)) seed...

  19. Non-destructive Quality control of tablets and blister packs by UV imaging

    DEFF Research Database (Denmark)

    Klukkert, Marten; Wu, Jian Xiong; Rantanen, Jukka


    Quality control of tablets and its primary packing material within the manufacturing line requires analytical routines that allow monitoring of the desired product attributes with high efficiency. The aim of this study was to evaluate the suitability of multispectral UV imaging combined with mult......Quality control of tablets and its primary packing material within the manufacturing line requires analytical routines that allow monitoring of the desired product attributes with high efficiency. The aim of this study was to evaluate the suitability of multispectral UV imaging combined...... with multivariate image analysis for verification of blister pack filling, differentiation of tablets of varying composition therein, as well as detection of imprint defects and surface cracks of bulk tablets. Moreover, the influence of polymer sealing foils on tablet characterization within blister cavities...... was investigated. Several tablets of different composition were imaged either as bulk, within unsealed blister packs, or within blister packs that were manually sealed with three different types of either PVC or PCTFE foils. It was demonstrated that UV imaging is a fast and reliable technique for counting...

  20. Conservation of biodiversity in sugar pine: effects of the blister rust epidemic on genetic diversity (United States)

    Constance I. Millar; Bohun B. Kinloch; Robert D. Westfall


    Genetic diversity in sugar plne will be severely reduced by the blister rust pandemic predicted within the next 50 to 75 years. We model effects of the epidemic on genetic diversity at the stand and landscape levels for both natural and artificial regeneration. In natural stands, because natural frequencies of the dominant gene (R) for resistance are low, the most...

  1. Blistering mucocutaneous diseases of the oral mucosa--a review: part 1. Mucous membrane pemphigoid. (United States)

    Darling, Mark R; Daley, Tom


    Oral mucous membranes may be affected by a variety of blistering mucocutaneous diseases. In this paper, we review the clinical manifestations, typical microscopic and immunofluorescence features, pathogenesis, biological behaviour and treatment of mucous membrane pemphigoid (MMP). As MMP is a relatively common condition, the general dentist must be able to diagnose, treat and monitor the progress of their affected patients or refer when appropriate.

  2. Selection for resistance to white pine blister rust affects the abiotic stress tolerances of limber pine (United States)

    Patrick J. Vogan; Anna W. Schoettle


    Limber pine (Pinus flexilis) mortality is increasing across the West as a result of the combined stresses of white pine blister rust (Cronartium ribicola; WPBR), mountain pine beetle (Dendroctonus ponderosae), and dwarf mistletoe (Arceuthobium cyanocarpum) in a changing climate. With the continued spread of WPBR, extensive mortality will continue with strong selection...

  3. Autoantibodies in autoimmune liver diseases. (United States)

    Sener, Asli Gamze


    Autoimmune hepatitis is a chronic hepatitis of unknown etiology characterized by clinical, histological, and immunological features, generally including circulating autoantibodies and a high total serum and/or gamma globulin. Liver-related autoantibodies are very significant for the correct diagnosis and classification of autoimmune liver diseases (AILD), namely autoimmune hepatitis types 1 and 2 (AIH-1 and 2), primary biliary cirrhosis (PBC), and the sclerosing cholangitis types in adults and children. This article intends to review recent studies that investigate autoantibodies in autoimmune liver diseases from a microbiological perspective. © 2015 APMIS. Published by John Wiley & Sons Ltd.

  4. [Autoimmune hemolytic anemia in children]. (United States)

    Becheur, M; Bouslama, B; Slama, H; Toumi, N E H


    Autoimmune hemolytic anemia is a rare condition in children which differs from the adult form. It is defined by immune-mediated destruction of red blood cells caused by autoantibodies. Characteristics of the autoantibodies are responsible for the various clinical entities. Classifications of autoimmune hemolytic anemia include warm autoimmune hemolytic anemia, cold autoimmune hemolytic anemia, and paroxysmal cold hemoglobinuria. For each classification, this review discusses the epidemiology, etiology, clinical presentation, laboratory evaluation, and treatment options. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  5. [Keratitis - Infectious or Autoimmune?]. (United States)

    Messmer, E M


    Histopathological evaluation of ocular tissues is important in differentiating between infectious and autoimmune disease. Inflammation, necrosis and keratolysis are common to most forms of keratitis. Histopathology can be of great help in identifying the causative organism, establishing a final diagnosis and/or managing the patient with herpes simplex virus keratitis, mycotic keratitis, acanthamoeba keratitis or microsporidia keratoconjunctivitis. Important pathogenetic knowledge with therapeutic relevance has been gained from histopathological studies in nummular keratitis after epidemic keratoconjunctivitis and atopic keratoconjunctivitis. Georg Thieme Verlag KG Stuttgart · New York.

  6. A minimum number of autoimmune T cells to induce autoimmunity? (United States)

    Bosch, Angela J T; Bolinger, Beatrice; Keck, Simone; Stepanek, Ondrej; Ozga, Aleksandra J; Galati-Fournier, Virginie; Stein, Jens V; Palmer, Ed


    While autoimmune T cells are present in most individuals, only a minority of the population suffers from an autoimmune disease. To better appreciate the limits of T cell tolerance, we carried out experiments to determine how many autoimmune T cells are required to initiate an experimental autoimmune disease. Variable numbers of autoimmune OT-I T cells were transferred into RIP-OVA mice, which were injected with antigen-loaded DCs in a single footpad; this restricted T cell priming to a few OT-I T cells that are present in the draining popliteal lymph node. Using selective plane illumination microscopy (SPIM) we counted the number of OT-I T cells present in the popliteal lymph node at the time of priming. Analysis of our data suggests that a single autoimmune T cell cannot induce an experimental autoimmune disease, but a "quorum" of 2-5 autoimmune T cells clearly has this capacity. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Autoimmune diseases and myelodysplastic syndromes. (United States)

    Komrokji, Rami S; Kulasekararaj, Austin; Al Ali, Najla H; Kordasti, Shahram; Bart-Smith, Emily; Craig, Benjamin M; Padron, Eric; Zhang, Ling; Lancet, Jeffrey E; Pinilla-Ibarz, Javier; List, Alan F; Mufti, Ghulam J; Epling-Burnette, Pearlie K


    Immune dysregulation and altered T-cell hemostasis play important roles in the pathogenesis of myelodysplastic syndromes (MDS). Recent studies suggest an increased risk of MDS among patients with autoimmune diseases. Here, we investigated the prevalence of autoimmune diseases among MDS patients, comparing characteristics and outcomes in those with and without autoimmune diseases. From our study group of 1408 MDS patients, 391 (28%) had autoimmune disease, with hypothyroidism being the most common type, accounting for 44% (n = 171) of patients (12% among all MDS patients analyzed). Other autoimmune diseases with ≥5% prevalence included idiopathic thrombocytopenic purpura in 12% (n = 46), rheumatoid arthritis in 10% (n = 41), and psoriasis in 7% (n = 28) of patients. Autoimmune diseases were more common in female MDS patients, those with RA or RCMD WHO subtype, and those who were less dependent on red blood cell transfusion. Median overall survival (OS) was 60 months (95% CI, 50-70) for patients with autoimmune diseases versus 45 months (95% CI, 40-49) for those without (log-rank test, P = 0.006). By multivariate analysis adjusting for revised IPSS and age >60 years, autoimmune diseases were a statistically significant independent factor for OS (HR 0.78; 95% CI, 0.66-0.92; P = 0.004). The rate of acute myeloid leukemia (AML) transformation was 23% (n = 89) in MDS patients with autoimmune disease versus 30% (n = 301) in those without (P = 0.011). Patient groups did not differ in response to azacitidine or lenalidomide treatment. Autoimmune diseases are prevalent among MDS patients. MDS patients with autoimmune diseases have better OS and less AML transformation. © 2016 Wiley Periodicals, Inc.

  8. Autoimmune liver disease and concomitant extrahepatic autoimmune disease. (United States)

    Muratori, Paolo; Fabbri, Angela; Lalanne, Claudine; Lenzi, Marco; Muratori, Luigi


    To assess the frequency and clinical impact of associated extrahepatic autoimmune diseases (EAD) on autoimmune liver diseases (ALD). We investigated 608 patients with ALD (327 autoimmune hepatitis - AIH and 281 primary biliary cirrhosis - PBC) for concomitant EAD. In both AIH and PBC, we observed a high prevalence of EAD (29.9 and 42.3%, respectively); both diseases showed a significant association with autoimmune thyroid disease, followed by autoimmune skin disease, celiac disease, and vasculitis in AIH patients and sicca syndrome, CREST syndrome, and celiac disease in PBC patients. At diagnosis, AIH patients with concurrent EAD were more often asymptomatic than patients with isolated AIH (Pautoimmune thyroid disease. In the light of our results, all patients with an EAD should be assessed for the concomitant presence of an asymptomatic ALD.

  9. [Hydroxychloroquine for autoimmune diseases]. (United States)

    Danza, Álvaro; Graña, Diego; Goñi, Mabel; Vargas, Andrea; Ruiz-Irastorza, Guillermo


    Hydroxychloroquine (HCQ) is by far the most frequently used antimalarial for the management of Systemic Autoimmune Diseases. It has immunomodulatory, hypolipidemic, hypoglycemic and antithrombotic properties and it diminishes the risk of malignancies. The most important mechanisms to explain the immunomodulatory actions are its ability to reduce inflammatory pathways and Toll-like receptors activation. The safety profile is favorable. In spite of its low frequency, retinal toxicity is potentially severe. In systemic lupus erythematous HCQ therapy reduces activity, the accrual of organ damage, risk of infections and thrombosis and improves the cardiometabolic profile. It contributes to induce lupus nephritis remission, spares steroid use and increases survival rates. In rheumatoid arthritis, it improves cardiometabolic risk and has a favorable effect in joint inflammation. In Sjögren's syndrome, an increased lacrimal quality as well as an improvement in objective and subjective inflammatory markers has been demonstrated with HCQ. In Antiphospholipid Syndrome, HCQ is effective in primary and secondary thrombosis prevention. The effectiveness of the drug in other systemic autoimmune diseases is less established. HCQ therapy may improve dermatological manifestations in Dermatomyositis and may have a positive effects in the treatment of Sarcoidosis and Still disease.

  10. Autoimmune hypophysitis: a study of natural course


    Vijaya Sarathi; Anish Kolly


    Background: Autoimmune hypophysitis is a rare autoimmune endocrinopathy. Literature on natural history of autoimmune hypophysitis is scarce. Methods: We prospectively studied patients with autoimmune hypophysitis between January 2013 to June 2015 and all subjects were followed for at least 6 months. Autoimmune hypophysitis was diagnosed based on clinicoradiologic findings. All patients diagnosed with autoimmune hypophysitis were followed every three monthly with evaluation for pituitary fu...

  11. Is Tolerance Broken in Autoimmunity?

    Directory of Open Access Journals (Sweden)

    Dama Laxminarayana


    Full Text Available Autoimmune diseases are classified into about 80 different types based on their specificity related to system, organ and/or tissue. About 5% of the western population is affected by this anomaly, but its worldwide incidence is unknown. Autoimmune diseases are heterogeneous in nature and clinical manifestations range from benign disorders to life-threatening conditions. Autoimmunity strikes at any stage of life, but age and/or gender also play role in onset of some of these anomalies. The autoimmune pathogenesis is initiated by the origination of autoantigens, which leads to the development of autoantibodies followed by auto-immunogenicity and the ultimate onset of autoimmunity. There is a lack of suitable therapies to treat autoimmune diseases, because mechanisms involved in the onset of these anomalies were poorly understood. Present therapies are limited to symptomatic treatment and come with severe side effects. Here, I described the molecular mechanisms and cellular events involved in the initiation of autoimmunity and proposed better strategies to modulate such molecular and cellular anomalies, which will help in preventing and/or controlling autoimmune pathogenesis and ultimately aid in enhancing the quality of life.

  12. [Autoimmune hepatitis and CREST syndrome]. (United States)

    Ngo Mandag, N; Van Gossum, M; Rickaert, F; Golstein, M


    We report the case of an autoimmune hepatitis in a 59-year old woman who was referred for a progressive jaundice. The patient had an history of CREST syndrome. The particularity of this case report is the rare association between these two autoimmune diseases.

  13. Spontaneous germinal centers and autoimmunity. (United States)

    Domeier, Phillip P; Schell, Stephanie L; Rahman, Ziaur S M


    Germinal centers (GCs) are dynamic microenvironments that form in the secondary lymphoid organs and generate somatically mutated high-affinity antibodies necessary to establish an effective humoral immune response. Tight regulation of GC responses is critical for maintaining self-tolerance. GCs can arise in the absence of purposeful immunization or overt infection (called spontaneous GCs, Spt-GCs). In autoimmune-prone mice and patients with autoimmune disease, aberrant regulation of Spt-GCs is thought to promote the development of somatically mutated pathogenic autoantibodies and the subsequent development of autoimmunity. The mechanisms that control the formation of Spt-GCs and promote systemic autoimmune diseases remain an open question and the focus of ongoing studies. Here, we discuss the most current studies on the role of Spt-GCs in autoimmunity.

  14. A modular theory of autoimmunity. (United States)

    Irie, Junichiro; Ridgway, William M


    The traditional overarching concept of disease pathogenesis entails the natural history of disease, i.e. the concept that any disease is a unified entity from beginning to termination. The concept of the natural history of disease encourages researchers and clinicians alike to conceptualize all clinical signs and symptoms in a patient as manifestations of a single disease process. Our experiences in dissecting the genetic control of autoimmune diseases and autoimmune phenotypes suggest that for many autoimmune processes, an alternative conceptual framework may be more useful. We term this approach a "modular" theory of autoimmunity. "Modules" are distinct, genetically controlled clinical or pathological phenotypes which can interact to construct a disease process. Modules may interact additively, synergistically, or antagonistically in any given individual. Multiple modules can coexist and produce unique disease phenotypes. We illustrate this concept with examples from the murine autoimmune model of type one diabetes, the nonobese diabetic (NOD) mouse.

  15. Effectiveness and side effects of anti-CD20 therapy for autoantibody-mediated blistering skin diseases: A comprehensive survey of 71 consecutive patients from the Initial use to 2007

    Directory of Open Access Journals (Sweden)

    Jennifer D Peterson


    Full Text Available Jennifer D Peterson1, Lawrence S Chan2,3,41Department of Dermatology, Texas Tech University Health Sciences Center at Lubbock, Lubbock, TX, USA; 2Department of Dermatology; 3Department of Microbiology/Immunology, University of Illinois at Chicago, Chicago, IL, USA; 4Medicine Service, Jesse Brown VA Medical Center, Chicago, IL, USAAbstract: In order to examine the efficacy and side effects of the monoclonal antibody anti-CD20 (rituximab on autoimmune blistering skin diseases, we performed a comprehensive survey of 71 consecutive patients from initial use up to 2007, using the PubMed database. A heterogeneous group of patients, including 51 patients with pemphigus vulgaris, one with pemphigus vegetans, nine with pemphigus foliaceus, five with paraneoplastic pemphigus, four with epidermolysis bullosa acquisita, and one with both bullous pemphigoid and graft vs host disease was included in this survey. Overall the monoclonal antibody seems to be effective in that 69% of patients showed complete response, 25% of patients showed partial response, whereas 6% of patients showed progressive disease. Six deaths occurred in association with the treatment, with four of these deaths in patients with paraneoplastic pemphigus, a disease characteristically resistant to conventional medication and with a high mortality rate. Of note, 11 patients who received combined rituximab and intravenous immune globulin treatments had the best outcome: complete response without any serious side effects. Therefore further investigation on rituximab with controlled clinical trial is a worthy pursuit.Keywords: blistering diseases, skin, anti-CD20, pemphigus, epidermolysis bullosa acquisita

  16. Reproduction in Laboratory and characterization of Blister of Hydride of zirconium in nuclear fuel pods; Reproduccion en laboratorio y caracterizacion de Blisters de hidroduro de circonio en muestras de vaina de combustible nuclear

    Energy Technology Data Exchange (ETDEWEB)

    Martin Rengel, M. A.; Ruiz-Hervias, J.; Munoz, P.


    This paper have replicated in laboratory blisters of different size in samples of pod of ZIRLO pre-hydrided evenly with 500 ppm of hydrogen. For these samples was used a technique of cathodic charging in basic medium. To produce the blister was heated up to about 350 degree centigrade in its outer surface sample. With the aim of producing a point cold on the surface of the sheath contacted the surface with a piece of aluminum water-cooled (cold finger). Was held a morphological characterization of the blisters by means of optical microscopy and found that the size of the produced blister is function of the contact time between fuel pod and cold finger. (Author)

  17. Psychoneuroimmunology - psyche and autoimmunity. (United States)

    Ziemssen, Tjalf


    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.

  18. Autoimmune premature ovarian failure

    Directory of Open Access Journals (Sweden)

    Beata Komorowska


    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.

  19. Selfie: Autoimmunity, boon or bane. (United States)

    Ahsan, Haseeb


    The immune system provides protection to tissues damaged by infectious microrganisms or physical damage. In autoimmune diseases, the immune system recognizes and attacks its own tissues, i.e., self-destruction. Various agents such as genetic factors and environmental triggers are thought to play a major role in the development of autoimmune diseases. A common feature of all autoimmune diseases is the presence of autoantibodies and inflammation, including mononuclear phagocytes, autoreactive T lymphocytes, and autoantibody producing B cells (plasma cells). It has long been known that B cells produce autoantibodies and, thereby, contribute to the pathogenesis of many autoimmune diseases. Autoimmune diseases can be classified as organ-specific or non-organ specific depending on whether the autoimmune response is directed against a particular tissue or against widespread antigens as in chronic inflammatory autoimmune diseases such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Both SLE and RA are characterized by the presence of autoantibodies which play a major role in their etiopathogenesis. SLE is characterized by circulating antibodies and immune complex deposition that can trigger an inflammatory damage in organs. RA is a progressive inflammatory disease in which T cells, B cells, and pro-inflammatory cytokines play a key role in its pathophysiology.

  20. Effect of periodic deuterium ion irradiation on deuterium retention and blistering in Tungsten

    Directory of Open Access Journals (Sweden)

    M. Oya


    Full Text Available The effect of periodic irradiation on Deuterium (D retention and blistering in Tungsten (W was investigated. W samples were exposed to D plasma at a fixed fluence while varying the irradiation cycle number (1-shot, 2-shots and 3-shots. Exposure energy and flux were ∼50eV and ∼1 ×1022 D m−2 s−1, respectively. Sample temperatures were 537K and 643K. At 573K, D retention and blister density decreased with increasing number of irradiation cycle. In contrast at 643K, D retention showed no dependence on number of irradiation cycle. Therefore, sample temperature during irradiation is an important parameter in comparing the results of continuous and periodic irradiation, especially in studies involving extremely-high-flux (>1024 D m−2 s−1 irradiation and fluence dependency of D retention.

  1. Blister formation and hydrogen retention in aluminium and beryllium: A modeling and experimental approach

    Directory of Open Access Journals (Sweden)

    C. Quirós


    Full Text Available Experiments were performed in a low pressure-high density plasma reactor in order to study the impact of hydrogen retention in aluminium under plasma conditions. Microscopy scans of the surface were performed before and after 1h plasma exposure (fluence 6.1 ×1023ions/m2 where it is seen that blisters start to nucleate at the grain boundaries. Investigation on blister growth kinetics was performed for fluences ranging between 6 ×1023 and 3.7 ×1024ions/m2. The evolution of the characteristic size of the projected area was also analyzed. Finally, a macroscopic rate equations (MRE code was used to simulate hydrogen retention and diffusion in Al and bubble growth in the bulk was simulated using experimental results. This model was also used to simulate these phenomena in Be and compare its behavior with respect to Al.

  2. Blisters in BDF-type control rods: Engineering final summary report

    Energy Technology Data Exchange (ETDEWEB)

    Riedeman, G.W.


    The scope of this report defies a concise abstract. In lieu of an abstract, the following topical outline will both indicate the subjects covered and show how these subjects are organized. Part I, Engineering Aspects: Blister Formation, Temperature Effects, Cooling Effects, Drive Connections, Housing Effects, Housing Materials, Radiation Effects. Part II, The Behavior of Boron Carbide-Aluminum Poisons: Swelling, Swelling Rates, Restraint, Material Behavior.

  3. First report of the white pine blister rust pathogen, Cronartium ribicola, in Arizona (United States)

    M. L. Fairweather; Brian Geils


    White pine blister rust, caused by Cronartium ribicola J.C. Fisch., was found on southwestern white pine (Pinus flexilis James var. reflexa Engelm., synonym P. strobiformis Engelm.) near Hawley Lake, Arizona (Apache County, White Mountains, 34.024°N, 109.776°W, elevation 2,357 m) in April 2009. Although white pines in the Southwest (Arizona and New Mexico) have been...

  4. Unruptured anterior communicating artery aneurysm with co-existing blister aneurysms: case report and review of literature

    Directory of Open Access Journals (Sweden)

    Karthikeyan Y. R.


    Full Text Available Blister aneurysms are a separate class of vascular malformations with a unique etiopathogenesis and clinical profile, elusive to radiological imaging and complex to manage. Unless identified and managed appropriately they often lead increased morbidity intra and post operatively. They are commonly reported in internal carotid artery. We are reporting a rare case of intraoperatively diagnosed blister aneurysm of the anterior cerebral artery, the management options and the importance of constant vigilance in cases where the aneurysm appears unruptured intraoperatively.

  5. Bullous impetigo and pregnancy: Case report and review of blistering conditions in pregnancy. (United States)

    Cohen, Philip R


     Bullous impetigo results from Staphylococcus aureus (S. aureus) release of exfoliative toxins type A and type B thatresults in flaccid, easily ruptured, bullae in the upper layers of the epidermis.  Physiologic, gestation-associated, and incidental skin changes can occur in pregnancy.  Blisters in pregnant women can occur secondary to either common skin disorders orspecific dermatoses of pregnancy.  To describe a pregnant woman with bullous impetigo and review bullous conditions in pregnant women.  PubMed was used to search the following terms, separately and in combination:  blister, blistering, bullous, gestationis, herpes, herpetiformis, impetigo, pemphigoid, pregnancy, pregnant, psoriasis, pustular, virus. All papers were reviewed and relevant manuscripts, along with their reference citations, were evaluated.  Flaccid, easily rupturing, pustules, which developed into superficial annular erosions with peripheral scale and central healing appeared in a woman of 7-weeks gestation and allergy to penicillin on her lower abdomen, suprapubic region, perineum, buttocks, and proximal legs.  A bacterial culture subsequently isolated methicillin-susceptible S. aureus.  All of the lesions resolved after treatment with clindamycin.  Bullous impetigo should be considered in the differential diagnosis of common skin diseases presenting as blistersin pregnant women.

  6. Deuterium implantation into Y2O3-doped and pure tungsten: Deuterium retention and blistering behavior (United States)

    Zhao, M.; Jacob, W.; Manhard, A.; Gao, L.; Balden, M.; von Toussaint, U.; Zhou, Z.


    The blistering and near-surface deuterium retention of a Y2O3-doped tungsten (W) and two different pure W grades were studied after exposure to deuterium (D) plasma at elevated temperatures (370, 450 and 570 K). Samples were exposed to a deuterium fluence of 6 × 1024 D m-2 applying a moderate ion flux of about 9 × 1019 D m-2 s-1 at an ion energy of 38 eV/D. Morphological modifications at the surface were analyzed by confocal laser scanning microscopy and scanning electron microscopy. The D depth profiles and the accumulated D inventories within the topmost 8 μm were determined by nuclear reaction analysis. Blistering and deuterium retention were strongly dependent on the implantation temperature. In addition, blistering was sensitively influenced by the used tungsten grade, although the total amount of retained D measured by nuclear reaction analysis was comparable. Among the three different investigated tungsten grades, Y2O3-doped W exhibited the lowest degree of surface modification despite a comparable total D retention.

  7. Superficial Dsg2 Expression Limits Epidermal Blister Formation Mediated by Pemphigus Foliaceus Antibodies and Exfoliative Toxins

    Directory of Open Access Journals (Sweden)

    Donna Brennan


    Full Text Available Cell-cell adhesion mediated by desmosomes is crucial for maintaining proper epidermal structure and function, as evidenced by several severe and potentially fatal skin disorders involving impairment of desmosomal proteins. Pemphigus foliaceus (PF and staphylococcal scalded skin syndrome (SSSS are subcorneal blistering diseases resulting from loss of function of the desmosomal cadherin, desmoglein 1 (Dsg1. To further study the pathomechanism of these diseases and to assess the adhesive properties of Dsg2, we employed a recently established transgenic (Tg mouse model expressing Dsg2 in the superficial epidermis. Neonatal Tg and wild type (WT mice were injected with purified ETA or PF Ig. We showed that ectopic expression of Dsg2 reduced the extent of blister formation in response to both ETA and PF Ig. In response to PF Ig, we observed either a dramatic loss or a reorganization of Dsg1-α, Dsg1-β, and, to a lesser extent, Dsg1-γ, in WT mice. The Inv-Dsg2 Tg mice showed enhanced retention of Dsg1 at the cell-cell border. Collectively, our data support the role for Dsg2 in cell adhesion and suggest that ectopic superficial expression of Dsg2 can increase membrane preservation of Dsg1 and limit epidermal blister formation mediated by PF antibodies and exfoliative toxins.

  8. Evaluation of haemoglobin in blister fluid as an indicator of paediatric burn wound depth. (United States)

    Tanzer, Catherine; Sampson, Dayle L; Broadbent, James A; Cuttle, Leila; Kempf, Margit; Kimble, Roy M; Upton, Zee; Parker, Tony J


    The early and accurate assessment of burns is essential to inform patient treatment regimens; however, this first critical step in clinical practice remains a challenge for specialist burns clinicians worldwide. In this regard, protein biomarkers are a potential adjunct diagnostic tool to assist experienced clinical judgement. Free circulating haemoglobin has previously shown some promise as an indicator of burn depth in a murine animal model. Using blister fluid collected from paediatric burn patients, haemoglobin abundance was measured using semi-quantitative Western blot and immunoassays. Although a trend was observed in which haemoglobin abundance increased with burn wound severity, several patient samples deviated significantly from this trend. Further, it was found that haemoglobin concentration decreased significantly when whole cells, cell debris and fibrinous matrix was removed from the blister fluid by centrifugation; although the relationship to depth was still present. Statistical analyses showed that haemoglobin abundance in the fluid was more strongly related to the time between injury and sample collection and the time taken for spontaneous re-epithelialisation. We hypothesise that prolonged exposure to the blister fluid microenvironment may result in an increased haemoglobin abundance due to erythrocyte lysis, and delayed wound healing. Copyright © 2015 Elsevier Ltd and ISBI. All rights reserved.

  9. Recent advances in understanding autoimmune thyroid disease

    DEFF Research Database (Denmark)

    Bliddal, Sofie; Nielsen, Claus Henrik; Feldt-Rasmussen, Ulla


    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 has...

  10. [Stress and auto-immunity]. (United States)

    Delévaux, I; Chamoux, A; Aumaître, O


    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 released by hypothalamic-pituitary-adrenal axis during stress will alter the balance Th1/Th2 and the balance Th17/Treg. Stress impairs cellular immunity, decreases immune tolerance and stimulates humoral immunity exposing individuals to autoimmune disease among others. The treatment for autoimmune disease should include stress management. Copyright © 2012 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.

  11. Epigenetic alterations underlying autoimmune diseases. (United States)

    Aslani, Saeed; Mahmoudi, Mahdi; Karami, Jafar; Jamshidi, Ahmad Reza; Malekshahi, Zahra; Nicknam, Mohammad Hossein


    Recent breakthroughs in genetic explorations have extended our understanding through discovery of genetic patterns subjected to autoimmune diseases (AID). Genetics, on the contrary, has not answered all the conundrums to describe a comprehensive explanation of causal mechanisms of disease etiopathology with regard to the function of environment, sex, or aging. The other side of the coin, epigenetics which is defined by gene manifestation modification without DNA sequence alteration, reportedly has come in to provide new insights towards disease apprehension through bridging the genetics and environmental factors. New investigations in genetic and environmental contributing factors for autoimmunity provide new explanation whereby the interactions between genetic elements and epigenetic modifications signed by environmental agents may be responsible for autoimmune disease initiation and perpetuation. It is aimed through this article to review recent progress attempting to reveal how epigenetics associates with the pathogenesis of autoimmune diseases.


    Directory of Open Access Journals (Sweden)

    Alina-Costina LUCA


    Full Text Available Involving systemic autoimmune diseases, they primarily affect the joints, muscles and connective tissues. Cardiovascular impairment is often common in these disease manifestations ranging from asymptomatic to life-situations in danger. Otherwise impaired cardiovascular reason may be the first presentation. This may require aggressive therapy immunosuppressed, therefore the diagnosis is very important for a good choice of therapy. This article discusses the cardiovascular manifestations of systemic autoimmune diseases, mainly rheumatic diseases, focusing on diagnosis and manangement cardiovascular implications.

  13. [Smoking and chronic autoimmune thyroiditis]. (United States)

    Buzoianu, Ioana Cristina; Arghir, Oana Cristina; Circo, E


    The chronic autoimmune thyroiditis are heterogeneous entities by the functional, lesional and evolutive point of view. Ethiopathogenic factors involved in chronic autoimmune thyroiditis are genetical factors, combines with environmental factors, hormonal factors, infectious factors etc. The exact role of smoking on the autoimmune mechanism is unclear, but smoking is known to have an antithyroid effect. Our study tries to estimate the influence of smoking on serum levels of antithyroid peroxidase antibodies and antithyroglobulin antibodies, in a group of patients with various clinical forms of chronic autoimmune thyroiditis. We studied a group consists of 310 patients with chronic autoimmune thyroiditis, hospitalised in the Endocrinology Department of Constanta County Hospital, between January 2006 - December 2009. We detected serum values of antithyroidperoxidase antibodies and antithyroglobulin antibodies of our patients. We also followed the age, sex and presence of smoking in our study group. For statistical processing of the data we use Student's t-test. In our study group 24.28% of patients were smokers. Serum levels of antithyroid peroxidase antibodies were significantly increased (p < 0.001) in the smokers patients, compared with the nonsmokers patients. Serum levels of antithyroglobulin antibodies were significantly increased (p < 0.01) in smokers patients, compared with those who were nonsmokers. Smoking increased the serum levels of antithyroid antibodies in patients with chronic autoimmune thyroiditis.

  14. Autoimmune Thyroiditis and Glomerulopathies

    Directory of Open Access Journals (Sweden)

    Domenico Santoro


    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.

  15. Autoimmune kidney diseases. (United States)

    Segelmark, Mårten; Hellmark, Thomas


    The second most common cause of chronic renal failure is glomerulonephritis, which is a collective term used for numerous diseases with the common denominator of histological renal inflammation emanating from the glomerular tuft. Whether all forms of glomerulonephritis should be considered as autoimmune disease is debatable, but immune mechanisms are important in all of them. This review focuses on four relatively well delineated forms of primary glomerulonephritis: Goodpastures or anti-GBM disease, IgA nephritis, membranous nephropathy and membranoproliferative glomerulonephritis. The autoantibodies are directed either to molecules within the glomeruli, such as the glomerular basement membrane in anti-GBM disease and to the podocytes in membranous glomerulonephritis, or to components of the immune system such as C3 convertase in membranoproliferative glomerulonephritis and IgA in IgA nephritis. Differences in diagnostic practices and classification controversies obscure comparative epidemiological studies, but there seem to be huge differences between incidence rates between countries and over time, both genetic factors and infections seem to matter but strong indications for a role of other environmental factors are still lacking. 2009 Elsevier B.V. All rights reserved.

  16. Treatment of Intraepidermal Autoimmune Bullous Diseases Sürekli Eğitim

    Directory of Open Access Journals (Sweden)

    Tamer İrfan Kaya


    Full Text Available Pemfigus is an autoimmune bullous skin disease, characterized by intraepidermal blisters. It is a severe and potentially life-threatening chronic disease with blisters and erosions on the mucosae and the skin. Treatment options do not differ for two most common types of pemphigus, pemphigus vulgaris and pemphigus foliaceus, except that the latter is usually less resistant to treatment and corticosteroids can often be started at lower doses. Systemic corticosteroids are still the most widely used drugs in the treatment of pemphigus and continue to be the mainstay of therapy for this disease. Adjuvant drugs are commonly used in combination with the aims of increasing efficacy and of having a steroid-sparing action, thereby allowing reduced corticosteroid side-effects. Mortality and complete remission rates have improved since the introduction of adjuvant drugs to pemphigus. Adjuvant drugs include immunoadsorbtion, corticosteroid pulse therapy, intravenous immunoglobulin (IVIG, immunosuppressive agents such as azathioprine, cyclophosphamide, mycophenolate mofetil and and anti-CD20 monoclonal antibody (rituximab. The lack of consensus in the published literature about the treatment of this disorder is responsible for different treatment strategies. Treatments need to be chosen after careful consideration of the potential benefits and side effects according to the patients’ medical condition. Here, both conventional therapies and novel treatment regimens for pemphigus are discussed. (Turkderm 2011; 45 Suppl 1: 44-53

  17. Autoimmune hepatitis in association with lymphocytic colitis.

    LENUS (Irish Health Repository)

    Cronin, Edmond M


    Autoimmune hepatitis is a rare, chronic inflammatory disorder which has been associated with a number of other auto-immune conditions. However, there are no reports in the medical literature of an association with microscopic (lymphocytic) colitis. We report the case of a 53-year-old woman with several autoimmune conditions, including lymphocytic colitis, who presented with an acute hepatitis. On the basis of the clinical features, serology, and histopathology, we diagnosed autoimmune hepatitis. To our knowledge, this is the first report of autoimmune hepatitis in association with lymphocytic colitis, and lends support to the theory of an autoimmune etiology for lymphocytic colitis.

  18. Investigation of the Cause of Low Blister Threshold Temperatures in the RERTR-12 and AFIP-4 Experiments

    Energy Technology Data Exchange (ETDEWEB)

    Mitchell K Meyer


    Blister–threshold testing of fuel plates is a standard method through which the safety margin for operation of plate-type in research and test reactors is assessed. The blister-threshold temperature is indicative of the ability of fuel to operate at high temperatures for short periods of time (transient conditions) without failure. This method of testing was applied to the newly developed U-Mo monolithic fuel system. Blister annealing studies on the U-Mo monolithic fuel plates began in 2007, with the Reduced Enrichment for Research and Test Reactors (RERTR)-6 experiment, and they have continued as the U-Mo fuel system has evolved through the research and development process. Blister anneal threshold temperatures from early irradiation experiments (RERTR-6 through RERTR-10) ranged from 400 to 500°C. These temperatures were projected to be acceptable for NRC-licensed research reactors and the high-power Advanced Test Reactor (ATR) and the High Flux Isotope Reactor (HFIR) based on current safety-analysis reports (SARs). Initial blister testing results from the RERTR-12 experiment capsules X1 and X2 showed a decrease in the blister-threshold temperatures. Blister threshold temperatures from this experiment ranged from 300 to 400°C. Selected plates from the AFIP-4 experiment, which was fabricated using a process similar to that used to fabricate the RERTR-12 experiment, also underwent blister testing to determine whether results would be similar. The measured blister-threshold temperatures from the AFIP-4 plates fell within the same blister-threshold temperature range measured in the RERTR-12 plates. Investigation of the cause of this decrease in bister threshold temperature is being conducted under the guidance of Idaho National Laboratory PLN-4155, “Analysis of Low Blister Threshold Temperatures in the RERTR-12 and AFIP-4 Experiments,” and is driven by hypotheses. The main focus of the investigation is in the following areas: 1. Fabrication variables 2. Pre

  19. Blister formation on 13Cr2MoNbVB ferritic-martensitic steel exposed to hydrogen plasma (United States)

    Nikitin, A. V.; Tolstolutskaya, G. D.; Ruzhytskyi, V. V.; Voyevodin, V. N.; Kopanets, I. E.; Karpov, S. A.; Vasilenko, R. L.; Garner, F. A.


    The influence of pre-irradiation specimen deformation level on surface blister formation and sub-surface cracking of dual-phase 13Cr2MoNbVB ferritic-martensitic steel was studied using glow discharge hydrogen plasma with ion energy of 1 keV to fluences of 2 × 1025 H/m2. Protium was used for most studies, but deuterium was used for measuring the depth dependence of hydrogen diffusion. Formation of blisters was observed in the temperature range 230-340 K. It was found that pre-irradiation deformation caused changes in the threshold fluences of blister formation and also in blister size distribution. Subsurface cracks located on grain boundaries far beyond the implantation zone were formed concurrently with blisters, arising from hydrogen diffusion and trapping at defects. It was observed that cracks as long as 1 mm in length were formed in 95% deformed steel at depths up to 500 μm from surface.

  20. Type 1 autoimmune pancreatitis

    Directory of Open Access Journals (Sweden)

    Zen Yoh


    Full Text Available Abstract Before the concept of autoimmune pancreatitis (AIP was established, this form of pancreatitis had been recognized as lymphoplasmacytic sclerosing pancreatitis or non-alcoholic duct destructive chronic pancreatitis based on unique histological features. With the discovery in 2001 that serum IgG4 concentrations are specifically elevated in AIP patients, this emerging entity has been more widely accepted. Classical cases of AIP are now called type 1 as another distinct subtype (type 2 AIP has been identified. Type 1 AIP, which accounts for 2% of chronic pancreatitis cases, predominantly affects adult males. Patients usually present with obstructive jaundice due to enlargement of the pancreatic head or thickening of the lower bile duct wall. Pancreatic cancer is the leading differential diagnosis for which serological, imaging, and histological examinations need to be considered. Serologically, an elevated level of IgG4 is the most sensitive and specific finding. Imaging features include irregular narrowing of the pancreatic duct, diffuse or focal enlargement of the pancreas, a peri-pancreatic capsule-like rim, and enhancement at the late phase of contrast-enhanced images. Biopsy or surgical specimens show diffuse lymphoplasmacytic infiltration containing many IgG4+ plasma cells, storiform fibrosis, and obliterative phlebitis. A dramatic response to steroid therapy is another characteristic, and serological or radiological effects are normally identified within the first 2 or 3 weeks. Type 1 AIP is estimated as a pancreatic manifestation of systemic IgG4-related disease based on the fact that synchronous or metachronous lesions can develop in multiple organs (e.g. bile duct, salivary/lacrimal glands, retroperitoneum, artery, lung, and kidney and those lesions are histologically identical irrespective of the organ of origin. Several potential autoantigens have been identified so far. A Th2-dominant immune reaction and the activation of

  1. Kidney transplantation during autoimmune diseases. (United States)

    Ounissi, M; Abderrahim, E; Hedri, H; Sfaxi, M; Fayala, H; Turki, S; Ben Maïz, H; Ben Abdallah, T; Chebil, M; Kheder, A


    Herein, we report the results of kidney transplantation in 9 of 376 patients who underwent kidney transplantation at our center between 1986 and 2007 because of chronic renal failure associated with autoimmune disease. Four of the 9 patients had systemic lupus erythematosus, 3 had Wegener granulomatosis, and 2 had Goodpasture syndrome. Six patients received organs from living donors, and 3 received cadaver organs. Infections were frequent and included cytomegalovirus and urinary tract infection in most cases. There was no difference in occurrence of metabolic and cardiovascular complications in our study patients compared with other transplant recipients. Incidence of allograft loss (n = 1) was similar to that in our entire transplantation population, with an overall rate of 2.9%. We conclude that kidney transplantation is a reasonable therapeutic option in patients with autoimmune disease with end-stage renal disease because of good graft and patient survival compared with kidney recipients without autoimmune diseases.

  2. A minimum number of autoimmune T cells to induce autoimmunity?

    Czech Academy of Sciences Publication Activity Database

    Bosch, A.J.T.; Bolinger, B.; Keck, S.; Štěpánek, Ondřej; Ozga, A.J.; Galati-Fournier, V.; Stein, J.V.; Palmer, E.


    Roč. 316, jaro (2017), s. 21-31 ISSN 0008-8749 R&D Projects: GA ČR GJ16-09208Y Institutional support: RVO:68378050 Keywords : T cell * Tolerance * Autoimmunity Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.172, year: 2016

  3. Genetics Home Reference: autoimmune Addison disease (United States)

    ... features of other genetic conditions, including X-linked adrenoleukodystrophy and autoimmune polyglandular syndrome, type 1, which are ... disease Patient Support and Advocacy Resources (3 links) Adrenoleukodystrophy Foundation American Autoimmune Related Diseases Association National Adrenal ...

  4. Shaking Out Clues to Autoimmune Disease (United States)

    ... of Autoimmunity-Causing T Cells Landmark Analysis Probes Nature vs. Nurture in Multiple Sclerosis Understanding Autoimmune Diseases Immune Cells References: Nature. 2013 Mar 6. doi: 10.1038/nature11981. [Epub ...

  5. Multiple autoimmune syndrome with celiac disease. (United States)

    Harpreet, Singh; Deepak, Jain; Kiran, B


    Multiple autoimmune syndrome (MAS) is a condition characterised by three or more autoimmune disorders in a same individual. Familial, immunologic and infectious factors are implicated in the development of MAS. Here we report a case of a 32-year-old woman with co-existence of four auto-immune diseases, namely autoimmune hypothyroidism, Sjögren's syndrome, systemic lupus erythematosus (SLE) and celiac disease which leads to the final diagnosis of multiple autoimmune syndrome type 3 with celiac disease. Patients with single autoimmune disorder are at 25% risk of developing other autoimmune disorders. The present case emphasises to clinicians that there is a need for continued surveillance for the development of new autoimmune disease in predisposed patients.

  6. Perception of self : Distinguishing autoimmunity from autoinflammation

    NARCIS (Netherlands)

    Van Kempen, Tessa S.; Wenink, Mark H.; Leijten, Emmerik F A; Radstake, Timothy R D J; Boes, Marianne


    Rheumatic diseases can be divided in two groups, autoinflammatory and autoimmune disorders. The clinical presentation of both types of diseases overlap, but the pathological pathways underlying rheumatic autoinflammation and autoimmunity are distinct and are the subject of ongoing research. There

  7. An autosomal locus causing autoimmune disease: Autoimmune polyglandular disease type I assigned to chromosome 21

    NARCIS (Netherlands)

    J. Aaltonen (Johanna); P. Björses (Petra); L.A. Sandkuijl (Lodewijk); J. Perheentupa (Jaakko); L. Peltonen (Leena Johanna)


    textabstractAutoimmune polyglandular disease type I (APECED) is an autosomal recessive autoimmune disease characterized by a variable combination of the failure of the endocrine glands. The pathogenesis of this unique autoimmune disease is unknown; unlike many other autoimmune diseases, APECED does

  8. Multiplex autoantibody detection for autoimmune liver diseases and autoimmune gastritis. (United States)

    Vanderlocht, Joris; van der Cruys, Mart; Stals, Frans; Bakker-Jonges, Liesbeth; Damoiseaux, Jan


    Autoantibody detection for autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC) and autoimmune gastritis (AIG) is traditionally performed by IIF on a combination of tissues. Multiplex line/dot blots (LIA/DIA) offer multiple advantages, i.e. automation, objective reading, no interfering reactivities, no coincidental findings. In the current study we evaluated automated DIA (D-Tek) for detecting autoantibodies related to autoimmune diseases of the gastrointestinal tract. We tested samples of the Dutch EQC program and compared the results with the consensus of the participating labs. For the autoimmune liver diseases and AIG, respectively, 64 and 36 samples were tested. For anti-mitochondrial and anti-smooth muscle antibodies a concordance rate of 97% and 88% was observed, respectively. The concordance rate for anti-parietal cell antibodies was 92% when samples without EQC consensus (n=15) were excluded. For antibodies against intrinsic factor a concordance of 96% was observed. For all these antibodies discrepancies were identified that relate to the different test characteristics and the preponderance of IIF utilizing labs in the EQC program. In conclusion, we observed good agreement of the tested DIA blots with the consensus results of the Dutch EQC program. Taken together with the logistic advantages these blots are a good alternative for autoantibody detection in the respective diseases. A large prospective multicenter study is warranted to position these novel tests further in the whole spectrum of assays for the detection of these antibodies in a routine autoimmune laboratory. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. [Seronegative systemic lupus erythematosus and autoimmune thyroiditis]. (United States)

    González-Gay, M A; Cereijo, M J; Agüero, J J; Alonso, M D; Fernández Sueiro, J L; Vidal, J I


    The association of systemic lupus erythematosus (SLE) and autoimmune thyroiditis has been previously described. We report a woman with negative antinuclear antibodies (ANA) and criteria for the diagnosis of SLE. The patient was also diagnosed with autoimmune thyroiditis. We review the clinical characteristics and the association of both entities. We also remark in this case the association of autoimmune thyroiditis with seronegative SLE.

  10. Levamisole toxicity mimicking autoimmune disease. (United States)

    Strazzula, Lauren; Brown, Katherine K; Brieva, Joaquin C; Camp, Brendan J; Frankel, Hillary C; Kissin, Eugene; Mahlberg, Matthew J; Mina, Mary Alice; Pomeranz, Miriam K; Brownell, Isaac; Kroshinsky, Daniela


    Levamisole is present as a contaminant or additive in most cocaine sold in the United States. Cases of agranulocytosis attributed to levamisole-tainted cocaine have been widely described. A vasculopathic reaction to levamisole has also been reported; however, diagnostic features such as antineutrophil cytoplasmic antibody (ANCA) and additional autoimmune marker positivity are not well recognized. As such, many patients are given a misdiagnosis, prompting aggressive and often unnecessary treatment. We hope to educate practitioners about the clinical and laboratory features of levamisole-induced vasculopathy to ensure accurate diagnosis and management. This was a case series. Six patients were admitted with purpuric lesions and vasculitic changes on biopsy specimen; 5 of them were given the diagnosis of and treated for autoimmune conditions before their true diagnosis was revealed. All patients had ANCA positivity, and 4 had additional abnormalities in autoimmune markers. All patients reported recent cocaine abuse, and were ultimately given the diagnosis of levamisole-induced vasculopathy. This observational study is limited by sample size. Patients presenting with purpuric lesions with ANCA positivity should be assessed for cocaine exposure. It is important to recognize that levamisole may not only induce ANCA positivity but also other autoimmune marker abnormalities. Patients can often be treated with less aggressive therapeutic strategies than what is used for primary ANCA-associated vasculitides. Copyright © 2013 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

  11. Vitiligo and Autoimmune Thyroid Disorders

    Directory of Open Access Journals (Sweden)

    Enke Baldini


    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.

  12. Vernal keratoconjunctivitis: atopy and autoimmunity. (United States)

    Zicari, A M; Nebbioso, M; Lollobrigida, V; Bardanzellu, F; Celani, C; Occasi, F; Cesoni Marcelli, A; Duse, M


    Vernal Keratoconjunctivitis (VKC) is a rare chronic ocular inflammatory disease and it mainly affects boys in the first decade of life. Although it is a self-limiting disease, patients may present many phases characterized by an exacerbation of inflammatory symptoms with a consequent decline of the quality of life. define the clinical and immunological profile of patients affected by VKC and investigate their familiar history of autoimmune disorders and their autoimmunity pattern. 28 children were enrolled (20 males, 71%) aged between 4 and 14 years of life affected by VKC. Family history of allergic and immunological diseases was collected for each patient. In particular, it was asked whether some components of their families were affected by Hashimoto's thyroiditis, type I diabetes, psoriasis or rheumatoid arthritis and Systemic Lupus Erythematosus (SLE). All VKC children underwent a serological evaluation of anti-nuclear antibodies (ANA). A family history of immunological disorders was found in 46% of patients, 28% of Hashimoto's thyroiditis, 14% of type I diabetes, 14% of psoriasis, and 1 of Systemic Lupus Erythematosus. Furthermore, 35% of patients was ANA positive and they corresponded to patients with a higher ocular score and with the most important clinical symptoms. the detection of ANA positivity and of a familiar history of autoimmune disorders in a high percentage of children with VKC may help us to better understand the association of this ocular inflammatory disease with systemic autoimmune disorders and atopic condition.

  13. Blister rust resistance among 19 families of whitebark pine, Pinus albicaulis, from Oregon and Washington – early results from an artificial inoculation trial (United States)

    Angelia Kegley; Richard A. Sniezko; Robert Danchok; Douglas P. Savin


    Whitebark pine is considered one of the most susceptible white pine species to white pine blister rust, the disease caused by the non-native pathogen Cronartium ribicola. High mortality from blister rust and other factors in much of the range in the United States and Canada have raised serious concerns about the future viability of this high-...

  14. Polyautoimmunity and familial autoimmunity in systemic sclerosis. (United States)

    Hudson, Marie; Rojas-Villarraga, Adriana; Coral-Alvarado, Paola; López-Guzmán, Silvia; Mantilla, Ruben D; Chalem, Philippe; Baron, Murray; Anaya, Juan-Manuel


    Characterization of the extent to which particular combinations of autoimmune diseases occur in excess of that expected by chance may offer new insights into possible common pathophysiological mechanisms. The goal of this study was to investigate the spectrum of polyautoimmunity (i.e. autoimmune diseases co-occurring within patients) and familial autoimmunity (i.e. diverse autoimmune diseases co-occurring within families) in patients with systemic sclerosis (SSc). A cross-sectional study of two convenience samples of patients with SSc, one in Canada and the other in Colombia, was performed. History of other autoimmune diseases in the SSc patients as well as a family history of autoimmunity was obtained. Of 719 patients, 273 (38%) had at least one other autoimmune disease. A total of 366 autoimmune diseases were reported, of which the most frequent were autoimmune thyroid disease (AITD, 38%), rheumatoid arthritis (RA, 21%), Sjögren's syndrome (18%), and primary biliary cirrhosis (4%). There were 260 (36%) patients with first-degree relatives with at least one autoimmune disease, of which the most frequent were RA (18%) and AITD (9%). Having at least one first-degree relative with autoimmune disease was a significant predictor of polyautoimmunity in SSc patients. No significant differences in polyautoimmunity or familial autoimmunity were noted between diffuse and limited subsets of disease. Our results indicate that polyautoimmunity is frequent in patients with SSc and autoimmune diseases cluster within families of these patients. Clinically different autoimmune phenotypes might share common susceptibility variants, which acting in epistatic pleiotropy may represent risk factors for autoimmunity.

  15. Rheumatic Manifestations in Autoimmune Liver Disease. (United States)

    Selmi, Carlo; Generali, Elena; Gershwin, Merrill Eric


    Autoimmune liver diseases coexist with rheumatic disorders in approximately 30% of cases and may also share pathogenic mechanisms. Autoimmune liver diseases result from an immune-mediated injury of different tissues, with autoimmune hepatitis (AIH) targeting hepatocytes, and primary biliary cholangitis (PBC) and primary sclerosing cholangitis targeting cholangiocytes. Sjogren syndrome is diagnosed in 7% of AIH cases and serologic autoimmunity profiles are a common laboratory abnormality, particularly in the case of serum antimitochondrial (PBC) or anti-liver kidney microsomal antibodies (AIH). Therapeutic strategies may overlap between rheumatic and autoimmune liver diseases and practitioners should be vigilant in managing bone loss. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. AIRE-mutations and autoimmune disease. (United States)

    Bruserud, Øyvind; Oftedal, Bergithe E; Wolff, Anette B; Husebye, Eystein S


    The gene causing the severe organ-specific autoimmune disease autoimmune polyendocrine syndrome type-1 (APS-1) was identified in 1997 and named autoimmune regulator (AIRE). AIRE plays a key role in shaping central immunological tolerance by facilitating negative selection of T cells in the thymus, building the thymic microarchitecture, and inducing a specific subset of regulatory T cells. So far, about 100 mutations have been identified. Recent advances suggest that certain mutations located in the SAND and PHD1 domains exert a dominant negative effect on wild type AIRE resulting in milder seemingly common forms of autoimmune diseases, including pernicious anemia, vitiligo and autoimmune thyroid disease. These findings indicate that AIRE also contribute to autoimmunity in more common organ-specific autoimmune disorders. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. The role of the autoimmunity laboratory in autoimmune diseases

    Directory of Open Access Journals (Sweden)

    SS Hasson


    Full Text Available Laboratory testing is of great value when evaluating a patient with a suspected autoimmune disease. The results can confirm a diagnosis, estimate disease severity, aid in assessing prognosis and are useful to follow disease activity. Components of the laboratory exam include complete blood count with differential, comprehensive metabolic panel, inflammatory markers, autoantibodies, and flow cytometry. Currently, autoimmunity laboratories are very vibrant owing to the constant and increasing availability of new tests, mainly due to the detection of new autoantibodies. The main characteristic that differentiates the autoimmunity laboratory from other laboratories is the use of immunoassays such as enzyme-linked immunosorbent assay (ELISA, as basic techniques which determines antibodies (autoantibodies and not antigens. For this reason, immunoassay techniques must employ antigens as reagents. However, over the last few years, a significant trend at autoimmunity laboratories has been the gradual replacement of immunofluorescence microscopy by immunoassay. Nowadays the revolution of new technology has taken place significantly, for examples; recombinant DNA technology has allowed the production of large quantities of antigens for autoantibody analysis. Flow cytometry for the analysis of microsphere-based immunoassays allows the simultaneous measurement of several autoantibodies. In the same way, autoantigen microarrays provide a practical means to analyse biological fluids in the search for a high number of autoantibodies. We are now at the beginning of an era of multiplexed analysis, with a high capacity of autoantibody specificities. The future tendency in this field will include immunoassays with greater analytical sensitivity, specificity, simultaneous multiplexed capability, the use of protein microarrays, and the use of other technologies such as microfluidics.

  18. Definition of human autoimmunity--autoantibodies versus autoimmune disease. (United States)

    Lleo, Ana; Invernizzi, Pietro; Gao, Bin; Podda, Mauro; Gershwin, M Eric


    The critical function of the immune system is to discriminate self from non-self. Tolerance against self-antigens is a highly regulated process and, in order to maintain it, the immune system must be able to distinguish self-reactive lymphocytes as they develop. The presence of autoantibodies is the consequence of breakdown of tolerance and, although they are an important serological feature of autoimmune diseases, their presence is not exclusive of these conditions. Antibodies against self-antigens are also found in cancer, during massive tissue damage and even in healthy subjects. Natural autoantibodies provide immediate protection against infection and also prevent inflammation by facilitating the clearance of oxidized lipids, oxidized proteins, and apoptotic cells; their role in development of autoimmunity is still unclear. Detection of serum autoantibodies in clinical practice has become more available to clinicians worldwide while providing a powerful diagnostic tool. This review discusses the clinical significance of autoantibodies, their pathogenic mechanisms in autoimmune diseases and, finally, illustrates the technology available for appropriate autoantibody detection. 2009 Elsevier B.V. All rights reserved.

  19. Random amplified polymorphic DNA markers tightly linked to a gene for resistance to white pine blister rust in sugar pine (United States)

    Michael E. Devey; Annette Delfino-Mix1; Bohun B. Kinloch; David B. NEALEt


    We have genetically mapped a gene for resistance to white pine blister rust (Cronartium ribicola Fisch.) in sugar pine (Pinus lambertiana Dougl.) by using an approach which relies on three factors: (i) the ability to assay for genetic markers in the haploid stage of the host's life cycle, using...

  20. Distribution and frequency of a gene for resistance to white pine blister rust in natural populations of sugar pine (United States)

    Bohun B. Kinloch Jr.


    The gametic frequency of a dominant allcle (R) for resistance to white pine blister rust, a disease caused by an introduced pathogen (Cronartium ribicola), in natural populations of sugar pine was estimated by the kind of leaf symptom expressed after artificial inoculation of wind-pollinated seedlings from susceptible seed-parent...

  1. Using landscape genetics simulations for planting blister rust resistant whitebark pine in the US northern Rocky Mountains (United States)

    Erin L. Landguth; Zachary A. Holden; Mary F. Mahalovich; Samuel A. Cushman


    Recent population declines to the high elevation western North America foundation species whitebark pine, have been driven by the synergistic effects of the invasive blister rust pathogen, mountain pine beetle (MPB), fire exclusion, and climate change. This has led to consideration for listing whitebark pine (WBP) as a threatened or endangered species under the...

  2. Mitigated blistering and deuterium retention in tungsten exposed to high-flux deuterium–neon mixed plasmas

    NARCIS (Netherlands)

    Cheng, L.; De Temmerman, G.; Morgan, T. W.; Schwartz-Selinger, T.; Yuan, Y.; Zhou, H. B.; Wang, B.; Zhang, Y.; Lu, G. H.


    Surface morphology and deuterium retention in tungsten exposed at surface temperature of  550 K to mixed deuterium–neon plasmas of different neon concentrations are investigated. It is found that the addition of neon up to 20% mitigates blistering on the surface. Cross-section view of the surface

  3. Influence of Process Temperatures on Blister Creation in Micro Film Insert Molding of a Dual Layer Membrane

    DEFF Research Database (Denmark)

    Wöhner, Timo; R. Whiteside, Ben; Tosello, Guido


    In this work the suitability of a dual layer membrane, consisting of a non-woven Polypropylene (PP) support and a membrane layer made out of Polyethylene Terephthalate (PET) for Micro Film Insert Molding (μFIM) was investigated. The emergence of blisters at the surface of the PET-membrane layer...

  4. Using Landscape Genetics Simulations for Planting Blister Rust Resistant Whitebark Pine in the US Northern Rocky Mountains (United States)

    Landguth, Erin L.; Holden, Zachary A.; Mahalovich, Mary F.; Cushman, Samuel A.


    Recent population declines to the high elevation western North America foundation species whitebark pine, have been driven by the synergistic effects of the invasive blister rust pathogen, mountain pine beetle (MPB), fire exclusion, and climate change. This has led to consideration for listing whitebark pine (WBP) as a threatened or endangered species under the Endangered Species Act, which has intensified interest in developing management strategies for maintaining and restoring the species. An important, but poorly studied, aspect of WBP restoration is the spatial variation in adaptive genetic variation and the potential of blister rust resistant strains to maintain viable populations in the future. Here, we present a simulation modeling framework to improve understanding of the long-term genetic consequences of the blister rust pathogen, the evolution of rust resistance, and scenarios of planting rust resistant genotypes of whitebark pine. We combine climate niche modeling and eco-evolutionary landscape genetics modeling to evaluate the effects of different scenarios of planting rust-resistant genotypes and impacts of wind field direction on patterns of gene flow. Planting scenarios showed different levels for local extirpation of WBP and increased population-wide blister rust resistance, suggesting that the spatial arrangement and choice of planting locations can greatly affect survival rates of whitebark pine. This study presents a preliminary, but potentially important, framework for facilitating the conservation of whitebark pine. PMID:28239390

  5. A paradigm shift for white pine blister rust: Non-Ribes alternate hosts for Cronartium ribicola in North America (United States)

    Paul J. Zambino; Bryce A. Richardson; Geral I. McDonald; Ned B. Klopfenstein; Mee-Sook. Kim


    Naturally occurring Cronartium ribicola infections were discovered in August and September, 2004 on Pedicularis racemosa and Castilleja miniata in a mixed stand of white pine blister rust-infected whitebark pine (Pinus albicaulis) and western white pine (P. monticola) in northern Idaho, at Roman Nose Lakes, ca 30 km west of Bonners Ferry. Infections were confirmed by...

  6. Non-Ribes alternate hosts of white pine blister rust: What this discovery means to whitebark pine (United States)

    Paul J. Zambino; Bryce A. Richardson; Geral I. McDonald; Ned B. Klopfenstein; Mee-Sook. Kim


    From early to present-day outbreaks, white pine blister rust caused by the fungus Cronartium ribicola, in combination with mountain pine beetle outbreaks and fire exclusion has caused ecosystem-wide effects for all five-needled pines (McDonald and Hoff 2001). To be successful, efforts to restore whitebark pine will require sound management decisions that incorporate an...

  7. A new genus and species of Cecidomyiidae (Diptera) from leaf blister galls on Ribes (Grosulariaceae)in North America (United States)

    Ribesia sarae Gagné, new genus, new species(Diptera: Cecidomyiidae), is described from simple leaf blister galls on Ribes aureum(Grossulariaceae) from Montana. The female abdomen is superficially similar to that of CystiphoraKieffer and SackenomyiaFelt. The three genera are compared. Because of stro...

  8. Chitosan-induced immunity in Camellia sinensis (L.) O. Kuntze against blister blight disease is mediated by nitric-oxide. (United States)

    Chandra, Swarnendu; Chakraborty, Nilanjan; Panda, Koustubh; Acharya, Krishnendu


    Blister blight disease, caused by an obligate biotrophic fungal pathogen, Exobasidium vexans Massee is posing a serious threat for tea cultivation in Asia. As the use of chemical pesticides on tea leaves substantially increases the toxic risks of tea consumption, serious attempts are being made to control such pathogens by boosting the intrinsic natural defense responses against invading pathogens in tea plants. In this study, the nature and durability of resistance offered by chitosan and the possible mechanism of chitosan-induced defense induction in Camellia sinensis (L.) O. Kuntze plants against blister blight disease were investigated. Foliar application of 0.01% chitosan solution at 15 days interval not only reduced the blister blight incidence for two seasons, but also maintained the induced expressions of different defense related enzymes and total phenol content compared to the control. Defense responses induced by chitosan were found to be down regulated under nitric oxide (NO) deficient conditions in vivo, indicating that the observed chitosan-induced resistance is probably activated via NO signaling. Such role of NO in host defense response was further established by application of the NO donor, sodium nitroprusside (SNP), which produced similar defense responses accomplished through chitosan treatment. Taken together, our results suggest that increased production of NO in chitosan-treated tea plants may play a critical role in triggering the innate defense responses effective against plant pathogens, including that causing the blister blight disease. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  9. Status of white pine blister rust and seed collections in california's high-elevation white pine species (United States)

    J. Dunlap


    White pine blister rust (caused by the non-native pathogen Cronartium ribicola) reached northern California about 80 years ago. Over the years its spread southward had been primarily recorded on sugar pine. However, observations on its occurrence had also been reported in several of the higher elevation five-needled white pine species in California. Since the late...

  10. Autoimmune regulator expression in thymomas with or without autoimmune disease. (United States)

    Liu, Yimei; Zhang, Hui; Zhang, Peng; Meng, Fanjie; Chen, Yuan; Wang, Yuanguo; Yao, Yuanyuan; Qi, Bin


    The autoimmune regulator (AIRE) regulates autoimmunity and self-antigen expression, such as acetylcholine receptor (AchR), in the thymus. Regulatory T cells (Tregs) can down-regulate autoimmunity, but also promote tumor growth. The objective of this study was to examine the levels of AIRE, AchR, and Foxp3 expression in thymomas. The relative levels of AIRE, AchR, and Foxp3 mRNA transcripts and the frequency of AIRE+, AchR+, and Foxp3+ cells were determined by quantitative RT-PCR and immunohistochemistry in 79 thymoma tissue samples from 21 patients with simple thymoma (the Tm group), 39 patients with myasthenia gravis (the MG group) and 19 patients with myasthenia gravis and one other autoimmune disease (the AD group). The numbers of peripheral blood CD4+CD25+Foxp3+ Tregs were determined by flow cytometry analysis. The relative levels of AIRE and AchR mRNA transcripts in the MG group were significantly lower than that in the Tm group (p=0.04, p=0.03), but higher than that in the AD group (p=0.03, p=0.04). The relative levels of Foxp3 mRNA transcripts in the Tm group were significantly higher than that in the MG and AD groups (p=0.03 for both). A similar pattern of the percentages of AIRE+, AchR+, and Foxp3+ cells in the thymoma tissues and the numbers of peripheral blood Tregs were detected in these patients. The levels of AIRE mRNA transcripts were correlated positively with that of the AchR and Foxp3 in this population. The levels of AIRE and AchR mRNA transcripts in the A/AB/B1 types of thymomas were significantly higher than that in the B2/B3/C types of thymomas in this population. Significantly lower levels of AIRE, AchR, and Foxp3 expression are associated with the development of thymoma-related autoimmune diseases. Copyright © 2014 Elsevier B.V. All rights reserved.

  11. A kinetic stochastic model of blistering and nanofilm islands deposition: self-organization problem

    Energy Technology Data Exchange (ETDEWEB)

    Zmievskaya, G I; Bondareva, A L; Levchenko, V D; Levchenko, T V [M V Keldysh Institute of Applied Mathematics, Russian Academy of Sciences, Moscow (Russian Federation)


    First-order phase transition at a fluctuation stage into non-linear dissipative plasma-like media is considered. The clustering of new phase germs (or nucleation) is represented by stochastic Wiener processes. Brownian motion of clusters induced by a long-range potential of indirect (through acoustic phonons and Friedel's oscillation of electron density) interaction between one another is taken into account. Kinetic models for blistering materials in a controlled thermonuclear reactor and for melted metal thin film islands deposition during surface CVD modification are both put forward. The non-steady-state distribution of clusters versus their size and position in space is calculated using Ito-Stratonovich stochastic differential equations. Formation of radiation stimulated porosity layers in a lattice as well as liquid island chains on the surface are to be discussed as characteristics of phase transition at fluctuation stages as well as a new kind of self-organization phenomenon.

  12. Activated charcoal and baking soda to reduce odor associated with extensive blistering disorders

    Directory of Open Access Journals (Sweden)

    Chakravarthi Arun


    Full Text Available Background: Skin disease leading to extensive blistering and loss of skin is associated with a characteristic smell. Odor can cause physiologic disturbances such as increase in heart rate and respiratory rate. It can also cause nausea and vomiting and is disturbing to bystanders. Aims: To test odor reducing capability of activated charcoal. Methods: In this blinded experimental study we used putrefied amniotic membrane to produce odor and studied the effectiveness of activated charcoal and soda-bi-carbonate to reduce odor. Results: Statistical analysis with Kruskal Wall′s Chi Square Test and Man Whitney U test showed significant reduction of odor using activated charcoal by itself or along with soda-bi-carbonate. Conclusion: We recommend the usage of activated charcoal with/without soda bicarbonate as an inexpensive practical measure to reduce foul odor associated with extensive skin loss.

  13. Activated charcoal and baking soda to reduce odor associated with extensive blistering disorders. (United States)

    Chakravarthi, Arun; Srinivas, C R; Mathew, Anil C


    Skin disease leading to extensive blistering and loss of skin is associated with a characteristic smell. Odor can cause physiologic disturbances such as increase in heart rate and respiratory rate. It can also cause nausea and vomiting and is disturbing to bystanders. To test odor reducing capability of activated charcoal. In this blinded experimental study we used putrefied amniotic membrane to produce odor and studied the effectiveness of activated charcoal and soda-bi-carbonate to reduce odor. Statistical analysis with Kruskal Wall's Chi Square Test and Man Whitney U test showed significant reduction of odor using activated charcoal by itself or along with soda-bi-carbonate. We recommend the usage of activated charcoal with/without soda bicarbonate as an inexpensive practical measure to reduce foul odor associated with extensive skin loss.

  14. Proteomics and autoimmune kidney disease. (United States)

    Rovin, Brad H; Klein, Jon B


    Proteomics has long been considered an ideal platform, and urine an ideal source for biomarker discovery in human autoimmune kidney diseases. A number of studies have examined the urine proteome to identify biomarkers of disease activity, kidney pathology, and response to therapy. Increasingly, proteomic studies of kidney disease have expanded to include blood, circulating cells and kidney tissue. Recently the clinical potential of renal proteomics has been realized through a handful of investigations whose results appear to be applicable to patient care. In this review, approaches to the proteomic evaluation of autoimmune kidney diseases will be considered in the context of developing clinically useful disease biomarkers. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Autoimmune encephalitis and sleep disorders

    Directory of Open Access Journals (Sweden)

    Yan HUANG


    Full Text Available Research shows that autoimmune encephalitis is associated with sleep disorders. Paraneoplastic neurological syndrome (PNS with Ma2 antibodies can cause sleep disorders, particularly narcolepsy and rapid eye movement sleep behavior disorder (RBD. Limbic encephalitis (LE and Morvan syndrome, associated with voltage - gated potassium channel (VGKC-complex antibodies, which include leucine-rich glioma-inactivated 1 (LGI1 antibody and contactin-associated protein 2 (Caspr2, can result in profound insomnia and other sleep disorders. Central neurogenic hypoventilation are found in patients with anti-N-methyl-D-aspartate (NMDA receptor encephalitis, whereas obstructive sleep apnea (OSA, stridor and parasomnia are prominent features of encephalopathy associated with IgLON5 antibodies. Sleep disorders are cardinal manifestations in patients with autoimmune encephalitis. Immunotherapy possiblely can improve clinical symptoms and prognosis in a positive way. DOI: 10.3969/j.issn.1672-6731.2017.10.004



    Alina-Costina LUCA; Constantin IORDACHE; Mariana PĂGUȚE


    Involving systemic autoimmune diseases, they primarily affect the joints, muscles and connective tissues. Cardiovascular impairment is often common in these disease manifestations ranging from asymptomatic to life-situations in danger. Otherwise impaired cardiovascular reason may be the first presentation. This may require aggressive therapy immunosuppressed, therefore the diagnosis is very important for a good choice of therapy. This article discusses the cardiovascular manifestations of sys...

  17. Helminth Immunomodulation in Autoimmune Disease


    John J. Miles; John J. Miles; John J. Miles; John J. Miles; Taylor B. Smallwood; Paul R. Giacomin; Alex Loukas; Jason P. Mulvenna; Jason P. Mulvenna; Jason P. Mulvenna; Richard J. Clark


    Helminths have evolved to become experts at subverting immune surveillance. Through potent and persistent immune tempering, helminths can remain undetected in human tissues for decades. Redirecting the immunomodulating “talents” of helminths to treat inflammatory human diseases is receiving intensive interest. Here, we review therapies using live parasitic worms, worm secretions, and worm-derived synthetic molecules to treat autoimmune disease. We review helminth therapy in both mouse models ...

  18. Migraine in Systemic Autoimmune Diseases. (United States)

    Cinzia, Cavestro; Marcella, Ferrero


    Migraine and systemic autoimmune diseases are 2-3-fold more common in women and various studies have reported an association between the two pathologies. This review takes into account epidemiological studies involving migraine and systemic lupus erythematosus, antiphospholipid syndrome, Sjogren's syndrome, and other diffuse connective tissue diseases. This scientific literature analysis consists of the main articles found in Medline with a search up to April 2017. Many epidemiological studies were carried out on patients suffering from systemic lupus erythematosus. Results showed that headache and migraine are more prevalent in systemic lupus erythematosus patients compared to controls, especially migraine with aura. Patients with Lupus and migraine show a higher lupus activity and association with Raynaud and/or antiphospholipids in these populations are contradictory. There are not enough data to establish an association between antiphospholipid syndrome and migraine. However, data are more consistent between antiphospholipid carrier condition and migraine. Systemic sclerosis is a rare disease, for this reason the amount of available data on this disorder are scanty. However, some studies reported an association between headache, migraine and systemic sclerosis, especially where gliotic brain lesions and Raynaud are coexisting. Finally, large propensity cohort population based studies suggested that systemic autoimmune diseases are more frequent in patients suffering from migraine. An attempt at explaining the possible link between these disorders and migraine is discussed at the end of the review. Several autoimmune alterations are shared by most autoimmune diseases and headache types. Endothelial dysfunction is the only alteration that is common among all these disorders. Copyright© Bentham Science Publishers; For any queries, please email at

  19. Proteomics and Autoimmune Kidney Disease


    Rovin, Brad H; Klein, Jon B.


    Proteomics has long been considered an ideal platform, and urine an ideal source for biomarker discovery in human autoimmune kidney diseases. A number of studies have examined the urine proteome to identify biomarkers of disease activity, kidney pathology, and response to therapy. Increasingly, proteomic studies of kidney disease have expanded to include blood, circulating cells and kidney tissue. Recently the clinical potential of renal proteomics has been realized through a handful of inves...

  20. Autoimmune Thyroiditis and Myasthenia Gravis

    Directory of Open Access Journals (Sweden)

    Angela Lopomo


    Full Text Available Autoimmune diseases (AIDs are the result of specific immune responses directed against structures of the self. In normal conditions, the molecules recognized as “self” are tolerated by immune system, but when the self-tolerance is lost, the immune system could react against molecules from the body, causing the loss of self-tolerance, and subsequently the onset of AID that differs for organ target and etiology. Autoimmune thyroid disease (ATD is caused by the development of autoimmunity against thyroid antigens and comprises Hashimoto’s thyroiditis and Graves disease. They are frequently associated with other organ or non-organ specific AIDs, such as myasthenia gravis (MG. In fact, ATD seems to be the most associated pathology to MG. The etiology of both diseases is multifactorial and it is due to genetic and environmental factors, and each of them has specific characteristics. The two pathologies show many commonalities, such as the organ-specificity with a clear pathogenic effect of antibodies, the pathological mechanisms, such as deregulation of the immune system and the implication of the genetic predisposition. They also show some differences, such as the mode of action of the antibodies and therapies. In this review that focuses on ATD and MG, the common features and the differences between the two diseases are discussed.

  1. Vitamin D and autoimmune diseases

    Directory of Open Access Journals (Sweden)

    E. A. Potrokhova


    Full Text Available The review discusses the effect of vitamin D on the tolerogenic modulation of an immune response, its relationship to cells of the monocyte-macrophage series, including dendritic cells, monocytes, and macrophages, in the context of the impact of the expression of anti-inflammatory proinflammatory cytokines in some autoimmune diseases (rheumatoid arthritis, systemic scleroderma, multiple sclerosis, type 1 diabetes mellitus, systemic lupus erythematosus, and Crohn`s disease. It discusses the role of vitamin D in the development of innate and adaptive immunity. Despite some conflicting evidence, the immune regulatory function of vitamin D is generally directed toward inhibition of the components of innate and acquired immunity, which are responsible for the induction of autoimmune reactions; in this connection there are a growing number of publications devoted to the issues of vitamin D supplementation in patients with autoimmune diseases, the preventive effect of vitamin D intake on the risk of an abnormality and that of therapeutic doses of the vitamin on its course. The maintenance of the threshold value for serum 25(OHD3 at least 30 ng/ml, which is achieved by the intake of about 2000 IU of vitamin D, is shown to be required for its immune regulatory function. The data given raise the question as to whether it is necessity to revise the Russian recommended daily dietary allowances for vitamin D through its infant food fortification.

  2. Human Cytomegalovirus and Autoimmune Disease (United States)


    Human cytomegalovirus (HCMV) represents a prototypic pathogenic member of the β-subgroup of the herpesvirus family. A range of HCMV features like its lytic replication in multiple tissues, the lifelong persistence through periods of latency and intermitting reactivation, the extraordinary large proteome, and extensive manipulation of adaptive and innate immunity make HCMV a high profile candidate for involvement in autoimmune disorders. We surveyed the available literature for reports on HCMV association with onset or exacerbation of autoimmune disease. A causative linkage between HCMV and systemic lupus erythematosus (SLE), systemic sclerosis (SSc), diabetes mellitus type 1, and rheumatoid arthritis (RA) is suggested by the literature. However, a clear association of HCMV seroprevalence and disease could not be established, leaving the question open whether HCMV could play a coresponsible role for onset of disease. For convincing conclusions population-based prospective studies must be performed in the future. Specific immunopathogenic mechanisms by which HCMV could contribute to the course of autoimmune disease have been suggested, for example, molecular mimicry by UL94 in SSc and UL83/pp65 in SLE patients, as well as aggravation of joint inflammation by induction and expansion of CD4+/CD28− T-cells in RA patients. Further studies are needed to validate these findings and to lay the grounds for targeted therapeutic intervention. PMID:24967373

  3. Human Cytomegalovirus and Autoimmune Disease

    Directory of Open Access Journals (Sweden)

    Anne Halenius


    Full Text Available Human cytomegalovirus (HCMV represents a prototypic pathogenic member of the β-subgroup of the herpesvirus family. A range of HCMV features like its lytic replication in multiple tissues, the lifelong persistence through periods of latency and intermitting reactivation, the extraordinary large proteome, and extensive manipulation of adaptive and innate immunity make HCMV a high profile candidate for involvement in autoimmune disorders. We surveyed the available literature for reports on HCMV association with onset or exacerbation of autoimmune disease. A causative linkage between HCMV and systemic lupus erythematosus (SLE, systemic sclerosis (SSc, diabetes mellitus type 1, and rheumatoid arthritis (RA is suggested by the literature. However, a clear association of HCMV seroprevalence and disease could not be established, leaving the question open whether HCMV could play a coresponsible role for onset of disease. For convincing conclusions population-based prospective studies must be performed in the future. Specific immunopathogenic mechanisms by which HCMV could contribute to the course of autoimmune disease have been suggested, for example, molecular mimicry by UL94 in SSc and UL83/pp65 in SLE patients, as well as aggravation of joint inflammation by induction and expansion of CD4+/CD28− T-cells in RA patients. Further studies are needed to validate these findings and to lay the grounds for targeted therapeutic intervention.

  4. Association of bullous pemphigoid with malignancy: A myth or reality?

    Directory of Open Access Journals (Sweden)

    Joycelin Fernandes


    Full Text Available Bullous pemphigoid (BP is an autoimmune sub-epidermal blistering disorder of the skin. The association of BP with internal malignancy has always been a matter of debate with no consensus reached despite many published case reports and clinical trials. However, we report a hitherto unreported association of BP with squamous cell carcinoma of the tongue, wherein the patient had a recalcitrant downhill course despite adequate treatment measures with control of skin lesions being achieved only following excision of the tumor, and relapse coinciding with detection of metastasis. Hence, given the clinical behavior, it is reasonable to speculate that the association of malignancy was more than co-incidental.

  5. Vitamin D in autoimmune liver disease. (United States)

    Smyk, Daniel S; Orfanidou, Timoklia; Invernizzi, Pietro; Bogdanos, Dimitrios P; Lenzi, Marco


    The development of autoimmune disease is based on the interaction of genetic susceptibility and environmental causes. Environmental factors include infectious and non-infectious agents, with some of these factors being implicated in several autoimmune diseases. Vitamin D is now believed to play a role in the development (or prevention) of several autoimmune diseases, based on its immunomodulatory properties. As well, the increasing incidence of autoimmune disease as one moves away from the equator, may be due to the lack of sunlight, which is crucial for the maintenance of normal vitamin D levels. A deficiency in vitamin D levels or vitamin D receptors is commonly indicated in autoimmune diseases, with multiple sclerosis (MS) being one of the best-studied and well-known examples. However, the role of vitamin D in other autoimmune diseases is not well defined, including autoimmune liver diseases such as primary biliary cirrhosis, autoimmune hepatitis, and primary sclerosing cholangitis. This review will examine the role of vitamin D as an immunomodulator, followed by a comparison of vitamin D in MS versus autoimmune liver disease. From this comparison, it will become clear that vitamin D likely plays a role in the development of autoimmune liver disease, but this area requires further investigation. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  6. Vimentin may reflect areas of pathologic involvement in biopsies from patients with autoimmune skin diseases

    Directory of Open Access Journals (Sweden)

    Ana Maria Abreu Velez


    Full Text Available Introduction: Autoimmune bullous skin diseases (ABDs represent a group of disorders of the skin and mucosa commonly associated with deposits of immunoglobulins, complement and fibrinogen, and usually directed against distinct adhesion molecules. After studing these diseases for many years, we noted alterations not only between the cells junctions of the epidermis and/or the dermal/epidermal junction, but also in dermal skin appendageal structures and in mesenchymal tissue around the blisters. Based on our findings, we wanted to determine if the observed patterns of autoimmunity correlated with cutaneous vimentin expression. Materials and Methods: Archival biopsies previously diagnosed with ABDs by clinical, hematoxylin and eosin (H&E and direct and/or immunofluorescence data were stained with antibodies directed against vimentin via immunohistochemistry (IHC. We tested 30 patients affected by endemic pemphigus, 30 controls from the endemic area, and 15 normal controls. We also tested 30 biopsies from patients with bullous pemphigoid (BP, 20 with pemphigus vulgaris (PV, 8 with pemphigus foliaceus, 14 with dermatitis herpetiformis (DH and 3 with Senear-Usher syndrome. Results: The H&E, DIF and vimentin patterns of positivity in the different ABDs confirmed that vimentin was compartmentalized around areas of dermal inflammation, around skin appendages and in epidermal, dermal and mesenchymal cell junction areas. Conclusion: Vimentin may be a useful tool for highlighting patterns of microenvironmental tissue alteration in multiple ABDs. The vimentin staining pattern observed was analogous to that we have previously described for proteases and protease inhibitors in patients affected by ABDs, expanding the concept that the autoimmune process extends beyond cell junctions.

  7. [Pulmonary arterial hypertension: a flavor of autoimmunity]. (United States)

    Perros, Frédéric; Humbert, Marc; Cohen-Kaminsky, Sylvia


    It is admitted that autoimmunity results from a combination of risks such as genetic background, environmental triggers, and stochastic events. Pulmonary arterial hypertension (PAH) shares with the so-called prototypic autoimmune diseases, genetic risk factors, female predominance and sex hormone influence, association with other chronic inflammatory and autoimmune diseases, defects in regulatory T cells function, and presence of autoantibodies. Case reports have been published indicating the beneficial effect of some immunosuppressive and anti-inflammatory therapies in PAH, supporting the potential role of immune mechanisms in the pathophysiology of the disease. In this review, we discuss the current knowledge on autoimmune mechanisms operating in PAH, especially mounting a local autoimmune response inside the pulmonary tissue, namely pulmonary lymphoid neogenesis. A better understanding of the role of autoimmunity in pulmonary vascular remodelling may help develop targeted immunomodulatory strategies in PAH. © 2013 médecine/sciences – Inserm.

  8. Sex-based differences in autoimmune diseases. (United States)

    Ortona, Elena; Pierdominici, Marina; Maselli, Angela; Veroni, Caterina; Aloisi, Francesca; Shoenfeld, Yehuda


    Autoimmune diseases are characterized by an exaggerated immune response leading to damage and dysfunction of specific or multiple organs and tissues. Most autoimmune diseases are more prevalent in women than in men. Symptom severity, disease course, response to therapy and overall survival may also differ between males and females with autoimmune diseases. Sex hormones have a crucial role in this sex bias, with estrogens being potent stimulators of autoimmunity and androgens playing a protective role. Accumulating evidence indicates that genetic, epigenetic and environmental factors may also contribute to sex-related differences in risk and clinical course of autoimmune diseases. In this review, we discuss possible mechanisms for sex specific differences in autoimmunity with a special focus on three paradigmatic diseases: systemic lupus erythematosus, rheumatoid arthritis, and multiple sclerosis.

  9. Vitiligo associated with other autoimmune diseases: polyglandular autoimmune syndrome types 3B+C and 4. (United States)

    Amerio, P; Tracanna, M; De Remigis, P; Betterle, C; Vianale, L; Marra, M E; Di Rollo, D; Capizzi, R; Feliciani, C; Tulli, A


    Vitiligo is a common skin disease characterized by depigmented maculae resulting from a reduction of the number and function of melanocytes. Many studies suggest that vitiligo might be an autoimmune disease. Vitiligo has been frequently described in association with other autoimmune diseases. Among the diseases described in association with vitiligo are the so-called autoimmune polyglandular syndromes (APS). Vitiligo can be present in all types of APS but the most frequent association appears to be in APS-3. APS-3 was defined as the association between autoimmune thyroiditis and another autoimmune disease. Here we report one patient with thyroiditis, vitiligo and autoimmune gastritis (APS-3B+C), one patient with chronic autoimmune thyroiditis, vitiligo and alopecia (APS-3C), and one case of a young patient with type 1 diabetes mellitus and vitiligo (APS-4), according to the newest classification. We stress the importance of a thorough assessment for autoimmune diseases in selected patients with vitiligo.

  10. Microbiota and Autoimmunity: exploring new avenues


    Yurkovetskiy, Leonid; Pickard, Joseph M.; Chervonsky, Alexander V.


    Given the recognized role of the commensal microbiota in regulating host immunity to pathogens, it is not surprising that microbiota are also capable of regulating autoimmune responses. The underlying mechanisms of autoimmune regulation by the microbiota are just beginning to emerge. Here, we discuss possible pressure points towards the development of autoimmune diseases that can be influenced by the microbiota. Besides acting on the adaptive and innate arms of the immune response, the microb...

  11. Recurrent Oral Inflammation in Autoimmune Lymphoproliferative Syndrome


    Pac, Malgorzata; Olczak-Kowalczyk, Dorota; Wolska-Kuśnierz, Beata; Piątosa, Barbara; Górska, Renata; Bernatowska, Ewa


    Abstract   Background and aim: Autoimmune lymphoproliferative syndrome (ALPS) is a disorder of abnormal lymphocyte survival caused by dysregulation of the Fas apoptotic pathway. In ALPS defective lymphocyte apoptosis manifests as a chronic, nonmalignant lymphadenopathy and/or splenomegaly/hepatosplenomegaly, expansion of double negative T cell (DNTC) – CD4-CD8-TCRαβ+ T cells, autoimmune cytopenias and other autoimmune diseases.  Patients demonstrate oral lesions which have not yet been repo...

  12. Role of Complement in Autoimmune Hemolytic Anemia


    Berentsen, Sigbj?rn


    Summary The classification of autoimmune hemolytic anemias and the complement system are reviewed. In autoimmune hemolytic anemia of the warm antibody type, complement-mediated cell lysis is clinically relevant in a proportion of the patients but is hardly essential for hemolysis in most patients. Cold antibody-mediated autoimmune hemolytic anemias (primary cold agglutinin disease, secondary cold agglutinin syndrome and paroxysmal cold hemoglobinuria) are entirely complement-mediated disorder...

  13. Castleman disease and associated autoimmune disease. (United States)

    Muskardin, Theresa W; Peterson, Bruce A; Molitor, Jerry A


    Castleman disease can occur in association with autoimmune connective tissue disease and confound the clinical picture, resulting in delayed diagnosis and suboptimal treatment. This review focuses on the intersection of Castleman disease and autoimmunity with an emphasis on shared pathology and mutually beneficial treatments. Targeting CD-20, interleukin-6, and the nuclear factor-κB pathway has shown promise in achieving long-term remission in patients with Castleman disease and associated autoimmune features. Advances in understanding of pathogenic cell types and cytokines in Castleman disease have allowed the development of targeted therapies successful in the treatment of both Castleman disease and associated autoimmune disease.

  14. Autoimmune hepatitis/primary biliary cirrhosis overlap syndrome and associated extrahepatic autoimmune diseases. (United States)

    Efe, Cumali; Wahlin, Staffan; Ozaslan, Ersan; Berlot, Alexandra Heurgue; Purnak, Tugrul; Muratori, Luigi; Quarneti, Chiara; Yüksel, Osman; Thiéfin, Gérard; Muratori, Paolo


    To assess the prevalence of concurrent extrahepatic autoimmune diseases in patients with autoimmune hepatitis (AIH)/primary biliary cirrhosis (PBC) overlap syndrome and applicability of the 'mosaic of autoimmunity' in these patients. The medical data of 71 AIH/PBC overlap patients were evaluated for associated autoimmune diseases. In the study population, 31 (43.6%) patients had extrahepatic autoimmune diseases, including autoimmune thyroid diseases (13 patients, 18.3%), Sjögren syndrome (six patients, 8.4%), celiac disease (three patients, 4.2%), psoriasis (three patients, 4.2%), rheumatoid arthritis (three patients, 4.2%), vitiligo (two patients, 2.8%), and systemic lupus erythematosus (two patients, 2.8%). Autoimmune hemolytic anemia, antiphospholipid syndrome, multiple sclerosis, membranous glomerulonephritis, sarcoidosis, systemic sclerosis, and temporal arteritis were identified in one patient each (1.4%). A total of 181 autoimmune disease diagnoses were found in our patients. Among them, 40 patients (56.4%) had two, 23 (32.3%) had three, and eight (11.3%) had four diagnosed autoimmune diseases. A large number of autoimmune diseases were associated with AIH/PBC overlap patients. Therefore, extended screening for existing autoimmune diseases during the routine assessment of these patients is recommended. Our study suggests that the concept of 'mosaic of autoimmunity' is a valid clinical entity that is applicable to patients with AIH/PBC overlap syndrome.

  15. Heat shock protein 90 inhibition: A potential double- or triple-edged sword in the treatment of mucous membrane pemphigoid. (United States)

    Kasperkiewicz, Michael; Płatkowska, Anna; Zalewska, Anna; Zillikens, Detlef


    Mucous membrane pemphigoid (MMP) is a subtype of autoimmune subepidermal blistering diseases characterized by autoantibodies to structural components of the hemidesmosome primarily affecting mucous membranes. Inflammation-related progressive scarring can lead to serious complications, including blindness, and the disease may be associated with malignancy. Conventional immunosuppressive treatment is often insufficiently effective and limited due to side effects, warranting new therapeutic options ideally targeting both inflammation and extensively recalcitrant cicatrization. Heat shock protein 90 (Hsp90) is a cell stress-inducible chaperone required for the function of a large number of client proteins, and its pharmacological inhibition has proven to be effective and relatively safe in patients with cancer. Recent observations also suggest a promising role of Hsp90 as drug target in preclinical in vivo murine models of autoimmune diseases such as subepidermal bullous and fibrotic autoimmune disorders comprising epidermolysis bullosa acquisita and systemic sclerosis, respectively, which exhibit some pathophysiological features reminiscent of MMP. This article thus hypothesizes that Hsp90 blockade could represent a double-edged sword in MMP treatment by targeting pathogenic factors of inflammatory blister and fibrosis formation. Moreover, Hsp90 inhibitors could even be proclaimed as a triple-edged sword in case of an underlying malignancy. Future studies investigating the role of Hsp90 in MMP are needed to clarify whether Hsp90 inhibition could become a novel treatment approach for patients with this potentially devastating disease. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Association between autoimmune pancreatitis and systemic autoimmune diseases. (United States)

    Terzin, Viktória; Földesi, Imre; Kovács, László; Pokorny, Gyula; Wittmann, Tibor; Czakó, László


    To investigate the association between autoimmune pancreatitis (AIP) and systemic autoimmune diseases (SAIDs) by measurement of serum immunoglobulin G4 (IgG4). The serum level of IgG4 was measured in 61 patients with SAIDs of different types who had not yet participated in glucocorticosteroid treatment. Patients with an elevated IgG4 level were examined by abdominal ultrasonography (US) and, in some cases, by computer tomography (CT). Elevated serum IgG4 levels (919 ± 996 mg/L) were detected in 17 (28%) of the 61 SAID patients. 10 patients had Sjögren's syndrome (SS) (IgG4: 590 ± 232 mg/L), 2 of them in association with Hashimoto's thyroiditis, and 7 patients (IgG4: 1388 ± 985.5 mg/L) had systemic lupus erythematosus (SLE). The IgG4 level in the SLE patients and that in patients with SS were not significantly different from that in AIP patients (783 ± 522 mg/L). Abdominal US and CT did not reveal any characteristic features of AIP among the SAID patients with an elevated IgG4 level. The serum IgG4 level may be elevated in SAIDs without the presence of AIP. The determination of serum IgG4 does not seem to be suitable for the differentiation between IgG4-related diseases and SAIDs.

  17. Autoimmune pancreatitis--recent advances. (United States)

    Novotný, I; Díte, P; Lata, J; Nechutová, H; Kianicka, B


    Autoimmune pancreatitis (AIP) is recognized as a distinct clinical entity, identified as a chronic inflammatory process of the pancreas in which the autoimmune mechanism is involved. Clinically and histologically, AIP has two subsets: type 1--lymphoplasmatic sclerosing pancreatitis with abundant infiltration of the pancreas and other affected organs with immunoglobulin G4-positive plasma cells, and type 2--duct centric fibrosis, characterized by granulocyte epithelial lesions in the pancreas without systemic involvement. In the diagnosis of AIP, two diagnostic criterions are used--the HISORt criteria and Asian Diagnostic Criteria. In the differential diagnosis, the pancreatic cancer must be excluded by endosonographically guided pancreatic biopsy. Typical signs of AIP are concomitant disorders in other organs (kidney, liver, biliary tract, salivary glands, colon, retroperitoneum, prostate). Novel clinicopathological entity was proposed as an 'IgG4-related sclerosing disease' (IgG4-RSC). Extensive IgG4-positive plasma cells and T lymphocyte infiltration is a common characteristics of this disease. Recently, IgG4-RSC syndrome was extended to a new entity, characterized by IgG4 hypergammaglobulinemia and IgG4-positive plasma cell infiltration, this being considered an expression of a lymphoproliferative disease, 'IgG4-positive multiorgan lymphoproliferative syndrome'. This syndrome includes Mikulicz's disease, mediastinal fibrosis, autoimmune hypophysitis, and inflammatory pseudotumor--lung, liver, breast. In the therapy of AIP, steroids constitute first-choice treatment. High response to the corticosteroid therapy is an important diagnostic criterion. In the literature, there are no case-control studies that determine if AIP predisposes to pancreatic cancer. Undoubtedly, AIP is currently a hot topic in pancreatology. Copyright (c) 2010 S. Karger AG, Basel.

  18. Autoimmune atrophic gastritis: current perspectives

    Directory of Open Access Journals (Sweden)

    Minalyan A


    Full Text Available Artem Minalyan,1 Jihane N Benhammou,1 Aida Artashesyan,1 Michael S Lewis,2 Joseph R Pisegna1 1Division of Gastroenterology, Hepatology and Parenteral Nutrition, 2Department of Pathology and Laboratory Medicine, VA Greater Los Angeles Healthcare System, Los Angeles, CA, USA Abstract: At present there is no universally accepted classification for gastritis. The first successful classification (The Sydney System that is still commonly used by medical professionals was first introduced by Misiewicz et al in Sydney in 1990. In fact, it was the first detailed classification after the discovery of Helicobacter pylori by Warren and Marshall in 1982. In 1994, the Updated Sydney System was proposed during the International Workshop on the Histopathology of Gastritis followed by the publication in The American Journal of Surgical Pathology by Dixon et al. Using the new classification, distinction between atrophic and nonatrophic gastritis was revised, and the visual scale grading was incorporated. According to the Updated Sydney System Classification, atrophic gastritis is categorized into multifocal (H. pylori, environmental factors, specific diet and corpus-predominant (autoimmune. Since metaplasia is a key histological characteristic in patients with atrophic gastritis, it has been recommended to use the word “metaplastic” in both variants of atrophic gastritis: autoimmune metaplastic atrophic gastritis (AMAG and environmental metaplastic atrophic gastritis. Although there are many overlaps in the course of the disease and distinction between those two entities may be challenging, the aim of this review article was to describe the etiology, epidemiology, pathogenesis, diagnosis, clinical manifestations and treatment in patients with AMAG. However, it is important to mention that H. pylori is the most common etiologic factor for the development of gastritis in the world. Keywords: autoimmune gastritis, pernicious anemia, gastric carcinoid

  19. Helminth Immunomodulation in Autoimmune Disease. (United States)

    Smallwood, Taylor B; Giacomin, Paul R; Loukas, Alex; Mulvenna, Jason P; Clark, Richard J; Miles, John J


    Helminths have evolved to become experts at subverting immune surveillance. Through potent and persistent immune tempering, helminths can remain undetected in human tissues for decades. Redirecting the immunomodulating "talents" of helminths to treat inflammatory human diseases is receiving intensive interest. Here, we review therapies using live parasitic worms, worm secretions, and worm-derived synthetic molecules to treat autoimmune disease. We review helminth therapy in both mouse models and clinical trials and discuss what is known on mechanisms of action. We also highlight current progress in characterizing promising new immunomodulatory molecules found in excretory/secretory products of helminths and their potential use as immunotherapies for acute and chronic inflammatory diseases.

  20. [Narcolepsy as an autoimmune disease]. (United States)

    Sarkanen, Tomi; Vaarala, Outi; Julkunen, Ilkka; Partinen, Markku


    Narcolepsy is a sleep disorder of central origin. Hypocretin deficiency is the essential feature of type 1 narcolepsy. The biological background of type 2 narcolepsy (without cataplexy) is less clear. Infections or other external factors are thought to function as triggers of narcolepsy. After the H1N1 vaccination campaign, the incidence of narcolepsy increased clearly in countries where a vaccine boosted with the AS03 adjuvant was used. According to the current view, the increase of narcolepsy in connection with the pandemic vaccine especially in children and adolescents was associated with the virus component of the vaccine, but the adjuvant may also have boosted the development of autoimmune response.

  1. Autoimmune Cytopenias In Common Variable Immunodeficiency (CVID

    Directory of Open Access Journals (Sweden)

    Roshini Sarah Abraham


    Full Text Available Common variable immunodeficiency (CVID is a humoral immunodeficiency whose primary diagnostic features include hypogammaglobulinemia involving two or more immunoglobulin isotypes and impaired functional antibody responses in the majority of patients. While increased susceptibility to respiratory and other infections is a common thread that binds a large cross-section of CVID patients, the presence of autoimmune complications in this immunologically and clinically heterogeneous disorder is recognized in up to two-thirds of patients. Among the autoimmune manifestations reported in CVID (20-50%(Chapel et al., 2008;Cunningham-Rundles, 2008, autoimmune cytopenias are by far the most common occurring variably in 4-20% (Michel et al., 2004;Chapel et al., 2008 of these patients who have some form of autoimmunity. Association of autoimmune cytopenias with granulomatous disease and splenomegaly has been reported. The spectrum of autoimmune cytopenias includes thrombocytopenia, anemia and neutropenia. While it may seem paradoxical prima facie that autoimmunity is present in patients with primary immune deficiencies, in reality, it could be considered two sides of the same coin, each reflecting a different but inter-connected facet of immune dysregulation. The expansion of CD21low B cells in CVID patients with autoimmune cytopenias and other autoimmune features has also been previously reported. It has been demonstrated that this unique subset of B cells is enriched for autoreactive germline antibodies. Further, a correlation has been observed between various B cell subsets, such as class-switched memory B cells and plasmablasts, and autoimmunity in CVID. This review attempts to explore the most recent concepts and highlights, along with treatment of autoimmune hematological manifestations of CVID.

  2. Susceptibility Genes in Thyroid Autoimmunity

    Directory of Open Access Journals (Sweden)

    Yoshiyuki Ban


    Full Text Available The autoimmune thyroid diseases (AITD are complex diseases which are caused by an interaction between susceptibility genes and environmental triggers. Genetic susceptibility in combination with external factors (e.g. dietary iodine is believed to initiate the autoimmune response to thyroid antigens. Abundant epidemiological data, including family and twin studies, point to a strong genetic influence on the development of AITD. Various techniques have been employed to identify the genes contributing to the etiology of AITD, including candidate gene analysis and whole genome screening. These studies have enabled the identification of several loci (genetic regions that are linked with AITD, and in some of these loci, putative AITD susceptibility genes have been identified. Some of these genes/loci are unique to Graves' disease (GD and Hashimoto's thyroiditis (HT and some are common to both the diseases, indicating that there is a shared genetic susceptibility to GD and HT. The putative GD and HT susceptibility genes include both immune modifying genes (e.g. HLA, CTLA-4 and thyroid specific genes (e.g. TSHR, Tg. Most likely, these loci interact and their interactions may influence disease phenotype and severity.

  3. Epigenetic histone code and autoimmunity. (United States)

    Dieker, Jürgen; Muller, Sylviane


    The multiple inter-dependent post-translational modifications of histones represent fine regulators of chromatin dynamics. These covalent modifications, including phosphorylation, acetylation, ubiquitination, deimination, and methylation, affect therefore the numerous processes involving chromatin, such as replication, repair, transcription, genome stability, and cell death. Specific enzymes introducing modified residues in histones are precisely regulated, and a single amino acid residue can be subjected to a single or several, independent modifications. Disruption of histone post-translational modifications perturbs the pattern of gene expression, which may result in disease manifestations. It has become evident in recent years that apoptosis-modified histones exert a central role in the induction of autoimmunity, for example in systemic lupus erythematosus and rheumatoid arthritis. Certain histone post-translational modifications are linked to cell death (apoptotic and non-apoptotic cell death) and might be involved in lupus in the activation of normally tolerant lymphocyte subpopulations. In this review, we discuss how these modifications can affect the antigenicity and immunogenicity of histones with potential consequences in the pathogenesis of autoimmune diseases.

  4. Methylthioadenosine reverses brain autoimmune disease. (United States)

    Moreno, Beatriz; Hevia, Henar; Santamaria, Monica; Sepulcre, Jorge; Muñoz, Javier; García-Trevijano, Elena R; Berasain, Carmen; Corrales, Fernando J; Avila, Matias A; Villoslada, Pablo


    To assess the immunomodulatory activity of methylthioadenosine (MTA) in rodent experimental autoimmune encephalomyelitis (EAE) and in patients with multiple sclerosis. We studied the effect of intraperitoneal MTA in the acute and chronic EAE model by quantifying clinical and histological scores and by performing immunohistochemistry stains of the brain. We studied the immunomodulatory effect of MTA in lymphocytes from EAE animals and in peripheral blood mononuclear cells from healthy control subjects and multiple sclerosis patients by assessing cell proliferation and cytokine gene expression, by real-time polymerase chain reaction, and by nuclear factor-kappaB modulation by Western blot. We found that MTA prevents acute EAE and, more importantly, reverses chronic-relapsing EAE. MTA treatment markedly inhibited brain inflammation and reduced brain damage. Administration of MTA suppressed T-cell activation in vivo and in vitro, likely through a blockade in T-cell signaling resulting in the prevention of inhibitor of kappa B (IkappaB-alpha) degradation and in the impaired activation transcription factor nuclear factor-kappaB. Indeed, MTA suppressed the production of proinflammatory genes and cytokines (interferon-gamma, tumor necrosis factor-alpha, and inducible nitric oxide synthase) and increased the production of antiinflammatory cytokines (interleukin-10). MTA has a remarkable immunomodulatory activity and may be beneficial for multiple sclerosis and other autoimmune diseases.

  5. Warm antibody autoimmune hemolytic anemia. (United States)

    Kalfa, Theodosia A


    Autoimmune hemolytic anemia (AIHA) is a rare and heterogeneous disease that affects 1 to 3/100 000 patients per year. AIHA caused by warm autoantibodies (w-AIHA), ie, antibodies that react with their antigens on the red blood cell optimally at 37°C, is the most common type, comprising ∼70% to 80% of all adult cases and ∼50% of pediatric cases. About half of the w-AIHA cases are called primary because no specific etiology can be found, whereas the rest are secondary to other recognizable underlying disorders. This review will focus on the postulated immunopathogenetic mechanisms in idiopathic and secondary w-AIHA and report on the rare cases of direct antiglobulin test-negative AIHA, which are even more likely to be fatal because of inherent characteristics of the causative antibodies, as well as because of delays in diagnosis and initiation of appropriate treatment. Then, the characteristics of w-AIHA associated with genetically defined immune dysregulation disorders and special considerations on its management will be discussed. Finally, the standard treatment options and newer therapeutic approaches for this chronic autoimmune blood disorder will be reviewed. © 2016 by The American Society of Hematology. All rights reserved.

  6. Cardiovascular Involvement in Autoimmune Diseases (United States)

    Amaya-Amaya, Jenny


    Autoimmune diseases (AD) represent a broad spectrum of chronic conditions that may afflict specific target organs or multiple systems with a significant burden on quality of life. These conditions have common mechanisms including genetic and epigenetics factors, gender disparity, environmental triggers, pathophysiological abnormalities, and certain subphenotypes. Atherosclerosis (AT) was once considered to be a degenerative disease that was an inevitable consequence of aging. However, research in the last three decades has shown that AT is not degenerative or inevitable. It is an autoimmune-inflammatory disease associated with infectious and inflammatory factors characterized by lipoprotein metabolism alteration that leads to immune system activation with the consequent proliferation of smooth muscle cells, narrowing arteries, and atheroma formation. Both humoral and cellular immune mechanisms have been proposed to participate in the onset and progression of AT. Several risk factors, known as classic risk factors, have been described. Interestingly, the excessive cardiovascular events observed in patients with ADs are not fully explained by these factors. Several novel risk factors contribute to the development of premature vascular damage. In this review, we discuss our current understanding of how traditional and nontraditional risk factors contribute to pathogenesis of CVD in AD. PMID:25177690

  7. Autoimmune hepatitis and juvenile systemic lupus erythematosus

    NARCIS (Netherlands)

    Deen, M. E. J.; Porta, G.; Fiorot, F. J.; Campos, L. M. A.; Sallum, A. M. E.; Silva, C. A. A.

    Juvenile systemic lupus erythematosus (JSLE) and autoimmune hepatitis (AIH) are both autoimmune disorders that are rare in children and have a widespread clinical manifestation. A few case reports have shown a JSLE-AIH associated disorder. To our knowledge, this is the first study that

  8. Chronic autoimmune urticaria : Where we stand ?

    Directory of Open Access Journals (Sweden)

    Goh C


    Full Text Available It is well-recognized that 30-40% of chronic idiopathic urticaria is autoimmune in nature. Chronic autoimmune urticaria is caused by anti-FcåRI and less frequently, by anti-IgE autoantibodies that lead to mast cell and basophil activation, thereby giving rise to the release of histamine and other proinflammatory mediators. Activation of the classical complement pathway and formation of C5a are important in dermal mast cell activation. C5a is also a neutrophil and eosinophil chemoattractant. Chronic autoimmune urticaria has been found to be associated with autoimmune thyroid disease. The autologous serum skin test is used as a screening test for chronic autoimmune urticaria and has a sensitivity and specificity of about 70 and 80%, respectively. The current gold standard diagnostic test is the basophil histamine release assay. The treatment of chronic autoimmune urticaria, as in chronic idiopathic urticaria, is with H1 antihistamines. Oral corticosteroids may be used during acute flares. Refractory cases have been shown to respond to cyclosporine and other immunomodulators. The prevalence of chronic autoimmune urticaria in Singapore is similar to that reported in Western countries at about 42%. The presence of thyroid autoimmunity appears to be higher than reported, with 22.5% of patients with chronic idiopathic urticaria here, exhibiting presence of thyroid autoantibodies.

  9. Autoimmune disease and subsequent urological cancer. (United States)

    Liu, Xiangdong; Ji, Jianguang; Forsti, Asta; Sundquist, Kristina; Sundquist, Jan; Hemminki, Kari


    We examined the subsequent risk and prognosis of urological cancer in individuals diagnosed with autoimmune disease. We systematically analyzed the risk and prognosis of prostate, kidney and bladder cancers in individuals diagnosed with any of 33 autoimmune diseases based on a national Swedish database for 1964 through 2008. The SIR and HR were calculated for subsequent urological cancers between 1964 and 2008 in individuals hospitalized for autoimmune disease. An increased SIR for urological cancer was recorded after 26 autoimmune diseases. An increased HR for cancer specific survival was noted after 4 autoimmune diseases and for overall survival after 18. The highest SIRs were seen for kidney cancer after polyarteritis nodosa (2.85) and polymyositis/dermatomyositis (2.68), and for bladder cancer after polymyositis/dermatomyositis (2.45). The highest risk of prostate cancer (1.70) was observed after polyarteritis nodosa. SIRs were lower during followup from 1990 to 2008 compared to the previous period. Individuals diagnosed with prostate and kidney cancers showed an improved cancer specific prognosis, in contrast to the poorer overall prognosis for all 3 urological cancers. The risk of urological cancer was increased after all autoimmune diseases. The most significant changes after individual autoimmune diseases were toward higher risk. Survival data were reassuring since autoimmune disease only marginally influences the prognosis of cancer specific mortality. However, overall survival was decreased for the 3 types of cancer. Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  10. Autoimmune diseases in adults with atopic dermatitis

    DEFF Research Database (Denmark)

    Andersen, Yuki M F; Egeberg, Alexander; Gislason, Gunnar H.


    Background: An increased susceptibility to autoimmune disease has been shown in patients with atopic dermatitis (AD), but data remain scarce and inconsistent. Objective: We examined the co-occurrence of selected autoimmune diseases in adult patients with AD. Methods: Nationwide health registers w...

  11. Autoimmune diseases in adults with atopic dermatitis. (United States)

    Andersen, Yuki M F; Egeberg, Alexander; Gislason, Gunnar H; Skov, Lone; Thyssen, Jacob P


    An increased susceptibility to autoimmune disease has been shown in patients with atopic dermatitis (AD), but data remain scarce and inconsistent. We examined the co-occurrence of selected autoimmune diseases in adult patients with AD. Nationwide health registers were used. Adult patients with a hospital diagnosis of AD in Denmark between 1997 and 2012 were included as cases (n = 8112) and matched with controls (n = 40,560). The occurrence of autoimmune diseases was compared in the 2 groups. Logistic regression was used to estimate odds ratios. AD was significantly associated with 11 of 22 examined autoimmune diseases. In addition, AD was associated with having multiple autoimmune comorbidities. Patients with a history of smoking had a significantly higher occurrence of autoimmune comorbidities compared to nonsmokers. This study was limited to adult patients with AD. No information about AD severity or degree of tobacco consumption was available. Results from a hospital population of AD patients cannot be generalized to the general population. Our results suggest a susceptibility of autoimmune diseases in adult patients with AD, especially in smokers. While we cannot conclude on causality based on these data, an increased awareness of autoimmune comorbidities in patients with AD may be warranted. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  12. Kaleidoscope of autoimmune diseases in HIV infection. (United States)

    Roszkiewicz, Justyna; Smolewska, Elzbieta


    Within the last 30 years, the human immunodeficiency virus (HIV) infection has changed its status from inevitably fatal to chronic disorder with limited impact on life span. However, this breakthrough was mainly the effect of introduction of the aggressive antiviral treatment, which has led to the clinically significant increase in CD4+ cell count, resulting in fewer cases of the acquired immunodeficiency syndrome (AIDS) and improved management of opportunistic infections occurring in the course of the disease. The occurrence of a particular autoimmune disease depends on degree of immunosuppression of the HIV-positive patient. In 2002, four stages of autoimmunity were proposed in patients infected by HIV, based on the absolute CD4+ cell count, feature of AIDS as well as on the presence of autoimmune diseases. Spectrum of autoimmune diseases associated with HIV infection seems to be unexpectedly wide, involving several organs, such as lungs (sarcoidosis), thyroid gland (Graves' disease), liver (autoimmune hepatitis), connective tissue (systemic lupus erythematosus, rheumatoid arthritis, polyarteritis nodosa and other types of vasculitis, antiphospholipid syndrome) or hematopoietic system (autoimmune cytopenias). This paper contains the state of art on possible coincidences between HIV infection and a differential types of autoimmune diseases, including the potential mechanisms of this phenomenon. As the clinical manifestations of autoimmunization often mimic those inscribed in the course of HIV infection, health care providers should be aware of this rare but potentially deadly association and actively seek for its symptoms in their patients.

  13. Gender and autoimmune comorbidity in multiple sclerosis

    DEFF Research Database (Denmark)

    Magyari, Melinda; Koch-Henriksen, Nils; Pfleger, Claudia C


    BACKGROUND: The female preponderance in incidence of multiple sclerosis (MS) calls for investigations into sex differences in comorbidity with other autoimmune diseases (ADs). OBJECTIVES: To determine whether male and female patients with MS have a higher frequency of autoimmune comorbidity than...

  14. Approaches to blister beetle control on millet: Botanical and biological agents, associational resistance, varietal resistance, and light and pheromone traps


    Touré, G.K.; Edwards, R.C.; Traoré, S.H.


    Metadata only record Several approaches to management of insect pests of pearl millet (Pennisetum americum) were compared in on-farm trials in four villages in north central Mali. Light traps were used for assessment of insect pest populations, installed in millet and fallow fields, and illuminated each night from 5 August to 14 October 1997. The blister beetles Psalydolytta spp. and Mylabris spp. reached their highest numbers in late August and early September, the same time period as in ...

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

    DEFF Research Database (Denmark)

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


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

  16. Effectiveness and side effects of anti-CD20 therapy for autoantibody-mediated blistering skin diseases: A comprehensive survey of 71 consecutive patients from the Initial use to 2007 (United States)

    Peterson, Jennifer D; Chan, Lawrence S


    In order to examine the efficacy and side effects of the monoclonal antibody anti-CD20 (rituximab) on autoimmune blistering skin diseases, we performed a comprehensive survey of 71 consecutive patients from initial use up to 2007, using the PubMed database. A heterogeneous group of patients, including 51 patients with pemphigus vulgaris, one with pemphigus vegetans, nine with pemphigus foliaceus, five with paraneoplastic pemphigus, four with epidermolysis bullosa acquisita, and one with both bullous pemphigoid and graft vs host disease was included in this survey. Overall the monoclonal antibody seems to be effective in that 69% of patients showed complete response, 25% of patients showed partial response, whereas 6% of patients showed progressive disease. Six deaths occurred in association with the treatment, with four of these deaths in patients with paraneoplastic pemphigus, a disease characteristically resistant to conventional medication and with a high mortality rate. Of note, 11 patients who received combined rituximab and intravenous immune globulin treatments had the best outcome: complete response without any serious side effects. Therefore further investigation on rituximab with controlled clinical trial is a worthy pursuit. PMID:19436603

  17. Molecular mechanisms of blister formation in bullous impetigo and staphylococcal scalded skin syndrome (United States)

    Hanakawa, Yasushi; Schechter, Norman M.; Lin, Chenyan; Garza, Luis; Li, Hong; Yamaguchi, Takayuki; Fudaba, Yasuyuki; Nishifuji, Koji; Sugai, Motoyuki; Amagai, Masayuki; Stanley, John R.


    Bullous impetigo due to Staphylococcus aureus is one of the most common bacterial infections of man, and its generalized form, staphylococcal scalded skin syndrome (SSSS), is a frequent manifestation of staphylococcal epidemics in neonatal nurseries. Both diseases are mediated by exfoliative toxins (ETs), which show exquisite pathologic specificity in blistering only the superficial epidermis. We show that these toxins act as serine proteases with extremely focused molecular specificity to cleave mouse and human desmoglein 1 (Dsg1) once after glutamic acid residue 381 between extracellular domains 3 and 4. Mutation of the predicted catalytically active serine to alanine completely inhibits cleavage. The mutated ETs bind specifically to Dsg1 by immunofluorescence colocalization and by coimmunoprecipitation. Thus, ETs, through specific recognition and proteolytic cleavage of one structurally critical peptide bond in an adhesion molecule, cause its dysfunction and allow S. aureus to spread under the stratum corneum, the main barrier of the skin, explaining how, although they circulate through the entire body in SSSS, they cause pathology only in the superficial epidermis. PMID:12093888

  18. Transcriptome Analysis Reveals Candidate Genes involved in Blister Blight defense in Tea (Camellia sinensis (L) Kuntze) (United States)

    Jayaswall, Kuldip; Mahajan, Pallavi; Singh, Gagandeep; Parmar, Rajni; Seth, Romit; Raina, Aparnashree; Swarnkar, Mohit Kumar; Singh, Anil Kumar; Shankar, Ravi; Sharma, Ram Kumar


    To unravel the molecular mechanism of defense against blister blight (BB) disease caused by an obligate biotrophic fungus, Exobasidium vexans, transcriptome of BB interaction with resistance and susceptible tea genotypes was analysed through RNA-seq using Illumina GAIIx at four different stages during ~20-day disease cycle. Approximately 69 million high quality reads were assembled de novo, yielding 37,790 unique transcripts with more than 55% being functionally annotated. Differentially expressed, 149 defense related transcripts/genes, namely defense related enzymes, resistance genes, multidrug resistant transporters, transcription factors, retrotransposons, metacaspases and chaperons were observed in RG, suggesting their role in defending against BB. Being present in the major hub, putative master regulators among these candidates were identified from predetermined protein-protein interaction network of Arabidopsis thaliana. Further, confirmation of abundant expression of well-known RPM1, RPS2 and RPP13 in quantitative Real Time PCR indicates salicylic acid and jasmonic acid, possibly induce synthesis of antimicrobial compounds, required to overcome the virulence of E. vexans. Compendiously, the current study provides a comprehensive gene expression and insights into the molecular mechanism of tea defense against BB to serve as a resource for unravelling the possible regulatory mechanism of immunity against various biotic stresses in tea and other crops.

  19. Metamodeling and Optimization of a Blister Copper Two-Stage Production Process (United States)

    Jarosz, Piotr; Kusiak, Jan; Małecki, Stanisław; Morkisz, Paweł; Oprocha, Piotr; Pietrucha, Wojciech; Sztangret, Łukasz


    It is often difficult to estimate parameters for a two-stage production process of blister copper (containing 99.4 wt.% of Cu metal) as well as those for most industrial processes with high accuracy, which leads to problems related to process modeling and control. The first objective of this study was to model flash smelting and converting of Cu matte stages using three different techniques: artificial neural networks, support vector machines, and random forests, which utilized noisy technological data. Subsequently, more advanced models were applied to optimize the entire process (which was the second goal of this research). The obtained optimal solution was a Pareto-optimal one because the process consisted of two stages, making the optimization problem a multi-criteria one. A sequential optimization strategy was employed, which aimed for optimal control parameters consecutively for both stages. The obtained optimal output parameters for the first smelting stage were used as input parameters for the second converting stage. Finally, a search for another optimal set of control parameters for the second stage of a Kennecott-Outokumpu process was performed. The optimization process was modeled using a Monte-Carlo method, and both modeling parameters and computed optimal solutions are discussed.

  20. Degradation of the blister agent sulfur mustard, bis(2-chloroethyl) sulfide, on concrete. (United States)

    Brevett, Carol A S; Sumpter, Kenneth B; Wagner, George W; Rice, Jeffrey S


    The products formed from the degradation of the blister agent sulfur mustard [bis(2-chloroethyl) sulfide] on concrete were identified using gas chromatography with mass spectrometry detection (GC/MSD), (1)H NMR, 2D (1)H-(13)C NMR and (13)C solid state magic angle spinning (SSMAS) NMR. In situ and extraction experiments were performed. Sulfur mustard was detected in the in situ (13)C SSMAS samples for 12 weeks, whereas less than 5% of the sulfur mustard was detected in extracts from the concrete monoliths after 8 days. Sulfonium ions and (2-chloroethylthio)ethyl ether (T) were observed on the in situ samples after a period of 12 weeks, whereas vinyl species and bis(2-chloroethyl) sulfoxide were observed in the extracts of the concrete monoliths within 24h. The differences between the extraction and the SSMAS data indicated that the sulfur mustard existed in the concrete in a non-extractable form prior to its degradation. Extraction methods alone were not sufficient to identify the products; methods to identify the presence of non-extractable degradation products were also required.

  1. Degradation of the blister agent sulfur mustard, bis(2-chloroethyl) sulfide, on concrete

    Energy Technology Data Exchange (ETDEWEB)

    Brevett, Carol A.S. [GEO-CENTERS Operations, SAIC, Gunpowder Branch, P.O. Box 68, APG, MD 21010-0068 (United States)]. E-mail:; Sumpter, Kenneth B. [CDR USA RDECOM, ATTN: AMSRD-ECB-RT-PD, 5183 Blackhawk Road, Aberdeen Proving Ground, MD 21010-5424 (United States)]. E-mail:; Wagner, George W. [CDR USA RDECOM, ATTN: AMSRD-ECB-RT-PD, 5183 Blackhawk Road, Aberdeen Proving Ground, MD 21010-5424 (United States)]. E-mail:; Rice, Jeffrey S. [CDR USA RDECOM, ATTN: AMSRD-ECB-RT-PD, 5183 Blackhawk Road, Aberdeen Proving Ground, MD 21010-5424 (United States)]. E-mail:


    The products formed from the degradation of the blister agent sulfur mustard [bis(2-chloroethyl) sulfide] on concrete were identified using gas chromatography with mass spectrometry detection (GC/MSD), {sup 1}H NMR, 2D {sup 1}H-{sup 13}C NMR and {sup 13}C solid state magic angle spinning (SSMAS) NMR. In situ and extraction experiments were performed. Sulfur mustard was detected in the in situ {sup 13}C SSMAS samples for 12 weeks, whereas less than 5% of the sulfur mustard was detected in extracts from the concrete monoliths after 8 days. Sulfonium ions and (2-chloroethylthio)ethyl ether (T) were observed on the in situ samples after a period of 12 weeks, whereas vinyl species and bis(2-chloroethyl) sulfoxide were observed in the extracts of the concrete monoliths within 24 h. The differences between the extraction and the SSMAS data indicated that the sulfur mustard existed in the concrete in a non-extractable form prior to its degradation. Extraction methods alone were not sufficient to identify the products; methods to identify the presence of non-extractable degradation products were also required.

  2. Elevated homocysteine levels in suction-induced blister fluid of active vitiligo lesions. (United States)

    Anbar, Tag; Zuel-Fakkar, Nehal Mohamed; Matta, Mary Fikry; Arbab, Mai Mohammed Ibrahim


    Vitiligo is the most prevalent acquired pigmentary disorder as a result of destruction of melanocytes. Several studies have reported increased serum levels of homocysteine (Hcy) in vitiligo patients which may be the result of decreased Vitamin B12 and folic acid levels. In addition, homocystinuria is associated with pigmentary dilution. On the other hand, other studies reported normal serum homocysteine levels. Our aim was to study the Hcy level in active vitiligo patients both in serum and in suction blister fluid obtained from the lesional skin. A total of 30 patients with active vitiligo of both sexes and 30 healthy volunteers were enrolled in this study. Sera from the blood and from lesional induced bullae were obtained from the patients and controls and were assayed for Hcy by enzyme-linked immunosorbent assay (ELISA). The collected data were analyzed by SPSS version 17. There were no significant differences in the serum levels of Hcy between patients and healthy controls, however, the increase in Hcy level was highly statistically significant in the patients' lesional induced bulla compared to the healthy controls. There was no significant difference in Hcy levels between males and females and between patients with negative or positive family histories of vitiligo. The presence of a high homocysteine level in active vitiligo lesions points to a local event occurring in this lesion, which is not reflected as an increase in the patient's serum level.

  3. A coupling model to simulate the dynamic process of blister-actuated nanosecond laser-induced forward transfer (United States)

    Hu, Yongxiang; Cheng, Han; Xu, Jiaxi; Yao, Zhenqiang


    The modeling of laser-induced forward transfer process (LIFT) is helpful to understand and optimize its complex transfer process. In this work, a coupling model is developed to investigate the dynamic response of a thin polymer layer used as the release layer in the blister-actuated LIFT. In this model, the vapor pressure generated by nanosecond laser irradiation is computed through coupling with the transient vapor volume obtained from different step durations to simulate the dynamic blister formation. And the model is validated by experiments on polyimide film irradiated with different laser fluences, which is found to be capable of providing a consistent prediction of blister profiles under several laser conditions. The calibrated energy conversion ratios imply that laser pulse energy is mainly allocated for the heating and vaporizing of polymers, but increasing laser fluence can make this expense gradually saturated to allow more pulse energy to increase the vapor pressure. Transient pressure development from the coupling model is observed to increase rapidly within the pulse duration, but then to decrease because of vapor expansion. Forward velocity in axial direction is also observed to increase with laser fluence. The maximum velocity is possible to exceed the sound velocity under a high laser fluence. And the thin polymer layer is more preferred to obtain a high transfer velocity.

  4. Monogenic autoimmune diseases of the endocrine system. (United States)

    Johnson, Matthew B; Hattersley, Andrew T; Flanagan, Sarah E


    The most common endocrine diseases, type 1 diabetes, hyperthyroidism, and hypothyroidism, are the result of autoimmunity. Clustering of autoimmune endocrinopathies can result from polygenic predisposition, or more rarely, may present as part of a wider syndrome due to a mutation within one of seven genes. These monogenic autoimmune diseases show highly variable phenotypes both within and between families with the same mutations. The average age of onset of the monogenic forms of autoimmune endocrine disease is younger than that of the common polygenic forms, and this feature combined with the manifestation of other autoimmune diseases, specific hallmark features, or both, can inform clinicians as to the relevance of genetic testing. A genetic diagnosis can guide medical management, give an insight into prognosis, inform families of recurrence risk, and facilitate prenatal diagnoses. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Autoimmune diseases in women with Turner's syndrome

    DEFF Research Database (Denmark)

    Jørgensen, Kristian T; Rostgaard, Klaus; Bache, Iben


    OBJECTIVE: In terms of number of X chromosomes, women with Turner's syndrome cytogenetically resemble men. An increased risk of autoimmune diseases has been observed among women with Turner's syndrome. This study was undertaken to investigate whether the autoimmune disease profile in women...... with Turner's syndrome is characterized by diseases with a female or male predominance. METHODS: Using the Danish Cytogenetic Central Register, the Danish National Patient Register, and the Danish Civil Registration System, we estimated relative risk of 46 different autoimmune diseases in a cohort of 798...... Danish women with Turner's syndrome followed up for 12,461 person-years between 1980 and 2004. Standardized incidence ratios (SIRs) of first hospitalization for autoimmune disease and 95% confidence intervals (95% CIs) were used as measures of relative risk. RESULTS: The overall risk of autoimmune...

  6. Autoimmune mechanisms in pernicious anaemia & thyroid disease. (United States)

    Osborne, David; Sobczyńska-Malefora, Agata


    Pernicious anaemia (PA) and some types of thyroid disease result from autoimmune processes. The autoimmune mechanisms in these conditions have not been fully elucidated. This review discusses the autoimmune mechanisms involved in PA and how these affect diagnosis and disease progression. In addition to gastric antibodies, antibodies to the vitamin B12 binding protein transcobalamin which can result in high serum B12 levels are also addressed with regard to how they affect clinical practice. The role of autoimmune susceptibility is investigated by comparing PA to one of its most common comorbidities, autoimmune thyroid disease (AITD). Thyroid disease (although not exclusively AITD) and B12 deficiency are both also implicated in the pathology of hyperhomocysteinemia, an elevated homocysteine in plasma. Since hyperhomocysteinemia is a risk factor for cardiovascular occlusive disease, this review also addresses how thyroid disease in particular leads to changes in homocysteine levels. Copyright © 2015 Elsevier B.V. All rights reserved.

  7. A randomised controlled trial to compare the safety, effectiveness and cost-effectiveness of doxycycline (200 mg/day) with that of oral prednisolone (0.5 mg/kg/day) for initial treatment of bullous pemphigoid: the Bullous Pemphigoid Steroids and Tetracyclines (BLISTER) trial. (United States)

    Chalmers, Joanne R; Wojnarowska, Fenella; Kirtschig, Gudula; Mason, James; Childs, Margaret; Whitham, Diane; Harman, Karen; Chapman, Anna; Walton, Shernaz; Schmidt, Enno; Godec, Thomas R; Nunn, Andrew J; Williams, Hywel C


    Bullous pemphigoid (BP) is an autoimmune blistering skin disorder with increased morbidity and mortality in the elderly. To evaluate the effectiveness, safety and cost-effectiveness of a strategy of initiating BP treatment with oral doxycycline or oral prednisolone. We hypothesised that starting treatment with doxycycline gives acceptable short-term blister control while conferring long-term safety advantages over starting treatment with oral prednisolone. Pragmatic multicentre two-armed parallel-group randomised controlled trial with an economic evaluation. A total of 54 dermatology secondary care centres in the UK and seven in Germany. Adults with BP [three or more blisters at two sites and positive direct and/or indirect immunofluorescence (immunoglobulin G and/or complement component 3 immunofluorescence at the dermal-epidermal junction)] and able to give informed consent. Participants were allocated using online randomisation to initial doxycycline treatment (200 mg/day) or prednisolone (0.5 mg/kg/day). Up to 30 g/week of potent topical corticosteroids was permitted for weeks 1-3. After 6 weeks, clinicians could switch treatments or alter the prednisolone dose as per normal practice. Primary outcomes: (1) the proportion of participants with three or fewer blisters at 6 weeks (investigator blinded) and (2) the proportion with severe, life-threatening and fatal treatment-related events at 52 weeks. A regression model was used in the analysis adjusting for baseline disease severity, age and Karnofsky score, with missing data imputed. Secondary outcomes included the effectiveness of blister control after 6 weeks, relapses, related adverse events and quality of life. The economic evaluation involved bivariate regression of costs and quality-adjusted life-years (QALYs) from a NHS perspective. In total, 132 patients were randomised to doxycycline and 121 to prednisolone. The mean patient age was 77.7 years and baseline severity was as follows: mild 31.6% (three

  8. Helminth Immunomodulation in Autoimmune Disease

    Directory of Open Access Journals (Sweden)

    John J. Miles


    Full Text Available Helminths have evolved to become experts at subverting immune surveillance. Through potent and persistent immune tempering, helminths can remain undetected in human tissues for decades. Redirecting the immunomodulating “talents” of helminths to treat inflammatory human diseases is receiving intensive interest. Here, we review therapies using live parasitic worms, worm secretions, and worm-derived synthetic molecules to treat autoimmune disease. We review helminth therapy in both mouse models and clinical trials and discuss what is known on mechanisms of action. We also highlight current progress in characterizing promising new immunomodulatory molecules found in excretory/secretory products of helminths and their potential use as immunotherapies for acute and chronic inflammatory diseases.

  9. Autoimmune pancreatitis: a case report. (United States)

    Salari, Masoumeh; Hosseini, Mousareza; Nekooei, Sirous; Ataei Azimi, Sajad; Farzanehfar, Mohammad Reza


    Autoimmune pancreatitis is a fibro-inflammatory form of chronic pancreatitis. It is diagnosed by the combination of imaging studies such as a CT scan and pancreatography, laboratory analyses that include IgG4 and/or autoantibodies, histopathological evaluations and positive response to corticosteroid therapy. We report the case of a 41-year-old female with a history of jaundice and increasing abdominal pain for two weeks prior to her clinic visit. Laboratory results were significant for an increase in alkaline phosphatase (ALP) and erythrocyte sedimentation rate (ESR). Magnetic resonance cholangiopancreatography (MRCP) confirmed areas of stenosis and dilatation in the pancreatic duct and in the intra- and extra-hepatic bile ducts similar to primary sclerosantcholangitis. Laboratory analyses showed increased levels of IgG4 with thepresence of antinuclear antibodies.

  10. Antiretinal antibody- proven autoimmune retinopathy

    Directory of Open Access Journals (Sweden)

    Sharanya Abraham


    Full Text Available A young female presented with bilateral subacute onset of progressive decrease in night vision and reduced peripheral field of vision. The short duration and rapid progression of symptoms along with the lack of family history of night blindness prompted a diagnosis of autoimmune retinopathy (AIR. Fundus fluorescein angiography, optical coherence tomography, visual fields, and electroretinogram were suggestive of AIR. A differential diagnosis of retinitis pigmentosa (RP was also made. Antiretinal autoantibodies were detected in the blood sample. Treatment was with oral steroids and subsequently oral immunosuppressive agents. Visual acuity was maintained, fundus examination reverted to normal, and investigations repeated at every visit were stable with improvement in visual fields. Our case suggests that AIR, if diagnosed early and treated appropriately, may have a good outcome and should be considered in patients with an atypical presentation of RP.

  11. Immunotherapy-induced autoimmune hypophysitis. (United States)

    Valecha, Gautam; Pant, Manisha; Ibrahim, Uroosa; Atallah, Jean P


    Autoimmune hypophysitis is an immune-related adverse event of immune checkpoint inhibitors. In this article, we present the case of a 58-year-old female patient who presented to the emergency room with gradually worsening nonspecific symptoms of headache, nausea, vomiting and decreased oral intake of one week duration. The patient had been diagnosed with relapsed extensive stage small cell lung cancer. She was being treated with a combination of ipilimumab and nivolumab after progression on chemotherapy. Gadolinium-enhanced magnetic resonance imaging of head revealed pituitary enlargement up to 1.5 cm and pituitary stalk enlargement up to 4 mm consistent with hypophysitis. The patient was treated with corticosteroids resulting in rapid resolution of her symptoms. The objective of our report is to highlight this rare but important adverse event associated with checkpoint inhibitors, and discuss its clinical features, diagnostic work-up and treatment.

  12. Criteria for Environmentally Associated Autoimmune Diseases (United States)

    Pollard, K. Michael; Parks, Christine G.; Germolec, Dori R.; Leung, Patrick S.C.; Selmi, Carlo; Humble, Michael C.; Rose, Noel R.


    Increasing evidence supports a role for the environment in the development of autoimmune diseases, as reviewed in the accompanying three papers from the National Institute of Environmental Health Sciences Expert Panel Workshop. An important unresolved issue, however, is the development of criteria for identifying autoimmune disease phenotypes for which the environment plays a causative role, herein referred to as environmentally associated autoimmune diseases. There are several different areas in which such criteria need to be developed, including: 1) identifying the necessary and sufficient data to define environmental risk factors for autoimmune diseases meeting current classification criteria; 2) establishing the existence of and criteria for new environmentally associated autoimmune disorders that do not meet current disease classification criteria; and 3) identifying in clinical practice specific environmental agents that induce autoimmune disease in individual patients. Here we discuss approaches that could be useful for developing criteria in these three areas, as well as factors that should be considered in evaluating the evidence for criteria that can distinguish individuals with such disorders from individuals without such disorders with high sensitivity and specificity. Current studies suggest that multiple lines of complementary evidence will be important and that in many cases there will be clinical, serologic, genetic, epigenetic, and/or other laboratory features that could be incorporated as criteria for environmentally associated autoimmune diseases to improve diagnosis and treatment and possibly allow for preventative strategies in the future. PMID:22771005

  13. Presence of Autoimmune Antibody in Chikungunya Infection

    Directory of Open Access Journals (Sweden)

    Wirach Maek-a-nantawat


    Full Text Available Chikungunya infection has recently re-emerged as an important arthropod-borne disease in Thailand. Recently, Southern Thailand was identified as a potentially endemic area for the chikungunya virus. Here, we report a case of severe musculoskeletal complication, presenting with muscle weakness and swelling of the limbs. During the investigation to exclude autoimmune muscular inflammation, high titers of antinuclear antibody were detected. This is the report of autoimmunity detection associated with an arbovirus infection. The symptoms can mimic autoimmune polymyositis disease, and the condition requires close monitoring before deciding to embark upon prolonged specific treatment with immunomodulators.

  14. Is Multiple Sclerosis an Autoimmune Disease?

    Directory of Open Access Journals (Sweden)

    Bharath Wootla


    Full Text Available Multiple sclerosis (MS is an inflammatory demyelinating disease of the central nervous system (CNS with varied clinical presentations and heterogeneous histopathological features. The underlying immunological abnormalities in MS lead to various neurological and autoimmune manifestations. There is strong evidence that MS is, at least in part, an immune-mediated disease. There is less evidence that MS is a classical autoimmune disease, even though many authors state this in the description of the disease. We show the evidence that both supports and refutes the autoimmune hypothesis. In addition, we present an alternate hypothesis based on virus infection to explain the pathogenesis of MS.

  15. Feasibility and safety of pipeline embolization device in patients with ruptured carotid blister aneurysms. (United States)

    Yoon, Jang W; Siddiqui, Adnan H; Dumont, Travis M; Levy, Elad I; Hopkins, L Nelson; Lanzino, Giuseppe; Lopes, Demetrius K; Moftakhar, Roham; Billingsley, Joshua T; Welch, Babu G; Boulos, Alan S; Yamamoto, Junichi; Tawk, Rabih G; Ringer, Andrew J; Hanel, Ricardo A


    Treatment of internal carotid ruptured blister aneurysms (IC-RBA) presents many challenges to neurosurgeons because of the high propensity for rebleeding during intervention. The role of a Pipeline Embolization Device (PED) in the treatment of this challenging aneurysm subtype remains undefined despite theoretical advantages. To present a series of 11 patients treated with a PED and to discuss the management and results of this novel application of flow diverters. Medical records of patients who presented with IC-RBA from May 2011 to March 2013 were retrospectively reviewed at 6 institutions in the United States. All relevant data were independently compiled. A total of 12 IC-RBAs in 11 patients were treated during the study period. Nine (75%) were treated with a single PED; 1 was treated with 2 PEDs; 1 was treated with coils and 1 PED; and 1 was treated with coils and 2 PEDs. Three (27%) had major perioperative complications: middle cerebral artery territory infarction, vision loss, and death. Seven patients demonstrated complete obliteration of the aneurysm in postoperative imaging. Early clinical outcomes were favorable (modified Rankin Scale score, 0-2) in all 10 survivors. This study demonstrates the feasibility and safety of using the PED to treat IC-RBA with fair initial results. The proper introduction and management of antiplatelet regimen are key for successful results. Bleeding complications related to dual antiplatelet therapy were similar to those in previous studies of stent-assisted coiling for the same population. Larger cohort analysis is needed to define the precise role of flow diverters in the treatment of IC-RBA.

  16. False Blister Beetles and the Expansion of Gymnosperm-Insect Pollination Modes before Angiosperm Dominance. (United States)

    Peris, David; Pérez-de la Fuente, Ricardo; Peñalver, Enrique; Delclòs, Xavier; Barrón, Eduardo; Labandeira, Conrad C


    During the mid-Cretaceous, angiosperms diversified from several nondiverse lineages to their current global domination [1], replacing earlier gymnosperm lineages [2]. Several hypotheses explain this extensive radiation [3], one of which involves proliferation of insect pollinator associations in the transition from gymnosperm to angiosperm dominance. However, most evidence supports gymnosperm-insect pollinator associations, buttressed by direct evidence of pollen on insect bodies, currently established for four groups: Thysanoptera (thrips), Neuroptera (lacewings), Diptera (flies), and now Coleoptera (beetles). Each group represents a distinctive pollination mode linked to a unique mouthpart type and feeding guild [4-9]. Extensive indirect evidence, based on specialized head and mouthpart morphology, is present for one of these pollinator types, the long-proboscid pollination mode [10], representing minimally ten family-level lineages of Neuroptera, Mecoptera (scorpionflies), and Diptera [8, 10, 11]. A recurring feature uniting these pollinator modes is host associations with ginkgoalean, cycad, conifer, and bennettitalean gymnosperms. Pollinator lineages bearing these pollination modes were categorized into four evolutionary cohorts during the 35-million-year-long angiosperm radiation, each defined by its host-plant associations (gymnosperm or angiosperm) and evolutionary pattern (extinction, continuation, or origination) during this interval [12]. Here, we provide the first direct evidence for one cohort, exemplified by the beetle Darwinylus marcosi, family Oedemeridae (false blister beetles), that had an earlier gymnosperm (most likely cycad) host association, later transitioning onto angiosperms [13]. This association constitutes one of four patterns explaining the plateau of family-level plant lineages generally and pollinating insects specifically during the mid-Cretaceous angiosperm radiation [12]. Published by Elsevier Ltd.

  17. Autoimmune polyendocrine syndrome type 1 and NALP5, parathyroid autoantigen

    NARCIS (Netherlands)

    Alimohammadi, Mohammad; Bjorklund, Peyman; Hallgren, Asa; Pontynen, Nora; Szinnai, Gabor; Shikama, Noriko; Keller, Marcel P.; Ekwall, Olov; Kinkel, Sarah A.; Husebye, Eystein S.; Gustafsson, Jan; Rorsman, Fredrik; Peltonen, Leena; Betterle, Corrado; Perheentupa, Jaakko; Akerstrom, Goran; Westin, Gunnar; Scott, Hamish S.; Hollaender, Georg A.; Kampe, Olle


    Background: Autoimmune polyendocrine syndrome type 1 (APS-1) is a multiorgan autoimmune disorder caused by mutations in AIRE, the autoimmune regulator gene. Though recent studies concerning AIRE deficiency have begun to elucidate the molecular pathogenesis of organ-specific autoimmunity in patients

  18. No major genes in autoimmune thyroid diseases: complex ...

    Indian Academy of Sciences (India)


    Aug 19, 2011 ... The autoimmune thyroid diseases (AITDs) include,. Graves' disease (GD), autoimmune hypothyroidism (AH):. Hashimoto's thyroiditis (HT) and atrophic autoimmune thy- roiditis (AAT). These are prevalent autoimmune diseases, affecting up to 2% of the general population. A widely accepted model for the ...

  19. A cross-sectional study of clinical, histopathological and direct immmunofluorescence diagnosis in autoimmune bullous diseases

    Directory of Open Access Journals (Sweden)

    Anchal Jindal


    Full Text Available Background: Immunobullous diseases are morphologically heterogeneous and the differentiation between various subtypes is essential for proper treatment and prognosis. Aim of our study was to analyze and correlate clinical, histopathological and immunofluorescence findings in autoimmune bullous diseases. Materials and Methods: A cross-sectional study was done over a period of two years (2010-2012 after approval of the ethics committee. Sixty patients, who met the inclusion criteria of immunobullous disease, were included in the study. Skin biopsy for histopathology and direct immunofluorescence (DIF examination was taken. DIF using salt-split technique was done in few of the cases. The final diagnosis was based on clinical, histopathology and DIF findings. Pearson′s coefficient of correlation (r was calculated. Statistical Analysis was done using Epi info version. 7.0. Results: Fifty-three cases with clinical diagnosis of autoimmune bullous diseases were evaluated. In 88.6% of cases, histopathology diagnosis was consistent with clinical diagnosis and in 75.5% of cases, DIF findings were consistent with clinical diagnosis. A positive relation was seen between clinical and DIF findings with r = 0.65 and between histopathology and DIF findings with r = 0.75. DIF positivity was seen in 100% cases of bullous pemphigoid (BP and pemphigus foliaceous and 94.7% cases of pemphigus vulgaris, which was statistically significant with p < 0.05. In DIF salt-split test, deposition was seen on roof of blister in BP whereas on floor in epidermolysis bullosa acquisita. Conclusion: Our study provides evidence-based guidance for the diagnosis and classification of various immunobullous disorders. DIF test should be done in conjunction with histopathology for definitive diagnosis and to minimize both: False-positive and false-negative results.

  20. Treatment of patients with severe autoimmune hepatitis

    DEFF Research Database (Denmark)

    Larsen, Finn Stolze


    and tacrolimus) might salvage patients from transplantation. Mycophenolate mofetil may also improve liver tests and reduce the requirement for corticosteroids. Besides, sirolimus is effective for treatment of de novo autoimmune hepatitis that sometimes develops after liver transplantation. Initial experience...

  1. Autoimmune pancreatitis : Diagnostic and immunological aspects

    NARCIS (Netherlands)

    M.J. van Heerde (Marianne)


    textabstractAutoimmune pancreatitis (AIP) is the pancreatic manifestation of a systemic fibro- inflammatory disease, characterized by infiltration with lymphoplasmacytic cells and extensive fibrosis, which leads to morphological changes (swelling, mass forming) and organ dysfunction. Often, but

  2. [Autoimmune diseases of the thyroid gland]. (United States)

    Allelein, S; Feldkamp, J; Schott, M


    Autoimmune diseases of the thyroid gland are considered to be the most frequent cause of thyroid gland disorders. Autoimmune thyroid diseases consist of two subgroups: autoimmune thyroiditis (AIT) and Graves' disease. The AIT is the most common human autoimmune disease. Infiltration of the thyroid gland with cytotoxic T‑cells can lead to an initial thyrotoxicosis und during the course to hypothyroidism due to destruction of the thyroid gland. Substitution with Levothyroxine is indicated for manifest hypothyroidism and subclinical hypothyroidism with increased thyroid antibodies with the intention of normalizing the serum thyroid stimulating hormone (TSH). Graves' disease is characterized by the appearance of stimulating TSH receptor antibodies leading to hyperthyroidism. Endocrine ophthalmopathy may also occur. Ablative therapy with radioiodine therapy or thyroidectomy is administered to patients with Graves' disease without remission after at least 1 year of antithyroid drug therapy.

  3. Is there an autoimmune basis for schizophrenia?

    Directory of Open Access Journals (Sweden)

    Abhinav Tewari


    Full Text Available Etiology of schizophrenia still remains a mystery. Schizophrenia with coexistence of myasthenia gravis in the same patient raises the suspicion of autoimmune mechanisms involved in causation of schizophrenia.

  4. Role of Complement in Autoimmune Hemolytic Anemia. (United States)

    Berentsen, Sigbjørn


    The classification of autoimmune hemolytic anemias and the complement system are reviewed. In autoimmune hemolytic anemia of the warm antibody type, complement-mediated cell lysis is clinically relevant in a proportion of the patients but is hardly essential for hemolysis in most patients. Cold antibody-mediated autoimmune hemolytic anemias (primary cold agglutinin disease, secondary cold agglutinin syndrome and paroxysmal cold hemoglobinuria) are entirely complement-mediated disorders. In cold agglutinin disease, efficient therapies have been developed in order to target the pathogenic B-cell clone, but complement modulation remains promising in some clinical situations. No established therapy exists for secondary cold agglutinin syndrome and paroxysmal cold hemoglobinuria, and the possibility of therapeutic complement inhibition is interesting. Currently, complement modulation is not clinically documented in any autoimmune hemolytic anemia. The most relevant candidate drugs and possible target levels of action are discussed.

  5. Autoimmune Cytopenias in Chronic Lymphocytic Leukemia

    Directory of Open Access Journals (Sweden)

    Giovanni D'Arena


    Full Text Available The clinical course of chronic lymphocytic leukemia (CLL may be complicated at any time by autoimmune phenomena.The most common ones are hematologic disorders, such as autoimmune hemolytic anemia (AIHA and immune thrombocytopenia (ITP. Pure red cell aplasia (PRCA and autoimmune agranulocytosis (AG are, indeed, more rarely seen. However, they are probably underestimated due to the possible misleading presence of cytopenias secondary to leukemic bone marrow involvement or to chemotherapy cytotoxicity. The source of autoantibodies is still uncertain, despite the most convincing data are in favor of the involvement of resting normal B-cells. In general, excluding the specific treatment of underlying CLL, the managementof these complications is not different from that of idiopathic autoimmune cytopenias or of those associated to other causes. Among different therapeutic approaches, monoclonal antibody rituximab, given alone or in combination, has shown to be very effective.

  6. Cardiovascular disease biomarkers across autoimmune diseases. (United States)

    Ahearn, Joseph; Shields, Kelly J; Liu, Chau-Ching; Manzi, Susan


    Cardiovascular disease is increasingly recognized as a major cause of premature mortality among those with autoimmune disorders. There is an urgent need to identify those patients with autoimmune disease who are at risk for CVD so as to optimize therapeutic intervention and ultimately prevention. Accurate identification, monitoring and stratification of such patients will depend upon a panel of biomarkers of cardiovascular disease. This review will discuss some of the most recent biomarkers of cardiovascular diseases in autoimmune disease, including lipid oxidation, imaging biomarkers to characterize coronary calcium, plaque, and intima media thickness, biomarkers of inflammation and activated complement, genetic markers, endothelial biomarkers, and antiphospholipid antibodies. Clinical implementation of these biomarkers will not only enhance patient care but also likely accelerate the pharmaceutical pipeline for targeted intervention to reduce or eliminate cardiovascular disease in the setting of autoimmunity. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. Differentiating antiepiligrin cicatricial pemphigoid from epidermolysis bullosa acquisita by indirect immunofluorescence of skin substrates lacking Type VII collagen or laminin 332: a case report and review of literature

    Directory of Open Access Journals (Sweden)

    Chih-Pin Chen


    Full Text Available Antiepiligrin cicatricial pemphigoid (AECP is a chronic autoimmune subepidermal blistering disease characterized by clinical features of cicatricial pemphigoid and circulating IgG antibasement membrane autoantibodies directed against laminin 332. There is growing evidence of an increased relative risk for solid cancers and lymphomas in AECP patients, especially in the 1st year after the onset of blisters. However, it is difficult to distinguish patients with initially skin-predominant AECP from similar findings of epidermolysis bullosa acquisita merely based on clinical, histopathologic, and immuno-pathologic examinations. This is a report on a case of AECP confirmed by indirect immunofluorescence of type VII collagen- and laminin 332-deficient skin as substrates to differentiate it from epidermolysis bullosa acquisita.

  8. Epidermolysis bullosa acquisita in a 17-year-old boy with Crohn's disease. (United States)

    Russo, Irene; Ferrazzi, Anna; Zanetti, Irene; Alaibac, Mauro


    Epidermolysis bullosa acquisita is a rare, acquired, autoimmune subepidermal blistering disease of the skin, characterised by blisters and erosions, especially in trauma-prone sites and extensor skin surface, scarring with formation of milia, skin fragility and nail dystrophy. Epidermolysis bullosa acquisita is extremely rare in childhood and it has been reported to be frequently associated with Crohn's disease. Furthermore, autoantibodies against type VII collagen have been found in a large number of patients with Crohn's disease without epidermolysis bullosa acquisita. We report a case of a 17-year-old boy affected by Crohn's disease who presented with milia on infiltrated erythematous plaques over the back of the hands. The diagnosis of epidermolysis bullosa acquisita was confirmed by histopathology, direct and indirect immunofluorescence analysis and ELISA. 2015 BMJ Publishing Group Ltd.

  9. Treatment of patients with severe autoimmune hepatitis

    DEFF Research Database (Denmark)

    Larsen, Finn Stolze


    Autoimmune hepatitis (AIH) is a progressive inflammatory diseases of unknown origin that is characterised by a necro-inflammatory and fibrotic process and may result in liver failure or uncompensated liver cirrhosis. Normally AIH is responsive to immunosuppressive therapy, and treatment aims...... and tacrolimus) might salvage patients from transplantation. Mycophenolate mofetil may also improve liver tests and reduce the requirement for corticosteroids. Besides, sirolimus is effective for treatment of de novo autoimmune hepatitis that sometimes develops after liver transplantation. Initial experience...

  10. Celiac disease and autoimmune thyroid disease. (United States)

    Ch'ng, Chin Lye; Jones, M Keston; Kingham, Jeremy G C


    Celiac disease (CD) or gluten sensitive enteropathy is relatively common in western populations with prevalence around 1%. With the recent availability of sensitive and specific serological testing, many patients who are either asymptomatic or have subtle symptoms can be shown to have CD. Patients with CD have modest increases in risks of malignancy and mortality compared to controls. The mortality among CD patients who comply poorly with a gluten-free diet is greater than in compliant patients. The pattern of presentation of CD has altered over the past three decades. Many cases are now detected in adulthood during investigation of problems as diverse as anemia, osteoporosis, autoimmune disorders, unexplained neurological syndromes, infertility and chronic hypertransaminasemia of uncertain cause. Among autoimmune disorders, increased prevalence of CD has been found in patients with autoimmune thyroid disease, type 1 diabetes mellitus, autoimmune liver diseases and inflammatory bowel disease. Prevalence of CD was noted to be 1% to 19% in patients with type 1 diabetes mellitus, 2% to 5% in autoimmune thyroid disorders and 3% to 7% in primary biliary cirrhosis in prospective studies. Conversely, there is also an increased prevalence of immune based disorders among patients with CD. The pathogenesis of co-existent autoimmune thyroid disease and CD is not known, but these conditions share similar HLA haplotypes and are associated with the gene encoding cytotoxic T-lymphocyte-associated antigen-4. Screening high risk patients for CD, such as those with autoimmune diseases, is a reasonable strategy given the increased prevalence. Treatment of CD with a gluten-free diet should reduce the recognized complications of this disease and provide benefits in both general health and perhaps life expectancy. It also improves glycemic control in patients with type 1 diabetes mellitus and enhances the absorption of medications for associated hypothyroidism and osteoporosis. It

  11. Coherent Somatic Mutation in Autoimmune Disease (United States)

    Ross, Kenneth Andrew


    Background Many aspects of autoimmune disease are not well understood, including the specificities of autoimmune targets, and patterns of co-morbidity and cross-heritability across diseases. Prior work has provided evidence that somatic mutation caused by gene conversion and deletion at segmentally duplicated loci is relevant to several diseases. Simple tandem repeat (STR) sequence is highly mutable, both somatically and in the germ-line, and somatic STR mutations are observed under inflammation. Results Protein-coding genes spanning STRs having markers of mutability, including germ-line variability, high total length, repeat count and/or repeat similarity, are evaluated in the context of autoimmunity. For the initiation of autoimmune disease, antigens whose autoantibodies are the first observed in a disease, termed primary autoantigens, are informative. Three primary autoantigens, thyroid peroxidase (TPO), phogrin (PTPRN2) and filaggrin (FLG), include STRs that are among the eleven longest STRs spanned by protein-coding genes. This association of primary autoantigens with long STR sequence is highly significant (). Long STRs occur within twenty genes that are associated with sixteen common autoimmune diseases and atherosclerosis. The repeat within the TTC34 gene is an outlier in terms of length and a link with systemic lupus erythematosus is proposed. Conclusions The results support the hypothesis that many autoimmune diseases are triggered by immune responses to proteins whose DNA sequence mutates somatically in a coherent, consistent fashion. Other autoimmune diseases may be caused by coherent somatic mutations in immune cells. The coherent somatic mutation hypothesis has the potential to be a comprehensive explanation for the initiation of many autoimmune diseases. PMID:24988487

  12. Updates on GMSCs treatment for autoimmune diseases. (United States)

    Huang, Feng; Liu, Zhong-Min; Zheng, Song Guo


    Autoimmune disease is a refractory disease. Accumulating Evidence has revealed that the manipulation of mesenchymal stem cells may have the potential to control or even treat autoimmune diseases. Human gingiva-derived mesenchymal stem cells (GMSCs) are emerging as a new line of mesenchymal stem cells that have displayed some potential advantages in controlling and treating autoimmune diseases. In this review, we briefly update the current understanding on the biology of GMSCs and their effects on preventing and treating autoimmune diseases. The availability of gingival mesenchymal stem cells (GMSCs), together with their potent capacity of multi-directional differentiation and inflammatory modulation, making GMSCs an ideal subtype of MSCs in treating autoimmune disease. Our and other studies have launched the earliest appraisal on GMSCs and carried out a lot of biological researches. The clinical trial of GMSCs on patients with autoimmune diseases will further approve their therapeutic effects, as well as its cellular and molecular mechanisms. Copyright© Bentham Science Publishers; For any queries, please email at

  13. Autoimmune connective tissue diseases and vaccination

    Directory of Open Access Journals (Sweden)

    Ewa Więsik-Szewczyk


    Full Text Available The idea that infectious agents can induce autoimmune diseases in genetically susceptible subjects has been a matter of discussion for years. Moreover, increased incidence of autoimmune diseases and introduction of prophylactic vaccinations from early childhood suggest that these two trends are linked. In the medical literature and even non-professional media, case reports or events temporally related to vaccination are reported. It raises the issue of vaccination safety. In everyday practice medical professionals, physicians, rheumatologists and other specialists will be asked their opinion of vaccination safety. The decision should be made according to evidence-based medicine and the current state of knowledge. The purpose of this paper is to discuss a potential mechanism which links infections, vaccinations and autoimmunity. We present an overview of published case reports, especially of systemic connective tissue diseases temporally related to vaccination and results from case-nested studies. As yet, no conclusive evidence supports a causal relationship between vaccination and autoimmune diseases. It has to be determined whether the performed studies are sufficiently Epsteinasensitive to detect the link. The debate is ongoing, and new data may be required to explain the pathogenesis of autoimmunity. We would like to underscore the need for prophylactic vaccination in patients with autoimmune rheumatic diseases and to break down the myth that the vaccines are contraindicated in this target group.

  14. Hemostasis in Hypothyroidism and Autoimmune Thyroid Disorders (United States)

    Ordookhani, Arash; Burman, Kenneth D.


    Context There are contradictory results on the effect of hypothyroidism on the changes in hemostasis. Inadequate population-based studies limited their clinical implications, mainly on the risk of venous thromboembolism (VTE). This paper reviews the studies on laboratory and population-based findings regarding hemostatic changes and risk of VTE in hypothyroidism and autoimmune thyroid disorders. Evidence Acquisition A comprehensive literature search was conducted employing MEDLINE database. The following words were used for the search: Hypothyroidism; thyroiditis, autoimmune; blood coagulation factors; blood coagulation tests; hemostasis, blood coagulation disorders; thyroid hormones; myxedema; venous thromboembolism; fibrinolysis, receptors thyroid hormone. The papers that were related to hypothyroidism and autoimmune thyroid disorder and hemostasis are used in this review. Results Overt hypothyroidism is more associated with a hypocoagulable state. Decreased platelet count, aggregation and agglutination, von Willebrand factor antigen and activity, several coagulation factors such as factor VIII, IX, XI, VII, and plasminogen activator-1 are detected in overt hypothyrodism. Increased fibrinogen has been detected in subclinical hypothyroidism and autoimmune thyroid disease rendering a tendency towards a hypercoagulability state. Increased factor VII and its activity, and plasminogen activator inhibitor-1 are among several findings contributing to a prothrombotic state in subclinical hypothyroidism. Conclusions Overt hypothyroidism is associated with a hypocoagulable state and subclinical hypothyroidism and autoimmune thyroid disorders may induce a prothrombotic state. However, there are contradictory findings for the abovementioned thyroid disorders. Prospective studies on the risk of VTE in various levels of hypofunctioning of the thyroid and autoimmune thyroid disorders are warranted. PMID:29026409

  15. NK cell autoreactivity and autoimmune diseases

    Directory of Open Access Journals (Sweden)

    Alessandro ePoggi


    Full Text Available Increasing evidences have pointed out the relevance of Natural Killer (NK cells in organ specific and systemic autoimmune diseases. NK cells bear a plethora of activating and inhibiting receptors that can play a role in regulating reactivity with autologous cells. The activating receptors recognize natural ligands upregulated on virus-infected or stressed or neoplastic cells. Of note, several autoimmune diseases are thought to be linked to viral infections as one of the first event in inducing autoimmunity. Also, it is conceivable that autoimmunity can be triggered when a dysregulation of innate immunity occurs, activating T and B lymphocytes to react with self-components. This would imply that NK cells can play a regulatory role during adaptive immunity; indeed, innate lymphoid cells (ILC, comprising the classical CD56+ NK cells, have a role in maintaining or alterating tissue homeostasis secreting protective and/or proinflammatory cytokines. In addition, NK cells display activating receptors involved in natural cytotoxicity and the activating isoforms of receptors for HLA class I that can interact with healthy host cells and induce damage without any evidence of viral infection or neoplastic-induced alteration. In this context, the interrelationship among ILC, extracellular matrix components and mesenchymal stromal cells can be considered a key point for the control of homeostasis. Herein, we summarize evidences for a role of NK cells in autoimmune diseases and will give a point of view of the interplay between NK cells and self-cells in triggering autoimmunity.

  16. Regulatory T-cells and autoimmunity.

    LENUS (Irish Health Repository)

    Ni Choileain, Niamh


    Approximately 20% of the population is affected by autoimmune or inflammatory diseases mediated by an abnormal immune response. A characteristic feature of autoimmune disease is the selective targeting of a single cell type, organ or tissue by certain populations of autoreactive T-cells. Examples of such diseases include rheumatoid arthritis, insulin-dependent diabetes mellitus, and systemic lupus erythematosus (SLE), all of which are characterized by chronic inflammation, tissue destruction and target organ malfunction. Although strong evidence links most autoimmune diseases to specific genes, considerable controversy prevails regarding the role of regulatory T-cell populations in the disease process. These cells are now also believed to play a key role in mediating transplantation tolerance and inhibiting the induction of tumor immunity. Though the concept of therapeutic immune regulation aimed at treating autoimmune pathology has been validated in many animal models, the development of strategies for the treatment of human autoimmune disorders remains in its infancy. The main obstacles to this include the conflicting findings of different model systems, as well as the contrasting functions of regulatory T-cells and cytokines involved in the development of such disorders. This review examines the role of regulatory T-cells in the pathogenesis of autoimmunity and describes the therapeutic potential of these cells for the prevention of immune-mediated pathologies in the future. Although much remains to be learned about such pathologies, a clearer understanding of the mechanisms by which regulatory T-cells function will undoubtedly lead to exciting new possibilities for immunotherapeutics.

  17. Virus infection, antiviral immunity, and autoimmunity. (United States)

    Getts, Daniel R; Chastain, Emily M L; Terry, Rachael L; Miller, Stephen D


    As a group of disorders, autoimmunity ranks as the third most prevalent cause of morbidity and mortality in the Western World. However, the etiology of most autoimmune diseases remains unknown. Although genetic linkage studies support a critical underlying role for genetics, the geographic distribution of these disorders as well as the low concordance rates in monozygotic twins suggest that a combination of other factors including environmental ones are involved. Virus infection is a primary factor that has been implicated in the initiation of autoimmune disease. Infection triggers a robust and usually well-coordinated immune response that is critical for viral clearance. However, in some instances, immune regulatory mechanisms may falter, culminating in the breakdown of self-tolerance, resulting in immune-mediated attack directed against both viral and self-antigens. Traditionally, cross-reactive T-cell recognition, known as molecular mimicry, as well as bystander T-cell activation, culminating in epitope spreading, have been the predominant mechanisms elucidated through which infection may culminate in an T-cell-mediated autoimmune response. However, other hypotheses including virus-induced decoy of the immune system also warrant discussion in regard to their potential for triggering autoimmunity. In this review, we discuss the mechanisms by which virus infection and antiviral immunity contribute to the development of autoimmunity. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  18. Autoimmune cytopenias related to common variable immunodeficiency

    Directory of Open Access Journals (Sweden)

    Vlasta Petric


    Full Text Available Background: Common variable immunodeficiency disorders are characterised by defective antibody production leading to recurrent infections. Noninfective complications are a consequence of autoimmunity, granuloma and polyclonal lymphoid infiltration. We often detect autoimmune cytopenias before primary immunodefciency is confirmed. Patients and methods: We report a case of 39-year old man with recurrent respiratory infections, autoimmune thrombocytopenia and haemolytic anemia who had common varible immunodeficiency confirmed. He had a lack of serum IgG, IgA and IgM, bronchiectasis, lymphadenopathy, splenomegaly, hepatic granuloma, autoimmune gastritis with B12 deficiency and Evans syndrome. We treated autoimmune cytopenias with methylprednisolon and cyclosporine. After substitution therapy with intravenous immunoglobulin the frequency of espiratory infections decreased. Occurrence of diarrhea is suspected for enteropathy, however, hystologic identification is required. Because of patologically changed gastric mucosa and signs of polyclonal lymphoid infiltration, the patient is at high risk for malignancy and the outcome of the disease remains unpredictable. Conclusions: Generally, we discover common variable immunodeficiency at management of noninfective complications, in wich intravenous immunoglobulin are not effective. Autoimmune cytopenias and some other complications are successfully treated with glucocorticoids. Careful monitorig of these patients is important because of a high risk for malignancy.

  19. Autoimmune diseases of oral cavity

    Directory of Open Access Journals (Sweden)

    Davide B. Gissi


    Full Text Available Most diseases of oral mucosa are either autoimmune in nature or are the results of immunologically-mediated events. These include Recurrent Aphthous Stomatitis (RAS, Erythema Multiforme (EM, the bullous diseases Pemphigus Vulgaris (PV and Mucous Membrane Pemphigoid (MMP and Lichen Planus (LP. These conditions are characterised by lesions of the oral mucosa often associated with extra-oral manifestations that include skin, eyes, nasal and pharyngeal mucosa as well as genitals. Despite a similar pathogenesis, they are characterised by different immunologic processes that involve T-cell mediated hypersensitivity in LP, humoral-mediated immunity to cadherin intercellular adhesion molecules in PV, antibody-mediated processes giving rise to junctional separation in MMP, and other not yet completely understood processes in RAS and EM. Differences are also present in the clinical outcome, that is always acute and auto-limiting in EM, auto-limiting and often recurrent in RAS, sub-acute and often recurrent in MMP and PV and always chronic in LP. Accurate diagnosis is not always possible solely on the basis of the oral presentation, and histological and often immunofluorescence examinations are needed in order to establish a definitive diagnosis. The condition that brings together all these diseases is that thay all benefit from similar therapeutic approaches, consisting in local or systemic immunosuppressive treatments. This review provides guidance to differentiate and correctly diagnose these conditions and discusses the most appropriate management.

  20. Autoimmune Polyglandular Syndrome Type 1

    Directory of Open Access Journals (Sweden)

    Vedeswari C Ponranjini


    Full Text Available Autoimmune Polyglandular Syndrome (APS Type 1 is a rare hereditary disorder that damages organs in the body. This disease entity is the result of a mutation in the AIRE gene. It is characterized by three classic clinical features - hypoparathyroidism, Addison′s disease, and chronic mucocutaneous candidiasis. For a patient to be diagnosed as having APS Type 1 syndrome at least two of these features needs to be present. The third entity may develop as the disease progresses. We report a case of a 35-year-old female patient with a history of seizure from the age of 11 years, who was managed with anticonvulsant drugs. With worsening of the seizure episodes, patient was diagnosed to have hypoparathyroidism together with the manifestations of oral candidiasis, nails dystrophy, enamel hypoplasia, and hypogonadism. A diagnosis of APS-1 was considered. The facility for genetic analysis of the AIRE gene mutation was not accessible, as the test costs were prohibitive and not affordable for the patient. Patient management was directed to treating individual disease components. However, cerebral and dental changes were irreversible.

  1. Treatment of autoimmune hemolytic anemias (United States)

    Zanella, Alberto; Barcellini, Wilma


    Autoimmune hemolytic anemia (AIHA) is a relatively uncommon disorder caused by autoantibodies directed against self red blood cells. It can be idiopathic or secondary, and classified as warm, cold (cold hemagglutinin disease (CAD) and paroxysmal cold hemoglobinuria) or mixed, according to the thermal range of the autoantibody. AIHA may develop gradually, or have a fulminant onset with life-threatening anemia. The treatment of AIHA is still not evidence-based. The first-line therapy for warm AIHA are corticosteroids, which are effective in 70–85% of patients and should be slowly tapered over a time period of 6–12 months. For refractory/relapsed cases, the current sequence of second-line therapy is splenectomy (effective approx. in 2 out of 3 cases but with a presumed cure rate of up to 20%), rituximab (effective in approx. 80–90% of cases), and thereafter any of the immunosuppressive drugs (azathioprine, cyclophosphamide, cyclosporin, mycophenolate mofetil). Additional therapies are intravenous immunoglobulins, danazol, plasma-exchange, and alemtuzumab and high-dose cyclophosphamide as last resort option. As the experience with rituximab evolves, it is likely that this drug will be located at an earlier point in therapy of warm AIHA, before more toxic immunosuppressants, and in place of splenectomy in some cases. In CAD, rituximab is now recommended as first-line treatment. PMID:25271314

  2. Reduced fibulin-2 contributes to loss of basement membrane integrity and skin blistering in mice lacking integrin α3β1 in the epidermis. (United States)

    Longmate, Whitney M; Monichan, Ruby; Chu, Mon-Li; Tsuda, Takeshi; Mahoney, My G; DiPersio, C Michael


    Deficient epidermal adhesion is a hallmark of blistering skin disorders and chronic wounds, implicating integrins as potential therapeutic targets. Integrin α3β1, a major receptor in the epidermis for adhesion to laminin-332 (LN-332), has critical roles in basement membrane (BM) organization during skin development. In the current study we identify a role for α3β1 in promoting stability of nascent epidermal BMs through induction of fibulin-2, a matrix-associated protein that binds LN-332. We demonstrate that mice lacking α3β1 in the epidermis display ruptured BM beneath neo-epidermis of wounds, characterized by extensive blistering. This junctional blistering phenocopies defects reported in newborn α3-null mice, as well as in human patients with α3 gene mutations, indicating that the developmental role of α3β1 in BM organization is recapitulated during wound healing. Mice lacking epidermal α3β1 also have reduced fibulin-2 expression, and fibulin-2-null mice display perinatal skin blisters similar to those in α3β1-deficient mice. Interestingly, α3-null wound epidermis or keratinocytes also show impaired processing of the LN-332 γ2 chain, although this defect was independent of reduced fibulin-2 and did not appear to cause blistering. Our findings indicate a role for integrin α3β1 in BM stability through fibulin-2 induction, both in neonatal skin and in adult wounds.

  3. Autoimmunity, Not a Developmental Defect, is the Cause for Subfertility of Autoimmune Regulator (Aire) Deficient Mice. (United States)

    Kekäläinen, E; Pöntynen, N; Meri, S; Arstila, T P; Jarva, H


    Autoimmune regulator's (AIRE) best characterized role is in the generation immunological tolerance, but it is also involved in many other processes such as spermatogenesis. Loss-of-function mutations in AIRE cause a disease called autoimmune polyendocrinopathy, candidiasis and ectodermal dystrophy (APECED; also called autoimmune polyendocrinopathy syndrome type 1, APS-1) that is dominated by various autoimmune manifestations, mainly endocrinopathies. Both patients with APECED and Aire(-/-) mice suffer from varying levels of infertility, but it is not clear if it is a result of an autoimmune tissue damage or more of a developmental defect. In this study, we wanted to resolve whether or not the reduced fertility of Aire(-/-) mice is dependent on the adaptive immune system and therefore a manifestation of autoimmunity in these mice. We generated lymphopenic mice without Aire expression that were devoid of the autoimmune manifestations previously reported in immunocompetent Aire(-/-) mice. These Aire(-/-) Rag1(-/-) mice regained full fertility. This confirms that the development of infertility in Aire(-/-) mice requires a functional adaptive immune system. We also show that only the male Aire(-/-) mice are subfertile, whereas Aire(-/-) females produce litters normally. Moreover, the male subfertility can be adoptively transferred with lymphocytes from Aire(-/-) donor mice to previously fertile lymphopenic Aire(-/-) recipients. Our data show that subfertility in Aire(-/-) mice is dependent on a functional adaptive immune system thus confirming its autoimmune aetiology. © 2015 John Wiley & Sons Ltd.

  4. Theoretical Study on Synchronous Characterization of Surface and Interfacial Mechanical Properties of Thin-Film/Substrate Systems with Residual Stress Based on Pressure Blister Test Technique

    Directory of Open Access Journals (Sweden)

    Zhi-xin Yang


    Full Text Available In this study, based on the pressure blister test technique, a theoretical study on the synchronous characterization of surface and interfacial mechanical properties of thin-film/substrate systems with residual stress was presented, where the problem of axisymmetric deformation of a blistering film with initial stress was analytically solved and its closed-form solution was presented. The expressions to determine Poisson’s ratios, Young’s modulus, and residual stress of surface thin films were derived; the work done by the applied external load and the elastic energy stored in the blistering thin film were analyzed in detail and their expressions were derived; and the interfacial adhesion energy released per unit delamination area of thin-film/substrate (i.e., energy release rate was finally presented. The synchronous characterization technique presented here has theoretically made a big step forward, due to the consideration for the residual stress in surface thin films.

  5. Triglyceride blisters in lipid bilayers: implications for lipid droplet biogenesis and the mobile lipid signal in cancer cell membranes.

    Directory of Open Access Journals (Sweden)

    Himanshu Khandelia

    Full Text Available Triglycerides have a limited solubility, around 3%, in phosphatidylcholine lipid bilayers. Using millisecond-scale course grained molecular dynamics simulations, we show that the model lipid bilayer can accommodate a higher concentration of triolein (TO than earlier anticipated, by sequestering triolein molecules to the bilayer center in the form of a disordered, isotropic, mobile neutral lipid aggregate, at least 17 nm in diameter, which forms spontaneously, and remains stable on at least the microsecond time scale. The results give credence to the hotly debated existence of mobile neutral lipid aggregates of unknown function present in malignant cells, and to the early biogenesis of lipid droplets accommodated between the two leaflets of the endoplasmic reticulum membrane. The TO aggregates give the bilayer a blister-like appearance, and will hinder the formation of multi-lamellar phases in model, and possibly living membranes. The blisters will result in anomalous membrane probe partitioning, which should be accounted for in the interpretation of probe-related measurements.

  6. Upper gastrointestinal symptoms in autoimmune gastritis (United States)

    Carabotti, Marilia; Lahner, Edith; Esposito, Gianluca; Sacchi, Maria Carlotta; Severi, Carola; Annibale, Bruno


    Abstract Autoimmune gastritis is often suspected for its hematologic findings, and rarely the diagnosis is made for the presence of gastrointestinal symptoms. Aims of this cross-sectional study were to assess in a large cohort of patients affected by autoimmune gastritis the occurrence and the pattern of gastrointestinal symptoms and to evaluate whether symptomatic patients are characterized by specific clinical features. Gastrointestinal symptoms of 379 consecutive autoimmune gastritis patients were systematically assessed and classified following Rome III Criteria. Association between symptoms and anemia pattern, positivity to gastric autoantibodies, Helicobacter pylori infection, and concomitant autoimmune disease were evaluated. In total, 70.2% of patients were female, median age 55 years (range 17–83). Pernicious anemia (53.6%), iron deficiency anemia (34.8%), gastric autoantibodies (68.8%), and autoimmune disorders (41.7%) were present. However, 56.7% of patients complained of gastrointestinal symptoms, 69.8% of them had exclusively upper symptoms, 15.8% only lower and 14.4% concomitant upper and lower symptoms. Dyspepsia, subtype postprandial distress syndrome was the most represented, being present in 60.2% of symptomatic patients. Univariate and multivariate analyses showed that age gastritis is associated in almost 60% of cases with gastrointestinal symptoms, in particular dyspepsia. Dyspepsia is strictly related to younger age, no smoking, and absence of anemia. PMID:28072728

  7. Autoimmune gastritis: Pathologist’s viewpoint (United States)

    Coati, Irene; Fassan, Matteo; Farinati, Fabio; Graham, David Y; Genta, Robert M; Rugge, Massimo


    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. PMID:26576102

  8. Autoimmune rheumatic disease and sleep: a review. (United States)

    Sangle, Shirish R; Tench, Colin M; D'Cruz, David P


    Sleep has an important role to play in the human immune system and it is critical in the restoration and maintenance of homeostasis. Sleep deprivation and disorders may have a profound impact on health, well being and the ability to resist infection. Autoimmune rheumatic diseases are multisystem disorders that involve complicated hormonal and immunological pathophysiology. Previous studies have suggested that sleep deprivation may lead to immunological disturbance in experimental mouse models. Sleep disorders may trigger immune system abnormalities inducing autoantibody production, possibly leading to the development of autoimmune disease such as systemic lupus erythematosus, scleroderma or rheumatoid arthritis. Indeed, in experimental models, it has been suggested that sleep deprivation may induce the onset of autoimmune disease. Chronic deprivation of sleep is common in modern society and has been seen in various autoimmune inflammatory rheumatic diseases. We have reviewed various aspects of sleep deprivation and sleep apnoea syndrome, and their effects on the immune system and their relevance to autoimmune diseases. We hope that these data will encourage greater awareness of the role that improved sleep hygiene may play in the management of these rheumatic diseases.

  9. Gene-environment interaction in autoimmune disease. (United States)

    Ellis, Justine A; Kemp, Andrew S; Ponsonby, Anne-Louise


    Autoimmune disease manifests in numerous forms, but as a disease group is relatively common in the population. It is complex in aetiology, with genetic and environmental determinants. The involvement of gene variants in autoimmune disease is well established, and evidence for significant involvement of the environment in various disease forms is growing. These factors may act independently, or they may interact, with the effect of one factor influenced by the presence of another. Identifying combinations of genetic and environmental factors that interact in autoimmune disease has the capacity to more fully explain disease risk profile, and to uncover underlying molecular mechanisms contributing to disease pathogenesis. In turn, such knowledge is likely to contribute significantly to the development of personalised medicine, and targeted preventative approaches. In this review, we consider the current evidence for gene-environment (G-E) interaction in autoimmune disease. Large-scale G-E interaction research efforts, while well-justified, face significant practical and methodological challenges. However, it is clear from the evidence that has already been generated that knowledge on how genes and environment interact at a biological level will be crucial in fully understanding the processes that manifest as autoimmunity.

  10. Recent Advances in Autoimmune Thyroid Diseases

    Directory of Open Access Journals (Sweden)

    Won Sang Yoo


    Full Text Available Autoimmune thyroid disease (AITD includes hyperthyroid Graves disease, hypothyroid autoimmune thyroiditis, and subtle subclinical thyroid dysfunctions. AITD is caused by interactions between genetic and environmental predisposing factors and results in autoimmune deterioration. Data on polymorphisms in the AITD susceptibility genes, related environmental factors, and dysregulation of autoimmune processes have accumulated over time. Over the last decade, there has been progress in the clinical field of AITD with respect to the available diagnostic and therapeutic methods as well as clinical consensus. The updated clinical guidelines allow practitioners to identify the most reasonable and current approaches for proper management. In this review, we focus on recent advances in understanding the genetic and environmental pathogenic mechanisms underlying AITD and introduce the updated set of clinical guidelines for AITD management. We also discuss other aspects of the disease such as management of subclinical thyroid dysfunction, use of levothyroxine plus levotriiodothyronine in the treatment of autoimmune hypothyroidism, risk assessment of long-standing antithyroid drug therapy in recurrent Graves' hyperthyroidism, and future research needs.

  11. PD-1 Checkpoint Inhibitor Associated Autoimmune Encephalitis

    Directory of Open Access Journals (Sweden)

    Stephanie Schneider


    Full Text Available Objective: To report first-hand narrative experience of autoimmune encephalitis and to briefly review currently available evidence of autoimmune encephalitis in cancer patients treated with immune checkpoint inhibitors. Setting: A case study is presented on the management of a patient who developed autoimmune encephalitis during nivolumab monotherapy occurring after 28 weeks on anti-PD-1 monotherapy (nivolumab 3 mg/kg every 2 weeks for non-small cell lung cancer. Results: No substantial improvement was observed by antiepileptic treatment. After administration of 80 mg methylprednisolone, neurologic symptoms disappeared within 24 h and the patient fully recovered. Conclusions: Immune checkpoint inhibitor treatment can lead to autoimmune encephalitis. Clinical trial data indicate a frequency of autoimmune encephalitis of ≥0.1 to <1% with a higher probability during combined or sequential anti-CTLA-4/anti-PD-1 therapy than during anti-PD-1 or anti-PD-L1 monotherapy. Further collection of evidence and translational research is warranted.

  12. Autoimmune Abnormalities of Postpartum Thyroid Diseases

    Directory of Open Access Journals (Sweden)

    Flavia Di Bari


    Full Text Available The year following parturition is a critical time for the de novo appearance or exacerbation of autoimmune diseases, including autoimmune thyroid disease. The vast majority of postpartum thyroid disease consists of postpartum thyroiditis (PPT and the minority by Graves’ disease and non-autoimmune thyroiditis. PPT has a worldwide prevalence ranging from 1 to 22% and averaging 5% based on a review published in 2012. Several factors confer risk for the development of PPT. Typically, the clinical course of PPT is characterized by three phases: thyrotoxic, hypothyroid, and euthyroid phase. Approximately half of PPT women will have permanent hypothyroidism. The best humoral marker for predictivity, already during the first trimester of gestation, is considered positivity for thyroperoxidase autoantibodies (TPOAb, though only one-third to half of such TPOAb-positive pregnant women will develop PPT. Nutraceuticals (such as selenium or omega-3-fatty acid supplements seem to have a role in prevention of PPT. In a recent study on pregnant women with stable dietary habits, we found that the fish consumers had lower rates of positivity (and lower serum levels of both TPOAb and thyroglobulin Ab compared to meat eaters. Finally, we remind the reader of other diseases that can be observed in the postpartum period, either autoimmune or non-autoimmune, thyroid or non-thyroid.

  13. Autoimmune Abnormalities of Postpartum Thyroid Diseases. (United States)

    Di Bari, Flavia; Granese, Roberta; Le Donne, Maria; Vita, Roberto; Benvenga, Salvatore


    The year following parturition is a critical time for the de novo appearance or exacerbation of autoimmune diseases, including autoimmune thyroid disease. The vast majority of postpartum thyroid disease consists of postpartum thyroiditis (PPT) and the minority by Graves' disease and non-autoimmune thyroiditis. PPT has a worldwide prevalence ranging from 1 to 22% and averaging 5% based on a review published in 2012. Several factors confer risk for the development of PPT. Typically, the clinical course of PPT is characterized by three phases: thyrotoxic, hypothyroid, and euthyroid phase. Approximately half of PPT women will have permanent hypothyroidism. The best humoral marker for predictivity, already during the first trimester of gestation, is considered positivity for thyroperoxidase autoantibodies (TPOAb), though only one-third to half of such TPOAb-positive pregnant women will develop PPT. Nutraceuticals (such as selenium) or omega-3-fatty acid supplements seem to have a role in prevention of PPT. In a recent study on pregnant women with stable dietary habits, we found that the fish consumers had lower rates of positivity (and lower serum levels) of both TPOAb and thyroglobulin Ab compared to meat eaters. Finally, we remind the reader of other diseases that can be observed in the postpartum period, either autoimmune or non-autoimmune, thyroid or non-thyroid.

  14. Prevalence of collagen VII-specific autoantibodies in patients with autoimmune and inflammatory diseases. (United States)

    Licarete, Emilia; Ganz, Susanne; Recknagel, Martin J; Di Zenzo, Giovanni; Hashimoto, Takashi; Hertl, Michael; Zambruno, Giovanna; Hundorfean, Gheorghe; Mudter, Jonas; Neurath, Markus F; Bruckner-Tuderman, Leena; Sitaru, Cassian


    Autoimmunity to collagen VII is typically associated with the skin blistering disease epidermolysis bullosa acquisita (EBA), but also occurs occasionally in patients with systemic lupus erythematosus or inflammatory bowel disease. The aim of our present study was to develop an accurate immunoassay for assessing the presence of autoantibodies against collagen VII in large cohorts of patients and healthy donors. Based on in silico antigenic analysis and previous wetlab epitope mapping data, we designed a chimeric collagen VII construct containing all collagen VII epitopes with higher antigenicity. ELISA was performed with sera from patients with EBA (n = 50), Crohn's disease (CD, n = 50), ulcerative colitis (UC, n = 50), bullous pemphigoid (BP, n = 76), and pemphigus vulgaris (PV, n = 42) and healthy donors (n = 245). By ELISA, the receiver operating characteristics analysis yielded an area under the curve of 0.98 (95% CI: 0.9638-1.005), allowing to set the cut-off at 0.32 OD at a calculated specificity of 98% and a sensitivity of 94%. Running the optimized test showed that serum IgG autoantibodies from 47 EBA (94%; 95% CI: 87.41%-100%), 2 CD (4%; 95% CI: 0%-9.43%), 8 UC (16%; 95% CI: 5.8%-26%), 2 BP (2.63%; 95% CI: 0%-6.23%), and 4 PV (9.52%; 95% CI: 0%-18.4%) patients as well as from 4 (1.63%; 95% CI: 0%-3.21%) healthy donors reacted with the chimeric protein. Further analysis revealed that in 34%, 37%, 16% and 100% of sera autoantibodies of IgG1, IgG2, IgG3, and IgG4 isotype, respectively, recognized the recombinant autoantigen. Using a chimeric protein, we developed a new sensitive and specific ELISA to detect collagen specific antibodies. Our results show a low prevalence of collagen VII-specific autoantibodies in inflammatory bowel disease, pemphigus and bullous pemphigoid. Furthermore, we show that the autoimmune response against collagen VII is dominated by IgG4 autoantibodies. The new immunoassay should prove a useful tool for clinical and translational

  15. Prevalence of collagen VII-specific autoantibodies in patients with autoimmune and inflammatory diseases

    Directory of Open Access Journals (Sweden)

    Licarete Emilia


    Full Text Available Abstract Background Autoimmunity to collagen VII is typically associated with the skin blistering disease epidermolysis bullosa acquisita (EBA, but also occurs occasionally in patients with systemic lupus erythematosus or inflammatory bowel disease. The aim of our present study was to develop an accurate immunoassay for assessing the presence of autoantibodies against collagen VII in large cohorts of patients and healthy donors. Methods Based on in silico antigenic analysis and previous wetlab epitope mapping data, we designed a chimeric collagen VII construct containing all collagen VII epitopes with higher antigenicity. ELISA was performed with sera from patients with EBA (n = 50, Crohn's disease (CD, n = 50, ulcerative colitis (UC, n = 50, bullous pemphigoid (BP, n = 76, and pemphigus vulgaris (PV, n = 42 and healthy donors (n = 245. Results By ELISA, the receiver operating characteristics analysis yielded an area under the curve of 0.98 (95% CI: 0.9638-1.005, allowing to set the cut-off at 0.32 OD at a calculated specificity of 98% and a sensitivity of 94%. Running the optimized test showed that serum IgG autoantibodies from 47 EBA (94%; 95% CI: 87.41%-100%, 2 CD (4%; 95% CI: 0%-9.43%, 8 UC (16%; 95% CI: 5.8%-26%, 2 BP (2.63%; 95% CI: 0%-6.23%, and 4 PV (9.52%; 95% CI: 0%-18.4% patients as well as from 4 (1.63%; 95% CI: 0%-3.21% healthy donors reacted with the chimeric protein. Further analysis revealed that in 34%, 37%, 16% and 100% of sera autoantibodies of IgG1, IgG2, IgG3, and IgG4 isotype, respectively, recognized the recombinant autoantigen. Conclusions Using a chimeric protein, we developed a new sensitive and specific ELISA to detect collagen specific antibodies. Our results show a low prevalence of collagen VII-specific autoantibodies in inflammatory bowel disease, pemphigus and bullous pemphigoid. Furthermore, we show that the autoimmune response against collagen VII is dominated by IgG4 autoantibodies. The new immunoassay should

  16. Recovery plan for Scots pine blister rust caused by Cronartium flaccidum (Alb. & Schwein.) G. Winter and Peridermium pini (Pers.) Lév. [syn. C. asclepiadeum (Willd.) Fr., Endocronartium pini (Pers.) Y. Hiratsuka (United States)

    Brian W. Geils; Ned B. Klopfenstein; Mee-Sook Kim; Pauline Spaine; Bryce A. Richardson; Paul J. Zambino; Charles G. Shaw; James Walla; Russ Bulluck; Laura Redmond; Kent. Smith


    The sexually reproducing form of Scots pine blister rust, C. flaccidum, completes its life cycle alternating between pines of the subgenus Pinus and seed-plants of various families. Scots pine blister rust is also caused by a form of the rust that spreads directly from pine to pine and is named, Peridermium pini...

  17. Dendritic cells and aging: consequences for autoimmunity. (United States)

    Agrawal, Anshu; Sridharan, Aishwarya; Prakash, Sangeetha; Agrawal, Harsh


    The immune system has evolved to mount immune responses against foreign pathogens and to remain silent against self-antigens. A balance between immunity and tolerance is required as any disturbance may result in chronic inflammation or autoimmunity. Dendritic cells (DCs) actively participate in maintaining this balance. Under steady-state conditions, DCs remain in an immature state and do not mount an immune response against circulating self-antigens in the periphery, which maintains a state of tolerance. By contrast, foreign antigens result in DC maturation and DC-induced T-cell activation. Inappropriate maturation of DCs due to infections or tissue injury may cause alterations in the balance between the tolerogenic and immunogenic functions of DCs and instigate the development of autoimmune diseases. This article provides an overview of the effects of advancing age on DC functions and their implications in autoimmunity.

  18. Autoimmune Hepatitis: A Risk Factor for Cholangiocarcinoma

    Directory of Open Access Journals (Sweden)

    Rajat Garg


    Full Text Available Cholangiocarcinoma (CCA is a very aggressive and lethal tumor, which arises from the epithelial cells of bile ducts. CCA comprises about 3% of all gastrointestinal malignancies and its incidence is on the rise in the recent years. Anatomically, it is classified into intrahepatic, perihilar, or extrahepatic (distal CCA. There are a number of risk factors associated with CCA including primary sclerosing cholangitis, fibropolycystic liver disease, parasitic infection, viral hepatitis, chronic liver disease, and genetic disorders like Lynch syndrome. Autoimmune hepatitis is also recently reported to have an association with development of CCA. We report an interesting case of perihilar CCA in the setting of autoimmune hepatitis along with a literature review. This case highlights the importance of early treatment and close clinical follow-up of patients with autoimmune hepatitis for development of CCA.

  19. The clinical extremes of autoimmune cholangitis

    Directory of Open Access Journals (Sweden)

    Sara Campos

    Full Text Available Autoimmune cholangitis (AIC was first described in 1987 as immunocholangitis in three women who presented with signs and symptoms of primary biliary cholangitis (PBC, but who were antimitochondrial (AMA negative and antinuclear antibodies (ANA positive, and responded to immunosuppressive therapy with azathioprine and prednisolone (1. AIC is a rare chronic cholestatic inflammatory disease characterized by the presence of high ANA or smooth muscle antibodies (SMA but AMA seronegativity. Histologically, AIC exhibits bile duct injury (2. In terms of therapeutics, in addition to response to ursodeoxycholic acid, a prompt response to corticosteroids has also been reported in earlier stages, distinguishing it from PBC. Herein the authors describe two cases with mixed signs of PBC and autoimmune hepatitis (AIH. The diagnostic differentiation between these diseases (AIC, PBC and AIH is essential because of the different therapeutic strategies. Our cases highlight the importance of clinician awareness of the autoimmune spectrum of liver diseases.

  20. Interferon regulatory factor signaling in autoimmune disease. (United States)

    Matta, Bharati; Song, Su; Li, Dan; Barnes, Betsy J


    Interferon regulatory factors (IRFs) play critical roles in pathogen-induced innate immune responses and the subsequent induction of adaptive immune response. Dysregulation of IRF signaling is therefore thought to contribute to autoimmune disease pathogenesis. Indeed, numerous murine in vivo studies have documented protection from or enhanced susceptibility to particular autoimmune diseases in Irf-deficient mice. What has been lacking, however, is replication of these in vivo observations in primary immune cells from patients with autoimmune disease. These types of studies are essential as the majority of in vivo data support a protective role for IRFs in Irf-deficient mice, yet IRFs are often found to be overexpressed in patient immune cells. A significant body of work is beginning to emerge from both of these areas of study - mouse and human. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Autoimmune manifestations in large granular lymphocyte leukemia. (United States)

    Bockorny, Bruno; Dasanu, Constantin A


    Large granular lymphocyte (LGL) leukemia features a group of indolent lymphoproliferative diseases that display a strong association with various autoimmune conditions. Notwithstanding, these autoimmune conditions have not been comprehensively characterized or systematized to date. As a result, their clinical implications remain largely unknown. The authors offer a comprehensive review of the existing literature on various autoimmune conditions documented in the course of T-cell LGL (T-LGL) leukemia. Though some of them are thought be secondary to the LGL leukemia, others could be primary and might even play a role in its pathogenesis. A considerable clinico-laboratory overlap between T-LGL leukemia associated with rheumatoid arthritis and Felty's syndrome suggests that they are just different eponyms for the same clinical entity. Published by Elsevier Inc.

  2. Epidemiology of autoimmune diseases in Denmark

    DEFF Research Database (Denmark)

    Eaton, William W.; Rose, N.R.; Kalaydijan, A.


    An epidemiologic study of the autoimmune diseases taken together has not been done heretofore. The National Patient Register of Denmark is used to estimate the population prevalence of 31 possible or probable autoimmune diseases. Record linkage is used to estimate 465 pairwise co...... diseases and weak across diseases. These data confirm the importance of the autoimmune diseases as a group and suggest that common etiopathologies exist among them......-morbidities in individuals among the 31 diseases, and familial aggregation among sibs, parents and offspring. The prevalence of any of the 31 diseases in the population is more than 5%. Within individuals, there is extensive comorbidity across the 31 diseases. Within families, aggregation is strongest for individual...

  3. Safety of vaccine adjuvants: focus on autoimmunity. (United States)

    van der Laan, Jan Willem; Gould, Sarah; Tanir, Jennifer Y


    Questions have been recently raised regarding the safety of vaccine adjuvants, particularly in relation to autoimmunity or autoimmune disease(s)/disorder(s) (AID). The International Life Sciences Institute (ILSI) Health and Environmental Sciences Institute (HESI) formed a scientific committee and convened a 2-day workshop, consisting of technical experts from around the world representing academia, government regulatory agencies, and industry, to investigate and openly discuss the issues around adjuvant safety in vaccines. The types of adjuvants considered included oil-in-water emulsions and toll-like receptor (TLR) agonists. The state of science around the use of animal models and biomarkers for the evaluation and prediction of AID were also discussed. Following extensive literature reviews by the HESI committee, and presentations by experts at the workshop, several key points were identified, including the value of animal models used to study autoimmunity and AID toward studying novel vaccine adjuvants; whether there is scientific evidence indicating an intrinsic risk of autoimmunity and AID with adjuvants, or a higher risk resulting from the mechanism of action; and if there is compelling clinical data linking adjuvants and AID. The tripartite group of experts concluded that there is no compelling evidence supporting the association of vaccine adjuvants with autoimmunity signals. Additionally, it is recommended that future research on the potential effects of vaccine adjuvants on AID should consider carefully the experimental design in animal models particularly if they are to be used in any risk assessment, as an improper design and model could result in misleading information. Finally, studies on the mechanistic aspects and potential biomarkers related to adjuvants and autoimmunity phenomena could be developed. Copyright © 2015. Published by Elsevier Ltd.. All rights reserved.

  4. [Autoimmune polyendocrine syndrome type 2 associated with autoimmune hypophysitis and coeliac disease]. (United States)

    Hrubisková, K; Jackuliak, P; Vanuga, P; Pura, M; Payer, J


    Autoimmune polyendocrine syndromes (APS) are organ-specific autoimmune disorders affecting multiple endocrine glands; these are gradually destroyed by action of autoantibodies. Similarly to other autoimmune diseases, the presence of certain genetic predisposition is an essential prerequisite to the disease development; polymorphism of the main histocompatible system (HLA in humans) appears to play the most important role. APS are categorized into four types, based on what combination of endocrine glands is affected. APS type 1, characterised by hypoparathyreosis, mucocutaneous candidiasis and Addison's disease, is frequently seen in childhood. For a more common APS type 2 to be diagnosed, Addison's disease together with autoimmune thyroiditis (Schmidt's syndrome) and/or together with diabetes mellitus type I (Carpenter's syndrome) must be present. The third type of autoimmune polyendocrine syndromes (APS type 3) involves the same disorder of endocrine glands as type 2 but usually without any defect of adrenal cortex. If the autoimmune endocrine gland disorder does not fulfil the criteria of APS 1-3, the disease may be categorized as autoimmune polyendocrine syndrome type 4. The authors present a case of 33 years old APS type 2 patient who, over 20 years, developed a wide range of autoimmune endocrinopathies, including endocrinopathies that are less common, such as adenohypophysitis, and are associated with other organ-specific diseases (coeliac disease). The case is presented to demonstrate the fact that APS represent a dynamic process and that it is always important to keep in mind that, over time, a patient may develop other autoimmune diseases. To conclude, the authors emphasise the recommendation to test patients with monoglandular endocrinopathy for the presence of any secondary endocrine disorders.

  5. Diagnosis and Management of Pediatric Autoimmune Liver Disease : ESPGHAN Hepatology Committee Position Statement

    NARCIS (Netherlands)

    Mieli-Vergani, Giorgina; Vergani, Diego; Baumann, Ulrich; Czubkowski, Piotr; Debray, Dominique; Dezsofi, Antal; Fischler, Björn; Gupte, Girish; Hierro, Loreto; Indolfi, Giuseppe; Jahnel, Jörg; Smets, Françoise; Verkade, Henkjan J; Hadžić, Nedim

    Paediatric autoimmune liver disease is characterized by inflammatory liver histology, circulating autoantibodies, and increased levels of IgG, in the absence of a known etiology. Three conditions have a likely autoimmune pathogenesis: autoimmune hepatitis (AIH), autoimmune sclerosing cholangitis,

  6. Autoimmune Inner Ear Disease- A Clinical Viewpoint

    Directory of Open Access Journals (Sweden)

    Amirala Khalessi


    Full Text Available Recent developments in medicine have given us a better insight into a group of disorders known as autoimmune diseases. In particular, advances have occurred in our understanding of the Autoimmune Inner Ear Disease (AIED. In this article, the authors review the different postulated theories in the pathogenesis of this disease. The clinical presentation, the available para-clinical diagnostic tools, and the important differential diagnoses will be summarized. The management methods, including steroid therapy, immunosuppressive medications, other biological agents and intra-tympanic injections, will be addressed. Cochlear implantation as a final solution to the advanced stages of the disease, causing total deafness, will also be discussed.

  7. Diagnosis and classification of autoimmune hemolytic anemia. (United States)

    Bass, Garrett F; Tuscano, Emily T; Tuscano, Joseph M


    Uncompensated autoantibody-mediated red blood cell (RBC) consumption is the hallmark of autoimmune hemolytic anemia (AIHA). Classification of AIHA is pathophysiologically based and divides AIHA into warm, mixed or cold-reactive subtypes. This thermal-based classification is based on the optimal autoantibody-RBC reactivity temperatures. AIHA is further subcategorized into idiopathic and secondary with the later being associated with a number of underlying infectious, neoplastic and autoimmune disorders. In most cases AIHA is confirmed by a positive direct antiglobulin test (DAT). The standard therapeutic approaches to treatment of AIHA include corticosteroids, splenectomy, immunosuppressive agents and monoclonal antibodies. Published by Elsevier B.V.

  8. Helicobacter pylori and autoimmune disease:Cause or bystander

    National Research Council Canada - National Science Library

    Daniel S Smyk Andreas L Koutsoumpas Maria G Myt-ilinaiou Eirini I Rigopoulou Lazaros I Sakkas Dimitrios P Bogdanos


    ... 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...

  9. Generalized Vitiligo Associated Autoimmune Diseases in Japanese Patients Their Families

    Directory of Open Access Journals (Sweden)

    Tomohiko Narita


    Conclusions: Among Japanese vitiligo patients, there is a subgroup with strong evidence of genetically determined susceptibility to not only vitiligo, but also to autoimmune thyroid disease and other autoimmune disorders.

  10. Shared genetic origins of allergy and autoimmune diseases

    DEFF Research Database (Denmark)

    Waage, J. E.; Kreiner-Møller, E.; Standl, M.


    Parallel increases in allergy and autoimmune disease prevalence in recent time suggest shared, but yet unknown, etiologies. Here, we investigated shared genetic loci and molecular pathways to identify possible shared disease mechanisms between allergy and autoimmune diseases....

  11. Genetics Home Reference: autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (United States)

    ... Facebook Twitter Home Health Conditions APECED Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy Printable PDF Open All Close All ... view the expand/collapse boxes. Description Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy ( APECED ) is an inherited condition that ...

  12. Complement inhibitors to treat IgM-mediated autoimmune hemolysis

    NARCIS (Netherlands)

    Wouters, Diana; Zeerleder, Sacha


    Complement activation in autoimmune hemolytic anemia may exacerbate extravascular hemolysis and may occasionally result in intravascular hemolysis. IgM autoantibodies as characteristically found in cold autoantibody autoimmune hemolytic anemia, in cold agglutinin disease but also in a considerable

  13. Breakdown of major gene resistance to white pine blister rust in sugar pine at Mountain Home Demonstration State Forest: what are the implications? (United States)

    Jr. Bohun B. Kinloch


    A virulent race of blister rust capable of neutralizing major gene resistance (MGR) in sugar pine made its first appearance nearly two decades ago at a test plantation of resistant sugar pines near Happy Camp, in northern California. Until this year (1996), it had not been found outside the very close neighborhood of this site. Its discovery last summer at Mountain...

  14. Ecology of whitebark pine populations in relation to white pine blister rust infection in subalpine forests of the Lake Tahoe Basin: Implications for restoration (United States)

    Patricia E. Maloney; Detlev R. Vogler; Camille E. Jensen; Annette. Delfino Mix


    For over a century, white pine blister rust (WPBR), caused by the introduced fungal pathogen, Cronartium ribicola J.C. Fisch., has affected white pine (Subgenus Strobus) individuals, populations, and associated forest communities in North America. We surveyed eight populations of whitebark pine (Pinus albicaulis Engelm.) across a range of environmental conditions in...

  15. White pine blister rust at mountain home demonstration state forest: a case study of the epidemic and prospects for genetic control. (United States)

    Bohun B. Kinloch; Dulitz Jr.


    The behavior of white pine blister rust at Mountain Home State Demonstration Forest and surrounding areas in the southern Sierra Nevada of California indicates that the epidemic has not yet stabilized and that the most likely prognosis is a pandemic on white pines in this region within the next few decades. The impact on sugar pines, from young regeneration to old...

  16. Effect of white pine blister rust (Cronartium ribicola) and rust-resistance breeding on genetic variation in western white pine Pinus monticola) (United States)

    M. -S. Kim; S. J. Brunsfeld; G. I. McDonald; N. B. Klopfenstein


    Western white pine (Pinus monticola) is an economically and ecologically important species from western North America that has declined over the past several decades mainly due to the introduction of blister rust (Cronartium ribicola) and reduced opportunities for regeneration. Amplified fragment length polymorphism (AFLP) was used...

  17. Synoptic climatology of the long-distance dispersal of white pine blister rust II. Combination of surface and upper level conditions (United States)

    K. L. Frank; B. W. Geils; L. S. Kalkstein; H. W. Thistle


    An invasive forest pathogen, Cronartium ribicola, white pine blister rust (WPBR), is believed to have arrived in the Sacramento Mountains of south-central New Mexico about 1970. Epidemiological and genetic evidence supports the hypothesis that introduction was the result of long-distance dispersal (LDD) by atmospheric transport from California. This...

  18. Antitumor effect of blister beetles: an ethno-medicinal practice in Karbi community and its experimental evaluation against a murine malignant tumor model. (United States)

    Verma, Akalesh Kumar; Prasad, Surya Bali


    The blister beetles Epicauta hirticornis and Mylabris cichorii are used as a folk medicine by the Karbi tribe in Karbi Anglong district of Assam, India for the treatment of different human ailments, including cancer cases. It includes field survey related to zoo-therapeutic aspects of two blister beetles in Karbi community, isolation of bio-active compound and evaluation of its antitumor potential with possible mode of action against murine Ehrlich ascites carcinoma (EAC). The main bio-active compound of blister beetles was isolated from ethyl acetate extract and the structure was confirmed as cantharidin using NMR, IR, Mass and X-ray diffractometer. The effect of cantharidin on apoptosis, necrosis, autophagy and the apoptosis related signaling pathways were determined using different bioassays, including cell cycle analysis, mitochondrial membrane potential, western blot analysis of cytochrome c, caspases 9, 3/7 assays, and lactate dehydrogenase (LDH) assay. Cantharidin induced apoptosis, necrosis and autophagy cell death in EAC cells. The decrease in mitochondrial membrane potential was observed, which may help to release cytochrome c from mitochondria to cytosol. Cantharidin treatment caused up-regulation of caspases 9 and -3/7 and a decrease in LDH activity in EAC cells. The major bioactive compound of these blister beetles is cantharidin which induces severe apoptosis in EAC cells involving mitochondrial intrinsic pathway. Cantharidin-mediated inhibition of LDH activity may lead to short supply of NAD(+) and cut off energy and anabolic supply to cancer cells. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  19. Autoimmune Addison disease: pathophysiology and genetic complexity. (United States)

    Mitchell, Anna L; Pearce, Simon H S


    Autoimmune Addison disease is a rare autoimmune disorder with symptoms that typically develop over months or years. Following the development of serum autoantibodies to the key steroidogenic enzyme, 21-hydroxylase, patients have a period of compensated or preclinical disease, characterized by elevations in adrenocortocotropic hormone and renin, before overt, symptomatic adrenal failure develops. We propose that local failure of steroidogenesis, causing breakdown of tolerance to adrenal antigens, might be a key factor in disease progression. The etiology of autoimmune Addison disease has a strong genetic component in man, and several dog breeds are also susceptible. Allelic variants of genes encoding molecules of both the adaptive and innate immune systems have now been implicated, with a focus on the immunological synapse and downstream participants in T lymphocyte antigen-receptor signaling. With the exception of MHC alleles, which contribute to susceptibility in both human and canine Addison disease, no major or highly penetrant disease alleles have been found to date. Future research into autoimmune Addison disease, making use of genome-wide association studies and next-generation sequencing technology, will address the gaps in our understanding of the etiology of this disease.

  20. Costimulation and autoimmune diabetes in BB rats

    NARCIS (Netherlands)

    Beaudette-Zlatanova, BC; Whalen, B; Zipris, D; Yagita, H; Rozing, J; Groen, H; Benjamin, CD; Hunig, T; Drexhage, HA; Ansari, MJ; Leif, J; Mordes, JP; Greiner, DL; Sayegh, MH; Rossini, AA

    Costimulatory signals regulate T-cell activation. To investigate the role of costimulation in autoimmunity and transplantation, we studied the BB rat model of type 1 diabetes. Diabetes-prone BB (BBDP) rats spontaneously develop disease when 55-120 days of age. We observed that two anti-CD28

  1. Autoimmune hepatitis : Pathogenesis, diagnosis and treatment

    NARCIS (Netherlands)

    van den Berg, AP

    Background: Autoimmune hepatitis (AIH) is a chronic necro-inflammatory disease of the liver. Early recognition is important in order to prevent the development of cirrosis. This review discusses recent developments in the fields of diagnosis, pathophysiology and management of AIH. Methods: Relevant

  2. Autoimmune Response Confers Decreased Cardiac Function in ...

    African Journals Online (AJOL)

    Purpose: To explore the effect of autoimmune response on the decreased cardiac function in patients with rheumatic mitral lesion following valve replacement. Methods: In this case-controlled study, 29 patients who had undergone valve replacement as a result of mitral lesion were enrolled (mean age = 48.7 years). Twenty ...

  3. Is Tourette's syndrome an autoimmune disease?

    NARCIS (Netherlands)

    Hoekstra, PJ; Kallenberg, CGM; Korf, J; Minderaa, RB


    We provide a review of recent research findings which support the involvement of autoimmunity in childhood-onset tic disorders, in particular the presence of antineuronal autoantibodies, D8/17 B lymphocyte overexpression, a marker of chorea associated with streptococcal infection, and possible

  4. Autism and Autoimmune Disease: A Family Study (United States)

    Money, John; And Others


    Described in a family in which the youngest boy has early infantile autism, Addison's disease, and moniliasis and two older boys have autoimmune disease with hypoparathyroidism, Addison's disease, moniliasis, and either alopecia totalis or diabetes mellitus, while the oldest boy and parents are symptom free. (KW)

  5. Alopecia areata and autoimmunity: A clinical study

    Directory of Open Access Journals (Sweden)

    Thomas Emy


    Full Text Available Alopecia areata (AA frequently occur in association with other autoimmune diseases such as thyroid disorders, anemias and other skin disorders with autoimmune etiology. Despite numerous studies related to individual disease associations in alopecia areata, there is paucity of literature regarding comprehensive studies on concomitant cutaneous and systemic diseases. The present study has been designed to determine if there is a significant association between alopecia areata and other autoimmune diseases. This study covers 71 patients with the diagnosis of alopecia areata as the case group and 71 patients with no evidence of alopecia areata as the control group. Among the cutaneous diseases associated with AA, atopic dermatitis (AD showed maximum frequency with an O/E ratio of 2.5, which indicates that it is two to three times more common in patients with alopecia areata. In our study, thyroid disorders showed the highest frequency with on O/E ratio of 3.2 and a P value of 0.01, which is statistically highly significant. Among the thyroid disorders, hypothyroidism was the most frequent association (14.1% in our study. Since systemic involvement is not infrequent in patients with alopecia areata, it is imperative to screen these patients for associated disorders, particularly atopy, thyroid diseases, anemias and other autoimmune disorders, especially if alopecia areata is chronic, recurrent and extensive.

  6. Probable autoimmune causal relationship between periodontitis and ...

    African Journals Online (AJOL)


    Mar 26, 2011 ... In 1965, Brandtzaeg and Kraus were the first to postulate the autoimmune ... thyroiditis are drawn with the evidence base, in this review. ... [17] Iodine is a necessary component of normal ..... data appear extremely relevant, as they would certainly ... work, in the form of cohort studies and controlled studies.

  7. Increased prevalence of autoimmunity in Turner syndrome

    DEFF Research Database (Denmark)

    Mortensen, K H; Cleemann, L; Hjerrild, B E


    Individuals with Turner syndrome (TS) are prone to develop autoimmune conditions such as coeliac disease (CD), thyroiditis and type 1 diabetes (T1DM). The objective of the present study was to examine TS of various karyotypes for autoantibodies and corresponding diseases. This was investigated...

  8. Autoimmun hepatitis. Fremtroedelsesformer, diagnostik og behandling

    DEFF Research Database (Denmark)

    Poulsen, L O; Tage-Jensen, U; Vyberg, M


    A retrospective study concerning ten patients with autoimmune hepatitis (AiH), diagnosed during a 2 1/2-year period is presented. The age of the patients ranged from 25 to 82 years and nine of the patients were women. Their symptoms included jaundice, pruritus, fever, anorexia and fatigue during...

  9. Genetic risk factors for autoimmune diseases

    NARCIS (Netherlands)

    Feltkamp, T.E.W.; Aarden, L.A.; Lucas, C.J.; Verweij, C.L.; Vries, R.R.P. de


    In most autoimmune diseases multigenic factors play a significant role in pathogenesis. Progress in identifying these genetic factors, many of which are located outside the major histocompatibility complex, was the subject of a recent meeting. Chemicals/CAS: Interleukin-10, 130068-27-8; Transforming

  10. The Role of Innate Immunity in Autoimmunity (United States)

    Bach, Jean-François; Bendelac, Albert; Brenner, Michael B.; Cantor, Harvey; De Libero, Gennaro; Kronenberg, Mitchell; Lanier, Lewis L.; Raulet, David H.; Shlomchik, Mark J.; von Herrath, Matthias G.


    During the 2004 International Congress of Immunology in Montreal, a panel of experts gathered for an “Ideashop” discussion on the potential role of innate immunity in autoimmunity and the ways in which this might be targeted in future therapies. PMID:15611284

  11. Overlap syndromes among autoimmune liver diseases

    NARCIS (Netherlands)

    Rust, Christian; Beuers, Ulrich


    The three major immune disorders of the liver are autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC). Variant forms of these diseases are generally called overlap syndromes, although there has been no standardise definition. Patients with overlap

  12. Inheritable and sporadic non-autoimmune hyperthyroidism. (United States)

    Ferraz, Carolina; Paschke, Ralf


    Hyperthyroidism is a clinical state that results from high thyroid hormone levels which has multiple etiologies, manifestations, and potential therapies. Excluding the autoimmune Graves disease, autonomic adenomas account for the most import cause of non-autoimmune hyperthyroidism. Activating germline mutations of the TSH receptor are rare etiologies for hyperthyroidism. They can be inherited in an autosomal dominant manner (familial or hereditary, FNAH), or may occur sporadically as a de novo condition, also called: persistent sporadic congenital non-autoimmune hyperthyroidism (PSNAH). These three conditions: autonomic adenoma, FNAH and PSNAH constitute the inheritable and sporadic non-autoimmune hyperthyroidism. Particularities in epidemiology, etiology, molecular and clinical aspects of these three entities will be discussed in this review in order to guide to an accurate diagnosis allowing among others genetic counseling and presymptomatic diagnosis for the affected families. The optimal treatment based on the right diagnosis will avoid consequences of a persistent or relapsing hyperthyroidism. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

  13. Is Tourette's syndrome an autoimmune disease?

    NARCIS (Netherlands)

    Hoekstra, P; Limburg, P; Kallenberg, C; Minderaa, R; Battistin, L


    Tourette's syndrome is a childhood-onset neuropsychiatric disorder characterized by the presence of both multiple motor and vocal tics. While its pathogenesis at a molecular and cellular level remains unknown, recent research findings point to the possible involvement of autoimmunity in at least a

  14. Autophagy and Autoimmunity CrossTalks

    Directory of Open Access Journals (Sweden)

    Abhisek eBhattacharya


    Full Text Available Autophagy, initially viewed as a conserved bulk-degradation mechanism, has emerged as a central player in a multitude of immune functions. Autophagy is important in host defense against intracellular and extracellular pathogens, metabolic syndromes, immune cell homeostasis, antigen processing and presentation and maintenance of tolerance. The observation that the above processes are implicated in triggering or exacerbating autoimmunity raises the possibility that the autophagy pathway is involved in mediating autoimmune processes, either directly or as a consequence of innate or adaptive functions mediated by the pathway. Genome-wide association studies have shown association between single nucleotide polymorphisms (SNPs in autophagy related gene 5 (Atg5, and Atg16l1 with susceptibility to systemic lupus erythematous (SLE and Crohn’s disease, respectively. Enhanced expression of Atg5 was also reported in blood of mice with experimental autoimmune encephalomyelitis (EAE, a mouse model of multiple sclerosis (MS, and in T cells isolated from blood or brain tissues from patients with active relapse of MS. This review explores the roles of autophagy pathway in the innate and adaptive immune systems on regulating or mediating the onset, progression or exacerbation of autoimmune processes.

  15. Autoimmun hypophysitis--en differentialdiagnose til hypofyseadenomer

    DEFF Research Database (Denmark)

    Krarup, Therese; Hagen, Claus


    A 66-year-old man with a headache in the left temporal region which had persisted for eight months is presented. The patient developed polydipsia and polyuria and also suffered from tinnitus, impaired hearing and episodes of double vision. The patient was diagnosed with autoimmune hypophysitis (AH...

  16. Autoimmun synaptisk encefalitis er en underdiagnosticeret sygdomsgruppe

    DEFF Research Database (Denmark)

    Nielsen, Signe Modvig; Høi-Hansen, Christina Engel; Uldall, Peter


    The term autoimmune synaptic encephalitis (ASE) comprises encephalitides associated with autoantibodies against structures of the neuronal synapse. We review four types of ASE (anti-N-methyl-D-aspartate receptor encephalitis, anti-α-amine-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor...

  17. Anti-cytokine autoantibodies in autoimmune diseases (United States)

    Cappellano, Giuseppe; Orilieri, Elisabetta; Woldetsadik, Abiy D; Boggio, Elena; Soluri, Maria F; Comi, Cristoforo; Sblattero, Daniele; Chiocchetti, Annalisa; Dianzani, Umberto


    An overview of the current literature is showing that autoantibodies (AutoAbs) against cytokines are produced in several pathological conditions, including autoimmune diseases, but can also be detected in healthy individuals. In autoimmune diseases, these AutoAbs may also be prognostic markers, either negative (such as AutoAbs to IL-8 and IL-1α in rheumatoid arthritis) or positive (such as AutoAbs to IL-6 in systemic sclerosis and those to osteopontin in rheumatoid arthritis). They may have neutralizing activity and influence the course of the physiological and pathological immune responses. High levels of AutoAbs against cytokines may even lead to immunodeficiency, such as those to IL-17 in autoimmune polyendocrine syndrome type I or those to IFN-γ in mycobacterial infections. Their role in human therapy may be exploited not only through passive immunization but also through vaccination, which may improve the costs for long lasting treatments of autoimmune diseases. Detection and quantification of these AutoAbs can be profoundly influenced by the technique used and standardization of these methods is needed to increase the value of their analysis. PMID:23885320

  18. Immunosensors for Biomarker Detection in Autoimmune Diseases. (United States)

    Zhang, Xuezhu; Zambrano, Amarayca; Lin, Zuan-Tao; Xing, Yikun; Rippy, Justin; Wu, Tianfu


    Autoimmune diseases occur when the immune system generates proinflammatory molecules and autoantibodies that mistakenly attack their own body. Traditional diagnosis of autoimmune disease is primarily based on physician assessment combined with core laboratory tests. However, these tests are not sensitive enough to detect early molecular events, and quite often, it is too late to control these autoimmune diseases and reverse tissue damage when conventional tests show positivity for disease. It is fortunate that during the past decade, research in nanotechnology has provided enormous opportunities for the development of ultrasensitive biosensors in detecting early biomarkers with high sensitivity. Biosensors consist of a biorecognition element and a transducer which are able to facilitate an accurate detection of proinflammatory molecules, autoantibodies and other disease-causing molecules. Apparently, novel biosensors could be superior to traditional metrics in assessing the drug efficacy in clinical trials, especially when specific biomarkers are indicative of the pathogenesis of disease. Furthermore, the portability of a biosensor enables the development of point-of-care devices. In this review, various types of biomolecule sensing systems, including electrochemical, optical and mechanical sensors, and their applications and future potentials in autoimmune disease treatment were discussed.

  19. Autoimmune hepatitis in children in Eastern Denmark

    DEFF Research Database (Denmark)

    Vitfell-Pedersen, Joanna; Jørgensen, Marianne Hørby; Müller, Klaus


    Autoimmune hepatitis (AIH) in childhood is a progressive chronic inflammatory liver disease. The aim of this study was to compare the clinical and biochemical characteristics of 33 paediatric patients diagnosed as having AIH with earlier described cohorts, and to examine the effect of early...

  20. Study of cytokines microenvironment during autoimmune diseases ...

    African Journals Online (AJOL)

    The development of autoimmun diseases involves an intricate network of cytokines that recruit and activate TREGS/ TH17 cells. This study was aimed to compare PBMC levels of pro-inflammatory and anti-inflammatory cytokines in AID patients and non-AID controls from Bobo Dioulasso. We prospectively enrolled 17 ...

  1. Autoimmune hemolytic anemia in chronic mucocutaneous candidiasis.


    Oyefara, B I; Kim, H. C.; Danziger, R N; Carroll, M; Greene, J M; Douglas, S D


    Chronic mucocutaneous candidiasis is an immunodeficiency disease characterized by T-cell dysregulation and chronic superficial candidal infections. We report on three patients with chronic mucocutaneous candidiasis who developed autoantibodies to erythrocytes. Our first patient, a 19-year-old female, developed autoimmune hemolytic anemia (AIHA) that required multiple courses of treatment, including corticosteroids, intravenous immunoglobulin, and danazol. During the last exacerbation of AIHA,...

  2. IL-35 and Autoimmunity: a Comprehensive Perspective. (United States)

    Choi, Jinjung; Leung, Patrick S C; Bowlus, Christopher; Gershwin, M Eric


    Interleukin 35 (IL-35) is the most recently identified member of the IL-12 family of cytokines and offers the potential to be a target for new therapies for autoimmune, inflammatory, and infectious diseases. Similar to other members of the IL-12 family including IL-12, IL-23, and IL-27, IL-35 is composed of a heterodimer of α and β chains, which in the case of IL-35 are the p35 and Epstein-Barr virus-induced gene 3 (EBI3) proteins. However, unlike its proinflammatory relatives, IL-35 has immunosuppressive effects that are mediated through regulatory T and B cells. Although there are limited data available regarding the role of IL-35 in human autoimmunity, several murine models of autoimmunity suggest that IL-35 may have potent effects in regulating immunoreactivity via IL-10-dependent mechanisms. We suggest that similar effects are operational in human disease and IL-35-directed therapies hold significant promise. In particular, we emphasize that IL-35 has immunosuppressive ability that are mediated via regulatory T and B cells that are IL-10 dependent. Further, although deletion of IL-35 does not result in spontaneous breach of tolerance, recombinant IL-35 can improve autoimmune responses in several experimental models.

  3. The complement system in systemic autoimmune disease

    NARCIS (Netherlands)

    Chen, Min; Daha, Mohamed R.; Kallenberg, Cees G. M.

    Complement is part of the innate immune system. Its major function is recognition and elimination of pathogens via direct killing and/or stimulation of phagocytosis. Activation of the complement system is, however, also involved in the pathogenesis of the systemic autoimmune diseases. Activation via

  4. Premature atherosclerosis in systemic autoimmune diseases

    NARCIS (Netherlands)

    Leeuw, Karina de


    Systemic autoimmune diseases such as systemic lupus erythematosus (SLE) and Wegener’s granulomatosis (WG) are associated with a significantly increased prevalence of cardiovascular disease (CVD) compared to age- and sex-matched controls. Many risk factors are involved in the pathogenesis of

  5. Renal involvement in autoimmune connective tissue diseases


    Kronbichler, Andreas; Mayer, Gert


    Connective tissue diseases (CTDs) are a heterogeneous group of disorders that share certain clinical presentations and a disturbed immunoregulation, leading to autoantibody production. Subclinical or overt renal manifestations are frequently observed and complicate the clinical course of CTDs. Alterations of kidney function in Sj?gren syndrome, systemic scleroderma (SSc), auto-immune myopathies (dermatomyositis and polymyositis), systemic lupus erythematosus (SLE), antiphospholipid syndrome n...

  6. Pharmacological properties of blister beetles (Coleoptera: Meloidae) promoted their integration into the cultural heritage of native rural Spain as inferred by vernacular names diversity, traditions, and mitochondrial DNA. (United States)

    Percino-Daniel, Nohemí; Buckley, David; García-París, Mario


    Beetles of the family Meloidae (blister beetles) are often reported in pharmacological literature because of their content of cantharidin. Cantharidin has a long history in human medicine and was commonly applied in the 19th and the early 20th centuries, although its use has been progressively abandoned since then. Contrary to most, even common, large species of Coleoptera, blister beetles of the genera Berberomeloe, Physomeloe and to a lesser extent Meloe, are usually recognized and often incorporated into local folk taxonomy by inhabitants of rural areas in Spain. To demonstrate the role that pharmacological properties of blister beetles must have played in their integration in the culture of early Iberian human societies, but also in the preservation of their identity until today, a rare case for Spanish insects. To achieve this purpose we document the diversity of vernacular names applied in rural areas of Spain, and we determine, using molecular data, the antiquity of the presence of two species of the better-known blister beetle in rural Spain, Berberomeloe majalis and Berberomeloe insignis. We try to document the extent of traditional knowledge of meloid beetles in rural areas by interviewing about 120 people from villages in central and southern Spain. We also use mitochondrial DNA sequences (Cytochrome Oxidase I and 16SrRNA) obtained from several populations of two species of the better known blister beetle in rural Spain, Berberomeloe majalis and Berberomeloe insignis, to determine whether these beetles were already present in the Iberian Peninsula when earlier ancient cultures were developing. Our results show that, based on mitochondrial DNA, blister beetles of the genus Berberomeloe were present in the Iberian Peninsula long before humans arrived, so ancient Iberian cultures were in contact with the same beetle species occurring now in rural areas. On the other hand, people interviewed in rural communities provided us with more than 28 different

  7. Imaging combined autoimmune and infectious disease microarrays (United States)

    Ewart, Tom; Raha, Sandeep; Kus, Dorothy; Tarnopolsky, Mark


    Bacterial and viral pathogens are implicated in many severe autoimmune diseases, acting through such mechanisms as molecular mimicry, and superantigen activation of T-cells. For example, Helicobacter pylori, well known cause of stomach ulcers and cancers, is also identified in ischaemic heart disease (mimicry of heat shock protein 65), autoimmune pancreatitis, systemic sclerosis, autoimmune thyroiditis (HLA DRB1*0301 allele susceptibility), and Crohn's disease. Successful antibiotic eradication of H.pylori often accompanies their remission. Yet current diagnostic devices, and test-limiting cost containment, impede recognition of the linkage, delaying both diagnosis and therapeutic intervention until the chronic debilitating stage. We designed a 15 minute low cost 39 antigen microarray assay, combining autoimmune, viral and bacterial antigens1. This enables point-of-care serodiagnosis and cost-effective narrowly targeted concurrent antibiotic and monoclonal anti-T-cell and anti-cytokine immunotherapy. Arrays of 26 pathogen and 13 autoimmune antigens with IgG and IgM dilution series were printed in triplicate on epoxysilane covalent binding slides with Teflon well masks. Sera diluted 1:20 were incubated 10 minutes, washed off, anti-IgG-Cy3 (green) and anti-IgM-Dy647 (red) were incubated for 5 minutes, washed off and the slide was read in an ArrayWoRx(e) scanning CCD imager (Applied Precision, Issaquah, WA). As a preliminary model for the combined infectious disease-autoimmune diagnostic microarray we surveyed 98 unidentified, outdated sera that were discarded after Hepatitis B antibody testing. In these, significant IgG or IgM autoantibody levels were found: dsDNA 5, ssDNA 11, Ro 2, RNP 7, SSB 4, gliadin 2, thyroglobulin 13 cases. Since control sera showed no autoantibodies, the high frequency of anti-DNA and anti-thyroglobulin antibodies found in infected sera lend increased support for linkage of infection to subsequent autoimmune disease. Expansion of the antigen

  8. Successful Management of Acquired Hemophilia A Associated with Bullous Pemphigoid: A Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Quentin Binet


    Full Text Available Background. Acquired hemophilia A (AHA is a rare condition, due to the spontaneous formation of neutralizing antibodies against endogenous factor VIII. About half the cases are associated with pregnancy, postpartum, autoimmune diseases, malignancies, or adverse drug reactions. Symptoms include severe and unexpected bleeding that may prove life-threatening. Case Study. We report a case of AHA associated with bullous pemphigoid (BP, a chronic, autoimmune, subepidermal, blistering skin disease. To our knowledge, this is the 25th documented case of such an association. Following treatment for less than 3 months consisting of methylprednisolone at decreasing dose levels along with four courses of rituximab (monoclonal antibody directed against the CD20 protein, AHA was completely cured and BP well-controlled. Conclusions. This report illustrates a rare association of AHA and BP, supporting the possibility of eradicating the inhibitor with a well-conducted short-term treatment.

  9. Cross-reactivity of autoantibodies from patients with epidermolysis bullosa acquisita with murine collagen VII. (United States)

    Csorba, Kinga; Sesarman, Alina; Oswald, Eva; Feldrihan, Vasile; Fritsch, Anja; Hashimoto, Takashi; Sitaru, Cassian


    The pathomechanism of antibody-mediated tissue damage in autoimmune diseases can be best studied in experimental models by passively transferring specific autoantibodies into animals. The reproduction of the disease in animals depends on several factors, including the cross-reactivity of patient autoantibodies with the animal tissue. Here, we show that autoantibodies from patients with epidermolysis bullosa acquisita (EBA), a subepidermal autoimmune blistering disease, recognize multiple epitopes on murine collagen VII. Indirect immunofluorescence microscopy revealed that EBA patients' IgG cross-reacts with mouse skin. Overlapping, recombinant fragments of murine collagen VII were used to characterize the reactivity of EBA sera and to map the epitopes on the murine antigen by ELISA and immunoblotting. The patients' autoantibody binding to murine collagen VII triggered pathogenic events as demonstrated by a complement fixing and an ex vivo granulocyte-dependent dermal-epidermal separation assay. These findings should greatly facilitate the development of improved disease models and novel therapeutic strategies.

  10. Effect of litter quality on foot pad dermatitis, hock burns and breast blisters in broiler breeders during the production period. (United States)

    Kaukonen, Eija; Norring, Marianna; Valros, Anna


    Foot pad dermatitis and hock burn lesions are a form of contact dermatitis, a condition affecting skin areas in contact with unsuitable or irritating material. Contact dermatitis is a common problem, reducing the welfare of broilers, and is believed to also affect broiler breeders. However, there is very little research on contact dermatitis in breeders. This study followed the severity of foot pad lesions in broiler breeders throughout the production period. At slaughter the presence of hock burns and breast blisters was also determined. In addition, changes in litter condition over time and the impact of litter quality on foot pads were evaluated. The study was performed on 10 broiler breeder farms, including altogether 18 flocks. Foot pads of 100 hens per flock were assessed at the end of rearing period, three times during the production period, and at slaughter. Foot pad and hock lesions, as well as litter condition were scored on a 5-point scale. Litter quality was evaluated as pH, moisture and ammonia content. The condition of foot pads deteriorated towards slaughter age, with the occurrence of severe lesions reaching a maximum of 64% on average at slaughter. Hock lesions and breast blisters were rare. The litter layer became drier over time. Although poorer litter condition and wetness influenced foot pad health negatively, the effect on severe lesions was not significant. We also observed a negative effect on foot pad condition of larger slat areas. In conclusion, maintaining good litter quality alone is not enough to ensure healthy foot pads in broiler breeders.

  11. Antineutrophil Cytoplasmic Antibodies, Autoimmune Neutropenia, and Vasculitis (United States)

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


    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

  12. Eating Disorders, Autoimmune, and Autoinflammatory Disease. (United States)

    Zerwas, Stephanie; Larsen, Janne Tidselbak; Petersen, Liselotte; Thornton, Laura M; Quaranta, Michela; Koch, Susanne Vinkel; Pisetsky, David; Mortensen, Preben Bo; Bulik, Cynthia M


    Identifying factors associated with risk for eating disorders is important for clarifying etiology and for enhancing early detection of eating disorders in primary care. We hypothesized that autoimmune and autoinflammatory diseases would be associated with eating disorders in children and adolescents and that family history of these illnesses would be associated with eating disorders in probands. In this large, nationwide, population-based cohort study of all children and adolescents born in Denmark between 1989 and 2006 and managed until 2012, Danish medical registers captured all inpatient and outpatient diagnoses of eating disorders and autoimmune and autoinflammatory diseases. The study population included 930 977 individuals (48.7% girls). Cox proportional hazards regression models and logistic regression were applied to evaluate associations. We found significantly higher hazards of eating disorders for children and adolescents with autoimmune or autoinflammatory diseases: 36% higher hazard for anorexia nervosa, 73% for bulimia nervosa, and 72% for an eating disorder not otherwise specified. The association was particularly strong in boys. Parental autoimmune or autoinflammatory disease history was associated with significantly increased odds for anorexia nervosa (odds ratio [OR] = 1.13, confidence interval [CI] = 1.01-1.25), bulimia nervosa (OR = 1.29; CI = 1.08-1.55) and for an eating disorder not otherwise specified (OR = 1.27; CI = 1.13-1.44). Autoimmune and autoinflammatory diseases are associated with increased risk for eating disorders. Ultimately, understanding the role of immune system disturbance for the etiology and pathogenesis of eating disorders could point toward novel treatment targets. Copyright © 2017 by the American Academy of Pediatrics.

  13. Transitioning from Idiopathic to Explainable Autoimmune Hepatitis. (United States)

    Czaja, Albert J


    Autoimmune hepatitis lacks an identifiable cause, and its diagnosis requires the exclusion of etiologically defined diseases that resemble it. Insights into its pathogenesis are moving autoimmune hepatitis from an idiopathic to explainable disease, and the goal of this review is to describe the insights that are hastening this transition. Two types of autoimmune hepatitis are justified by serological markers, but they also have distinctive genetic associations (DRB1 and DQB1 genes) and autoantigens. DRB1 alleles are the principal susceptibility factors in white adults, and a six amino acid sequence encoded in the antigen-binding groove of class II molecules of the major histocompatibility complex can influence the selection of autoantigens. Polymorphisms, including variants of SH2B3 and CARD10 genes, may affect immune reactivity and disease severity. The cytochrome mono-oxygenase, CYP2D6, is the autoantigen associated with type 2 autoimmune hepatitis, and it shares homologies with multiple viruses that might promote self-intolerance by molecular mimicry. Chemokines, especially CXCL9 and CXCL10, orchestrate the migration of effector cells to sites of injury and are associated with disease severity. Cells of the innate and adaptive immune responses promote tissue damage, and possible deficiencies in the number and function of regulatory T cells may facilitate the injurious process. Receptor-mediated apoptosis is the principal mechanism of hepatocyte loss, and cell-mediated and antibody-dependent mechanisms of cytotoxicity also contribute. Insights that explain autoimmune hepatitis will allow triggering exogenous antigens to be characterized, risk management to be improved, prognostic indices to be refined, and site-specific therapeutic interventions to emerge.

  14. Genomics and proteomics: Applications in autoimmune diseases

    Directory of Open Access Journals (Sweden)

    Wolfgang Hueber


    Full Text Available Wolfgang Hueber1,2,3, William H Robinson1,21VA Palo Alto Health Care System, Palo Alto, CA, USA; 2Division of Immunology and Rheumatology, Stanford University School of Medicine, Stanford, CA, USA; 3Novartis Institutes of Biomedical Research, Novartis, Basle, SwitzerlandAbstract: Tremendous progress has been made over the past decade in the development and refinement of genomic and proteomic technologies for the identification of novel drug targets and molecular signatures associated with clinically important disease states, disease subsets, or differential responses to therapies. The rapid progress in high-throughput technologies has been preceded and paralleled by the elucidation of cytokine networks, followed by the stepwise clinical development of pathway-specific biological therapies that revolutionized the treatment of autoimmune diseases. Together, these advances provide opportunities for a long-anticipated personalized medicine approach to the treatment of autoimmune disease. The ever-increasing numbers of novel, innovative therapies will need to be harnessed wisely to achieve optimal long-term outcomes in as many patients as possible while complying with the demands of health authorities and health care providers for evidence-based, economically sound prescription of these expensive drugs. Genomic and proteomic profiling of patients with autoimmune diseases holds great promise in two major clinical areas: (1 rapid identification of new targets for the development of innovative therapies and (2 identification of patients who will experience optimal benefit and minimal risk from a specific (targeted therapy. In this review, we attempt to capture important recent developments in the application of genomic and proteomic technologies to translational research by discussing informative examples covering a diversity of autoimmune diseases.Keywords: proteomics, genomics, autoimmune diseases, antigen microarrays, 2-Dih, rheumatoid arthritis

  15. Impact of Autoantibodies against Glycolytic Enzymes on Pathogenicity of Autoimmune Retinopathy and Other Autoimmune Disorders

    Directory of Open Access Journals (Sweden)

    Grazyna Adamus


    Full Text Available Autoantibodies (AAbs against glycolytic enzymes: aldolase, α-enolase, glyceraldehyde-3-phosphate dehydrogenase, and pyruvate kinase are prevalent in sera of patients with blinding retinal diseases, such as paraneoplastic [cancer-associated retinopathy (CAR] and non-paraneoplastic autoimmune retinopathies, as well as in many other autoimmune diseases. CAR is a degenerative disease of the retina characterized by sudden vision loss in patients with cancer and serum anti-retinal AAbs. In this review, we discuss the widespread serum presence of anti-glycolytic enzyme AAbs and their significance in autoimmune diseases. There are multiple mechanisms responsible for antibody generation, including the innate anti-microbial response, anti-tumor response, or autoimmune response against released self-antigens from damaged, inflamed tissue. AAbs against enolase, GADPH, and aldolase exist in a single patient in elevated titers, suggesting their participation in pathogenicity. The lack of restriction of AAbs to one disease may be related to an increased expression of glycolytic enzymes in various metabolically active tissues that triggers an autoimmune response and generation of AAbs with the same specificity in several chronic and autoimmune conditions. In CAR, the importance of serum anti-glycolytic enzyme AAbs had been previously dismissed, but the retina may be without pathological consequence until a failure of the blood–retinal barrier function, which would then allow pathogenic AAbs access to their retinal targets, ultimately leading to damaging effects.

  16. Recent insights into the role and molecular mechanisms of the autoimmune regulator (AIRE) gene in autoimmunity. (United States)

    Fierabracci, Alessandra


    Since many years immunologists have being tried to answer the tantalizing enigma of immunological tolerance. Complex mechanisms in both thymus (central tolerance) and peripheral lymphoid organs (peripheral tolerance) underly lymphocyte tolerance and its maintenance. The genesis of autoimmunity involves environmental and genetic mechanisms, both contributing to the disruption and deregulation of central and peripheral tolerance, allowing autoreactive pathogenetic T and B-cell clones arising. Among genetic factors the autoimmune regulator (AIRE) gene is one of the best candidates to understand the complex scenario of autoimmunity. Autoimmune polyendocrinopathy syndrome type 1 is a rare autosomal recessive disease caused by mutations in the AIRE gene. Therefore, the disorder has certainly been a powerful model to address the question concerning how a tolerant state is achieved or maintained and to explore how it has gone lost in the context of autoimmunity. AIRE has been proposed to function as a 'non classical' transcription factor, strongly implicated in the regulation of organ-specific antigen expression in thymic epithelial cells and in the imposition of T cell tolerance, thus regulating the negative selection of autoreactive T cell clones. A plethora of proposal have been suggested for AIRE's potential mechanism of action, thus regulating the negative selection of autoreactive T cells. In this review recent discoveries are presented into the role and molecular mechanisms of the AIRE protein in APECED and other autoimmune diseases. Copyright © 2010 Elsevier B.V. All rights reserved.

  17. A case of Kikuchi-Fujimoto disease with autoimmune thyroiditis. (United States)

    Go, Eun Ji; Jung, You Jin; Han, Seung Beom; Suh, Byung Kyu; Kang, Jin Han


    Kikuchi-Fujimoto disease (KFD) is a benign self-limiting disease characterized by fever and lymphadenitis. The etiology and pathogenesis of KFD is unclear. However, two hypotheses have been suggested: a viral infection hypothesis and an autoimmune hypothesis. Several KFD patients with various types of autoimmune diseases have been reported, and these reports support the hypothesis for autoimmune pathogenesis of KFD. Here, we report the case of a 17-year-old female patient diagnosed with KFD and autoimmune thyroiditis. This case serves as additional evidence that the etiology of KFD is autoimmune origin.

  18. Helicobacter pylori and autoimmune disease: Cause or bystander (United States)

    Smyk, Daniel S; Koutsoumpas, Andreas L; Mytilinaiou, Maria G; Rigopoulou, Eirini I; Sakkas, Lazaros I; Bogdanos, Dimitrios P


    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

  19. [Coexistence of autoimmune polyglandular syndrome type 3 with diabetes insipidus]. (United States)

    Krysiak, Robert; Okopień, Bogusław


    Autoimmune polyglandular syndromes are conditions characterized by the combination of two or more organ-specific disorders. The underestimation oftheir real frequency probable results from physicians' inadequate knowledge of these clinical entities and sometimes their atypical clinical presentation. Because they comprise a wide spectrum of autoimmune disorders, autoimmune polyglandular syndromes are divided into four types, among which type-3 is the most common one. In this article, we report the case of a young female, initially diagnosed with diabetes mellitus who several years later developed full-blown autoimmune polyglandular syndrome type 3 consisting of autoimmune thyroid disorder and latent autoimmune diabetes in adults.The discussed case suggests that in selected patients diabetes insipidus may coexist with autoimmune endocrinopathies and nonendocrine autoimmunopathies, as well as that in some patients idiopathic diabetes insipidus may be secondary to lymphocytic infiltration and destruction of the hypothalamic supraoptic and paraventricular nuclei and/or the supraoptic-hypophyseal tract

  20. Involvement of hypothalamus autoimmunity in patients with autoimmune hypopituitarism: role of antibodies to hypothalamic cells. (United States)

    De Bellis, A; Sinisi, A A; Pane, E; Dello Iacovo, A; Bellastella, G; Di Scala, G; Falorni, A; Giavoli, C; Gasco, V; Giordano, R; Ambrosio, M R; Colao, A; Bizzarro, A; Bellastella, A


    Antipituitary antibodies (APA) but not antihypothalamus antibodies (AHA) are usually searched for in autoimmune hypopituitarism. Our objective was to search for AHA and characterize their hypothalamic target in patients with autoimmune hypopituitarism to clarify, on the basis of the cells stained by these antibodies, the occurrence of autoimmune subclinical/clinical central diabetes insipidus (CDI) and/or possible joint hypothalamic contribution to their hypopituitarism. We conducted a cross-sectional cohort study. Ninety-five APA-positive patients with autoimmune hypopituitarism, 60 without (group 1) and 35 with (group 2) lymphocytic hypophysitis, were studied in comparison with 20 patients with postsurgical hypopituitarism and 50 normal subjects. AHA by immunofluorescence and posterior pituitary function were evaluated; then AHA-positive sera were retested by double immunofluorescence to identify the hypothalamic cells targeted by AHA. AHA were detected at high titer in 12 patients in group 1 and in eight patients in group 2. They immunostained arginine vasopressin (AVP)-secreting cells in nine of 12 in group 1 and in four of eight in group 2. All AVP cell antibody-positive patients presented with subclinical/clinical CDI; in contrast, four patients with GH/ACTH deficiency but with APA staining only GH-secreting cells showed AHA targeting CRH- secreting cells. The occurrence of CDI in patients with lymphocytic hypophysitis seems due to an autoimmune hypothalamic involvement rather than an expansion of the pituitary inflammatory process. To search for AVP antibody in these patients may help to identify those of them prone to develop an autoimmune CDI. The detection of AHA targeting CRH-secreting cells in some patients with GH/ACTH deficiency but with APA targeting only GH-secreting cells indicates that an autoimmune aggression to hypothalamus is jointly responsible for their hypopituitarism.

  1. The mechanisms behind helminth's immunomodulation in autoimmunity. (United States)

    Bashi, Tomer; Bizzaro, Giorgia; Ben-Ami Shor, Dana; Blank, Miri; Shoenfeld, Yehuda


    The incidence of autoimmune diseases has risen throughout the last half a century, mostly in the industrialized world. Helminths and their derivatives were found to have a protective role in autoimmunity and inflammatory conditions, as they manipulate the immune network, attenuating the host's cellular and humoral responses. Indeed, various helminth species used in several human and animal models were shown to limit inflammatory activity in a variety of diseases including inflammatory bowel disease, multiple sclerosis, type 1 diabetes, and rheumatoid arthritis. Our review will focus on the main mechanisms by which helminths and their secreted molecules modulate the host's immune system. The main pathways induce a shift from Th1 to Th2 phenotype, accelerate T regulatory and B regulatory phenotypes, and attenuate the levels of the inflammatory cytokines, leading to a tolerable scenario. Copyright © 2014 Elsevier B.V. All rights reserved.

  2. Total lymphoid irradiation in alloimmunity and autoimmunity

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    Strober, S.


    Total lymphoid irradiation has been used as an immunosuppressive regimen in autoimmune disease and organ transplantation. The rationale for its use originated from studies of patients with Hodgkin disease, in whom this radiotherapy regimen was noted to induce profound and long-lasting immune suppression and yet was well tolerated, with few long-term side effects. Total lymphoid irradiation is a unique immunosuppressive regimen that produces a selective (and long-lasting) reduction in the number and function of helper T cells and certain subsets of B cells. Conventional immunosuppressive drugs show little selectivity, and their effects are short-lived. The most important aspect of total lymphoid irradiation is the potential for achieving transplantation tolerance and permanent remissions in autoimmune disease in laboratory animals. Attempts are being made to achieve similar goals in humans given total lymphoid irradiation, so that immunosuppressive drugs can be ultimately withdrawn from transplant recipients and patients with lupus nephritis. 28 references.

  3. Autoimmunity in the pathogenesis of hypertension. (United States)

    Rodríguez-Iturbe, Bernardo; Pons, Héctor; Quiroz, Yasmir; Lanaspa, Miguel A; Johnson, Richard J


    Hypertension affects more than one-third of the adult population of the world. However, the cause of high blood pressure is unknown in the vast majority of patients, classified as patients with essential hypertension. Evidence accumulated over the past decade supports the participation of inflammation in the development of experimental hypertension. Investigations have also demonstrated that immune reactivity to overexpressed heat shock protein 70 (HSP70) is involved in the pathogenesis of salt-induced hypertension. This article reviews, first, the role of T cell-induced inflammation in the arteries, kidney and central nervous system in hypertension and the amelioration of hypertension induced by regulatory T cells. Second, experiments showing that autoimmunity directed to HSP70 in the kidney impairs the pressure natriuresis relationship and has a pivotal role in the pathogenesis of salt sensitive hypertension. Finally, we highlight the clinical evidence that supports the participation of autoimmunity in essential hypertension.

  4. Hypertension as an autoimmune and inflammatory disease. (United States)

    Solak, Yalcin; Afsar, Baris; Vaziri, Nosratola D; Aslan, Gamze; Yalcin, Can Ege; Covic, Adrian; Kanbay, Mehmet


    Hypertension that is considered idiopathic is called essential hypertension and accordingly has no clear culprit for its cause. However, basic research and clinical studies in recent years have expanded our understanding of the mechanisms underlying the development of essential hypertension. Of these, increased oxidative stress, both in the kidney and arterial wall, closely coupled with inflammatory infiltration now appear to have a prominent role. Discovery of regulatory and interleukin-17-producing T cells has enabled us to better understand the mechanism by which inflammation and autoimmunity, or autoinflammation, lead to the development of hypertension. Despite achieving considerable progress, the intricate interactions between oxidative stress, the immune system and the development of hypertension remain to be fully elucidated. In this review, we summarize recent developments in the pathophysiology of hypertension with a focus on the oxidant stress-autoimmunity-inflammation interaction.

  5. Autoimmune Progesterone Dermatitis: A Case Report

    Directory of Open Access Journals (Sweden)

    Rachana George


    Full Text Available Background. Autoimmune progesterone dermatitis is a rare cyclic premenstrual allergic reaction to progesterone produced during the luteal phase of a woman's menstrual cycle. Patients present with a variety of conditions including erythema multiforme, eczema, urticaria, angioedema, and progesterone-induced anaphylaxis. Case. Thirty-eight-year-old woman G2P2002 presents with erythema multiforme and urticarial rash one week prior to her menses starting one year after menarche. She was treated with oral contraceptive pills and the symptoms resolved. Conclusion. This is a typical case of progesterone autoimmunity. The diagnosis is based on cyclic nature of the dermatitis. This differentiates the condition from other allergies or systemic diseases with skin manifestations. Inhibition of ovulation in such cases results in decrease in progesterone secretion and prevention of symptoms.

  6. Autoimmune Hemolytic Anemia Induced by Levofloxacin

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    Marwan Sheikh-Taha


    Full Text Available Drug-induced autoimmune hemolytic anemia is a rare condition. We report the case of a 32-year-old white female who presented to the emergency department with generalized fatigue, fever, and jaundice. The patient reported using levofloxacin few days prior to presentation for urinary tract infection. The patient had evidence of hemolytic anemia with a hemoglobin of 6.7 g/dL which dropped to 5 g/dL on day 2, the direct Coombs test was positive, indirect bilirubin was 5.5 mg/dL, and LDH was 1283 IU/L. Further testing ruled out autoimmune disease, lymphoma, and leukemia as etiologies for the patient’s hemolytic anemia. Levofloxacin was immediately stopped with a gradual hematologic recovery within few days.

  7. Th17 cells in autoimmune demyelinating disease. (United States)

    Segal, Benjamin Matthew


    Recently published studies in multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE) have demonstrated an association between the development of demyelinating plaques and the accumulation of Th17 cells in the central nervous system and periphery. However, a causal relationship has been difficult to establish. In fact, in reports published thus far, interleukin (IL)-17A deficiency or neutralization in vivo attenuates, but does not completely abrogate, EAE. There is growing evidence that clinically similar forms of autoimmune demyelinating disease can be driven by myelin-specific T cells of distinct lineages with different degrees of dependence on IL-17A production to achieve their pathological effects. While such observations cast doubts about the potential therapeutic efficacy of Th17 blocking agents in MS, the collective data suggest that IL-17A expression in peripheral blood mononuclear cells could serve as a surrogate biomarker of neuroinflammation and plaque formation and be a useful outcome measure for future clinical trials.

  8. Defensins: Potential Effectors in Autoimmune Rheumatic Disorders

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    Stefan Vordenbäumen


    Full Text Available Defensins are small cationic peptides with antimicrobial properties. They constitute a highly conserved innate immune defense mechanism across species. Based on the arrangement of disulfide-bonds, α- and β-defensins are distinguished in humans. Both types of defensin comprise several distinct molecules that are preferentially expressed at epithelial surfaces and in blood cells. In the last decade, multiple immunomodulatory functions of defensins have been recognized, including chemotactic activity, the promotion of antigen presentation, and modulations of proinflammatory cytokine secretion. These findings suggested a role for defensins not only as a first line of defense, but also as connectors of innate and adaptive immune responses. Recently, increasingly accumulating evidence has indicated that defensins may also be involved in the pathogenesis of autoimmune rheumatic disorders such as systemic lupus erythematosus and rheumatoid arthritis. The current review summarizes the data connecting defensins to autoimmunity.

  9. Neuroelectrophysiological studies on neurological autoimmune diseases

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    Yin-hong LIU


    Full Text Available The neuroelectrophysiological manifestations of four clinical typical neurological autoimmune diseases including multiple sclerosis (MS, Guillain-Barré syndrome (GBS, myasthenia gravis (MG, and polymyositis and dermatomyositis were reviewed in this paper. The diagnostic value of evoked potentials for multiple sclerosis, nerve conduction studies (NCS for Guillain-Barré syndrome, repetitive nerve stimulation (RNS and single-fiber electromyography (SFEMG for myasthenia gravis, and needle electromyography for polymyositis and dermatomyositis were respectively discussed. This review will help to have comprehensive understanding on electrophysiological examinations and their clinical significance in the diagnosis of neurological autoimmune diseases. doi: 10.3969/j.issn.1672-6731.2014.09.004

  10. Eating Disorders, Autoimmune, and Autoinflammatory Disease

    DEFF Research Database (Denmark)

    Zerwas, Stephanie; Larsen, Janne Tidselbak; Petersen, Liselotte


    OBJECTIVES: Identifying factors associated with risk for eating disorders is important for clarifying etiology and for enhancing early detection of eating disorders in primary care. We hypothesized that autoimmune and autoinflammatory diseases would be associated with eating disorders in children...... and autoinflammatory diseases are associated with increased risk for eating disorders. Ultimately, understanding the role of immune system disturbance for the etiology and pathogenesis of eating disorders could point toward novel treatment targets.......OBJECTIVES: Identifying factors associated with risk for eating disorders is important for clarifying etiology and for enhancing early detection of eating disorders in primary care. We hypothesized that autoimmune and autoinflammatory diseases would be associated with eating disorders in children...... and adolescents and that family history of these illnesses would be associated with eating disorders in probands. METHODS: In this large, nationwide, population-based cohort study of all children and adolescents born in Denmark between 1989 and 2006 and managed until 2012, Danish medical registers captured all...

  11. Gene expression profiling in autoimmune diseases

    DEFF Research Database (Denmark)

    Bovin, Lone Frier; Brynskov, Jørn; Hegedüs, Laszlo


    A central issue in autoimmune disease is whether the underlying inflammation is a repeated stereotypical process or whether disease specific gene expression is involved. To shed light on this, we analysed whether genes previously found to be differentially regulated in rheumatoid arthritis (RA......) patients and healthy individuals were specific for the arthritic process or likewise altered in other chronic inflammatory diseases such as chronic autoimmune thyroiditis (Hashimoto's thyroiditis, HT) and inflammatory bowel disease (IBD). Using qPCR for 18 RA-discriminative genes, there were no significant...... differences in peripheral blood mononuclear cell (MNC) gene expression patterns between 15 newly diagnosed HT patients and 15 matched healthy controls. However, the MNC expression levels of five genes were significantly upregulated in 25 IBD patients, compared to 18 matched healthy controls (CD14, FACL2, FCN1...

  12. Abdominal aortic aneurysms: an autoimmune disease? (United States)

    Jagadesham, Vamshi P; Scott, D Julian A; Carding, Simon R


    Abdominal aortic aneurysms (AAAs) are a multifactorial degenerative vascular disorder. One of the defining features of the pathophysiology of aneurysmal disease is inflammation. Recent developments in vascular and molecular cell biology have increased our knowledge on the role of the adaptive and innate immune systems in the initiation and propagation of the inflammatory response in aortic tissue. AAAs share many features of autoimmune disease, including genetic predisposition, organ specificity and chronic inflammation. Here, this evidence is used to propose that the chronic inflammation observed in AAAs is a consequence of a dysregulated autoimmune response against autologous components of the aortic wall that persists inappropriately. Identification of the molecular and cellular targets involved in AAA formation will allow the development of therapeutic agents for the treatment of AAA.

  13. Hormones and autoimmunity: animal models of arthritis. (United States)

    Wilder, R L


    Hormones, particularly those involved in the hypothalamic-pituitary-gonadal and -adrenal axes (HPG and HPA), play important roles in various animal models of autoimmunity such as systemic lupus erythematosus in mice and collagen-induced arthritis (CIA) in mice and rats, and the streptococcal cell wall, adjuvant and avridine arthritis models in rats. Intimately linked to the subject of hormones and autoimmunity are gender, sex chromosomes and age. The importance of these factors in the various animal models is emphasized in this chapter. Several major themes are apparent. First, oestrogens promote B-cell dependent immune-complex mediated disease (e.g. lupus nephritis) but suppress T-cell dependent pathology (CIA in mice and rats), and vice versa. Second, testosterone's effects are complicated and depend on species and disease model. In rats, testosterone suppresses both T-cell and B-cell immunity. In mice, the effects are complex and difficult to interpret, e.g. they tend to enhance CIA arthritis and suppress lupus. Sex chromosome/sex hormone interactions are clearly involved in generating these complicated effects. Third, studies in Lewis and Fischer F344 rats exemplify the importance of corticosteroids, corticotrophin releasing hormone and the HPA axis in the regulation of inflammation and the predisposition to autoimmune diseases. Fourth, the HPA axis is intimately linked to the HPG axis and is sexually dimorphic. Oestrogens stimulate higher corticosteroid responses in females. The animal model data have major implications for understanding autoimmunity in humans. In particular, adrenal and gonadal hormone deficiency is likely to facilitate T-cell dependent diseases like rheumatoid arthritis, while high oestrogen levels or effects, relative to testosterone, are likely to promote B-cell dependent immune-complex-mediated diseases such as lupus nephritis.

  14. Extracellular Vesicles: Evolving Contributors in Autoimmunity


    Katsiougiannis, Stergios


    Extracellular vesicles, including microvesicles, exosomes and apoptotic bodies are recognized as carriers of pathogen-associated molecules with direct involvement in immune signaling and inflammation. Those observations have enforced the way these membranous vesicles are being considered as promising immunotherapeutic targets. In this review, we discuss the emerging roles of extracellular vesicles in autoimmunity and highlights their potential use as disease biomarkers as well as targets for ...

  15. Endothelial dysfunction in rheumatic autoimmune diseases. (United States)

    Murdaca, Giuseppe; Colombo, Barbara Maria; Cagnati, Paola; Gulli, Rossella; Spanò, Francesca; Puppo, Francesco


    Rheumatic autoimmune diseases have been associated with accelerated atherosclerosis and various types of vasculopathies. Atherosclerosis is an inflammatory condition which starts as a "response to injury" favoring endothelial dysfunction which is associated with increased expression of adhesion molecules, pro-inflammatory cytokines, pro-thrombotic factors, oxidative stress upregulation and abnormal vascular tone modulation. Endothelial dysfunction in rheumatic autoimmune diseases involves innate immune responses, including macrophages and dendritic cells expression of scavenger and toll-like receptors for modified or native LDL as well as neutrophil and complement activation, and dysregulation of adaptive immune responses, including proliferation of autoreactive T-helper-1 lymphocytes and defective function of dendritic and regulatory T cells. Specific differences for endothelial function among different disorders include: a) increased amounts of pro-atherogenic hormones, decreased amounts of anti-atherogenic hormones and increased insulin resistance in rheumatoid arthritis; b) autoantibodies production in systemic lupus erythematosus and antiphospholipid syndrome; c) smooth muscle cells proliferation, destruction of internal elastic lamina, fibrosis and coagulation and fibrinolytic system dysfunction in systemic sclerosis. Several self-antigens (i.e. high density lipoproteins, heat shock proteins, β2-glycoprotein1) and self-molecules modified by oxidative events (i.e. low density lipoproteins and oxidized hemoglobin) have been identified as targets of autoimmune responses. Endothelial dysfunction leads to accelerated atherosclerosis in rheumatoid arthritis, systemic lupus erythematosus and spondyloarthropaties whereas obliterative vasculopathy is associated with systemic sclerosis. In this paper, we will briefly review the most relevant information upon endothelial dysfunction and inflammatory mechanisms in atherosclerosis and we will summarize the similarities


    Andrese, Elena; Vâţă, D; Ciobanu, Delia; Stătescu, Laura; Solovăstru, Laura Gheucă


    Localized cutaneous amyloidosis is a rare disease among white people, being more common in South-Asia, China and South America. The disease is characterized by deposition of amyloid material in the papillary dermis without visceral involvement. Nevertheless, there is a growing list of immune-mediated disorders that have been linked to cutaneous amyloidosis. We present two cases of concomitant occurrence of lichen amyloidosis and autoimmune thyroiditis/atopic dermatitis in two Caucasian women.

  17. Primary biliary cirrhosis--autoimmune hepatitis overlap syndrome associated with dermatomyositis, autoimmune thyroiditis and antiphospholipid syndrome. (United States)

    Pamfil, Cristina; Candrea, Elisabeta; Berki, Emese; Popov, Horațiu I; Radu, Pompilia I; Rednic, Simona


    Autoimmune liver diseases may be associated with extrahepatic autoimmune pathology. We report the case of a 52-year old woman who initially presented to the gastroenterology department for extreme fatigue, pale stools, dark urine and pruritus. Laboratory tests showed significant cholestasis and elevation of aminotransferase levels. Immunological tests revealed positive antinuclear (ANA=1:320) and antimitochondrial antibodies (AMA=1:40) with negative anti-smooth muscle and liver kidney microsomal type 1 antibodies. The biopsy was compatible with overlap syndrome type 1. The patient was commenced on immunosuppressive therapy according to standard of care (azathioprine 50mg, ursodeoxycholic acid and prednisone 0.5mg/kg), with moderate biochemical improvement. She subsequently developed proximal symmetrical weakness and cutaneous involvement and was diagnosed with biopsy-proven dermatomyositis. The immunosuppressive regimen was intensified to 150 mg azathioprine. At the three-month follow-up, her symptoms subsided and aminotransferases and muscle enzymes normalized. Upon further investigation the patient was diagnosed with autoimmune thyroiditis and antiphospholipid syndrome. To our knowledge, this is the first case of primary biliary cirrhosis - autoimmune hepatitis overlap syndrome associated with dermatomyositis, autoimmune thyroiditis and antiphospholipid syndrome.

  18. Dominant Mutations in the Autoimmune Regulator AIRE Are Associated with Common Organ-Specific Autoimmune Diseases. (United States)

    Oftedal, Bergithe E; Hellesen, Alexander; Erichsen, Martina M; Bratland, Eirik; Vardi, Ayelet; Perheentupa, Jaakko; Kemp, E Helen; Fiskerstrand, Torunn; Viken, Marte K; Weetman, Anthony P; Fleishman, Sarel J; Banka, Siddharth; Newman, William G; Sewell, W A C; Sozaeva, Leila S; Zayats, Tetyana; Haugarvoll, Kristoffer; Orlova, Elizaveta M; Haavik, Jan; Johansson, Stefan; Knappskog, Per M; Løvås, Kristian; Wolff, Anette S B; Abramson, Jakub; Husebye, Eystein S


    The autoimmune regulator (AIRE) gene is crucial for establishing central immunological tolerance and preventing autoimmunity. Mutations in AIRE cause a rare autosomal-recessive disease, autoimmune polyendocrine syndrome type 1 (APS-1), distinguished by multi-organ autoimmunity. We have identified multiple cases and families with mono-allelic mutations in the first plant homeodomain (PHD1) zinc finger of AIRE that followed dominant inheritance, typically characterized by later onset, milder phenotypes, and reduced penetrance compared to classical APS-1. These missense PHD1 mutations suppressed gene expression driven by wild-type AIRE in a dominant-negative manner, unlike CARD or truncated AIRE mutants that lacked such dominant capacity. Exome array analysis revealed that the PHD1 dominant mutants were found with relatively high frequency (>0.0008) in mixed populations. Our results provide insight into the molecular action of AIRE and demonstrate that disease-causing mutations in the AIRE locus are more common than previously appreciated and cause more variable autoimmune phenotypes. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Alcoholic Cirrhosis Increases Risk for Autoimmune Diseases

    DEFF Research Database (Denmark)

    Grønbæk, Lisbet; Vilstrup, Hendrik; Deleuran, Bent


    IRR, 1.56; 95% CI, 1.26-1.92), celiac disease (aIRR, 5.12; 95% CI, 2.58-10.16), pernicious anemia (aIRR, 2.35; 95% CI, 1.50-3.68), and psoriasis (aIRR, 4.06; 95% CI, 3.32-4.97). There was no increase in the incidence rate for rheumatoid arthritis (aIRR, 0.89; 95% CI, 0.69-1.15); the incidence rate......BACKGROUND & AIMS: Alcoholic cirrhosis is associated with hyperactivation and dysregulation of the immune system. In addition to its ability to increase risk for infections, it also may increase the risk for autoimmune diseases. We studied the incidence of autoimmune diseases among patients...... (controls) of the same sex and age. The incidence rates of various autoimmune diseases were compared between patients with cirrhosis and controls and adjusted for the number of hospitalizations in the previous year (a marker for the frequency of clinical examination). RESULTS: Of the 24,679 patients...

  20. Experimental models of autoimmune inflammatory ocular diseases

    Directory of Open Access Journals (Sweden)

    Fabio Gasparin


    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.

  1. Overlap syndromes among autoimmune liver diseases (United States)

    Rust, Christian; Beuers, Ulrich


    The three major immune disorders of the liver are autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC). Variant forms of these diseases are generally called overlap syndromes, although there has been no standardized definition. Patients with overlap syndromes present with both hepatitic and cholestatic serum liver tests and have histological features of AIH and PBC or PSC. The AIH-PBC overlap syndrome is the most common form, affecting almost 10% of adults with AIH or PBC. Single cases of AIH and autoimmune cholangitis (AMA-negative PBC) overlap syndrome have also been reported. The AIH-PSC overlap syndrome is predominantly found in children, adolescents and young adults with AIH or PSC. Interestingly, transitions from one autoimmune to another have also been reported in a minority of patients, especially transitions from PBC to AIH-PBC overlap syndrome. Overlap syndromes show a progressive course towards liver cirrhosis and liver failure without treatment. Therapy for overlap syndromes is empiric, since controlled trials are not available in these rare disorders. Anticholestatic therapy with ursodeoxycholic acid is usually combined with immunosuppressive therapy with corticosteroids and/or azathioprine in both AIH-PBC and AIH-PSC overlap syndromes. In end-stage disease, liver transplantation is the treatment of choice. PMID:18528934

  2. Autoimmune pancreatitis: medical and surgical management. (United States)

    Toomey, Desmond P; Swan, Niall; Torreggiani, William; Conlon, Kevin C


    Autoimmune pancreatitis is characterised by a lymphoplasmacytic infiltrate consisting in part of plasma cells that produce large amounts of IgG4. It can manifest as focal or diffuse enlargement of the pancreas with associated strictures of the pancreato-bilary tree giving rise to symptoms including abdominal pain, weight loss and obstructive jaundice; thus it can be extremely difficult in both presentation and investigation to distinguish from pancreatic carcinoma. Recent advances now facilitate preoperative diagnosis and effective medical management, including steroid treatment of autoimmune pancreatitis so preventing major surgical intervention. Two cases of autoimmune pancreatitis are described, each of which presented with obstructive jaundice and a relatively painless pancreatic mass, one with vascular involvement. They each had elevated serum CA 19-9 and ultimately required surgical exploration to definitely exclude malignancy before embarking on non operative treatment. The first case settled spontaneously while the second rapidly improved with steroid treatment. These two cases illustrate the difficulties in diagnosing this condition, the efficacy of steroid therapy and the role of surgical intervention in unresponsive cases or those where a diagnostic dilemma remains.

  3. Resilience in women with autoimmune rheumatic diseases. (United States)

    Rojas, Manuel; Rodriguez, Yhojan; Pacheco, Yovana; Zapata, Elizabeth; Monsalve, Diana M; Mantilla, Rubén D; Rodríguez-Jimenez, Monica; Ramírez-Santana, Carolina; Molano-González, Nicolás; Anaya, Juan-Manuel


    To evaluate the relationship between resilience and clinical outcomes in patients with autoimmune rheumatic diseases. Focus groups, individual interviews, and chart reviews were done to collect data on 188 women with autoimmune rheumatic diseases, namely rheumatoid arthritis (n=51), systemic lupus erythematosus (n=70), systemic sclerosis (n=35), and Sjögren's syndrome (n=32). Demographic, clinical, and laboratory variables were assessed including disease activity by patient reported outcomes. Resilience was evaluated by using the Brief Resilience Scale. Bivariate, multiple linear regression, and classification and regression trees were used to analyse data. Resilience was influenced by age, duration of disease, and socioeconomic status. Lower resilience scores were observed in younger patients (50years) had higher resilience scores regardless of socioeconomic status. There was no influence of disease activity on resilience. A particular behaviour was observed in systemic sclerosis in which patients with high socioeconomic status and regular physical activity had higher resilience scores. Resilience in patients with autoimmune rheumatic diseases is a continuum process influenced by age and socioeconomic status. The ways in which these variables along with exercise influence resilience deserve further investigation. Copyright © 2017 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.

  4. Immunotherapy Treatments of Warm Autoimmune Hemolytic Anemia

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    Bainan Liu


    Full Text Available Warm autoimmune hemolytic anemia (WAIHA is one of four clinical types of autoimmune hemolytic anemia (AIHA, with the characteristics of autoantibodies maximally active at body temperature. It produces a variable anemia—sometimes mild and sometimes severe. With respect to the absence or presence of an underlying condition, WAIHA is either idiopathic (primary or secondary, which determines the treatment strategies in practice. Conventional treatments include immune suppression with corticosteroids and, in some cases, splenectomy. In recent years, the number of clinical studies with monoclonal antibodies and immunosuppressants in the treatment of WAIHA increased as the knowledge of autoimmunity mechanisms extended. This thread of developing new tools of treating WAIHA is well exemplified with the success in using anti-CD20 monoclonal antibody, Rituximab. Following this success, other treatment methods based on the immune mechanisms of WAIHA have emerged. We reviewed these newly developed immunotherapy treatments here in order to provide the clinicians with more options in selecting the best therapy for patients with WAIHA, hoping to stimulate researchers to find more novel immunotherapy strategies.

  5. T cells and autoimmune kidney disease. (United States)

    Suárez-Fueyo, Abel; Bradley, Sean J; Klatzmann, David; Tsokos, George C


    Glomerulonephritis is traditionally considered to result from the invasion of the kidney by autoantibodies and immune complexes from the circulation or following their formation in situ, and by cells of the innate and the adaptive immune system. The inflammatory response leads to the proliferation and dysfunction of cells of the glomerulus, and invasion of the interstitial space with immune cells, resulting in tubular cell malfunction and fibrosis. T cells are critical drivers of autoimmunity and related organ damage, by supporting B-cell differentiation and antibody production or by directly promoting inflammation and cytotoxicity against kidney resident cells. T cells might become activated by autoantigens in the periphery and become polarized to secrete inflammatory cytokines before entering the kidney where they have the opportunity to expand owing to the presence of costimulatory molecules and activating cytokines. Alternatively, naive T cells could enter the kidney where they become activated after encountering autoantigen and expand locally. As not all individuals with a peripheral autoimmune response to kidney antigens develop glomerulonephritis, the contribution of local kidney factors expressed or produced by kidney cells is probably of crucial importance. Improved understanding of the biochemistry and molecular biology of T cells in patients with glomerulonephritis offers unique opportunities for the recognition of treatment targets for autoimmune kidney disease.

  6. Renal involvement in autoimmune connective tissue diseases. (United States)

    Kronbichler, Andreas; Mayer, Gert


    Connective tissue diseases (CTDs) are a heterogeneous group of disorders that share certain clinical presentations and a disturbed immunoregulation, leading to autoantibody production. Subclinical or overt renal manifestations are frequently observed and complicate the clinical course of CTDs. Alterations of kidney function in Sjögren syndrome, systemic scleroderma (SSc), auto-immune myopathies (dermatomyositis and polymyositis), systemic lupus erythematosus (SLE), antiphospholipid syndrome nephropathy (APSN) as well as rheumatoid arthritis (RA) are frequently present and physicians should be aware of that.In SLE, renal prognosis significantly improved based on specific classification and treatment strategies adjusted to kidney biopsy findings. Patients with scleroderma renal crisis (SRC), which is usually characterized by severe hypertension, progressive decline of renal function and thrombotic microangiopathy, show a significant benefit of early angiotensin-converting-enzyme (ACE) inhibitor use in particular and strict blood pressure control in general. Treatment of the underlying autoimmune disorder or discontinuation of specific therapeutic agents improves kidney function in most patients with Sjögren syndrome, auto-immune myopathies, APSN and RA.In this review we focus on impairment of renal function in relation to underlying disease or adverse drug effects and implications on treatment decisions.

  7. Azathioprine-induced fever in autoimmune hepatitis (United States)

    Khoury, Tawfik; Ollech, Jacob E; Chen, Shmuel; Mizrahi, Meir; Shalit, Meir


    Underdiagnosis of drug-induced fever leads to extensive investigation and prolongation of hospitalization, and may lead to multiple unnecessary invasive procedures and a wrong diagnosis. Azathioprine is a widely used immunosuppressive drug. We report a case of a 53-year-old female patient diagnosed with autoimmune hepatitis treated with azathioprine, who presented to the emergency room with a 6-wk history of fever and chills without other associated symptoms. Since the patient’s fever was of unknown origin, she was hospitalized. All treatment was stopped and an extensive workup to explore the source of fever and chills was performed. Results of chest X-ray, viral, urine, and blood cultures, autoimmune serology, transthoracic and transesophageal echocardiography, and abdominal ultrasound revealed no source of infection. A rechallenge test of azathioprine was performed and the fever and chills returned within a few hours. Azathioprine was established as the definite cause following rechallenge. Fever as an adverse drug reaction is often unrecognized. Azathioprine has been reported to cause drug-induced fever in patients with inflammatory bowel disease, rheumatoid arthritis, and sarcoidosis. To the best of our knowledge there have been no previous reports documenting azathioprine-induced fever in patients with autoimmune hepatitis. The occurrence of fever following the readministration of azathioprine suggests the diagnosis of drug-induced fever, particularly after the exclusion of other causes. A careful rechallenge is recommended to confirm the diagnosis. PMID:23840156

  8. Genetic variation associated with cardiovascular risk in autoimmune diseases. (United States)

    Perrotti, Pedro P; Aterido, Adrià; Fernández-Nebro, Antonio; Cañete, Juan D; Ferrándiz, Carlos; Tornero, Jesús; Gisbert, Javier P; Domènech, Eugeni; Fernández-Gutiérrez, Benjamín; Gomollón, Fernando; García-Planella, Esther; Fernández, Emilia; Sanmartí, Raimon; Gratacós, Jordi; Martínez-Taboada, Víctor Manuel; Rodríguez-Rodríguez, Luís; Palau, Núria; Tortosa, Raül; Corbeto, Mireia L; Lasanta, María L; Marsal, Sara; Julià, Antonio


    Autoimmune diseases have a higher prevalence of cardiovascular events compared to the general population. The objective of this study was to investigate the genetic basis of cardiovascular disease (CVD) risk in autoimmunity. We analyzed genome-wide genotyping data from 6,485 patients from six autoimmune diseases that are associated with a high socio-economic impact. First, for each disease, we tested the association of established CVD risk loci. Second, we analyzed the association of autoimmune disease susceptibility loci with CVD. Finally, to identify genetic patterns associated with CVD risk, we applied the cross-phenotype meta-analysis approach (CPMA) on the genome-wide data. A total of 17 established CVD risk loci were significantly associated with CVD in the autoimmune patient cohorts. From these, four loci were found to have significantly different genetic effects across autoimmune diseases. Six autoimmune susceptibility loci were also found to be associated with CVD risk. Genome-wide CPMA analysis identified 10 genetic clusters strongly associated with CVD risk across all autoimmune diseases. Two of these clusters are highly enriched in pathways previously associated with autoimmune disease etiology (TNFα and IFNγ cytokine pathways). The results of this study support the presence of specific genetic variation associated with the increase of CVD risk observed in autoimmunity.

  9. Celiac Disease Autoimmunity in Patients with Autoimmune Diabetes and Thyroid Disease among Chinese Population.

    Directory of Open Access Journals (Sweden)

    Zhiyuan Zhao

    Full Text Available The prevalence of celiac disease autoimmunity or tissue transglutaminase autoantibodies (TGA amongst patients with type 1 diabetes (T1D and autoimmune thyroid disease (AITD in the Chinese population remains unknown. This study examined the rate of celiac disease autoimmunity amongst patients with T1D and AITD in the Chinese population. The study included 178 patients with type 1 diabetes and 119 with AITD where 36 had both T1D and AITD, classified as autoimmune polyglandular syndrome type 3 variant (APS3v. The study also included 145 patients with type 2 diabetes (T2D, 97 patients with non-autoimmune thyroid disease (NAITD, and 102 healthy controls. Serum islet autoantibodies, thyroid autoantibodies and TGA were measured by radioimmunoassay. TGA positivity was found in 22% of patients with either type 1 diabetes or AITD, much higher than that in patients with T2D (3.4%; p< 0.0001 or NAITD (3.1%; P < 0.0001 or healthy controls (1%; p<0.0001. The patients with APS3v having both T1D and AITD were 36% positive for TGA, significantly higher than patients with T1D alone (p = 0.040 or with AITD alone (p = 0.017. T1D and AITD were found to have a 20% and 30% frequency of overlap respectively at diagnosis. In conclusion, TGA positivity was high in the Chinese population having existing T1D and/or AITD, and even higher when both diseases were present. Routine TGA screening in patients with T1D or AITD will be important to early identify celiac disease autoimmunity for better clinical care of patients.

  10. Study of the mechanical behavior of the hydride blister/rim structure in Zircaloy-4 using in-situ synchrotron X-ray diffraction (United States)

    Lin, Jun-li; Han, Xiaochun; Heuser, Brent J.; Almer, Jonathan D.


    High-energy synchrotron X-ray diffraction was utilized to study the mechanical response of the f.c.c δ hydride phase, the intermetallic precipitation with hexagonal C14 lave phase and the α-Zr phase in the Zircaloy-4 materials with a hydride rim/blister structure near one surface of the material during in-situ uniaxial tension experiment at 200 °C. The f.c.c δ was the only hydride phase observed in the rim/blister structure. The conventional Rietveld refinement was applied to measure the macro-strain equivalent response of the three phases. Two regions were delineated in the applied load versus lattice strain measurement: a linear elastic strain region and region that exhibited load partitioning. Load partitioning was quantified by von Mises analysis. The three phases were observed to have similar elastic modulus at 200 °C.

  11. Stress as an environmnetal risk factor for autoimmune diseases

    Directory of Open Access Journals (Sweden)

    Anna Kawalec


    Full Text Available eases and a factor which contributes to disease exacerbation. Emotional stress before the disease onset is reported by up to 80% of patients suffering from autoaggressive diseases. A significant increase in the prevalence of autoimmune diseases in recent years and the growing number of stressors in our daily lives, including the work environment, raise a question about a link between psychological stress and autoimmune disorders. Therefore, the objective of this paper is to highlight the potential role of stress in both development and exacerbation of autoimmune diseases. The potential mechanisms by which stress can affect autoimmunity are characterised. In particular, the focus is on rheumatic diseases, autoimmune endocrine disorders, multiple sclerosis, and psoriasis. In addition, the role of post-traumatic stress disorder is underlined, as well as the possible association between stress present in the work environment and the development of autoimmune diseases among employees.

  12. Shared Genetic Relationships Underlying Generalized Vitiligo and Autoimmune Thyroid Disease (United States)


    Background Generalized vitiligo is an autoimmune disease of skin pigmentation that is associated with increased prevalence of other autoimmune diseases, particularly autoimmune thyroid disease (AITD; principally Hashimoto's disease and Graves' disease), both in vitiligo patients and their close relatives, suggesting a heritable predisposition involving, in part, shared susceptibility genes. Summary This review summarizes current knowledge of vitiligo epidemiology and genetics, highlighting recent findings from genome-wide approaches to disease gene identification, emphasizing susceptibility loci shared with other autoimmune diseases, particularly AITD, as well as some important differences. Conclusions Inherited susceptibility to generalized vitiligo involves a number of specific genes, many of which are shared with other autoimmune diseases that are epidemiologically associated with vitiligo, including AITD, confirming a longstanding hypothesis about the genetic basis of these disorders. These genes provide potential therapeutic targets for novel approaches to treatment as well as for approaches to presymptomatic diagnosis and disease prevention in individuals with inherited susceptibility to this group of autoimmune diseases. PMID:20578892

  13. Infections as risk factor for autoimmune diseases - A nationwide study

    DEFF Research Database (Denmark)

    Nielsen, Philip Rising; Kragstrup, Tue Wenzel; Deleuran, Bent Winding


    Viruses, bacteria and other infectious pathogens are the major postulated environmental triggers of autoimmunity. In the present nation-wide study we describe the association between infections and 29 autoimmune diseases. We used the Danish Civil Registration System to identify 4.5 million persons...... born between 1945 and 2000. Information on infections and autoimmune diseases was obtained from the Danish Hospital Register. The cohort was followed from 1977 to 2012. Incidence rate ratios for developing an autoimmune disease were estimated using poisson regression. We found an association between...... hospital admission for an infection and 29 autoimmune diseases. This study shows that infections are risk factors for a broad spectrum of autoimmune diseases in a dose-response and temporal manner, in agreement with the hypothesis that infections are an environmental risk factor contributing...

  14. The MicroRNA-21 in Autoimmune Diseases. (United States)

    Wang, Shaowen; Wan, Xiaochun; Ruan, Qingguo


    MicroRNA-21 (miR-21) is an oncomiR and significantly upregulated in a wide range of cancers. It is strongly involved in apoptosis and oncogenesis, since most of its reported targets are tumor suppressors. Recently, miR-21 was found to be correlated with the pathogenesis of autoimmune diseases and may play an essential role in regulating autoimmune responses. In particular, miR-21 promotes Th17 cell differentiation, which mediates the development of multiple autoimmune diseases. In this article, we review the current research on the mechanisms that regulate miR-21 expression, the potential of miR-21 as a diagnostic biomarker for autoimmune disease and the mechanisms by which miR-21 promotes the development of autoimmune disease. We also discussed the therapeutic potential of targeting miR-21 in treating patients with autoimmune disease.

  15. [Research advances in autoimmune liver diseases in 2016]. (United States)

    Li, B; Wang, Q X; Ma, X


    Autoimmune liver diseases are a group of abnormal autoimmune-mediated inflammatory hepatobiliary injuries, mainly including autoimmune hepatitis(AIH), primary biliary cholangitis(PBC), and primary sclerosing cholangitis (PSC). The diagnosis and treatment of autoimmune liver diseases, an important type of non-viral liver disease, have become a prominent issue in hepatology. In 2016, many new advances have been achieved in the clinical and basic research on autoimmune liver diseases, including the phase 3 clinical trial of obeticholic acid, the proposal of UK-PBC risk score, and the research on gut microbiota associated with PSC. This article reviews the research advances in the diagnosis and treatment of autoimmune liver diseases in 2016.

  16. Flow cytometric analysis of skin blister fluid induced by mosquito bites in a patient with chronic active Epstein-Barr virus infection


    Wada, Taizo; Yokoyama, Tadafumi; Nakagawa, Hiroyasu; Asai, Erika; Taga, Akiko; Sakakibara, Yasuhisa; Shibata, Fumie; Tone, Yumi; Shimizu, Masaki; Toma, Tomoko; Yachie, Akihiro


    In chronic active Epstein-Barr virus (EBV) infection (CAEBV), ectopic EBV infection has been described in T or natural killer (NK) cells. NK cell-type infection (NK-CAEBV) is characterized by large granular lymphocytosis, high IgE levels and unusual reactions to mosquito bites, including severe local skin reactions, fever and liver dysfunction. However, the mechanisms underlying these reactions remain undetermined. Herein, we describe a patient with NK-CAEBV whose blister fluid after mosquito...

  17. Carboplatin Induced Fatal Autoimmune Hemolytic Anemia: First Reported Case


    Dacha, Sunil; Reddivari, Anil K; Latta, Shadi; Devidi, Manjari; Iroegbu, Nkemakolam


    Carboplatin is an alkylating anti-neoplastic drug used in various cancers especially ovarian cancer, germ cell tumors, endometrial cancer besides others. We present a case of acute autoimmune hemolytic anemia during Carboplatin infusion in a patient previously exposed to the drug, resulting in the death of the patient. Published reports of Carboplatin induced autoimmune hemolytic anemia suggest these are usually nonfatal and improve after discontinuation of the drug. Fatal autoimmune hemolysi...

  18. Metabolic disorders and nutritional status in autoimmune thyroid diseases


    Anna Kawicka; Bożena Regulska-Ilow


    In recent years, the authors of epidemiological studies have documented that autoimmune diseases are a major problem of modern society and are classified as diseases of civilization. Autoimmune thyroid diseases (ATDs) are caused by an abnormal immune response to autoantigens present in the thyroid gland – they often coexist with other autoimmune diseases. The most common dysfunctions of the thyroid gland are hypothyroidism, Graves-Basedow disease and Hashimoto’s disease. Hashimoto’s thyroidit...

  19. [Clinical immunological diagnostics of overlap syndrome during autoimmune hepatic disorders]. (United States)

    Sagynbaeva, V É; Lazebnik, L B; Gudkova, R B; Efremov, L I; Vinnitskaia, E V; Dorofeev, A S


    The complex determination of serum autoantibodies to hepatic antigens using enzyme immunoassay and immunoblot allows to increase the frequency of overlap syndrome identification during autoimmune hepatic disorders and its early diagnostics, that has a big clinical, diagnostic and prognostic importance. The levels of overlap autoantibodies combine with biochemical index and with disease activity and intensity of autoimmune processes during overlap syndrome of primary biliary cirrhosis/autoimmune hepatitis (PBC/AIH).

  20. Autoimmune hepatitis related autoantibodies in children with type 1 diabetes


    Al-Hussaini, Abdulrahman A; Alzahrani, Musa D; Alenizi, Ahmed S; Suliman, Nimer M; Khan, Mannan A; Alharbi, Sahar A; Chentoufi, Aziz A


    Background and objectives The frequency of Type 1 diabetes (T1D)-related autoantibodies was determined in children with autoimmune hepatitis. However, the incidence of autoimmune hepatitis related autoantibodies in children with T1D has been poorly investigated. The aim of the present cross sectional prospective study was to determine the occurrence of autoimmune hepatitis-related autoantibodies in children with T1D. Methods Children with T1D following in diabetic clinic in our center were sc...

  1. Non-invasive measurement of reepithelialization and microvascularity of suction-blister wounds with benchmarking to histology

    DEFF Research Database (Denmark)

    Larsen, Heidi Fhaer; Ahlström, Malin Glindvad; Gjerdrum, Lise Mette Rahbek


    blister (10 mm) was induced on each buttock in 30 healthy volunteers (15 females:15 males) and de-roofed on day 0. The wounds were randomized to daily treatment with 1.4% zinc sulfate shower gel (n = 20), placebo (n = 20) or control (n = 20). Digital photography coupled with planimetry, transepidermal...... groups but increased more with the placebo than with the zinc shower gel (p = 0.003) or the control treatment (p = 0.002) and correlated (rS = 0.313, p = 0.015) with the inflammatory response on day 4, as determined by histology. Coagulase-negative staphylococci were more common in wounds compared...... with skin (p = 0.002) and was reduced (p = 0.030) with zinc sulfate treatment. Planimetric analysis of digital wound images was not biased (p = 0.234) compared with histology, and TEWL measurements showed no correlation (rS = 0.052, p = 0.691) with epithelialization. Neoepidermal formation, determined...

  2. Successful treatment of a blood blister-like aneurysm of the internal carotid artery by trapping with a high-flow bypass. (United States)

    Kawashima, Akitsugu; Okada, Yoshikazu; Kawamata, Takakazu; Onda, Hideaki; Kubo, Osami; Hori, Tomokatsu


    Treatment of blood blister-like aneurysms of the internal carotid artery (ICA) is difficult because the wall of the aneurysm is fragile and there is a high risk of rebleeding. There has been no consensus on the best way to treat these aneurysms. A 32-year-old woman presented with subarachnoid hemorrhage (SAH) caused by a ruptured blood blister-like aneurysm of the ICA. The site of the aneursym was clipped. Although angiography 1week after the operation showed that the aneurysm had been treated successfully, 3 weeks after the initial operation, the aneurysm was found to have recurred to the distal side. In a second operation, the aneurysm was successfully treated by trapping with a high-flow bypass. This case shows that clipping of the rupture site can be insufficient to treat blood blister-like aneurysm of the ICA causing SAH, even if the aneurysm seems to have resolved in follow-up angiographic studies. Trapping of the ICA with a bypass, if necessary a high-flow bypass, is recommended.

  3. Achalasia in a Patient with Polyglandular Autoimmune Syndrome Type II

    Directory of Open Access Journals (Sweden)

    Bashar S. Amr


    Full Text Available Achalasia is a rare disease characterized by aperistalsis of the esophageal body and failure of the lower esophageal sphincter to relax. The etiology of this disease remains unknown. Polyglandular autoimmune syndrome type II is a well-identified disease characterized by the occurrence of autoimmune Addison's disease in combination with autoimmune thyroid disease and/or type 1 diabetes mellitus. We report a case that suggests autoimmunity and immunogenicity as a probable contributing factor for association of these two rare disorders.

  4. Transient Non-Autoimmune Hyperthyroidism of Early Pregnancy (United States)

    Goldman, Alexander M.; Mestman, Jorge H.


    It is characterized by chemical and sometimes clinical hyperthyroidism, without evidence of thyroid autoimmunity that resolves spontaneously by 16 weeks gestation without significant obstetrical complications. PMID:21785688

  5. Transient Non-Autoimmune Hyperthyroidism of Early Pregnancy


    Goldman, Alexander M.; Mestman, Jorge H.


    It is characterized by chemical and sometimes clinical hyperthyroidism, without evidence of thyroid autoimmunity that resolves spontaneously by 16 weeks gestation without significant obstetrical complications.

  6. Transient non-autoimmune hyperthyroidism of early pregnancy. (United States)

    Goldman, Alexander M; Mestman, Jorge H


    It is characterized by chemical and sometimes clinical hyperthyroidism, without evidence of thyroid autoimmunity that resolves spontaneously by 16 weeks gestation without significant obstetrical complications.

  7. Autoimmune Disease in Children and Adolescents with Psoriasis

    DEFF Research Database (Denmark)

    Blegvad, Christoffer; Egeberg, Alexander; Tind Nielsen, Tilde E.


    Psoriasis is an immune-mediated inflammatory disease, which, in studies among adults, have been shown to cluster with autoimmune disease. The aim of this cross-sectional register study was to examine possible associations between 9 pre-selected autoimmune diseases and psoriasis in children...... arthritis (adjusted OR 6.61; 2.75-15.87) and vitiligo (adjusted OR 4.76; 1.71-13.20) showed strong associations with psoriasis. In addition to increased risk of selected autoimmune diseases, the presence of psoriasis was associated with increased risk of multiple concurrent autoimmune diseases compared...

  8. Associations Between Autoimmune Diseases and Attention-Deficit/Hyperactivity Disorder

    DEFF Research Database (Denmark)

    Nielsen, Philip Finn Rising; Benros, Michael Eriksen; Dalsgaard, Søren


    by an incidence rate ratio of 1.24 (95% CI 1.10-1.40). The primary analyses associated maternal autoimmune disease with ADHD in the offspring (incidence rate ratio 1.12, 95% CI 1.06-1.19), whereas a paternal history of autoimmune diseases was not significantly associated with ADHD in the offspring. In exploratory...... analyses, an increased risk of ADHD was observed for children with a family history of thyrotoxicosis, type 1 diabetes, autoimmune hepatitis, psoriasis, and ankylosing spondylitis. CONCLUSION: A personal history and a maternal history of autoimmune disease were associated with an increased risk of ADHD...

  9. Autoimmunity in common variable immunodeficiency: epidemiology, pathophysiology and management. (United States)

    Azizi, Gholamreza; Abolhassani, Hassan; Asgardoon, Mohammad Hosein; Alinia, Tina; Yazdani, Reza; Mohammadi, Javad; Rezaei, Nima; Ochs, Hans D; Aghamohammadi, Asghar


    Common variable immunodeficiency (CVID) comprises a large heterogeneous group of patients with primary antibody deficiency. Areas covered: The affected patients are characterized by increased susceptibility to infections and low levels of serum immunoglobulin. However, enteropathy, granulomatous organ infiltrates, malignancy, inflammatory and autoimmune conditions are also prevalent. The concomitance of immunodeficiency and autoimmunity appears to be paradoxical and creates difficulties in the management of autoimmune complications affecting these patients. Expert commentary: The management of autoimmunity in patients with CVID requires special considerations because dysregulation and dysfunctions of the immune system along with persistent inflammation impair the process of diagnosis and treatment.

  10. Transient Non-Autoimmune Hyperthyroidism of Early Pregnancy

    Directory of Open Access Journals (Sweden)

    Alexander M. Goldman


    Full Text Available It is characterized by chemical and sometimes clinical hyperthyroidism, without evidence of thyroid autoimmunity that resolves spontaneously by 16 weeks gestation without significant obstetrical complications.

  11. Type 1 diabetes and polyglandular autoimmune syndrome: A review (United States)

    Hansen, Martin P; Matheis, Nina; Kahaly, George J


    Type 1 diabetes (T1D) is an autoimmune disorder caused by inflammatory destruction of the pancreatic tissue. The etiopathogenesis and characteristics of the pathologic process of pancreatic destruction are well described. In addition, the putative susceptibility genes for T1D as a monoglandular disease and the relation to polyglandular autoimmune syndrome (PAS) have also been well explored. The incidence of T1D has steadily increased in most parts of the world, especially in industrialized nations. T1D is frequently associated with autoimmune endocrine and non-endocrine diseases and patients with T1D are at a higher risk for developing several glandular autoimmune diseases. Familial clustering is observed, which suggests that there is a genetic predisposition. Various hypotheses pertaining to viral- and bacterial-induced pancreatic autoimmunity have been proposed, however a definitive delineation of the autoimmune pathomechanism is still lacking. In patients with PAS, pancreatic and endocrine autoantigens either colocalize on one antigen-presenting cell or are expressed on two/various target cells sharing a common amino acid, which facilitates binding to and activation of T cells. The most prevalent PAS phenotype is the adult type 3 variant or PAS type III, which encompasses T1D and autoimmune thyroid disease. This review discusses the findings of recent studies showing noticeable differences in the genetic background and clinical phenotype of T1D either as an isolated autoimmune endocrinopathy or within the scope of polyglandular autoimmune syndrome. PMID:25685279

  12. Autoimmune vitiligo in rheumatic disease in the mestizo Mexican population (United States)

    Avalos-Díaz, Esperanza; Pérez-Pérez, Elena; Rodríguez-Rodríguez, Mayra; Pacheco-Tovar, María-Guadalupe; Herrera-Esparza, Rafael


    Vitiligo is a chronic disease characterized by the dysfunction or destruction of melanocytes with secondary depigmentation. The aim of the present study was to determine the prevalence of vitiligo associated with autoimmune rheumatic diseases. The clinical records from a 10-year database of patients with rheumatic diseases and associated vitiligo was analysed, with one group of patients having autoimmune rheumatic disease and another non-autoimmune rheumatic disease. Available serum samples were used to assess the anti-melanocyte antibodies. A total of 5,251 individual clinical files were archived in the last 10 years, and these patients underwent multiple rheumatology consultations, with 0.3% of the group presenting with vitiligo. The prevalence of vitiligo in the autoimmune rheumatic disease group was 0.672%, which was mainly associated with lupus and arthritis. However, patients with more than one autoimmune disease had an increased relative risk to develop vitiligo, and anti-melanocyte antibodies were positive in 92% of these patients. By contrast, the prevalence was 0.082% in the group that lacked autoimmune rheumatic disease and had negative autoantibodies. In conclusion, the association between vitiligo and autoimmune rheumatic diseases was relatively low. However, the relative risk increased when there were other autoimmune comorbidities, such as thyroiditis or celiac disease. Therefore, the presence of multiple autoimmune syndromes should be suspected. PMID:27446537

  13. Disruption of immunological tolerance: role of AIRE gene in autoimmunity. (United States)

    Rizzi, M; Ferrera, F; Filaci, G; Indiveri, F


    The mechanism underlying the generation of T and B autoreactive clones in autoimmune diseases is still unknown. Among genetic factors implicated in autoimmunity, Autoimmune Regulator gene (AIRE) is one of the candidates to better understand the complex scenario of autoimmune manifestations. AIRE mutations are responsible for the development of autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED) with monogenic autosomal recessive inheritance; it has been shown that AIRE regulates the negative selection of autoreactive T cells clones, driving the transcription of tissue-specific antigens in thymic epithelial cells. In various autoimmune manifestations correlated or not to APECED, AIRE variants act in a semidominant manner, leading to a reduction in AIRE protein amount per cell, and consequently to a marked decrease in ectopic proteins expression in the thymus. The co-occurrence of autoimmune diseases in the same individual has prompted several studies aimed to recognize shared patho-physiological mechanisms; in this scenario small reductions in function could explain the predisposition to autoimmunity in AIRE-heterozygous carriers of missense mutations; further studies to investigate whether the AIRE gene is involved in determining these autoimmune manifestations should be carried out.

  14. Autoimmune Neurology of the Central Nervous System. (United States)

    Tobin, W Oliver; Pittock, Sean J


    This article reviews the rapidly evolving spectrum of autoimmune neurologic disorders with a focus on those that involve the central nervous system, providing an understanding of how to approach the diagnostic workup of patients presenting with central nervous system symptoms or signs that could be immune mediated, either paraneoplastic or idiopathic, to guide therapeutic decision making. The past decade has seen a dramatic increase in the discovery of novel neural antibodies and their targets. Many commercial laboratories can now test for these antibodies, which serve as diagnostic markers of diverse neurologic disorders that occur on an autoimmune basis. Some are highly specific for certain cancer types, and the neural antibody profiles may help direct the physician's cancer search. The diagnosis of an autoimmune neurologic disorder is aided by the detection of an objective neurologic deficit (usually subacute in onset with a fluctuating course), the presence of a neural autoantibody, and improvement in the neurologic status after a course of immunotherapy. Neural autoantibodies should raise concern for a paraneoplastic etiology and may inform a targeted oncologic evaluation (eg, N-methyl-D-aspartate [NMDA] receptor antibodies are associated with teratoma, antineuronal nuclear antibody type 1 [ANNA-1, or anti-Hu] are associated with small cell lung cancer). MRI, EEG, functional imaging, videotaped evaluations, and neuropsychological evaluations provide objective evidence of neurologic dysfunction by which the success of immunotherapy may be measured. Most treatment information emanates from retrospective case series and expert opinion. Nonetheless, early intervention may allow reversal of deficits in many patients and prevention of future disability.

  15. Dendritic cells in autoimmune thyroid disease. (United States)

    Kabel, P J; Voorbij, H A; van der Gaag, R D; Wiersinga, W M; de Haan, M; Drexhage, H A


    Dendritic cells form a morphologically distinct class of cells characterized by shape, reniform nucleus, absent to weak acid-phosphatase activity and strong Class II MHC determinant positivity. Functionally they are the most efficient cells in antigen presentation to T-lymphocytes which indicates their role in the initiation of an immune response. Using immunehistochemical techniques we studied the presence of dendritic cells in normal Wistar rat and human thyroids, in thyroids of BBW rats developing thyroid autoimmunity and in Graves' goitres. Dendritic cells could be identified in all thyroids studied and were positioned underneath the thyrocytes in between the follicles. Skin dendritic cells travel via lymphatics to draining lymph nodes, thus forming an antigen presenting cell system. It is likely that a similar cell system exists on the level of the thyroid for dendritic cells have also been detected in thyroid draining lymph nodes. In normal thyroid tissue of both human and rat dendritic cells were relatively scarce. During the initial phases of the thyroid autoimmune response in the BBW rat (before the appearance of Tg-antibodies in the circulation) numbers of thyroid dendritic cells increased. Intrathyroidal T-helper cells, B-cells or plasma cells could not be found. The thyroid draining lymph node contained large numbers of plasma cells. During the later stages of the thyroid autoimmune response in the BB/W rat (after the appearance of Tg-antibodies in the circulation) and in Graves' goitres dendritic cells were not only present in high number, but 20-30% were seen in contact with now-present intrathyroidal T-helper lymphocytes.(ABSTRACT TRUNCATED AT 250 WORDS)

  16. Paradoxical development of polymyositis-like autoimmunity through augmented expression of autoimmune regulator (AIRE). (United States)

    Nishijima, Hitoshi; Kajimoto, Tatsuya; Matsuoka, Yoshiki; Mouri, Yasuhiro; Morimoto, Junko; Matsumoto, Minoru; Kawano, Hiroshi; Nishioka, Yasuhiko; Uehara, Hisanori; Izumi, Keisuke; Tsuneyama, Koichi; Okazaki, Il-Mi; Okazaki, Taku; Hosomichi, Kazuyoshi; Shiraki, Ayako; Shibutani, Makoto; Mitsumori, Kunitoshi; Matsumoto, Mitsuru


    Autoimmunity is prevented by the function of the autoimmune regulator [AIRE (Aire in mice)], which promotes the expression of a wide variety of tissue-restricted antigens (TRAs) from medullary thymic epithelial cells (mTECs) and from a subset of peripheral antigen-presenting cells (APCs). We examined the effect of additive expression of human AIRE (huAIRE) in a model of autoimmune diabetes in NOD mice. Unexpectedly, we observed that mice expressing augmented AIRE/Aire developed muscle-specific autoimmunity associated with incomplete maturation of mTECs together with impaired expression of Aire-dependent TRAs. This led to failure of deletion of autoreactive T cells together with dramatically reduced production of regulatory T cells in the thymus. In peripheral APCs, expression of costimulatory molecules was augmented. We suggest that levels of Aire expression need to be tightly controlled for maintenance of immunological tolerance. Our results also highlight the importance of coordinated action between central tolerance and peripheral tolerance under the common control of Aire. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  17. Anti-Saccharomyces cerevisiae autoantibodies in autoimmune diseases: from bread baking to autoimmunity. (United States)

    Rinaldi, Maurizio; Perricone, Roberto; Blank, Miri; Perricone, Carlo; Shoenfeld, Yehuda


    Saccharomyces cerevisiae is best known as the baker's and brewer's yeast, but its residual traces are also frequent excipients in some vaccines. Although anti-S. cerevisiae autoantibodies (ASCAs) are considered specific for Crohn's disease, a growing number of studies have detected high levels of ASCAs in patients affected with autoimmune diseases as compared with healthy controls, including antiphospholipid syndrome, systemic lupus erythematosus, type 1 diabetes mellitus, and rheumatoid arthritis. Commensal microorganisms such as Saccharomyces are required for nutrition, proper development of Peyer's aggregated lymphoid tissue, and tissue healing. However, even the commensal nonclassically pathogenic microbiota can trigger autoimmunity when fine regulation of immune tolerance does not work properly. For our purposes, the protein database of the National Center for Biotechnology Information (NCBI) was consulted, comparing Saccharomyces mannan to several molecules with a pathogenetic role in autoimmune diseases. Thanks to the NCBI bioinformation technology tool, several overlaps in molecular structures (50-100 %) were identified when yeast mannan, and the most common autoantigens were compared. The autoantigen U2 snRNP B″ was found to conserve a superfamily protein domain that shares 83 % of the S. cerevisiae mannan sequence. Furthermore, ASCAs may be present years before the diagnosis of some associated autoimmune diseases as they were retrospectively found in the preserved blood samples of soldiers who became affected by Crohn's disease years later. Our results strongly suggest that ASCAs' role in clinical practice should be better addressed in order to evaluate their predictive or prognostic relevance.

  18. Airway Autoimmune Inflammatory Response (AAIR) Syndrome: An Asthma-Autoimmune Overlap Disorder? (United States)

    Spencer, Chantal Y; Millman, Jennifer; Veiga, Keila; Vicencio, Alfin G


    Asthma encompasses numerous phenotypes that may require alternate approaches to diagnosis and therapy, particularly for patients whose symptoms remain poorly controlled despite escalating treatment. We describe 3 patients with apparent asthma who demonstrated unusual findings on cryobiopsy by flexible bronchoscopy and responded to therapy directed against autoimmune disease. Copyright © 2018 by the American Academy of Pediatrics.

  19. Latent autoimmune diabetes of adulthood: case report. (United States)

    Page, Cristen P; Fitzgerald, Brian; Hawes, Emily M


    Primary care clinicians will see a higher incidence of type 2 diabetes in adult patients, and the diagnosis and management of an initial presentation of type 1 diabetes can pose challenges to clinicians who see it less frequently. Symptoms of hyperglycemia and risk of ketoacidosis may be missed. Further, endocrine autoimmune disease can run together in patients and families. A 49-year-old Caucasian female with history of pituitary adenoma and Graves' disease with history of thyroid ablation presented in the outpatient setting due to hand tingling of her right middle finger that was worse in the mornings and improved throughout the day. She also complained of excessive thirst, finding herself drinking more water than usual and waking up in the night to urinate. There was no dysuria or haematuria, and no other neurologic symptoms. She did report feeling hungry. She had no family history of diabetes, normal body mass index of 21.7, and reported taking her thyroid replacement medication every day. The differential diagnosis for her thirst included dehydration, psychogenic polydipsia, diabetes mellitus, diabetes insipidus, and anxiety. The patient had normal vital signs and was well appearing; labs were ordered for her on her way home from clinic with no medications. Labs revealed a random blood glucose level of 249 mg/dL, normal renal function, a normal B12 of 996 pg/mL, and an elevated thyroid stimulating hormone level of 25.67 u[iU]/mL. On follow up with her primary care provider 5 days later, additional labs were drawn showing A1C of 11.5%, 1+ ketonuria, a negative Acetest, and a normal basic metabolic panel, except for a fasting glucose of 248 mg/dL, and Free T3 of 2.42 pg/mL, and Free T4 of 1.7 ng/dL. Islet cell antibodies and glutamic acid decarboxylase antibodies were both positive, consistent with type 1 diabetes. She was started on insulin and improved. Given the patient's age, this is a less common presentation of type 1 diabetes mellitus, as a part of

  20. Autoimmun hypophysitis--en differentialdiagnose til hypofyseadenomer

    DEFF Research Database (Denmark)

    Krarup, Therese; Hagen, Claus


    A 66-year-old man with a headache in the left temporal region which had persisted for eight months is presented. The patient developed polydipsia and polyuria and also suffered from tinnitus, impaired hearing and episodes of double vision. The patient was diagnosed with autoimmune hypophysitis (A......) in 2007. This case story displays the importance of knowing AH, as it is an important differential diagnosis to pituitary gland adenomas and to diseases in the hypothalamus because it can be treated medically as opposed to surgically....

  1. Role of extracellular vesicles in autoimmune diseases. (United States)

    Turpin, Delphine; Truchetet, Marie-Elise; Faustin, Benjamin; Augusto, Jean-François; Contin-Bordes, Cécile; Brisson, Alain; Blanco, Patrick; Duffau, Pierre


    Extracellular vesicles (EVs) consist of exosomes released upon fusion of multivesicular bodies with the cell plasma membrane and microparticles shed directly from the cell membrane of many cell types. EVs can mediate cell-cell communication and are involved in many processes including inflammation, immune signaling, angiogenesis, stress response, senescence, proliferation, and cell differentiation. Accumulating evidence reveals that EVs act in the establishment, maintenance and modulation of autoimmune processes among several others involved in cancer and cardiovascular complications. EVs could also present biomedical applications, as disease biomarkers and therapeutic targets or agents for drug delivery. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. Clinical immunology--autoimmunity in the Netherlands. (United States)

    Tervaert, Jan Willem Cohen; Kallenberg, Cees G M


    Clinical immunology is in the Netherlands a separate clinical specialty within internal medicine and pediatrics. Clinical immunologists work closely together with nephrologists, rheumatologists and many other medical specialists. Apart from research and teaching, clinical immunologists are taking care of patients with immune-deficiencies, vasculitides and systemic auto-immune diseases. Clinical immunology in the Netherlands has always been an important contributor to basic and clinical science in the Netherlands. Major scientific contributions were made in the field of Systemic Lupus Erythematosus and ANCA associated vasculitis. These Dutch contributions will be reviewed in this article. Copyright © 2014 Elsevier B.V. All rights reserved.

  3. Autoimmune and non-autoimmune thyroid diseases have different patterns of cellular HLA class II expression

    Directory of Open Access Journals (Sweden)

    Denise Engelbrecht Zantut-Wittmann

    Full Text Available CONTEXT: Surface HLA-DR antigen is usually only expressed by antigen-presenting cells (APC. In autoimmune thyroid disease, follicle cells function as APC, thus expressing HLA-DR. However, non-autoimmune thyroid diseases may also express surface class II antigens. OBJECTIVE: To evaluate the presence and pattern of HLA class II expression in autoimmune and non-autoimmune thyroid disorders. DESIGN: Retrospective: histopathological and immunohistochemical analysis. LOCATION: Referral center, university hospital. SAMPLE: Ten histologically normal thyroids, 11 Graves’ disease, 7 Hashimoto’s thyroiditis, 10 atoxic multinodular goiter and 3 toxic adenomas were analyzed by immunohistochemistry, using a monoclonal antibody anti-HLA-DR. MAIN MEASUREMENTS: The presence of these antigens in thyroid follicular cells and their relation to inflammatory infiltrate was evaluated. The pattern of HLA-DR expression in thyroid follicular cells was analyzed: membrane, cytoplasmic or both. RESULTS: Although HLA-DR antigens were sparsely present in one of the 8 normal thyroids, in 6 of the 9 atoxic multinodular goiter and in 2 of the 3 toxic adenomas a net positivity could be seen in large areas. In all 5 Hashimoto’s thyroiditis and in 7 of the 10 Graves’ disease cases. This expression occurred in follicle cells either in contact with inflammatory cells or not. In non-autoimmune thyroid disease, HLA-DR positivity was essentially cytoplasmic, whereas in Graves’ disease and Hashimoto thyroiditis it was mainly in cell membranes. CONCLUSIONS: It is suggested that the HLA class II expression on the surface of follicle cells could be related to auto-antigen presentation to the immune system by these cells, leading to inflammation.

  4. PRKDC mutations associated with immunodeficiency, granuloma, and autoimmune regulator–dependent autoimmunity (United States)

    Mathieu, Anne-Laure; Verronese, Estelle; Rice, Gillian I.; Fouyssac, Fanny; Bertrand, Yves; Picard, Capucine; Chansel, Marie; Walter, Jolan E.; Notarangelo, Luigi D.; Butte, Manish J.; Nadeau, Kari Christine; Csomos, Krisztian; Chen, David J.; Chen, Karin; Delgado, Ana; Rigal, Chantal; Bardin, Christine; Schuetz, Catharina; Moshous, Despina; Reumaux, Héloïse; Plenat, François; Phan, Alice; Zabot, Marie-Thérèse; Balme, Brigitte; Viel, Sébastien; Bienvenu, Jacques; Cochat, Pierre; van der Burg, Mirjam; Caux, Christophe; Kemp, E. Helen; Rouvet, Isabelle; Malcus, Christophe; Méritet, Jean-Francois; Lim, Annick; Crow, Yanick J.; Fabien, Nicole; Ménétrier-Caux, Christine; De Villartay, Jean-Pierre; Walzer, Thierry; Belot, Alexandre


    Background PRKDC encodes for DNA-dependent protein kinase catalytic subunit (DNA-PKcs), a kinase that forms part of a complex (DNA-dependent protein kinase [DNA-PK]) crucial for DNA double-strand break repair and V(D)J recombination. In mice DNA-PK also interacts with the transcription factor autoimmune regulator (AIRE) to promote central T-cell tolerance. Objective We sought to understand the causes of an inflammatory disease with granuloma and autoimmunity associated with decreasing T- and B-cell counts over time that had been diagnosed in 2 unrelated patients. Methods Genetic, molecular, and functional analyses were performed to characterize an inflammatory disease evocative of a combined immunodeficiency. Results We identified PRKDC mutations in both patients. These patients exhibited a defect in DNA double-strand break repair and V(D)J recombination. Whole-blood mRNA analysis revealed a strong interferon signature. On activation, memory T cells displayed a skewed cytokine response typical of TH2 and TH1 but not TH17. Moreover, mutated DNA-PKcs did not promote AIRE-dependent transcription of peripheral tissue antigens in vitro. The latter defect correlated in vivo with production of anti–calcium-sensing receptor autoantibodies, which are typically found in AIRE-deficient patients. In addition, 9 months after bone marrow transplantation, patient 1 had Hashimoto thyroiditis, suggesting that organ-specific autoimmunity might be linked to nonhematopoietic cells, such as AIRE-expressing thymic epithelial cells. Conclusion Deficiency of DNA-PKcs, a key AIRE partner, can present as an inflammatory disease with organ-specific autoimmunity, suggesting a role for DNA-PKcs in regulating autoimmune responses and maintaining AIRE-dependent tolerance in human subjects. PMID:25842288

  5. Autoimmune Regulator Deficiency Results in a Decrease in STAT1 Levels in Human Monocytes

    NARCIS (Netherlands)

    Zimmerman, O.; Rosen, L.B.; Swamydas, M.; Ferre, E.M.N.; Natarajan, M.; Veerdonk, F.L. van de; Holland, S.M.; Lionakis, M.S.


    Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a rare primary immunodeficiency disorder typically caused by biallelic autoimmune regulator (AIRE) mutations that manifests with chronic mucocutaneous candidiasis (CMC) and autoimmunity. Patients with STAT1 gain-of-function

  6. Cacao polyphenols ameliorate autoimmune myocarditis in mice. (United States)

    Zempo, Hirofumi; Suzuki, Jun-ichi; Watanabe, Ryo; Wakayama, Kouji; Kumagai, Hidetoshi; Ikeda, Yuichi; Akazawa, Hiroshi; Komuro, Issei; Isobe, Mitsuaki


    Myocarditis is a clinically severe disease; however, no effective treatment has been established. The aim of this study was to determine whether cacao bean (Theobroma cacao) polyphenols ameliorate autoimmune myocarditis. We used an experimental autoimmune myocarditis (EAM) model in Balb/c mice. Mice with induced EAM were treated with a cacao polyphenol extract (CPE, n=12) or vehicle (n=12). On day 21, hearts were harvested and analyzed. Elevated heart weight to body weight and fibrotic area ratios as well as high cardiac cell infiltration were observed in the vehicle-treated EAM mice. However, these increases were significantly suppressed in the CPE-treated mice. Reverse transcriptase-PCR revealed that mRNA expressions of interleukin (Il)-1β, Il-6, E-selectin, vascular cell adhesion molecule-1 and collagen type 1 were lower in the CPE group compared with the vehicle group. The mRNA expressions of nicotinamide adenine dinucleotide phosphate-oxidase (Nox)2 and Nox4 were increased in the vehicle-treated EAM hearts, although CPE treatment did not significantly suppress the transcription levels. However, compared with vehicle treatment of EAM hearts, CPE treatment significantly suppressed hydrogen peroxide concentrations. Cardiac myeloperoxidase activity, the intensity of dihydroethidium staining and the phosphorylation of nuclear factor-κB p65 were also lower in the CPE group compared with the vehicle group. Our data suggest that CPE ameliorates EAM in mice. CPE is a promising dietary supplement to suppress cardiovascular inflammation and oxidative stress.

  7. Maternal autoimmune thyroid disease and pregnancy complication

    Directory of Open Access Journals (Sweden)

    Gudović Aleksandra


    Full Text Available Background/Aim. Thyroid disorders exert a great impact on pregnancy course and outcome. The aim of the study was to investigate impact of autoimmune thyroid disorders on pregnancy course and outcome, frequency of pregnancy complications and pregnancy loss. Methods. We followed 63 pregnancies prospectively during the period 1985-2007, 28 with hyperthyroid and 15 with hypothyroid autoimmune disorders, and 20 healthy pregnancies. Follow up included clinical, sonographic and laboratory investigations, including OGTT and postprandial glicemia. Results. There was no difference between previous preterm and term labor in the observed groups (χ² = 2.309; p > 0.05. Analysis of previous early pregnancy loss showed no significance (χ² = 4.918; p > 0.05, including varieties of spontaneous and missed abortion (Fisher, p < 0.05. The hypothyroid patiens developed gestational diabetes more frequently than the controls (χ² = 7.638; p = 0.022, which is not the case with hyperthyroid patients (χ² = 1.078; p > 0.05, or between the groups with thyroid disorders (χ² = 3.619; p > 0.05. There was no difference among the groups in developing pregnancyinduced hypertension (χ ² = 1.953; p > 0.05. Conclusions. Controlling thyroid diseases reduces pregnancy complications. Development of gestational diabetes in hypothyroid patients requires controlling glycoregulation in all pregnant women with hypothyroidism.

  8. The role of CR2 in autoimmunity. (United States)

    Isaák, Andrea; Prechl, József; Gergely, János; Erdei, Anna


    Complement activation is one of the most powerful mechanisms taking place during inflammation and immune responses. Over the last 30 years increasing evidence has proven the role of C3 and receptors for its activation fragments in the initiation and regulation of immune responses. Since complement also has a basic importance in the maintenance of immune homeostasis, abnormalities affecting complement proteins and their receptors may lead to pathological conditions. Autoimmune conditions develop as a result of a range of genetic and environmental factors. Findings obtained from animal models support the notion that malfunctioning of complement receptors, particularly CR2, might be involved in the breakdown of tolerance and excessive antibody production by auto reactive B-cell clones. In addition to B cells, activated, CR2-bearing T cells may also contribute to the pathogenesis of autoimmunity as they can receive activating/survival signals in the inflamed tissue. Results obtained from mouse experiments however, should be extended to the human system with great care, since there are basic differences between the structure and function of human and murine CR1 and CR2.

  9. Autoimmune hemolytic anemia: transfusion challenges and solutions

    Directory of Open Access Journals (Sweden)

    Barros MM


    Full Text Available Melca M O Barros, Dante M Langhi Jr, José O Bordin Department of Clinical and Experimental Oncology, Universidade Federal de São Paulo, São Paulo, Brazil Abstract: Autoimmune hemolytic anemia (AIHA is defined as the increased destruction of red blood cells (RBCs in the presence of anti-RBC autoantibodies and/or complement. Classification of AIHA is based on the optimal auto-RBC antibody reactivity temperatures and includes warm, cold-reactive, mixed AIHA, and drug-induced AIHA subtypes. AIHA is a rare disease, and recommendations for transfusion are based mainly on results from retrospective data and relatively small cohort studies, including heterogeneous patient samples or single case reports. In this article, we will review the challenges and solutions to safely transfuse AIHA patients. We will reflect on the indication for transfusion in AIHA and the difficulty in the accomplishment of immunohematological procedures for the selection of the safest and most compatible RBC units. Keywords: hemolytic anemia, RBC autoantibodies, autoimmunity, hemolysis, direct ­antiglobulin test

  10. [Novel Developments in Autoimmune Liver Diseases]. (United States)

    Schramm, Christoph; Strassburg, Christian P


    Serologische Diagnostik bei autoimmunen Lebererkrankungen Die Serologie ist ein wichtiger Baustein in der Differenzialdiagnose autoimmuner Lebererkrankungen. Das Immunfluoreszenzmuster der antinukleären Antikörper (ANA) liefert wichtige Hinweise auf das Vorliegen einer primär biliären Cholangitis (PBC) und sollte berichtet werden. Autoimmune Hepatitis (AIH) Die Beurteilung der Leberhistologie ist für die Diagnose der AIH wichtig. Über den Verlauf der Erkrankung geben in der Regel die Transaminasen, das Serum IgG (beide sollten im Normbereich liegen) und nicht-invasive Methoden der Fibrosebestimmung (wie die transiente Elastografie) ausreichende Informationen. Primär Biliäre Cholangitis (PBC) Ca. 30 % der PBC-Patienten sprechen nicht ausreichend auf die Standardtherapie mit Ursodeoxycholsäure (UDCA) an. Für diese Patienten wurde kürzlich die zusätzliche Therapie mit Obeticholsäure zugelassen. Primär Sklerosierende Cholangitis (PSC) Die MRT/MRCP hat in der Diagnostik und Verlaufskontrolle der Gallengangspathologie eine zentrale Stellung. Nach einer endoskopischen Dilatationstherapie von Stenosen sollte, wenn möglich, auf eine Stenteinlage verzichtet werden. IgG4-assoziierte Cholangitis (IAC) Die Diagnose der IAC ist nach wie vor schwierig. Die IAC spricht in den frühen Stadien sehr gut auf eine Steroidtherapie an, wobei 20 – 40 mg pro Tag Prednisolon in der Initialtherapie ausreichen.

  11. Impaired psychometric testing in polyglandular autoimmunity. (United States)

    Storz, S M; Wylenzek, S A M; Matheis, N; Weber, M M; Kahaly, G J


    Patients with the autoimmune polyglandular syndrome (APS) could be exposed to many limitations in daily life owing to their illness. To quantify the degree of physical and emotional distress, the psychometric profile of these patients was evaluated prospectively. After a complete endocrine investigation, three international validated self-assessment questionnaires were applied in 75 patients with APS: the health-related quality of life Short-Form 36 (SF-36), the Giessen Complaint List (GBB-24) and the Hospital Anxiety and Depression Scale (HADS). Average duration of APS was 7.7 years. The most frequent disease combination was type 1 diabetes and autoimmune thyroid disease (n=47, 62.6%). Every scale of the SF-36, GBB-24, and the HADS anxiety score demonstrated markedly impaired physical and emotional well-being, foremost in female subjects (Pvitality (-0.8), social functioning (-0.8), emotional role limitations (-1.1) and mental health (-0.5). Also, the global score of discomfort was increased in comparison with the reference population (27.27 vs 13.93, P<0.001). Generalized anxiety (25%, P<0.001) and depression episode (18.1%, P<0.001) were prevalent in APS. Neither time interval between two endocrine diseases, duration of APS, age, nor autoantibody positivity influenced psychometric testing results. Patients with APS have a severely impaired psychometric profile. Treatment modalities that would improve their well-being are warranted. © 2011 Blackwell Publishing Ltd.

  12. Autoimmune pancreatitis can develop into chronic pancreatitis (United States)


    Autoimmune pancreatitis (AIP) has been recognized as a distinct type of pancreatitis that is possibly caused by autoimmune mechanisms. AIP is characterized by high serum IgG4 and IgG4-positive plasma cell infiltration in affected pancreatic tissue. Acute phase AIP responds favorably to corticosteroid therapy and results in the amelioration of clinical findings. However, the long-term prognosis and outcome of AIP remain unclear. We have proposed a working hypothesis that AIP can develop into ordinary chronic pancreatitis resembling alcoholic pancreatitis over a long-term course based on several clinical findings, most notably frequent pancreatic stone formation. In this review article, we describe a series of study results to confirm our hypothesis and clarify that: 1) pancreatic calcification in AIP is closely associated with disease recurrence; 2) advanced stage AIP might have earlier been included in ordinary chronic pancreatitis; 3) approximately 40% of AIP patients experience pancreatic stone formation over a long-term course, for which a primary risk factor is narrowing of both Wirsung’s and Santorini’s ducts; and 4) nearly 20% of AIP patients progress to confirmed chronic pancreatitis according to the revised Japanese Clinical Diagnostic Criteria, with independent risk factors being pancreatic head swelling and non-narrowing of the pancreatic body duct. PMID:24884922

  13. [microRNA in autoimmune disorders]. (United States)

    Jinnin, Masatoshi


    microRNAs, short ribonucleic acid molecules which is typically 20-25 nucleotides long, can bind to complementary sequences in the three prime untranslated regions of target mRNAs, leading to the inhibition of translation or degradation of the mRNA. Theologically, human genome may have more than 1000 microRNAs, which target about 60% of human mRNAs. Thus, microRNAs have been implicated in the pathogenesis of various disorders. This paper discusses the present day understanding about the expression and role in various autoimmune diseases including rheumatoid arthritis, Sjogren syndrome, polymyositis/dermatomyositis, systemic lupus erythematosus, scleroderma, type I diabetis, and psoriasis. For example, the expression of miR-29, which targets type I collagen mRNA, is reported to be down-regulated in cultured dermal fibroblasts derived from scleroderma skin, contributing to excessive collagen production in this disease. Supplementation of the microRNA results in the decrease of collagen expression in scleroderma fibroblasts. In addition, serum miR-29a levels are significantly decreased in the very early stage of scleroderma. Investigation of the involvement of microRNAs in the pathogenesis of each autoimmune disease may lead to develop new biomarker and new therapeutic approach.

  14. Autoimmune diseases in the TH17 era

    Directory of Open Access Journals (Sweden)

    D. Mesquita Jr.


    Full Text Available A new subtype of CD4+ T lymphocytes characterized by the production of interleukin 17, i.e., TH17 cells, has been recently described. This novel T cell subset is distinct from type 1 and type 2 T helper cells. The major feature of this subpopulation is to generate significant amounts of pro-inflammatory cytokines, therefore appearing to be critically involved in protection against infection caused by extracellular microorganisms, and in the pathogenesis of autoimmune diseases and allergy. The dynamic balance among subsets of T cells is important for the modulation of several steps of the immune response. Disturbances in this balance may cause a shift from normal immunologic physiology to the development of immune-mediated disorders. In autoimmune diseases, the fine balance between the proportion and degree of activation of the various T lymphocyte subsets can contribute to persistent undesirable inflammatory responses and tissue replacement by fibrosis. This review highlights the importance of TH17 cells in this process by providing an update on the biology of these cells and focusing on their biology and differentiation processes in the context of immune-mediated chronic inflammatory diseases.

  15. Conversion of autoimmune hypothyroidism to hyperthyroidism. (United States)

    Furqan, Saira; Haque, Naeem-ul; Islam, Najmul


    Graves' disease and Hashimoto's thyroiditis are the two autoimmune spectrum of thyroid disease. Cases of conversion from hyperthyroidism to hypothyroidism have been reported but conversion from hypothyroidism to hyperthyroidism is very rare. Although such cases have been reported rarely in the past we are now seeing such conversions from hypothyroidism to hyperthyroidism more frequently in clinical practice. We are reporting three cases of middle aged Asian females who presented with classical symptoms of hypothyroidism and the investigations showed elevated thyroid stimulating hormone with positive thyroid antibodies. Diagnosis of autoimmune hypothyroidism was made and thyroxine replacement therapy was initiated. Patients became asymptomatic with normalization of thyroid stimulating hormone level. After few years they developed symptoms of hyperthyroidism with suppressed thyroid stimulating hormone level. Over replacement of thyroxine was considered and the dose of thyroxine was decreased, but they remain symptomatic. After gradual decrease in the dose of thyroxine it was stopped finally. Even after few months of stopping thyroxine, the symptoms of hyperthyroidism did not improve and the biochemical and imaging modalities confirmed that the patients have developed hyperthyroidism. Anti-thyroid treatment was then started and the patients became symptom free. High index of suspicion should be there for possible conversion of hypothyroidism to hyperthyroidism if a patient with primary hypothyroidism develops persistent symptoms of hyperthyroidism. Otherwise it can be missed easily considering it as an over replacement with thyroid hormone.

  16. Advances in treatment of autoimmune pancreatitis

    Directory of Open Access Journals (Sweden)

    LI Ji


    Full Text Available Autoimmune pancreatitis (AIP is a type of chronic pancreatitis characterized by an autoimmune inflammatory process. Treatment protocols for AIP are still evolving. According to the articles about AIP treatment in recent years, the indications for steroid therapy include specific clinical manifestations (jaundice, abdominal pain, etc., markedly abnormal imaging findings, and extrapancreatic organ involvement. The initial dose of steroid (prednisone is usually 0.6 mg·kg-1·d-1 or 30-40 mg/d; after 3 weeks to 1 month of treatment with the initial dose, the dose is decreased by 5-10 mg every 1-2 weeks until it drops to 2.5-5 mg/d; this dose is maintained for 6 months to 3 years. No consensus has been reached on the adverse effect of steroid on diabetes mellitus complicating AIP. Immunosuppressive agents should be used for the patients with disease relapses or with important extrapancreatic organs involved. Rituximab might become one of the therapies for refractory AIP. Although some patients achieved remission after surgical treatment, surgery is still not recommended as a routine treatment protocol due to the complications after surgery.

  17. The Role of Pathogenic Autoantibodies in Autoimmunity

    Directory of Open Access Journals (Sweden)

    Merrill J. Rowley


    Full Text Available The serological presence of autoantibodies is diagnostic of autoimmunity, and these autoantibodies may be present for many years before the presentation of autoimmune disease (AID. Although a pathogenic role has been demonstrated for various autoantibodies reactive with cell surface and extracellular autoantigens, studies using monoclonal antibodies (mAb show not all antibodies in the polyclonal response are pathogenic. Differences depend on Fab-mediated diversity in epitope specificity, Fc-mediated effects based on immunoglobulin (Ig class and subclass, activation of complement, and the milieu in which the reaction occurs. These autoantibodies often occur in organ-specific AID and this review illustrates their pathogenic and highly specific effects. The role of autoantibodies associated with intracellular antigens is less clear. In vitro they may inhibit or adversely affect well-defined intracellular biochemical pathways, yet, in vivo they are separated from their autoantigens by multiple cellular barriers. Recent evidence that Ig can traverse cell membranes, interact with intracellular proteins, and induce apoptosis has provided new evidence for a pathogenic role for such autoantibodies. An understanding of how autoantibodies behave in the polyclonal response and their role in pathogenesis of AID may help identify populations of culprit B-cells and selection of treatments that suppress or eliminate them.

  18. [Assessment of endothelial function in autoimmune diseases]. (United States)

    Benhamou, Y; Bellien, J; Armengol, G; Gomez, E; Richard, V; Lévesque, H; Joannidès, R


    Numerous autoimmune-inflammatory rheumatic diseases have been associated with accelerated atherosclerosis or other types of vasculopathy leading to an increase in cardiovascular disease incidence. In addition to traditional cardiovascular risk factors, endothelial dysfunction is an important early event in the pathogenesis of atherosclerosis, contributing to plaque initiation and progression. Endothelial dysfunction is characterized by a shift of the actions of the endothelium toward reduced vasodilation, a proinflammatory and a proadhesive state, and prothrombic properties. Therefore, assessment of endothelial dysfunction targets this vascular phenotype using several biological markers as indicators of endothelial dysfunction. Measurements of soluble adhesion molecules (ICAM-1, VCAM-1, E-selectin), pro-thrombotic factors (thrombomodulin, von Willebrand factor, plasminogen activator inhibitor-1) and inflammatory cytokines are most often performed. Regarding the functional assessment of the endothelium, the flow-mediated dilatation of conduit arteries is a non-invasive method widely used in pathophysiological and interventional studies. In this review, we will briefly review the most relevant information upon endothelial dysfunction mechanisms and explorations. We will summarize the similarities and differences in the biological and functional assessments of the endothelium in different autoimmune diseases. Copyright © 2013 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.

  19. Epigenetic alterations in autoimmune rheumatic diseases. (United States)

    Ballestar, Esteban


    The potential roles of epigenetic alterations in the pathogenesis of autoimmune rheumatic diseases are raising great expectations among clinicians and researchers. Epigenetic mechanisms regulate gene expression and are sensitive to external stimuli, bridging the gap between environmental and genetic factors. Considerable evidence of epigenetic changes, particularly altered patterns of DNA methylation, exists in diseases such as systemic lupus erythematosus (SLE) and rheumatoid arthritis. The importance of such changes in the pathology of rheumatic diseases has been demonstrated by examining the relationship between gene-specific methylation and SLE in monozygotic twins discordant for the disease, in whom genetic variability is excluded as a cause for discordance. Several studies have highlighted the importance of the tissue-specificity of DNA methylation changes, an aspect which-in contrast with genetic analysis-must be considered when designing epigenetic studies. Here I discuss the proposed mechanisms and implications of DNA methylation changes in the pathogenesis of autoimmune rheumatic diseases, the prospects for future epigenetic studies in rheumatology, the relevance of specific DNA methylation markers and the potential use of drugs with an epigenetic effect in the clinical management of these diseases.

  20. Autoimmunity in chronic urticaria and urticarial vasculitis. (United States)

    Napoli, D C; Freeman, T M


    In contrast to acute urticaria, etiology cannot be identified in most cases of chronic urticaria. Recent evidence suggests that a subset of patients with chronic urticaria may have an autoimmune basis for their condition. The demonstration of antithyroid autoantibodies in some patients with chronic idiopathic urticaria (CIU) provides support for an association. However, the discovery of a positive skin test response to intradermal injection of autologous serum in as many as 60% of patients with CIU led to the identification of autoantibodies to IgE and the alpha-chain of the high-affinity IgE receptor, Fc epsilon RI alpha. Additional studies have demonstrated that some of these autoantibodies are capable of releasing histamine from donor basophils and mast cells. This article reviews the literature that addresses a possible autoimmune etiology in a subset of patients with CIU. Urticarial vasculitis is differentiated from chronic urticaria based on clinical features and biopsy findings of leukocytoclastic vasculitis. Most cases of urticarial vasculitis are secondary to an underlying systemic disease. The presence of autoantibodies has also been demonstrated in a subset of patients with primary urticarial vasculitis. This article briefly reviews some of this data.