Novel Phospholipid-Protein Conjugates Allow Improved Detection of Antibodies in Patients with Autoimmune Diseases

DEFF Research Database (Denmark)

Samuelsen, Simone V; Maity, Arindam; Nybo, Mads

2016-01-01

Reliable measurement of clinically relevant autoimmune antibodies toward phospholipid-protein conjugates is highly desirable in research and clinical assays. To date, the development in this field has been limited to the use of natural heterogeneous antigens. However, this approach does not take ...... on the correlation of detected autoantibodies with disease activity and manifestations. This confirms the crucial importance of antigens' composition on research and diagnostic assays, and opens up exciting perspectives for synthetic antigens in future studies of autoimmunity.......Reliable measurement of clinically relevant autoimmune antibodies toward phospholipid-protein conjugates is highly desirable in research and clinical assays. To date, the development in this field has been limited to the use of natural heterogeneous antigens. However, this approach does not take...... structural features of biologically active antigens into account and leads to low reliability and poor scientific test value. Here we describe novel phospholipid-protein conjugates for specific detection of human autoimmune antibodies. Our synthetic approach includes mild oxidation of synthetic phospholipid...

Cre-mediated cell ablation contests mast cell contribution in models of antibody- and T cell-mediated autoimmunity.

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Feyerabend, Thorsten B; Weiser, Anne; Tietz, Annette; Stassen, Michael; Harris, Nicola; Kopf, Manfred; Radermacher, Peter; Möller, Peter; Benoist, Christophe; Mathis, Diane; Fehling, Hans Jörg; Rodewald, Hans-Reimer

2011-11-23

Immunological functions of mast cells remain poorly understood. Studies in Kit mutant mice suggest key roles for mast cells in certain antibody- and T cell-mediated autoimmune diseases. However, Kit mutations affect multiple cell types of both immune and nonimmune origin. Here, we show that targeted insertion of Cre-recombinase into the mast cell carboxypeptidase A3 locus deleted mast cells in connective and mucosal tissues by a genotoxic Trp53-dependent mechanism. Cre-mediated mast cell eradication (Cre-Master) mice had, with the exception of a lack of mast cells and reduced basophils, a normal immune system. Cre-Master mice were refractory to IgE-mediated anaphylaxis, and this defect was rescued by mast cell reconstitution. This mast cell-deficient strain was fully susceptible to antibody-induced autoimmune arthritis and to experimental autoimmune encephalomyelitis. Differences comparing Kit mutant mast cell deficiency models to selectively mast cell-deficient mice call for a systematic re-evaluation of immunological functions of mast cells beyond allergy. Copyright © 2011 Elsevier Inc. All rights reserved.

New-Onset Headache in Patients With Autoimmune Encephalitis Is Associated With anti-NMDA-Receptor Antibodies.

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Schankin, Christoph J; Kästele, Fabian; Gerdes, Lisa Ann; Winkler, Tobias; Csanadi, Endy; Högen, Tobias; Pellkofer, Hannah; Paulus, Walter; Kümpfel, Tania; Straube, Andreas

2016-06-01

We tested the hypotheses (i) that autoimmune encephalitis is associated with new-onset headache, and (ii) that the occurrence of headache is associated with the presence of anti-N-methyl-D-aspartate (NMDA)-receptor antibodies. Autoimmune encephalitis presents with cognitive dysfunction as well as neuro-psychiatric symptoms. Its pathophysiology might involve antibody-mediated dysfunction of the glutamatergic system as indicated by the presence of anti-NMDA-receptor antibodies in some patients. In this cross-sectional study, patients with autoimmune encephalitis were assessed with a standardized interview for previous headache and headache associated with autoimmune encephalitis. Headache was classified according to the International Classification of Headache Disorders, second edition. Clinical and paraclinical findings were correlated with the occurrence of headache. Of 40 patients with autoimmune encephalitis, 19 did not have a history of headache. Of those, nine suffered from encephalitis-associated headache. Seven of these nine had anti-NMDA-receptor antibodies in contrast to only two among the remaining 10 patients without new-onset headache (P = .023, odds ratio: 14, 95% confidence interval: 1.5; 127). In most patients headache occurred in attacks on more than 15 days/month, was severe, and of short duration (less than 4 hours). International Headache Society criteria for migraine were met in three patients. New-onset headache is a relevant symptom in patients with autoimmune encephalitis who have no history of previous headache, especially in the subgroup with anti-NMDA-receptor antibodies. This indicates a thorough investigation for secondary headaches including anti-NMDA-R antibodies for patients with new-onset headache and neuropsychiatric findings. Glutamatergic dysfunction might be important for the generation of head pain but may only occasionally be sufficient to trigger migraine-like attacks in nonmigraineurs. © 2016 American Headache Society.

Glutamic acid decarboxylase (anti-GAD & tissue transglutaminase (anti-TTG antibodies in patients with thyroid autoimmunity

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R K Marwaha

2013-01-01

Full Text Available Background & objectives: Several autoimmune disorders have been reported to be associated with autoimmune thyroiditis and may coexist with other organ-specific autoantibodies. The aim of the present study was to evaluate the presence of tissue transglutaminase (anti-TTG and glutamic acid decarboxylase (anti-GAD antibodies in patients suffering from autoimmune thyroiditis as diagnosed by anti-thyroid peroxidase (anti-TPO antibodies, which may indicate high risk for developing celiac disease or type 1 diabetes mellitus. Methods: Five thousand children and 2800 adults were screening as part of a general health examination done on a voluntary basis in four different parts of Delhi. A total of 577 subjects positive for anti-TPO antibody constituted the cases. Equal number of age and sex matched anti-TPO antibody negative controls were randomly selected from the same cohort to form paired case control study. The cases and controls were further divided into two groups as follows: group-1 (children and adolescent 18 yr. Serum samples of cases and controls were analysed for thyroid function test (FT3, FT4, and TSH, anti-TTG and anti-GAD antibodies. Results: A total of 1154 subjects (577 cases and 577 controls were included in this study. Hypothyroidism was present in 40.2 per cent (232 cases compared to only 4.7 per cent (27 in controls (P<0.001. Anti-TTG and anti-GAD antibodies were present in 6.9 and 12.5 per cent subjects among cases compared to 3.5 per cent (P=0.015 and 4.3 per cent (P=0.001 in controls, respectively. Only anti-GAD antibody were significantly positive in cases among children and adolescents (P =0.0044 and adult (P=0.001 compared to controls. Levels of anti-TTG and anti-GAD antibodies increased with increasing titre of anti-TPO antibody. Interpretation & conclusions: Our findings showed high positivity of anti-GAD and anti-TTG antibodies among subjects with thyroid autoimmunity. It is, therefore, important to have high clinical index

Successful treatment of acute autoimmune limbic encephalitis with negative VGKC and NMDAR antibodies.

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Modoni, Anna; Masciullo, Marcella; Spinelli, Pietro; Marra, Camillo; Tartaglione, Tommaso; Andreetta, Francesca; Tonali, Pietro; Silvestri, Gabriella

2009-03-01

To describe a case of acute nonherpetic limbic encephalitis (LE) with negative testing for antibodies directed against onconeuronal and cell membrane antigens, including voltage-gated potassium channels and N-methyl-D-aspartate receptor, that showed a dramatic response to immune therapy. A 30-year-old woman manifested generalized seizures, altered consciousness, and memory impairment shortly after a prodromal viral illness. Few days later the patient developed a drug-resistant epileptic status. Electroencephalograph showed bitemporal slowing and paroxysmal slow wave bursts. Brain magnetic resonance imaging showed bilateral swelling in the medial temporal lobes. Cerebrospinal fluid analysis ruled out viral etiologies. A diagnostic search for cancer, including serum testing for known onconeuronal antibodies proved negative. Screening for cell membrane antigen antibodies, including voltage-gated potassium channels and N-methyl-D-aspartate receptor, was also negative. Suspecting an autoimmune etiology, we started an immunomodulatory treatment with intravenous immunoglobulin followed by a short course of oral prednisone, obtaining a full clinical recovery. Our report confirms previous observations of "seronegative" autoimmune LE, suggesting the presence of other, still unknown central nervous system antigens representing a target of a postinfectious, autoimmune response in these patients. Moreover, it emphasizes the importance of early recognition and treatment of acute autoimmune LE, to reduce the risk of intensive care unit-related complications and the occurrence of permanent cognitive or behavioral defects.

[Antibodies and physiopathogeny of autoimmune hepatitis].

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García-Leiva, Jorge; Ríos-Vaca, Aurelio; Torre-Delgadillo, Aldo

2003-01-01

Autoimmune hepatitis (AIH) is an inflammatory disease of unknown cause characterized by periportal hepatitis, increased serum globulins and the presence of certain antibodies. The disorder can be classified in three types. Type 1 AIH is characterized by the presence of antinuclear antibodies (ANA) and smooth muscle autoantibodies (SMA) in up to 70-80% of patients. ANA and SMA can be the only antibodies present in 13 and 33% of cases respectively. Type 2 AIH is defined by the presence of liver and kidney antimicrosomal antibodies (LKM1). Type 2 AIH is the only form of the disease in which the autoantigen has been identified: cytochrome mono-oxygenase (P-450 IID6) CYP2D6. In type 3 AIH the presence of anti-SLA/LP (soluble liver antigen/liver pancreas) targets a cytosolic protein involved in the incorporation of selenocysteine into peptidic chains. The pathophysiology of AIH is complex and involves genetic predisposition, previous exposure to antigens (autoantigens), presence of triggering factors and defects in immunoregulation. In spite of the advances in the understanding of AIH, the role of autoantibodies in the pathophysiology of this disease has not been fully established and their presence does not clearly distinguish any prognostic groups. Further investigations will help in the diagnosis of this disorder, the comprehension of its origins and the establishment of new forms of treatment.

Detection of autoimmune antibodies in localized scleroderma by synthetic oligonucleotide antigens

DEFF Research Database (Denmark)

Samuelsen, Simone; Jørgensen, Christian Damsgaard; Mellins, Elizabeth D

2018-01-01

In this study, we developed a series of synthetic oligonucleotides that allowed us to investigate the details on the antigen recognition by autoimmune antibodies in localized scleroderma subjects. Besides dramatically improved analytical specificity of the assay, our data suggests a potential...... linking for antibodies to DNA to the biological status of disease state in localized scleroderma. Moreover, introducing chemical modifications into short synthetic deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) molecules completely changed the binding titers of corresponding antibodies...... and their clinical relevance. The strongest observed effect was registered for the localized scleroderma skin damage index (LoSDI) on the IgG antibodies to TC dinucleotide-rich double-stranded antigen (p

Oxidative and nitrosative stress in trichloroethene-mediated autoimmune response

International Nuclear Information System (INIS)

Wang Gangduo; Cai Ping; Ansari, G.A.S.; Khan, M. Firoze

2007-01-01

Reactive oxygen and nitrogen species (RONS) are implicated in the pathogenesis of several autoimmune diseases. Also, increased lipid peroxidation and protein nitration are reported in systemic autoimmune diseases. Lipid peroxidation-derived aldehydes (LPDAs) such as malondialdehyde (MDA) and 4-hydroxynonenal (HNE) are highly reactive and bind proteins covalently, but their potential to elicit an autoimmune response and contribution to disease pathogenesis remain unclear. Similarly, nitration of protein could also contribute to disease pathogenesis. To assess the status of lipid peroxidation and/or RONS, autoimmune-prone female MRL+/+ mice (5-week old) were treated with trichloroethene (TCE), an environmental contaminant known to induce autoimmune response, for 48 weeks (0.5 mg/ml via drinking water), and formation of antibodies to LPDA-protein adducts was followed in the sera of control and TCE-treated mice. TCE treatment led to greater formation of both anti-MDA- and -HNE-protein adduct antibodies and higher serum iNOS and nitrotyrosine levels. The increase in TCE-induced oxidative stress was associated with increases in anti-nuclear-, anti-ssDNA- and anti-dsDNA-antibodies. These findings suggest that TCE exposure not only leads to oxidative/nitrosative stress, but is also associated with induction/exacerbation of autoimmune response in MRL+/+ mice. Further interventional studies are needed to establish a causal role of RONS in TCE-mediated autoimmunity

N-Acetylcysteine protects against trichloroethene-mediated autoimmunity by attenuating oxidative stress

Energy Technology Data Exchange (ETDEWEB)

Wang, Gangduo; Wang, Jianling; Ma, Huaxian; Ansari, G.A.S.; Khan, M. Firoze, E-mail: mfkhan@utmb.edu

2013-11-15

Exposure to trichloroethene (TCE), a ubiquitous environmental contaminant, is known to induce autoimmunity both in humans and animal models. However, mechanisms underlying TCE-mediated autoimmunity remain largely unknown. Previous studies from our laboratory in MRL +/+ mice suggest that oxidative stress may contribute to TCE-induced autoimmune response. The current study was undertaken to further assess the role of oxidative stress in TCE-induced autoimmunity by supplementing with an antioxidant N-acetylcysteine (NAC). Groups of female MRL +/+ mice were given TCE, NAC or TCE + NAC for 6 weeks (TCE, 10 mmol/kg, i.p., every 4th day; NAC, 250 mg/kg/day through drinking water). TCE exposure led to significant increases in serum levels of anti-nuclear, anti-dsDNA and anti-Sm antibodies. TCE exposure also led to significant induction of anti-malondiadelhyde (MDA)- and anti-hydroxynonenal (HNE)-protein adduct antibodies which were associated with increased ANA in the sera along with increased MDA-/HNE-protein adducts in the livers and kidneys, and increases in protein oxidation (carbonylation) in the sera, livers and kidneys, suggesting an overall increase in oxidative stress. Moreover, TCE exposure also resulted in increased release of IL-17 from splenocytes and increases in IL-17 mRNA expression. Remarkably, NAC supplementation attenuated not only the TCE-induced oxidative stress, IL-17 release and mRNA expression, but also the markers of autoimmunity, as evident from decreased levels of ANA, anti-dsDNA and anti-Sm antibodies in the sera. These results provide further support to a role of oxidative stress in TCE-induced autoimmune response. Attenuation of TCE-induced autoimmunity in mice by NAC provides an approach for preventive and/or therapeutic strategies. - Highlights: • TCE led to increased autoantibodies, supporting its potential to induce autoimmunity. • TCE exposure led to increases in lipid perioxidation and protein carbonyls. • TCE exposure resulted in

N-Acetylcysteine protects against trichloroethene-mediated autoimmunity by attenuating oxidative stress

International Nuclear Information System (INIS)

Wang, Gangduo; Wang, Jianling; Ma, Huaxian; Ansari, G.A.S.; Khan, M. Firoze

2013-01-01

Exposure to trichloroethene (TCE), a ubiquitous environmental contaminant, is known to induce autoimmunity both in humans and animal models. However, mechanisms underlying TCE-mediated autoimmunity remain largely unknown. Previous studies from our laboratory in MRL +/+ mice suggest that oxidative stress may contribute to TCE-induced autoimmune response. The current study was undertaken to further assess the role of oxidative stress in TCE-induced autoimmunity by supplementing with an antioxidant N-acetylcysteine (NAC). Groups of female MRL +/+ mice were given TCE, NAC or TCE + NAC for 6 weeks (TCE, 10 mmol/kg, i.p., every 4th day; NAC, 250 mg/kg/day through drinking water). TCE exposure led to significant increases in serum levels of anti-nuclear, anti-dsDNA and anti-Sm antibodies. TCE exposure also led to significant induction of anti-malondiadelhyde (MDA)- and anti-hydroxynonenal (HNE)-protein adduct antibodies which were associated with increased ANA in the sera along with increased MDA-/HNE-protein adducts in the livers and kidneys, and increases in protein oxidation (carbonylation) in the sera, livers and kidneys, suggesting an overall increase in oxidative stress. Moreover, TCE exposure also resulted in increased release of IL-17 from splenocytes and increases in IL-17 mRNA expression. Remarkably, NAC supplementation attenuated not only the TCE-induced oxidative stress, IL-17 release and mRNA expression, but also the markers of autoimmunity, as evident from decreased levels of ANA, anti-dsDNA and anti-Sm antibodies in the sera. These results provide further support to a role of oxidative stress in TCE-induced autoimmune response. Attenuation of TCE-induced autoimmunity in mice by NAC provides an approach for preventive and/or therapeutic strategies. - Highlights: • TCE led to increased autoantibodies, supporting its potential to induce autoimmunity. • TCE exposure led to increases in lipid perioxidation and protein carbonyls. • TCE exposure resulted in

A case of autoimmune epilepsy associated with anti-leucine-rich glioma inactivated subunit 1 antibodies manifesting electrical shock-like sensations and transparent sadness

Directory of Open Access Journals (Sweden)

Yoshiko Murata

2015-01-01

Full Text Available Autoimmune epilepsy is an isolated phenotype of autoimmune encephalitis, which may be suspected in patients with unexplained adult-onset seizure disorders or resistance to antiepileptic drugs (AEDs. Antibodies against leucine-rich glioma inactivated subunit 1 of the voltage-gated potassium channel (VGKC complex, recently termed anti-LGI-1 antibodies, are one of the causes of autoimmune epilepsies. Bizarre symptoms with extremely short duration and high frequency are clues to the possible presence of autoimmune epilepsy with anti-LGI-1 antibodies. Precise diagnosis is important because autoimmune epilepsy is treatable and the prognosis can be predicted.

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

OpenAIRE

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

1998-01-01

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

The ability of anti-carbonic anhydrase II antibody to distinguish autoimmune cholangitis from primary biliary cirrhosis in Japanese patients.

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Akisawa, N; Nishimori, I; Miyaji, E; Iwasaki, S; Maeda, T; Shimizu, H; Sato, N; Onishi, S

1999-06-01

Serum antibody against carbonic anhydrase (CA) II has been described as a serological marker for distinguishing autoimmune cholangitis (AIC) from primary biliary cirrhosis (PBC). To validate this finding in a Japanese population, we evaluated sera from patients with PBC and AIC for antibody to human CA II. An enzyme-linked immunosorbent assay was employed to quantify serum antibody against CA II in patients with PBC (n = 40), AIC (n = 23), autoimmune hepatitis (n = 10), and extrahepatic obstructive jaundice (n = 10). Compared with the finding of a 4% prevalence of anti-CAII antibody in healthy subjects (n = 24), a significantly higher prevalence of anti-CA II antibody was detected in patients with PBC (35%) and AIC (30%) (P jaundice. No significant difference was observed between PBC and AIC patients. These results showed that AIC and PBC would be indistinguishable by anti-CA II antibody testing in Japanese patients. However, the finding of serum anti-CA II antibody in patients with PBC and AIC supports the disease concept of autoimmune exocrinopathy.

[Seric 21-hydroxilase antibodies in patients with anti-microsomal fraction antibodies. Autoimmune polyendocrine syndrome].

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Botta, Silvia; Roveto, Silvana; Rimoldi, Daniel

2007-01-01

Autoimmune polyendocrine syndrome (APS) is the association of autoimmune endocrine diseases, with other autoimmune nonendocrine disorders. APS types 1, 2 and 4 include autoimmune adrenalitis; this suggests the presence of autoantibodies. A specific serological marker for these is the anti 21- hydroxilase autoantibody (a21-OH). APS type 2 is the association of autoimmune adrenalitis, to autoimmune thyroid disease and/or diabetes mellitus, all these are induced by autoantibodies. Alopecia, vitiligo, myasthenia and other manifestations can be minor components. We sought to establish the prevalence of seric a21-OH in patients with positive anti-microsomal fraction autoantibodies, autoimmune thyroid disease and/or non-endocrine autoimmune diseases. We also aimed to diagnose incomplete forms of APS and to follow up patients at risk of progression to complete forms of APS. A population of 72 patients and another of 60 controls with negative anti-microsomal fraction autoantibodies were studied. Elevated seric a21-OH were found in two patients. Patient A with 47 U/ml had autoimmune hypothyroidism and myasthenia; and patient B with 8.75 U/ml had autoimmune hypothyrodism and vitiligo; they both lacked adrenal insufficiency. Seric a21-OH had a prevalence of 2.8%. Regarding the adrenal component, patients A and B had an incomplete and latent APS type 2. Considering a21-OH as markers of latent endocrine autoimmune diseases and taking into account the eventual risk of developing clinical manifestations, periodic biochemical and clinical follow-ups are recommended.

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

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Cascio, Michael J; Jen, Kuang-Yu

2018-01-01

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

Meta-analysis reveals an association of STAT4 polymorphisms with systemic autoimmune disorders and anti-dsDNA antibody.

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Zheng, Junfeng; Yin, Junping; Huang, Renliang; Petersen, Frank; Yu, Xinhua

2013-08-01

Signal transducer and activator of transcription 4 (STAT4) has been recently identified as a susceptibility gene for multiple autoimmune diseases. Here we performed a comprehensive analysis of the association between STAT4 and several different autoimmune disorders to identify potential common inflammatory principles behind this association. Our meta-analysis revealed that the STAT4 rs7574865 polymorphism is associated with four autoimmune diseases with systemic pathology, including systemic lupus erythematosus (OR = 1.52; 95% CI = 1.48 - 1.56, Prs7574865 polymorphism is associated with the presence of autoantibodies with systemic reactivity (anti-ds-DNA antibodies) in SLE patients (OR = 1.37; 95% CI = 1.21 - 1.56, P = 1.12 × 10(-6)). However, no such specific association was seen in RA with regard to the presence of non-systemically reacting antibodies, including rheumatoid factor and anti-cyclic citrullinated peptide antibodies. Taken together, these results suggest that STAT4 polymorphisms are associated with autoimmune diseases which are characterized by a systemic pathology and anti-dsDNA antibody. Copyright © 2013 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

Sperm, nuclear, phospholipid, and red blood cell antibodies and isotype RF in infertile couples and patients with autoimmune rheumatic diseases.

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Fichorova, R; Nakov, L; Baleva, M; Nikolov, K; Gegova, I

1996-12-01

To determine if measuring of nonorgan-specific autoantibodies is useful for better understanding and management of unexplained infertility. Sera were obtained from 70 infertile couples, 57 rheumatic patients, and 76 fertile donors. Sperm antibodies (SA) were detected by the tests of Kibrick and Friberg, anti-histones, anti-cardiolipin antibodies, and RF isotypes by ELISA, antinuclear antibodies by indirect immunofluorescence, and anti-red blood cell antibodies by Capture-R. Multiple autoimmune reactivity (both partners positive and/or more than one type of autoantibody involved), higher than naturally occurring in fertile individuals, was found in 55% of the idiopathically infertile couples. IgA-RF was the dominant autoimmune marker. SA revealed similar rates in patients with rheumatic diseases and in infertiles with or without other autoantibodies. Although no single autoimmunity marker could predict occurrence of SA, the coincidence of enhanced polyclonal autoimmunity in both partners of infertile couples might potentiate their negative effect on reproduction.

Glutamate receptor antibodies in neurological diseases: anti-AMPA-GluR3 antibodies, anti-NMDA-NR1 antibodies, anti-NMDA-NR2A/B antibodies, anti-mGluR1 antibodies or anti-mGluR5 antibodies are present in subpopulations of patients with either: epilepsy, encephalitis, cerebellar ataxia, systemic lupus erythematosus (SLE) and neuropsychiatric SLE, Sjogren's syndrome, schizophrenia, mania or stroke. These autoimmune anti-glutamate receptor antibodies can bind neurons in few brain regions, activate glutamate receptors, decrease glutamate receptor's expression, impair glutamate-induced signaling and function, activate blood brain barrier endothelial cells, kill neurons, damage the brain, induce behavioral/psychiatric/cognitive abnormalities and ataxia in animal models, and can be removed or silenced in some patients by immunotherapy.

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Levite, Mia

2014-08-01

Glutamate is the major excitatory neurotransmitter of the Central Nervous System (CNS), and it is crucially needed for numerous key neuronal functions. Yet, excess glutamate causes massive neuronal death and brain damage by excitotoxicity--detrimental over activation of glutamate receptors. Glutamate-mediated excitotoxicity is the main pathological process taking place in many types of acute and chronic CNS diseases and injuries. In recent years, it became clear that not only excess glutamate can cause massive brain damage, but that several types of anti-glutamate receptor antibodies, that are present in the serum and CSF of subpopulations of patients with a kaleidoscope of human neurological diseases, can undoubtedly do so too, by inducing several very potent pathological effects in the CNS. Collectively, the family of anti-glutamate receptor autoimmune antibodies seem to be the most widespread, potent, dangerous and interesting anti-brain autoimmune antibodies discovered up to now. This impression stems from taking together the presence of various types of anti-glutamate receptor antibodies in a kaleidoscope of human neurological and autoimmune diseases, their high levels in the CNS due to intrathecal production, their multiple pathological effects in the brain, and the unique and diverse mechanisms of action by which they can affect glutamate receptors, signaling and effects, and subsequently impair neuronal signaling and induce brain damage. The two main families of autoimmune anti-glutamate receptor antibodies that were already found in patients with neurological and/or autoimmune diseases, and that were already shown to be detrimental to the CNS, include the antibodies directed against ionotorpic glutamate receptors: the anti-AMPA-GluR3 antibodies, anti-NMDA-NR1 antibodies and anti-NMDA-NR2 antibodies, and the antibodies directed against Metabotropic glutamate receptors: the anti-mGluR1 antibodies and the anti-mGluR5 antibodies. Each type of these anti

Induction of a protein-targeted catalytic response in autoimmune prone mice: antibody-mediated cleavage of HIV-1 glycoprotein GP120.

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Ponomarenko, Natalia A; Vorobiev, Ivan I; Alexandrova, Elena S; Reshetnyak, Andrew V; Telegin, Georgy B; Khaidukov, Sergey V; Avalle, Bérangère; Karavanov, Alexander; Morse, Herbert C; Thomas, Daniel; Friboulet, Alain; Gabibov, Alexander G

2006-01-10

We have induced a polyclonal IgG that degrades the HIV-1 surface antigen, glycoprotein gp120, by taking advantage of the susceptibility of SJL mice to a peptide-induced autoimmune disorder, experimental autoimmune encephalomyelitis (EAE). Specific pathogen-free SJL mice were immunized with structural fragments of gp120, fused in-frame with encephalitogenic peptide MBP(85-101). It has resulted in a pronounced disease-associated immune response against antigens. A dramatic increase of gp120 degradation level by purified polyclonal IgG from immunized versus nonimmunized mice has been demonstrated by a newly developed fluorescence-based assay. This activity was inhibited by anti-mouse immunoglobulin antibodies as well as by Ser- and His-reactive covalent inhibitors. A dominant proteolysis site in recombinant gp120 incubated with purified polyclonal IgG from immunized mice was shown by SDS-PAGE. The SELDI-based mass spectrometry revealed that these antibodies exhibited significant specificity toward the Pro484-Leu485 peptide bond. The sequence surrounding this site is present in nearly half of the HIV-I variants. This novel strategy can be generalized for creating a catalytic vaccine against viral pathogens.

Anti-asialo GM1 antibodies prevents guanethidine-induced sympathectomy in athymic rats

DEFF Research Database (Denmark)

Thygesen, P; Hougen, H P; Christensen, H B

1992-01-01

Guanethidine sulphate induces destruction of peripheral sympathetic neurons and infiltration of mononuclear cells in rat sympathetic ganglia. The effect of guanethidine is believed to be an autoimmune reaction. In order to determine the effect of anti-asialo GM1, an antibody that binds to the gly......Guanethidine sulphate induces destruction of peripheral sympathetic neurons and infiltration of mononuclear cells in rat sympathetic ganglia. The effect of guanethidine is believed to be an autoimmune reaction. In order to determine the effect of anti-asialo GM1, an antibody that binds...... to the glycolipid asialo GM1 expressed on rodent natural killer cells, athymic Lewis rats received guanethidine 40 mg/kg i.p. daily from day 1 to 14 and anti-asialo GM1 i.p. 1 mg/rat on day -2, 0, 2, 6, and 10 in the study period. Saline and anti-asialo GM1 were given alone in the same doses as control. The number...... of neurons in the sympathetic ganglia were counted and the ganglionic volume determined. The presence of natural killer cells in the ganglia were determined by immunohistochemical methods. Our results shows that anti-asialo GM1 can prevent guanethidine-induced reduction of sympathetic neurons...

Anti-IL-39 (IL-23p19/Ebi3) polyclonal antibodies ameliorate autoimmune symptoms in lupus-like mice

Science.gov (United States)

Wang, Xiaoqian; Zhang, Yu; Wang, Zhiding; Liu, Xiaoling; Zhu, Gaizhi; Han, Gencheng; Chen, Guojiang; Hou, Chunmei; Wang, Tianxiao; Shen, Beifen; Li, Yan; Xiao, He; Ma, Ning; Wang, Renxi

2018-01-01

The interleukin (IL)-12 family cytokines have been examined as therapeutic targets in the treatment of several autoimmune diseases. Our previous study showed that a novel IL-12 family cytokine, IL-39 (IL-23p19/Ebi3) mediates inflammation in lupus-like mice. In the present study, the effect of anti-mouse IL-39 polyclonal antibodies on autoimmune symptoms in lupus-like mice was investigated. Rabbit anti-mouse IL-39 polyclonal antibodies were produced by immunization with recombinant mouse IL-39, and purified using protein A chromatography. These antibodies were subsequently used to treat lupus-like mice. Flow cytometry, captured images, ELISA and H&E staining were used to determine the effect of anti-IL-39 polyclonal antibodies on inflammatory cells, autoantibody titers, proteinuria, infiltrating inflammatory cells and the structure of the glomerular region. The anti-IL-39 polyclonal antibodies effectively reduced the numbers of inflammatory cells, splenomegaly, autoantibody titers, proteinuria, infiltrating inflammatory cells, and restored the structure of the glomerular region in MRL/lpr mice. Taken together, these results suggested that anti-IL-39 polyclonal antibodies ameliorated autoimmune symptoms in lupus-like mice. Therefore, IL-39 may be used as a possible target for the treatment of systemic lupus erythematosus. PMID:29138852

Detection of anti-lactoferrin antibodies and anti-myeloperoxidase antibodies in autoimmune hepatitis: a retrospective study.

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Tan, Liming; Zhang, Yuhong; Peng, Weihua; Chen, Juanjuan; Li, Hua; Ming, Feng

2014-01-01

Anti-lactoferrin antibodies (ALA) and anti-myeloperoxidase antibodies (AMPA) are specific serological markers for autoimmune hepatitis (AIH). The project aimed to detect ALA and AMPA and explore their clinical significances in AIH patients. 59 AIH patients, 217 non AIH patients, and 50 healthy controls were enrolled in this study. ALA and AMPA were detected by ELISA. Antineutropil cytoplasmic antibodies (ANCA) and anti-smooth muscle antibodies (ASMA) were examined by indirect immunofluorescence. Antimitochondrial antibody M2 subtype (AMA-M2), anti-liver kidney microsomal antibody Type 1 (LKM1), anti-liver cytosol antibody Type 1 (LC1), and anti-soluble liver antigen/liver-pancreas antibodies (SLA/LP) were tested by immunoblot. The positivity for ALA was 18.6% in AIH group, only one patient in non-AIH group was positive for ALA; the positivity for AMPA was 59.3% in AIH group, with significant differences (P < 0.01) compared with other groups. The specificities for ALA and AMPA were 99.63% and 97.75%; the sensitivities were 18.64% and 59.32%; and the accuracy rates were 84.97% and 90.80%, respectively. A certain correlation was observed between ALA and SLA/LP, AMPA and ANCA, ASMA in AIH group. ALA and AMPA were associated with AIH, and had high clinical diagnostic value. Co-detection with other relative autoantibodies could play an important role in differential diagnosis of AIH.

Autoimmune severe hypertriglyceridemia induced by anti-apolipoprotein C-II antibody.

Science.gov (United States)

Yamamoto, Hiroyasu; Tanaka, Minoru; Yoshiga, Satomi; Funahashi, Tohru; Shimomura, Iichiro; Kihara, Shinji

2014-05-01

Among type V hyperlipoproteinemias, only one-fourth of the patients have genetic defects in lipoprotein lipase (LPL) or in its associated molecules; the exact mechanism in other patients is usually unknown. The aim of the study was to report a case of severe hypertriglyceridemia induced by anti-apolipoprotein (apo) C-II autoantibody and to clarify its pathogenesis. A 29-year-old Japanese woman presented with severe persistent hypertriglyceridemia since the age of 20 years. The past history was negative for acute pancreatitis, eruptive xanthomas, or lipemia retinalis. LPL mass and activities were normal. Plasma apo C-II levels were extremely low, but no mutation was observed in APOC2. Apo C-II protein was detected in the serum by immunoprecipitation and Western blotting. Large amounts of IgG and IgM were incorporated with apo C-II protein coimmunoprecipitated by anti-apo C-II antibody. IgG, but not IgM, purified from the serum prevented interaction of apo C-II with lipid substrate and diminished LPL hydrolysis activity. We identified anti-apo C-II antibody in a myeloma-unrelated severe hypertriglyceridemic patient. In vitro analysis confirmed that the autoantibody disrupted the interaction between apo C-II and lipid substrate, suggesting the etiological role of anti-apo C-II antibody in severe hypertriglyceridemia in this patient.

Overexpression of BID in thyroids of transgenic mice increases sensitivity to iodine-induced autoimmune thyroiditis

Science.gov (United States)

2014-01-01

Background BID functions as a bridge molecule between death-receptor and mitochondrial related apoptotic pathways to amplify apoptotic signaling. Our previous studies have demonstrated a substantial increase in BID expression in primary normal thyroid epithelia cells treated with inflammatory cytokines, including the combination of IFNγ and IL-1β or IFNγ and TNFα. The aim of this study was to determine whether an increase in BID expression in thyroid can induce autoimmune thyroiditis. Methods A transgenic mouse line that expresses human BID in thyroid cells was established by fusing a mouse thyroglobulin (Tg) promoter upstream of human BID (Tg-BID). We tested whether the increased expression of pro-apoptotic BID in thyroid would induce autoimmune thyroiditis, both in the presence and absence of 0.3% iodine water. Results Our data show that Tg-BID mice in a CBA/J (H-2 k) background do not spontaneously develop autoimmune thyroiditis for over a year. However, upon ingestion of iodine in the drinking water, autoimmune thyroiditis does develop in Tg-BID transgenic mice, as shown by a significant increase in anti-Tg antibody and mononuclear cell infiltration in the thyroid glands in 30% of mice tested. Serum T4 levels, however, were similar between iodine-treated Tg-BID transgenic mice and the wild type mice. Conclusions Our data demonstrate that increased thyroid expression of BID facilitates the development of autoimmune thyroiditis induced by iodine uptake. However, the overexpression of BID itself is not sufficient to initiate thyroiditis in CBA/J (H-2 k) mice. PMID:24957380

Liver/kidney microsomal antibody type 1 and liver cytosol antibody type 1 concentrations in type 2 autoimmune hepatitis

OpenAIRE

Muratori, L; Cataleta, M; Muratori, P; Lenzi, M; Bianchi, F

1998-01-01

Background—Liver/kidney microsomal antibody type 1 (LKM1) and liver cytosol antibody type 1 (LC1) are the serological markers of type 2 autoimmune hepatitis (AIH). 
Aims—Since LKM1 and LC1 react against two distinct liver specific autoantigens (cytochrome P450IID6 (CYP2D6) and a 58 kDa cytosolic polypeptide respectively), the aim was to see whether LKM1 and LC1 concentrations correlate with liver disease activity. 
Patients—Twenty one patients with type 2 AIH were studied. 
Methods—A...

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

Science.gov (United States)

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

2017-07-01

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

Antibody proteases: induction of catalytic response.

Science.gov (United States)

Gabibov, A G; Friboulet, A; Thomas, D; Demin, A V; Ponomarenko, N A; Vorobiev, I I; Pillet, D; Paon, M; Alexandrova, E S; Telegin, G B; Reshetnyak, A V; Grigorieva, O V; Gnuchev, N V; Malishkin, K A; Genkin, D D

2002-10-01

Most of the data accumulated throughout the years on investigation of catalytic antibodies indicate that their production increases on the background of autoimmune abnormalities. The different approaches to induction of catalytic response toward recombinant gp120 HIV-1 surface protein in mice with various autoimmune pathologies are described. The peptidylphosphonate conjugate containing structural part of gp120 molecule is used for reactive immunization of NZB/NZW F1, MRL, and SJL mice. The specific modification of heavy and light chains of mouse autoantibodies with Val-Ala-Glu-Glu-Glu-Val-PO(OPh)2 reactive peptide was demonstrated. Increased proteolytic activity of polyclonal antibodies in SJL mice encouraged us to investigate the production of antigen-specific catalytic antibodies on the background of induced experimental autoimmune encephalomyelitis (EAE). The immunization of autoimmune-prone mice with the engineered fusions containing the fragments of gp120 and encephalitogenic epitope of myelin basic protein (MBP(89-104)) was made. The proteolytic activity of polyclonal antibodies isolated from the sera of autoimmune mice immunized by the described antigen was shown. Specific immune response of SJL mice to these antigens was characterized. Polyclonal antibodies purified from sera of the immunized animals revealed proteolytic activity. The antiidiotypic approach to raise the specific proteolytic antibody as an "internal image" of protease is described. The "second order" monoclonal antibodies toward subtilisin Carlsberg revealed pronounced proteolytic activity.

Antibodies against human cytochrome P-450db1 in autoimmune hepatitis type II.

OpenAIRE

Zanger, U M; Hauri, H P; Loeper, J; Homberg, J C; Meyer, U A

1988-01-01

In a subgroup of children with chronic active hepatitis, circulating autoantibodies occur that bind to liver and kidney endoplasmic reticulum (anti-liver/kidney microsome antibody type I or anti-LKM1). Anti-LKM1 titers follow the severity of the disease and the presence of these antibodies serves as a diagnostic marker for this autoimmune hepatitis type II. We demonstrate that anti-LKM1 IgGs specifically inhibit the hydroxylation of bufuralol in human liver microsomes. Using two assay systems...

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

Science.gov (United States)

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

2017-08-01

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

EFFECT OF PLASMAPHERESIS AND PASSAGE OF ANTI-RETINAL ANTIBODIES THROUGH THE PLACENTA IN A CASE OF NON-PARANEOPLASTIC AUTOIMMUNE RETINOPATHY.

Science.gov (United States)

Sierpina, David I; Skale, David M; Fan, Joseph T

2017-01-01

To present a case of nonparaneoplastic autoimmune retinopathy in association with myasthenia gravis in a young woman, and to report the effect of plasmapheresis as well as passage of antiretinal antibodies through the placenta. Case report. A 31-year-old woman presented with a history of myasthenia gravis and rapidly progressive vision loss at the age of 23. Funduscopic appearance and fluorescein angiographic findings on presentation were consistent with an autoimmune retinopathy. Paraneoplastic etiology was ruled out, and antiretinal antibody testing revealed positivity for autoantibodies against GAPDH, aldolase, enolase, arrestin, as well as unnamed 48-kDa and 60-kDa proteins. ARA Western Blot and immunohistochemistry profiles were unchanged by either plasmapheresis therapy or passage of serum through the maternal placenta. However, the patient's 6-month and 8-year-old daughters appeared unaffected. This is the first report of nonparaneoplastic autoimmune retinopathy associated with myasthenia gravis, although a strong history of autoimmune disorders is a known risk factor. Our patient's antiretinal antibody panel was unaffected immediately after plasmapheresis treatment. Antibodies to GAPDH and unnamed 38-kDa and 86-kDa proteins were able to pass through the placenta into the fetal circulation, although their effect on the growing fetus is not clear.

Antibody to liver cytosol (anti-LC1) in patients with autoimmune chronic active hepatitis type 2.

Science.gov (United States)

Martini, E; Abuaf, N; Cavalli, F; Durand, V; Johanet, C; Homberg, J C

1988-01-01

A new autoantibody was detected by immunoprecipitation in the serum of 21 patients with chronic active hepatitis. The antibody reacted against a soluble cytosolic antigen in liver. The antibody was organ specific but not species specific and was therefore called anti-liver cytosol antibody Type 1 (anti-LC1). In seven of 21 cases, no other autoantibody was found; the remaining 14 cases had anti-liver/kidney microsome antibody Type 1 (anti-LKM1). With indirect immunofluorescence, a distinctive staining pattern was observed with the seven sera with anti-LC1 and without anti-LKM1. The antibody stained the cytoplasm of hepatocytes from four different animal species and spared the cellular layer around the central veins of mouse and rat liver that we have called juxtavenous hepatocytes. The immunofluorescence pattern disappeared after absorption of sera by a liver cytosol fraction. The 14 sera with both antibodies displayed anti-LC1 immunofluorescent pattern after absorption of anti-LKM1 by the liver microsomal fraction. The anti-LC1 was found in the serum only in patients with chronic active hepatitis of unknown cause. Anti-LC1 antibody was not found in sera from 100 patients with chronic active hepatitis associated with anti-actin antibody classic chronic active hepatitis Type 1, 100 patients with primary biliary cirrhosis, 157 patients with drug-induced hepatitis and a large number of patients with liver and nonliver diseases. This new antibody was considered a second marker of chronic active hepatitis associated with anti-LKM1 (anti-LKM1 chronic active hepatitis) or autoimmune chronic active hepatitis Type 2.

Multiplex autoantibody detection for autoimmune liver diseases and autoimmune gastritis.

Science.gov (United States)

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

2017-09-01

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.

Novel Phospholipid-Protein Conjugates Allow Improved Detection of Antibodies in Patients with Autoimmune Diseases.

Directory of Open Access Journals (Sweden)

Simone V Samuelsen

Full Text Available Reliable measurement of clinically relevant autoimmune antibodies toward phospholipid-protein conjugates is highly desirable in research and clinical assays. To date, the development in this field has been limited to the use of natural heterogeneous antigens. However, this approach does not take structural features of biologically active antigens into account and leads to low reliability and poor scientific test value. Here we describe novel phospholipid-protein conjugates for specific detection of human autoimmune antibodies. Our synthetic approach includes mild oxidation of synthetic phospholipid cardiolipin, and as the last step, coupling of the product with azide-containing linker and copper-catalyzed click chemistry with β2-glycoprotein I and prothrombin. To prove utility of the product antigens, we used enzyme-linked immunosorbent assay and three cohorts of samples obtained from patients in Denmark (n = 34 and the USA (n = 27 and n = 14. Afterwards we analyzed correlation of the obtained autoantibody titers with clinical parameters for each patient. Our results prove that using novel antigens clinically relevant autoantibodies can be detected with high repeatability, sensitivity and specificity. Unlike previously used antigens the obtained autoantibody titers strongly correlate with high disease activity and in particular, with arthritis, renal involvement, anti-Smith antibodies and high lymphocyte count. Importantly, chemical composition of antigens has a strong influence on the correlation of detected autoantibodies with disease activity and manifestations. This confirms the crucial importance of antigens' composition on research and diagnostic assays, and opens up exciting perspectives for synthetic antigens in future studies of autoimmunity.

Sialylated Autoantigen-Reactive IgG Antibodies Attenuate Disease Development in Autoimmune Mouse Models of Lupus Nephritis and Rheumatoid Arthritis

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Yannic C. Bartsch

2018-06-01

Full Text Available Pro- and anti-inflammatory effector functions of IgG antibodies (Abs depend on their subclass and Fc glycosylation pattern. Accumulation of non-galactosylated (agalactosylated; G0 IgG Abs in the serum of rheumatoid arthritis and systemic lupus erythematosus (SLE patients reflects severity of the diseases. In contrast, sialylated IgG Abs are responsible for anti-inflammatory effects of the intravenous immunoglobulin (pooled human serum IgG from healthy donors, administered in high doses (2 g/kg to treat autoimmune patients. However, whether low amounts of sialylated autoantigen-reactive IgG Abs can also inhibit autoimmune diseases is hardly investigated. Here, we explore whether sialylated autoantigen-reactive IgG Abs can inhibit autoimmune pathology in different mouse models. We found that sialylated IgG auto-Abs fail to induce inflammation and lupus nephritis in a B cell receptor (BCR transgenic lupus model, but instead are associated with lower frequencies of pathogenic Th1, Th17 and B cell responses. In accordance, the transfer of small amounts of immune complexes containing sialylated IgG Abs was sufficient to attenuate the development of nephritis. We further showed that administration of sialylated collagen type II (Col II-specific IgG Abs attenuated the disease symptoms in a model of Col II-induced arthritis and reduced pathogenic Th17 cell and autoantigen-specific IgG Ab responses. We conclude that sialylated autoantigen-specific IgG Abs may represent a promising tool for treating pathogenic T and B cell immune responses in autoimmune diseases.

Auto-immune hepatitis following delivery.

Science.gov (United States)

Saini, Vandana; Gupta, Mamta; Mishra, S K

2013-05-01

Auto-immune hepatitis first presenting in the early postpartum period is rare. Immunosuppressive effects of pregnancy result in delayed manifestation of auto-immune hepatitis, and in established cases, the spontaneous improvements are there. Auto-immune hepatitis should be considered in the differential diagnosis of liver dysfunction first presenting in the early postpartum period. A case of postpartum hepatitis of auto-immune aetiology is being presented here. It is disease of unknown aetiology, characterised by inflammation of liver (as evidenced by raised serum transaminases, presence of interface hepatitis on histological examination), hypergammaglobulinaemia (> 1.5 times normal), presence of auto-antibodies [(antinuclear antibodies (ANA)], smooth muscle antibody (SMA) and antibody to liver-kidney microsome type 1 (LKM1) in the absence of viral markers ie, hepatitis B (HBsAg) and C (AntiHCV) and excellent response to corticosteroid therapy.

Low Serum Vitamin D Is Associated with Anti-Thyroid Peroxidase Antibody in Autoimmune Thyroiditis

OpenAIRE

Shin, Dong Yeob; Kim, Kwang Joon; Kim, Daham; Hwang, Sena; Lee, Eun Jig

2014-01-01

Purpose The association between autoimmune thyroid diseases (AITDs) and vitamin D deficiency is controversial. We aimed to evaluate the relationship between serum 25-hydroxy-vitamin D3 [25(OH)D3] and anti-thyroid antibody levels. Materials and Methods 25(OH)D3, anti-thyroid antibodies, and thyroid function measured in 304 patients who visited the endocrinology clinic were analyzed. The patients were subgrouped into the AITDs or non-AITDs category according to the presence or absence of anti-t...

Autoimmune process in CNS under Cs-137 inner irradiation

International Nuclear Information System (INIS)

Lisyany, N.I.; Liubich, L.D.

1996-01-01

Autoimmune hypothesis as to the development of radiation-induced brain injuries stands high among the concepts of the CNS post-radiation damage pathogenesis. To study the changes occurring in a living organism affected by a small-dose radiation due to incorporated radionuclides as well as to create adequate models are of critical importance in the post-Chernobyl period. The effects of chronic small-dose inner radiation on the development of autoimmune responses were evaluated by determining the level of the CNS proteins and protein-induced antibodies to the CNS components. (author)

Paraneoplastic autoimmune movement disorders.

Science.gov (United States)

Lim, Thien Thien

2017-11-01

To provide an overview of paraneoplastic autoimmune disorders presenting with various movement disorders. The spectrum of paraneoplastic autoimmune disorders has been expanding with the discovery of new antibodies against cell surface and intracellular antigens. Many of these paraneoplastic autoimmune disorders manifest as a form of movement disorder. With the discovery of new neuronal antibodies, an increasing number of idiopathic or neurodegenerative movement disorders are now being reclassified as immune-mediated movement disorders. These include anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis which may present with orolingual facial dyskinesia and stereotyped movements, CRMP-5 IgG presenting with chorea, anti-Yo paraneoplastic cerebellar degeneration presenting with ataxia, anti-VGKC complex (Caspr2 antibodies) neuromyotonia, opsoclonus-myoclonus-ataxia syndrome, and muscle rigidity and episodic spasms (amphiphysin, glutamic acid decarboxylase, glycine receptor, GABA(A)-receptor associated protein antibodies) in stiff-person syndrome. Movement disorders may be a presentation for paraneoplastic autoimmune disorders. Recognition of these disorders and their common phenomenology is important because it may lead to the discovery of an occult malignancy. Copyright © 2017 Elsevier Ltd. All rights reserved.

Insulin autoimmune syndrome induced by methimazole in a Korean girl with Graves' disease

Directory of Open Access Journals (Sweden)

Sun Hee Lee

2013-03-01

Full Text Available Hypoglycemia was detected in a 15-year-old girl due to loss of consciousness. She was diagnosed with Graves' disease and was being treated with methimazole for the past 4 months. A paradoxically increased insulin levels was found when she suffered from the hypoglycemic episode. An imaging study showed no mass lesion in the pancreas, and insulin antibodies were found in the serum. She was diagnosed with insulin autoimmune syndrome. Her HLA typing was performed, and it revealed HLA-DRB1 *04:06. The patient was treated with a corticosteroid for 2 months. After discontinuing the steroid, the insulin antibody titer decreased dramatically, and she did not have any episode of hypoglycemia since. This is the first report of insulin autoimmune syndrome in a Korean girl, and we have revealed the connection between HLA type and insulin autoimmune syndrome in Korea.

Autoimmune hepatitis in children: what is different from adult AIH?

Science.gov (United States)

Mieli-Vergani, Giorgina; Vergani, Diego

2009-08-01

Autoimmune hepatitis (AIH) is characterized by inflammatory liver histology, circulating non-organ-specific autoantibodies, and increased levels of immunoglobulin (Ig) G in the absence of a known etiology. Two types of childhood AIH are recognized according to seropositivity: smooth muscle antibody (SMA) and/or antinuclear antibody (ANA), which is AIH type 1; and antibodies to liver-kidney microsome type 1 (anti-LKM1), which is AIH type 2. There is a female predominance in both. Autoimmune hepatitis type 2 presents more acutely, at a younger age, and commonly with IgA deficiency; however, duration of symptoms before diagnosis, clinical signs, family history of autoimmunity, presence of associated autoimmune disorders, response to treatment, and long-term prognosis are similar in the two groups. Immunosuppressive treatment with steroids and azathioprine, which should be instituted promptly to avoid progression to cirrhosis, induces remission in 80% of cases. Relapses are common, often due to nonadherence. Drugs effective in refractory cases include cyclosporine and mycophenolate mofetil. Long-term treatment is usually required, with only some 20% of AIH type 1 patients able to discontinue therapy successfully. In childhood, sclerosing cholangitis with strong autoimmune features, including interface hepatitis and serological features identical to AIH type 1, is as prevalent as AIH, but it affects boys and girls equally. The differential diagnosis relies on cholangiographic studies. In autoimmune sclerosing cholangitis, liver parenchymal damage responds satisfactorily to immunosuppressive treatment, whereas bile duct disease tends to progress. Copyright Thieme Medical Publishers.

Autoimmunity in diabetics induced by hormonal contaminants of insulin

International Nuclear Information System (INIS)

Bloom, S.R.; Barnes, A.J.; Adrian, T.E.; Polak, J.M.

1979-01-01

Several commercial insulin preparations were found to contain significant quantities of pancreatic glucagon, pancreatic polypeptide (P.P.), vasoactive intestinal peptide (V.I.P.), and somatostatin, though these substances were effectively absent from the new highly purified or monocomponent insulins. Of 448 insulin-dependent diabetics receiving conventional insulins, 63% had circulating antibodies to human P.P., 6% antibodies to V.I.P., 6% to glucagon, and 0.5% to somatostatin. The antibodies were of high affinity and were commonest in the younger diabetics. No antibodies were detected in 167 maturity-onset diabetics, in 125 healthy controls, or in 22 patients treated only with monocomponent insulin. Immuno-cytochemical testing showed that antibody-positive diabetic plasmas reacted specifically against the corresponding hormone-producing pancreatic endocrine cells, against enteroglucagon and somatostatin cells outside the pancreas, and against V.I.P.-containing autonomic nerves throughout the body. The finding of iatrogenic autoimmunity to naturally occurring hormones in large numbers of insulin-dependent diabetics raises important questions about long-term treatment. (author)

Autoimmunity in diabetics induced by hormonal contaminants of insulin

Energy Technology Data Exchange (ETDEWEB)

Bloom, S R; Barnes, A J; Adrian, T E; Polak, J M [Royal Postgraduate Medical School, London (UK)

1979-01-06

Several commercial insulin preparations were found to contain significant quantities of pancreatic glucagon, pancreatic polypeptide (P.P.), vasoactive intestinal peptide (V.I.P.), and somatostatin, though these substances were effectively absent from the new highly purified or monocomponent insulins. Of 448 insulin-dependent diabetics receiving conventional insulins, 63% had circulating antibodies to human P.P., 6% antibodies to V.I.P., 6% to glucagon, and 0.5% to somatostatin. The antibodies were of high affinity and were commonest in the younger diabetics. No antibodies were detected in 167 maturity-onset diabetics, in 125 healthy controls, or in 22 patients treated only with monocomponent insulin. Immuno-cytochemical testing showed that antibody-positive diabetic plasmas reacted specifically against the corresponding hormone-producing pancreatic endocrine cells, against enteroglucagon and somatostatin cells outside the pancreas, and against V.I.P.-containing autonomic nerves throughout the body. The finding of iatrogenic autoimmunity to naturally occurring hormones in large numbers of insulin-dependent diabetics raises important questions about long-term treatment.

Antibodies to SS-A/Ro-52kD and centromere in autoimmune liver disease: a clue to diagnosis and prognosis of primary biliary cirrhosis.

Science.gov (United States)

Granito, A; Muratori, P; Muratori, L; Pappas, G; Cassani, F; Worthington, J; Ferri, S; Quarneti, C; Cipriano, V; de Molo, C; Lenzi, M; Chapman, R W; Bianchi, F B

2007-09-15

Primary biliary cirrhosis (PBC) may be associated with various rheumatological disorders. To investigate the frequency and significance of 'rheumatological' antinuclear antibodies in the field of autoimmune chronic liver disease, with special regard to PBC. We studied 105 patients with PBC, 162 autoimmune liver disease controls (type 1 and 2 autoimmune hepatitis, primary sclerosing cholangitis), 30 systemic lupus erythematosus and 50 blood donors. Sera were tested for the presence of antibodies to extractable nuclear antigens (anti-ENA) by counterimmunoelectrophoresis, enzyme-linked and immunoblot (IB) assay, and for the presence of anti-centromere antibodies (ACA) by indirect immunofluorescence on HEp-2 cells and IB. The overall prevalence of IB-detected anti-ENA in PBC (30%) was higher than in type 1 autoimmune hepatitis (2.5%, P < 0.0001), type 2 autoimmune hepatitis (0%, P < 0.0001) and primary sclerosing cholangitis (11.5%, P = 0.006) and lower than in systemic lupus erythematosus (53%, P = 0.03). The most frequent anti-ENA reactivity in PBC was anti-SSA/Ro-52kD (28%). ACA were detected by IB in 21% PBC patients and never in the other subjects (P < 0.0001). Anti-SS-A/Ro/52kD positive PBC patients had at the time of diagnosis a more advanced histological stage (P = 0.01) and higher serum levels of bilirubin (P = 0.01) and IgM (P = 0.03) compared with negative ones. In the autoimmune liver disease setting, anti-SS-A/Ro-52kD and ACA have a high specificity for PBC and can thus be of diagnostic relevance in anti-mitochondrial antibodies negative cases. If confirmed in further studies with adequate follow-up, anti-SS-A/Ro-52kD antibodies might identify PBC patients with a more advanced and active disease.

Impact of Vitamin D Supplementation on the Level of Thyroid Peroxidase Antibodies in Patients with Autoimmune Hypothyroidism

Directory of Open Access Journals (Sweden)

I.V. Pan’kiv

2016-08-01

Full Text Available In spite of studying the relationship between the deficiency and the lack of vitamin D in autoimmune thyroid disorders, the effect of additional administration of the preparations of this vitamin has not been clear in such pathology. The aim of study was to investigate the effect of vitamin D on the content of thyroid peroxidase antibodies (TPO in patients with newly diagnosed hypothyroidism on the background of autoimmune thyroiditis (AIT. Materials and methods. The study included 52 patients with newly diagnosed hypothyroidism on the background of AIT, who were randomized into two groups. Patients of the first group additionally received cholecalciferol 2000 IU/day (14 000 IU/week and calcium preparations in a dose of 1000 mg/day for 12 weeks. Patients of the second group were administered only calcium preparations at a dose of 1000 mg/day for 12 weeks in addition to levothyroxine. A positive result of treatment was considered a reduction of antibodies to TPO of at least 25 %. Results. 94.2 % of patients with hypothyroidism had the deficiency and the lack of vitamin D. In patients with hypothyroidism, there was a significant negative correlation between the levels of 25(OHD and the titer of antibodies to TPO (r = –0.172; p = 0.046. Vitamin D supplementation resulted in a significant decrease of the level of antibodies to TPO (–48.1 % in patients with hypothyroidism. In general, lowering the level of antibodies to TPO by 25 % or more has been achieved in 73.1 % of patients. Administration of vitamin D contributed to a significant increase of the content of 25(OHD in the blood serum with a corresponding reduction in the concentration of intact parathyroid hormone in patients with hypothyroidism resulted from AIT. Conclusions. The positive effect of supplemental vitamin D has been established in terms of the level of antibodies to TPO in patients with autoimmune hypothyroidism.

Beta-endorphin and the immune system--possible role in autoimmune diseases

DEFF Research Database (Denmark)

Mørch, H; Pedersen, B K

1995-01-01

The immune system and the neuroendocrine system are closely interconnected having such means of bidirectional communication and regulation. In this review, a hypothesis is put forward regarding the possible role of beta-endorphins in the pathogenesis of autoimmune diseases: It is suggested...... that the increased cytokine production in immunoinflammatory disorders induces production of beta-endorphins from the pituitary and the lymphocytes; the enhanced level of beta-endorphin causes inhibition of human T helper cell function, which potentially down-regulate the antibody production. Also the beta......-endorphin-induced enhancement of the natural killer cell activity may suppress the B cell function. In addition, beta-endorphin also exerts a direct inhibitory effect on the antibody production. Thus, in autoimmune disorders the enhanced cytokine level may via stimulation of the production of beta-endorphins exert a negative...

AUTOIMMUNE HEPATITIS

Directory of Open Access Journals (Sweden)

Yusri Dianne Jurnalis

2010-05-01

; Aetiopathogenesis; Lymphocyte disease; Cellular immune attack; Histocompatibility lymphocyte antigen, Immunosuppressive therapy, Cyclosporine, transplantasi hatiAbstractAutoimmune hepatitis is a severe and inflammatory disease of the liver of unknown etiology carrying high morbidity and mortality. All ages and genders are concerned with a peak of incidence in girls in prepubertal age, even if the diseaseTINJAUAN PUSTAKA2has been diagnosed as early as 6 months. Autoimmune hepatitis may be classified in two major subgroups on a presence of a specific set of autoantibodies: smooth muscle antibody (SMA mostly with anti-actin specificity and/or by antinuclear antibody (ANA in type 1 and liver-kidney microsome antibody (LKM1 and/or the anti-liver cytosol in type 2. The histological hallmark is “interface hepatitis”, with a mononuclear cell infiltrate in the portal tracts, variable degrees of necrosis, and progressive fibrosis. The disease follows a chronic but fluctuating course usually progressing to cirrhosis and liver failure.The most frequent type onset is similar to that of an acute viral hepatitis with acute liver failure in some patients; about a third of patients have an insidious onset with progressive fatigue and jaundice while 10-15% are asymptomatic and are accidentally discovered by the finding of hepatomegaly and/or an increase of serum aminotransferase activity. There is a female predominance in both. LKM1-positive patients tend to present more acutely, at a younger age, and commonly have immunoglobulin A (IgA deficiency, while duration of symptoms before diagnosis, clinical signs, family history of autoimmunity, presence of associated autoimmune disorders, response to treatment and long-term prognosis are similar in both groups.Corticosteroids alone or in conjunction with azathioprine are the treatment of choice inducing remission in over 90% of patients. An alternative therapeutic strategy is cyclosporine. Withdrawal of immunosuppression is associated with high risk

[Autoimmune hepatitis: Immunological diagnosis].

Science.gov (United States)

Brahim, Imane; Brahim, Ikram; Hazime, Raja; Admou, Brahim

2017-11-01

Autoimmune hepatopathies (AIHT) including autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC) and autoimmune cholangitis (AIC), represent an impressive entities in clinical practice. Their pathogenesis is not perfectly elucidated. Several factors are involved in the initiation of hepatic autoimmune and inflammatory phenomena such as genetic predisposition, molecular mimicry and/or abnormalities of T-regulatory lymphocytes. AIHT have a wide spectrum of presentation, ranging from asymptomatic forms to severe acute liver failure. The diagnosis of AIHT is based on the presence of hyperglobulinemia, cytolysis, cholestasis, typical even specific circulating auto-antibodies, distinctive of AIH or PBC, and histological abnormalities as well as necrosis and inflammation. Anti-F actin, anti-LKM1, anti-LC1 antibodies permit to distinguish between AIH type 1 and AIH type 2. Anti-SLA/LP antibodies are rather associated to more severe hepatitis, and particularly useful for the diagnosis of seronegative AIH for other the antibodies. Due to the relevant diagnostic value of anti-M2, anti-Sp100, and anti-gp210 antibodies, the diagnosis of PBC is more affordable than that of PSC and AIC. Based on clinical data, the immunological diagnosis of AIHT takes advantage of the various specialized laboratory techniques including immunofluorescence, immunodot or blot, and the Elisa systems, provided of a closer collaboration between the biologist and the physician. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Autoimmunity-Basics and link with periodontal disease.

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Kaur, Gagandeep; Mohindra, Kanika; Singla, Shifali

2017-01-01

Autoimmune reactions reflect an imbalance between effector and regulatory immune responses, typically develop through stages of initiation and propagation, and often show phases of resolution (indicated by clinical remissions) and exacerbations (indicated by symptomatic flares). The fundamental underlying mechanism of autoimmunity is defective elimination and/or control of self-reactive lymphocytes. Periodontal diseases are characterized by inflammatory conditions that directly affect teeth-supporting structures, which are the major cause of tooth loss. Several studies have demonstrated the involvement of autoimmune responses in periodontal disease. Evidence of involvement of immunopathology has been reported in periodontal disease. Bacteria in the dental plaque induce antibody formation. Autoreactive T-cells, natural killer cells, ANCA, heat shock proteins, autoantibodies, and genetic factors are reported to have an important role in the autoimmune component of periodontal disease. The present review describes the involvement of autoimmune responses in periodontal diseases and also the mechanisms underlying these responses. Copyright © 2016 Elsevier B.V. All rights reserved.

Paediatric autoimmune encephalopathies: clinical features, laboratory investigations and outcomes in patients with or without antibodies to known central nervous system autoantigens

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Hacohen, Yael; Wright, Sukhvir; Waters, Patrick; Agrawal, Shakti; Carr, Lucinda; Cross, Helen; De Sousa, Carlos; DeVile, Catherine; Fallon, Penny; Gupta, Rajat; Hedderly, Tammy; Hughes, Elaine; Kerr, Tim; Lascelles, Karine; Lin, Jean-Pierre; Philip, Sunny; Pohl, Keith; Prabahkar, Prab; Smith, Martin; Williams, Ruth; Clarke, Antonia; Hemingway, Cheryl; Wassmer, Evangeline; Vincent, Angela; Lim, Ming J

2013-01-01

Objective To report the clinical and investigative features of children with a clinical diagnosis of probable autoimmune encephalopathy, both with and without antibodies to central nervous system antigens. Method Patients with encephalopathy plus one or more of neuropsychiatric symptoms, seizures, movement disorder or cognitive dysfunction, were identified from 111 paediatric serum samples referred from five tertiary paediatric neurology centres to Oxford for antibody testing in 2007–2010. A blinded clinical review panel identified 48 patients with a diagnosis of probable autoimmune encephalitis whose features are described. All samples were tested/retested for antibodies to N-methyl-D-aspartate receptor (NMDAR), VGKC-complex, LGI1, CASPR2 and contactin-2, GlyR, D1R, D2R, AMPAR, GABA(B)R and glutamic acid decarboxylase. Results Seizures (83%), behavioural change (63%), confusion (50%), movement disorder (38%) and hallucinations (25%) were common. 52% required intensive care support for seizure control or profound encephalopathy. An acute infective organism (15%) or abnormal cerebrospinal fluid (32%), EEG (70%) or MRI (37%) abnormalities were found. One 14-year-old girl had an ovarian teratoma. Serum antibodies were detected in 21/48 (44%) patients: NMDAR 13/48 (27%), VGKC-complex 7/48(15%) and GlyR 1/48(2%). Antibody negative patients shared similar clinical features to those who had specific antibodies detected. 18/34 patients (52%) who received immunotherapy made a complete recovery compared to 4/14 (28%) who were not treated; reductions in modified Rankin Scale for children scores were more common following immunotherapies. Antibody status did not appear to influence the treatment effect. Conclusions Our study outlines the common clinical and paraclinical features of children and adolescents with probable autoimmune encephalopathies. These patients, irrespective of positivity for the known antibody targets, appeared to benefit from immunotherapies and further

Phenotypic expression of autoimmune autistic disorder (AAD): a major subset of autism.

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Singh, Vijendra K

2009-01-01

Autism causes incapacitating neurologic problems in children that last a lifetime. The author of this article previously hypothesized that autism may be caused by autoimmunity to the brain, possibly triggered by a viral infection. This article is a summary of laboratory findings to date plus new data in support of an autoimmune pathogenesis for autism. Autoimmune markers were analyzed in the sera of autistic and normal children, but the cerebrospinal fluid (CSF) of some autistic children was also analyzed. Laboratory procedures included enzyme-linked immunosorbent assay and protein immunoblotting assay. Autoimmunity was demonstrated by the presence of brain autoantibodies, abnormal viral serology, brain and viral antibodies in CSF, a positive correlation between brain autoantibodies and viral serology, elevated levels of proinflammatory cytokines and acute-phase reactants, and a positive response to immunotherapy. Many autistic children harbored brain myelin basic protein autoantibodies and elevated levels of antibodies to measles virus and measles-mumps-rubella (MMR) vaccine. Measles might be etiologically linked to autism because measles and MMR antibodies (a viral marker) correlated positively to brain autoantibodies (an autoimmune marker)--salient features that characterize autoimmune pathology in autism. Autistic children also showed elevated levels of acute-phase reactants--a marker of systemic inflammation. The scientific evidence is quite credible for our autoimmune hypothesis, leading to the identification of autoimmune autistic disorder (AAD) as a major subset of autism. AAD can be identified by immune tests to determine immune problems before administering immunotherapy. The author has advanced a speculative neuroautoimmune (NAI) model for autism, in which virus-induced autoimmunity is a key player. The latter should be targeted by immunotherapy to help children with autism.

Autoimmune/inflammatory syndrome induced by adjuvants (Shoenfeld's syndrome) - An update.

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Watad, A; Quaresma, M; Brown, S; Cohen Tervaert, J W; Rodríguez-Pint, I; Cervera, R; Perricone, C; Shoenfeld, Y

2017-06-01

Autoimmune/inflammatory syndrome induced by adjuvants (ASIA) has been widely described in many studies conducted thus far. The syndrome incorporates five immune-mediated conditions, all associated with previous exposure to various agents such as vaccines, silicone implants and several others. The emergence of ASIA syndrome is associated with individual genetic predisposition, for instance those carrying HLA-DRB1*01 or HLA-DRB4 and results from exposure to external or endogenous factors triggering autoimmunity. Such factors have been demonstrated as able to induce autoimmunity in both animal models and humans via a variety of proposed mechanisms. In recent years, physicians have become more aware of the existence of ASIA syndrome and the relationship between adjuvants exposure and autoimmunity and more cases are being reported. Accordingly, we have created a registry that includes at present more than 300 ASIA syndrome cases that have been reported by different physicians worldwide, describing various autoimmune conditions induced by diverse adjuvants. In this review, we have summarized the updated literature on ASIA syndrome and the knowledge accumulated since 2013 in order to elucidate the association between the exposure to various adjuvant agents and its possible clinical manifestations. Furthermore, we especially referred to the relationship between ASIA syndrome and systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS).

Liver cytosolic 1 antigen-antibody system in type 2 autoimmune hepatitis and hepatitis C virus infection.

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Lenzi, M; Manotti, P; Muratori, L; Cataleta, M; Ballardini, G; Cassani, F; Bianchi, F B

1995-01-01

Within the multiform liver/kidney microsomal (LKM) family, a subgroup of sera that reacts with a liver cytosolic (LC) protein has been isolated and the new antigen-antibody system is called LC1. Unlike LKM antibody type 1 (anti-LKM1), anti-LC1 is said to be unrelated to hepatitis C virus (HCV) infection and has therefore been proposed as a marker of 'true' autoimmune hepatitis type 2. Altogether 100 LKM1 positive sera were tested by immunodiffusion (ID). Twenty five gave a precipitation line with human liver cytosol; 17 of the 25 also reacted with rat liver cytosol. Thirteen of the 25 sera were anti-HCV positive by second generation ELISA: anti-HCV positive patients were significantly older (p LKM1, and that it is an additional marker of juvenile autoimmune hepatitis type 2. It does not, however, discriminate between patients with and without HCV infection. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 PMID:7797126

Is There an Association Between Heparin-Induced Thrombocytopenia (HIT) and Autoimmune Disease?

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Klinkhammer, Brent; Gruchalla, Michael

2018-03-01

Heparin-induced thrombocytopenia (HIT) is a drug-induced, immunoglobulin G medicated autoimmune disorder associated with several negative clinical outcomes including increased morbidity, mortality, and increased medical costs. Previous studies have shown associations between comorbid autoimmune diseases, but there is little known about associations between HIT and autoimmunity. To provide clinical data to suggest an association between HIT and autoimmunity. Retrospective chart review of 59 cases with a diagnosis of HIT and 251 matched controls without a HIT diagnosis, comparing the prevalence of autoimmunity in each group. A single, large upper Midwest health care system. Patients with a diagnosis of HIT were significantly more likely to have a comorbid autoimmune disease than those without a HIT diagnosis (55.9% vs 10.8%, P HIT were significantly more likely to have a diagnosis of antiphospholipid syndrome (15.3% vs 0.0%, P HIT were significantly older than controls ( P HIT and autoimmune disease and suggests a need for more research into the relationship between HIT and autoimmunity. These results could alter the anticoagulation management of venous thromboembolism and acute coronary syndrome in patients with a previously identified autoimmune disease. Copyright© Wisconsin Medical Society.

Absence of cross-reactivity to myeloperoxidase of anti-thyroid microsomal antibodies in patients with autoimmune thyroid diseases

NARCIS (Netherlands)

Freire, BA; Paula, ID; Paula, F; Kallenberg, GGM; Limburg, PC; Queluz, TT

Background: Thyroperoxidase is the major antigen of the thyroid microsomal antibodies (TMA) detected in autoimmune thyroid diseases. Its amino acid sequence has 44% homology with myeloperoxidase (MPO), an enzyme present in the primary granules of neutrophils and one of the major antineutrophil

[Antibody therapy for Alzheimer's disease].

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Tabira, Takeshi; Matsumoto, Shin-Ei; Jin, Haifeng

2011-11-01

In order to avoid Abeta-induced autoimmune encephalitis, several monoclonal and polyclonal antibodies are in clinical trials. These are bapineuzumab, solanezumab, ponezumab, gantenerumab, BAN2401, gammaguard and octagam. Since each antibody has a different antigen epitope of Abeta, anti-amyloid activities are different. It is unknown which antibody is effective for Alzheimer disease, and we must wait for the result of clinical trials. Some patients who developed tissue amyloid plaque immuno-reactive (TAPIR) antibody showed slower decline after AN-1792 vaccination. We developed TAPIR-like monoclonal antibody, which was found to react with Abeta oligomers preferentially.

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

International Nuclear Information System (INIS)

Mellergaard, Johan; Havarinasab, Said; Hultman, Per

2004-01-01

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

Epstein-Barr Virus Lytic Reactivation Activates B Cells Polyclonally and Induces Activation-Induced Cytidine Deaminase Expression: A Mechanism Underlying Autoimmunity and Its Contribution to Graves' Disease.

Science.gov (United States)

Nagata, Keiko; Kumata, Keisuke; Nakayama, Yuji; Satoh, Yukio; Sugihara, Hirotsugu; Hara, Sayuri; Matsushita, Michiko; Kuwamoto, Satoshi; Kato, Masako; Murakami, Ichiro; Hayashi, Kazuhiko

2017-04-01

Graves' disease is an autoimmune disease that results in and is the most common cause of hyperthyroidism, and the reactivation of persisting Epstein-Barr virus (EBV) in B lymphocytes induces the differentiation of host B cells into plasma cells. We previously reported that some EBV-infected B cells had thyrotropin receptor antibodies (TRAbs) as surface immunoglobulins (Igs), and EBV reactivation induced these TRAb+EBV+ cells to produce TRAbs. EBV reactivation induces Ig production from host B cells. The purpose of the present study was to examine total Ig productions from B cell culture fluids and to detect activation-induced cytidine deaminase (AID), nuclear factor kappa B (NF-κB), and EBV latent membrane protein (LMP) 1 in culture B cells during EBV reactivation induction and then we discussed the mechanisms of EBV reactivation-induced Ig production in relation to autoimmunity. We showed that the EBV reactivation induces the production of every isotype of Ig and suggested that the Ig production was catalyzed by AID through LMP1 and NF-κB. The results that the amount of IgM was significantly larger compared with IgG suggested the polyclonal B cell activation due to LMP1. We proposed the pathway of EBV reactivation induced Ig production; B cells newly infected with EBV are activated by polyclonal B cell activation and produce Igs through plasma cell differentiation induced by EBV reactivation. LMP1-induced AID enabled B cells to undergo class-switch recombination to produce every isotype of Ig. According to this mechanism, EBV rescues autoreactive B cells to produce autoantibodies, which contribute to the development and exacerbation of autoimmune diseases.

Autoantibodies in Autoimmune Hepatitis.

Science.gov (United States)

Muratori, Luigi; Deleonardi, Gaia; Lalanne, Claudine; Barbato, Erica; Tovoli, Alessandra; Libra, Alessia; Lenzi, Marco; Cassani, Fabio; Muratori, Paolo

2015-01-01

The detection of diagnostic autoantibodies such as antinuclear antibodies (ANA), anti-smooth muscle antibodies (SMA), anti-liver/kidney microsomal type 1 (anti-LKM1), anti-liver cytosol type 1 (anti-LC1) and anti-soluble liver antigen (anti-SLA) is historically associated with the diagnosis of autoimmune hepatitis. When autoimmune hepatitis is suspected, the detection of one or any combination of diagnostic autoantibodies, by indirect immunofluorescence or immuno-enzymatic techniques with recombinant antigens, is a pivotal step to reach a diagnostic score of probable or definite autoimmune hepatitis. Diagnostic autoantibodies (ANA, SMA, anti-LKM1, anti-LC1, anti-SLA) are a cornerstone in the diagnosis of autoimmune hepatitis. Other ancillary autoantibodies, associated with peculiar clinical correlations, appear to be assay-dependent and institution-specific, and validation studies are needed. © 2015 S. Karger AG, Basel.

Endogenous interleukin (IL)-17A promotes pristane-induced systemic autoimmunity and lupus nephritis induced by pristane.

Science.gov (United States)

Summers, S A; Odobasic, D; Khouri, M B; Steinmetz, O M; Yang, Y; Holdsworth, S R; Kitching, A R

2014-06-01

Interleukin (IL)-17A is increased both in serum and in kidney biopsies from patients with lupus nephritis, but direct evidence of pathogenicity is less well established. Administration of pristane to genetically intact mice results in the production of autoantibodies and proliferative glomerulonephritis, resembling human lupus nephritis. These studies sought to define the role of IL-17A in experimental lupus induced by pristane administration. Pristane was administered to wild-type (WT) and IL-17A(-/-) mice. Local and systemic immune responses were assessed after 6 days and 8 weeks, and autoimmunity, glomerular inflammation and renal injury were measured at 7 months. IL-17A production increased significantly 6 days after pristane injection, with innate immune cells, neutrophils (Ly6G(+)) and macrophages (F4/80(+)) being the predominant source of IL-17A. After 8 weeks, while systemic IL-17A was still readily detected in WT mice, the levels of proinflammatory cytokines, interferon (IFN)-γ and tumour necrosis factor (TNF) were diminished in the absence of endogenous IL-17A. Seven months after pristane treatment humoral autoimmunity was diminished in the absence of IL-17A, with decreased levels of immunoglobulin (Ig)G and anti-dsDNA antibodies. Renal inflammation and injury was less in the absence of IL-17A. Compared to WT mice, glomerular IgG, complement deposition, glomerular CD4(+) T cells and intrarenal expression of T helper type 1 (Th1)-associated proinflammatory mediators were decreased in IL-17A(-/-) mice. WT mice developed progressive proteinuria, but functional and histological renal injury was attenuated in the absence of IL-17A. Therefore, IL-17A is required for the full development of autoimmunity and lupus nephritis in experimental SLE, and early in the development of autoimmunity, innate immune cells produce IL-17A. © 2014 British Society for Immunology.

Thyroid Antibodies, Autoimmunity and Cognitive Decline: Is There a Population-Based Link

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Kate Napthali

2014-05-01

Full Text Available Background: Autoimmunity is considered an uncommon but under-recognised cause of cognitive decline. Methods: Serum samples from 3,253 randomly selected subjects enrolled in the Hunter Community Study, aged 55-85 years, were assayed for thyrotropin stimulatory hormone, anti-thyroid peroxidase antibodies (TPO-Ab, anti-nuclear antibodies (ANA and extractable nuclear antigens (ENA. Cognitive function was assessed using the Audio Recorded Cognitive Screen (ARCS tool. Results: TPO-Ab were found in 8.4% and ANA in 27.9% of the study population, of whom 3% had positive ENA findings. No relationship was found between the ARCS score and either TPO-Ab (coefficient = 0.133; 95% CI -0.20, 0.82, p = 0.616, ANA at a low (coefficient = 1.01; 95% CI -2.58, 0.55, p = 0.203 or a high titre (coefficient = -0.65; 95% CI -2.59, 1.28, p = 0.508, or ENA antibodies (coefficient = 5.12; 95% CI -0.53, 10.77; p = 0.076. Conclusions: Autoantibody findings are common in an aging population and are not associated with cognitive decline.

Thyroid dysfunction: an autoimmune aspect.

Science.gov (United States)

Khan, Farah Aziz; Al-Jameil, Noura; Khan, Mohammad Fareed; Al-Rashid, May; Tabassum, Hajera

2015-01-01

Auto immune thyroid disease (AITD) is the common organ specific autoimmune disorder, Hashimoto thyroiditis (HT) and Grave's disease (GD) are its well-known sequelae. It occurs due to loss of tolerance to autoantigens thyroid peroxidase (TPO), thyroglobulin (Tg), thyroid stimulating hormone receptor (TSH-R) which leads to the infiltration of the gland. T cells in chronic autoimmune thyroiditis (cAIT) induce apoptosis in thyroid follicular cells and cause destruction of the gland. Presences of TPO antibodies are common in HT and GD, while Tg has been reported as an independent predictor of thyroid malignancy. Cytokines are small proteins play an important role in autoimmunity, by stimulating B and T cells. Various cytokines IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-13, IL-14, TNF-α and IFN-γ are found in thyroid follicular cells which enhance inflammatory response with nitric oxide (NO) and prostaglandins.

What Is Antiphospholipid Antibody Syndrome?

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... Back To Health Topics / Antiphospholipid Antibody Syndrome Antiphospholipid Antibody Syndrome Also known as What Is Antiphospholipid (AN-te-fos-fo-LIP-id) antibody syndrome (APS) is an autoimmune disorder. Autoimmune disorders ...

Enhanced Autoimmunity Associated with Induction of Tumor Immunity in Thyroiditis-Susceptible Mice

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Kari, Suresh; Flynn, Jeffrey C.; Zulfiqar, Muhammad; Snower, Daniel P.; Elliott, Bruce E.

2013-01-01

Background: Immunotherapeutic modalities to bolster tumor immunity by targeting specific sites of the immune network often result in immune dysregulation with adverse autoimmune sequelae. To understand the relative risk for opportunistic autoimmune disorders, we studied established breast cancer models in mice resistant to experimental autoimmune thyroiditis (EAT). EAT is a murine model of Hashimoto's thyroiditis, an autoimmune syndrome with established MHC class II control of susceptibility. The highly prevalent Hashimoto's thyroiditis is a prominent autoimmune sequela in immunotherapy, and its relative ease of diagnosis and treatment could serve as an early indicator of immune dysfunction. Here, we examined EAT-susceptible mice as a combined model for induction of tumor immunity and EAT under the umbrella of disrupted regulatory T cell (Treg) function. Methods: Tumor immunity was evaluated in female CBA/J mice after depleting Tregs by intravenous administration of CD25 monoclonal antibody and/or immunizing with irradiated mammary adenocarcinoma cell line A22E-j before challenge; the role of T cell subsets was determined by injecting CD4 and/or CD8 antibodies after tumor immunity induction. Tumor growth was monitored 3×/week by palpation. Subsequent EAT was induced by mouse thyroglobulin (mTg) injections (4 daily doses/week over 4 weeks). For some experiments, EAT was induced before establishing tumor immunity by injecting mTg+interleukin-1, 7 days apart. EAT was evaluated by mTg antibodies and thyroid infiltration. Results: Strong resistance to tumor challenge after Treg depletion and immunization with irradiated tumor cells required participation of both CD4+ and CD8+ T cells. This immunity was not altered by induction of mild thyroiditis with our protocol of Treg depletion and adjuvant-free, soluble mTg injections. However, the increased incidence of mild thyroiditis can be directly related to Treg depletion needed to achieve strong tumor immunity. Moreover

APPEARANCE OF AUTOIMMUNE DISEASES IN PATIENTS WITH ENDOMETRIOSIS

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Nina Slabe

2018-02-01

Full Text Available Background. Endometriosis is a comon, complex gynecological syndrom defined as the growth of endometrial glands and stroma in an extra-uterine location. It affects 5 – 20 % of women of reproductive age.1 Nowadays, prevailing opinion about endometriosis is based on presumption, that endometriosis is a result of changed immune system, according to autoimmune theory.2, 3 Characteristics of autoimmune disease that are also found in endometriosis are female preponderance, multiorgan involvement, family occurence, possible genetic basis, response to hormonal manipulation, tissue damage, polyclonal B lymphocite activation, immunological abnormalities in T lymphocite and B lymphocite function and associated autoimmune disease. Women with endometriosis are more frequently affected by asthma, rheumatoid arthritis, systemic lupus erythematosus, Sjögren syndrom and Hashimoto’s thyroiditis. Autoimmune disease is characterized by the production of autoantibodies against components of apoptotic cells. Anti-endometrial antibodies of IgG and IgM classes could be detected in 60 % of endometriosis patients. They show reactivity in glandular epithelium and stroma. Anti-endothelial antibodies specifically react with vascular endothelium and might be with anti-endometrial antibodies partially responsible for failure of implantation leading to infertility, wich is common in endometriosis patients. Anti-nuclear antibodies are frequent serological findings in patients with autoimmune disease, and could be detected in 29–47 % of women with endometriosis.4 Generation of anti-nuclear antibodies is a risk factor for development of other autoimmune disease in women of reproductive age. Studies have shown conflicting results on the presence of anti-ovarian antibodies in the serum of endometriosis patients and in the peritoneal fluid. Their presence is one of the possible causes of infertility. Conclusions. Ethiopathogenesis of endometriosis still remains uncelar but

Pegylated interferon de novo-induce autoimmune haemolytic anaemia in chronic hepatitis C patient.

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Said, Ashraf; Elbahrawy, Ashraf; Alfiomy, Mohamed; Abdellah, Mohamed; Shahat, Khaled; Salah, Mohamed; Mostafa, Sadek; Elwassief, Ahmed; Aboelfotoh, Attef; Abdelhafeez, Hafez; El-Sherif, Assem

2011-08-11

A 55-year-old Egyptian woman with chronic hepatitis C undergoing treatment with pegylated interferon (Peg-IFN) alfa-2a plus ribavirin was referred to our hospital on November 2010 with prolonged easy fatigability and an attack of syncope; she had no prior history of autoimmune disorders or allergy. Laboratory investigations documented the presence of Peg-IFN induced autoimmune haemolytic anaemia and autoimmune thyroiditis. Intravenous γ globulin (IVGG) failed to correct the autoimmune process; on the other hand steroid therapy dramatically corrected both haematological and thyroid values, and step down the immune process. Our report indicated that Peg-IFN de novo-induce autoimmune haemolysis, documenting a previous report. IVGG failed to step down the immune process in our case.

Autoimmune hepatitis-specific antibodies against soluble liver antigen and liver cytosol type 1 in patients with chronic viral hepatitis

OpenAIRE

Rigopoulou, Eirini I; Mytilinaiou, Maria; Romanidou, Ourania; Liaskos, Christos; Dalekos, George N

2007-01-01

Background Non-organ specific autoantibodies are highly prevalent in patients with chronic hepatitis C (HCV). Among them, anti-liver kidney microsomal type 1 (LKM1) antibody – the serological marker of type 2 autoimmune hepatitis (AIH-2)- is detected in up to 11% of the HCV-infected subjects. On the other hand, anti-liver cytosol type 1 antibodies (anti-LC1) – either in association with anti-LKM1, or in isolation- and anti-soluble liver antigen antibodies (anti-SLA) have been considered as us...

Diagnosis and classification of autoimmune orchitis.

Science.gov (United States)

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

2014-01-01

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

Current topics in autoimmune hepatitis.

Science.gov (United States)

Muratori, Luigi; Muratori, Paolo; Granito, Alessandro; Pappas, Giorgios; Cassani, Fabio; Lenzi, Marco

2010-11-01

Autoimmune hepatitis is a chronic liver disease of unknown aetiology characterized by interface hepatitis, hypergammaglobulinaemia and circulating autoantibodies. In the last decade a number of advancements have been made in the field of clinical and basic research: the simplified diagnostic criteria, the complete response defined as normalization of transaminase levels, the molecular identification of the antigenic targets of anti-liver cytosol antibody type 1 and anti-soluble liver antigen, the detection of anti-actin antibodies, the description of de novo autoimmune hepatitis after liver transplantation for non-autoimmune liver diseases, the characterization of autoimmune hepatitis with overlapping features of primary biliary cirrhosis or primary sclerosing cholangitis, the preliminary experience with novel treatment strategies based on cyclosporine, mycophenolate mofetil and budesonide, the role played by "impaired" regulatory T cells and the development of novel animal models of autoimmune hepatitis. Copyright © 2010 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

A Rationally Designed TNF-α Epitope-Scaffold Immunogen Induces Sustained Antibody Response and Alleviates Collagen-Induced Arthritis in Mice.

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Li Zhang

Full Text Available The TNF-α biological inhibitors have significantly improved the clinical outcomes of many autoimmune diseases, in particular rheumatoid arthritis. However, the practical uses are limited due to high costs and the risk of anti-drug antibody responses. Attempts to develop anti-TNF-α vaccines have generated encouraging data in animal models, however, data from clinical trials have not met expectations. In present study, we designed a TNF-α epitope-scaffold immunogen DTNF7 using the transmembrane domain of diphtheria toxin, named DTT as a scaffold. Molecular dynamics simulation shows that the grafted TNF-α epitope is entirely surface-exposed and presented in a native-like conformation while the rigid helical structure of DTT is minimally perturbed, thereby rendering the immunogen highly stable. Immunization of mice with alum formulated DTNF7 induced humoral responses against native TNF-α, and the antibody titer was sustained for more than 6 months, which supports a role of the universal CD4 T cell epitopes of DTT in breaking self-immune tolerance. In a mouse model of rheumatoid arthritis, DTNF7-alum vaccination markedly delayed the onset of collagen-induced arthritis, and reduced incidence as well as clinical score. DTT is presumed safe as an epitope carrier because a catalytic inactive mutant of diphtheria toxin, CRM197 has good clinical safety records as an active vaccine component. Taken all together, we show that DTT-based epitope vaccine is a promising strategy for prevention and treatment of autoimmune diseases.

Simultaneous measurements of auto-immune and infectious disease specific antibodies using a high throughput multiplexing tool.

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Atul Asati

Full Text Available Considering importance of ganglioside antibodies as biomarkers in various immune-mediated neuropathies and neurological disorders, we developed a high throughput multiplexing tool for the assessment of gangliosides-specific antibodies based on Biolpex/Luminex platform. In this report, we demonstrate that the ganglioside high throughput multiplexing tool is robust, highly specific and demonstrating ∼100-fold higher concentration sensitivity for IgG detection than ELISA. In addition to the ganglioside-coated array, the high throughput multiplexing tool contains beads coated with influenza hemagglutinins derived from H1N1 A/Brisbane/59/07 and H1N1 A/California/07/09 strains. Influenza beads provided an added advantage of simultaneous detection of ganglioside- and influenza-specific antibodies, a capacity important for the assay of both infectious antigen-specific and autoimmune antibodies following vaccination or disease. Taken together, these results support the potential adoption of the ganglioside high throughput multiplexing tool for measuring ganglioside antibodies in various neuropathic and neurological disorders.

A study of autoimmune markers in hepatitis C infection.

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Agarwal, N; Handa, R; Acharya, S K; Wali, J P; Dinda, A K; Aggarwal, P

2001-05-01

Hepatitis C virus (HCV) infection is associated with several autoimmune markers. Despite HCV being common in India, no information on this aspect is available. This study was undertaken to ascertain the frequency and clinical significance of autoimmune markers like rheumatoid factor (RF), antinuclear antibodies (ANA), antibodies to double stranded deoxyribonucleic acid (dsDNA), anti neutrophil cytoplasmic antibody (ANCA), anti smooth muscle antibodies (ASMA), anti liver kidney microsomal 1 antibodies (anti LKM1), anti gastric parietal cell antibodies (anti GPCA), anti mitochondrial antibodies (AMA), anti cardiolipin antibodies (ACL) and cryoglobulins in HCV infection and to determine the effect of treatment on these markers. Twenty five patients with chronic hepatitis C and 25 healthy controls were studied. Cryoglobulins were detected by cryoprecipitation, RF by latex agglutination, anti dsDNA and ACL by ELISA while indirect immunofluorescence was used to detect all other autoantibodies. Eighteen patients (72%) demonstrated autoimmune markers. RF, cryoglobulins and anti LKM1 antibodies were the most frequently detected markers (in 32% patients each). ASMA, perinuclear ANCA (pANCA), ANA and anti GPCA were seen in 24, 20, 12 and 4 per cent patients respectively. None of the patients exhibited ACL, AMA or antibodies to dsDNA. No antibodies were detected in healthy controls. Sixty per cent of the patients had rheumatological symptoms. Of the seven patients followed up after treatment with alpha interferon, only two exhibited persistence of RF, while symptoms and other markers disappeared. Rheumatological symptoms and autoimmune markers are common in HCV infection and are usually overlooked. Patients with unexplained joint pains and/or palpable purpura should be screened for HCV. Further studies are needed to delineate fully the link between infection and autoimmunity.

The value of Autoimmune Syndrome Induced by Adjuvant (ASIA) - Shedding light on orphan diseases in autoimmunity.

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Segal, Yahel; Dahan, Shani; Sharif, Kassem; Bragazzi, Nicola Luigi; Watad, Abdulla; Amital, Howard

2018-05-01

Autoimmune Syndrome Induced by Adjuvant (ASIA) is a definition aimed to describe the common etiological process at the root of five clinical entities sharing similar symptomatology: macrophagic myofasciitis syndrome (MMF), Gulf War Syndrome (GWS), sick building syndrome (SBS), siliconosis, and post vaccination autoimmune phenomena. ASIA illustrates the role of environmental immune stimulating agents, or adjuvants, in the instigation of complex autoimmune reactions among individuals bearing a genetic preponderance for autoimmunity. The value of ASIA lies first in the acknowledgment it provides for patients suffering from these as yet ill-defined medical conditions. Equally important is the spotlight it sheds for further research of these poorly understood conditions sharing a common pathogenesis. In this article we elaborate on the significance of ASIA, review the current evidence in support of the syndrome, and address recent reservations raised regarding its validity. Copyright © 2018 Elsevier B.V. All rights reserved.

[Analysis of the main components of inner ear antigens inducing autoimmune Meniere's disease in guinea pigs].

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Lu, Ling; Tan, Chang-Qiang; Cui, Yu-Gui; Ding, Gui-Peng; Ju, Xiao-Bin; Li, Yu-Jin; Cai, Wen-Jun

2008-08-01

To investigate the main components of inner ear antigens inducing autoimmune Meniere's disease (AIMD) in guinea pigs. The guinea pigs were immunized with isologous crude inner ear antigens (ICIEAg). Then, the hearing function was measured with auditory brainstem response (ABR), the vestibular function was measured with electronystagmography (including spontaneous nystagmus and caloric test), and inner ear histopathological changes were observed by inner ear celloidin section with haematoxylin-eosin staining and observed under light microscope. According to these results, the AIMD-model animals from non-AIMD-model ones were distinguished. The special antibodies against ICIEAg in sera were measured with ELISA. The antigen-antibody reactions against different components of ICIEAg were detected by Western blotting with sera of AIMD and non-AIMD guinea pigs respectively. Then, we analysed the contrast between them and found the main components of the ICIEAg that were positive reaction in AIMD guinea pigs and negative reaction in non-AIMD guinea pigs. The result of ELISA demonstrated that the sera of both the AIMD and non-AIMD guniea pigs contained the special antibodies against ICIEAg after immunized with ICIEAg. The difference of the amount of antibody against ICIEAg between AIMD guinea pig group and non-AIMD guinea pig group was not significant. Western blotting assay showed only the sera of AIMD guinea pig contained the antibodies against the specific antigens with the molecular of 68 000, 58 000, 42 000 and 28 000. ICIEAg contain many different components, the AIMD might only happen in the guinea pigs in which the special immunization against the main components that could induce this kind of disorder appeared. The inner ear antigens with molecular of 68 000, 58 000, 42 000 and 28 000 might be the main components inducing AIMD in guinea pigs.

Nitrosative stress and nitrated proteins in trichloroethene-mediated autoimmunity.

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Gangduo Wang

Full Text Available Exposure to trichloroethene (TCE, a ubiquitous environmental contaminant, has been linked to a variety of autoimmune diseases (ADs including SLE, scleroderma and hepatitis. Mechanisms involved in the pathogenesis of ADs are largely unknown. Earlier studies from our laboratory in MRL+/+ mice suggested the contribution of oxidative/nitrosative stress in TCE-induced autoimmunity, and N-acetylcysteine (NAC supplementation provided protection by attenuating oxidative stress. This study was undertaken to further evaluate the contribution of nitrosative stress in TCE-mediated autoimmunity and to identify proteins susceptible to nitrosative stress. Groups of female MRL +/+ mice were given TCE, NAC or TCE + NAC for 6 weeks (TCE, 10 mmol/kg, i.p., every 4th day; NAC, ∼ 250 mg/kg/day via drinking water. TCE exposure led to significant increases in serum anti-nuclear and anti-histone antibodies together with significant induction of iNOS and increased formation of nitrotyrosine (NT in sera and livers. Proteomic analysis identified 14 additional nitrated proteins in the livers of TCE-treated mice. Furthermore, TCE exposure led to decreased GSH levels and increased activation of NF-κB. Remarkably, NAC supplementation not only ameliorated TCE-induced nitrosative stress as evident from decreased iNOS, NT, nitrated proteins, NF-κB p65 activation and increased GSH levels, but also the markers of autoimmunity, as evident from decreased levels of autoantibodies in the sera. These findings provide support to the role of nitrosative stress in TCE-mediated autoimmune response and identify specific nitrated proteins which could have autoimmune potential. Attenuation of TCE-induced autoimmunity in mice by NAC provides an approach for designing therapeutic strategies.

Pendrin and NIS antibodies are absent in healthy individuals and are rare in autoimmune thyroid disease

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Brix, Thomas H; Hegedüs, Laszlo; Weetman, Anthony P

2014-01-01

prevalence than the controls: NISAb: 17% vs 0% (P Graves' disease (GD) and 14% (5/37) of patients with Hashimoto's thyroiditis (HT) had NISAb, (P ...OBJECTIVE: Antibodies against thyroglobulin, thyroid peroxidase and the TSH receptor are accepted as pathophysiological and diagnostic biomarkers in autoimmune thyroid disease (AITD). In contrast, the prevalence, aetiology and clinical relevance of autoantibodies against the human sodium...

Novel aspects of defensins' involvement in virus-induced autoimmunity in the central nervous system.

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Kazakos, Evangelos I; Kountouras, Jannis; Polyzos, Stergios A; Deretzi, Georgia

2017-05-01

Recent research on re-circulation of interstitial fluid from the brain parenchyma to the periphery and its inferred importance in immune surveillance dysregulation are changing our conceptualization of the pathophysiology of virus-induced autoimmunity. In this context, it is necessary to reassess the immunomodulatory properties of human defensins that are variably expressed by cerebral microglia, astrocytes and choroid plexus epithelial cells and exhibit complex and often confounding roles in neuroinflammatory processes. Therefore, in this review we describe current contributions in this field and we propose novel hypotheses regarding the potential impact of defensin-related pathways on virus-driven autoimmune neurodegeneration. In this regard, we have previously proposed that abnormal expression of defensins by penetrating the blood-brain barrier (BBB) may contribute to the pathophysiology of Helicobacter pylori-related brain neurodegenerative disorders through variable modulations of innate and adaptive immune responses. We hereby propose that impaired expression of defensins by structural components of the BBB may impede glymphatic circulation and disrupt receptor signalling in pericytes that is essential for microvascular stability, thereby retaining blood-derived toxins and bystander activated T-cells in the brain and further impairing BBB integrity and hampering viral clearance. Autoreactive T-cell infiltrates in neuronaxonal lesions characteristic of chronic central nervous system diseases, such as multiple sclerosis, are directed against both, myelin and non-myelin, antigens the precise nature of which remains enigmatic. Inadequate expression of the autoimmune regulator (AIRE), a gene expressed in medullary thymic epithelial cells, induces the recruitment of defensin-specific T-cells. These cells may access the brain, thereby causing a decrease in defensin expression and subsequent down-regulation of CD91/LRP1-mediated clearance of amyloid-β that

Autoimmune liver disease 2007.

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Muratori, Paolo; Granito, Alessandro; Pappas, Georgios; Muratori, Luigi; Lenzi, Marco; Bianchi, Francesco B

2008-01-01

Autoimmune liver disease (ALD) includes a spectrum of diseases which comprises both cholestatic and hepatitic forms: autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC) and the so called "overlap" syndromes where hepatitic and cholestatic damage coexists. All these diseases are characterized by an extremely high heterogeneity of presentation, varying from asymptomatic, acute (as in a subset of AIH) or chronic (with aspecific symptoms such as fatigue and myalgia in AIH or fatigue and pruritus in PBC and PSC). The detection and characterization of non organ specific autoantibodies plays a major role in the diagnostic approach of autoimmune liver disease; anti nuclear reactivities (ANA) and anti smooth muscle antibodies (SMA) mark type 1 AIH, liver kidney microsomal antibody type 1 (LKM1) and liver cytosol type 1 (LC1) are the serological markers of type 2 AIH; antimitochondrial antibodies (AMA) are associated with PBC, while no specific marker is found in PSC, since anticytoplasmic neutrophil antibodies with perinuclear pattern (atypical p-ANCA or p-ANNA) are also detected in a substantial proportion of type 1 AIH cases. Treatment options rely on immunosoppressive therapy (steroids and azathioprine) in AIH and on ursodeoxycholic acid in cholestatic conditions; in all these diseases liver transplantation remains the only therapeutical approach for the end stage of liver disease.

Acquisition and Cure of Autoimmune Disease Following Allogeneic Hematopoietic Stem Cell Transplantation

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Hsin-An Hou

2007-09-01

Full Text Available Hematopoietic stem cell transplantation (HSCT can either cause or eliminate autoimmune disease. Here, we report two cases. One was a 33-year-old woman with myelodysplastic syndrome (refractory anemia who received bone marrow transplantation from her human leukocyte antigen (HLA-identical sister who had a history of Graves' disease. Antithyroid antibodies, including antimicrosomal antibody and antithy-roglobulin antibody, appeared 4 months after transplantation. Clinical hyperthyroidism appeared 7 months after transplantation, and a hypothyroid state was noted 2 months later. The other case was a 50-year-old woman with Sjögren's syndrome and hypothyroidism who was diagnosed with peripheral T cell non-Hodgkin's lymphoma. She received allogeneic peripheral blood stem cell transplantation (PBSCT from her histocompatible sister owing to only partial response to traditional chemotherapy. Cure of lymphoma and remission of Sjögren's syndrome was noted 4 years after PBSCT. These two illustrative cases, one of acquisition of hyperthyroidism and the other of remission of Sjögren's syndrome after transplantation, highlights that HSCT can induce adoptive autoimmune disease or cure coincidental autoimmune disease. Donor selection and attentive monitoring is required in such circumstances.

CD44 antibodies and immune thrombocytopenia in the amelioration of murine inflammatory arthritis.

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Patrick J Mott

Full Text Available Antibodies to CD44 have been used to successfully ameliorate murine models of autoimmune disease. The most often studied disease model has been murine inflammatory arthritis, where a clear mechanism for the efficacy of CD44 antibodies has not been established. We have recently shown in a murine passive-model of the autoimmune disease immune thrombocytopenia (ITP that some CD44 antibodies themselves can induce thrombocytopenia in mice, and the CD44 antibody causing the most severe thrombocytopenia (IM7, also is known to be highly effective in ameliorating murine models of arthritis. Recent work in the K/BxN serum-induced model of arthritis demonstrated that antibody-induced thrombocytopenia reduced arthritis, causing us to question whether CD44 antibodies might primarily ameliorate arthritis through their thrombocytopenic effect. We evaluated IM7, IRAWB14.4, 5035-41.1D, KM201, KM114, and KM81, and found that while all could induce thrombocytopenia, the degree of protection against serum-induced arthritis was not closely related to the length or severity of the thrombocytopenia. CD44 antibody treatment was also able to reverse established inflammation, while thrombocytopenia induced by an anti-platelet antibody targeting the GPIIbIIIa platelet antigen, could not mediate this effect. While CD44 antibody-induced thrombocytopenia may contribute to some of its therapeutic effect against the initiation of arthritis, for established disease there are likely other mechanisms contributing to its efficacy. Humans are not known to express CD44 on platelets, and are therefore unlikely to develop thrombocytopenia after CD44 antibody treatment. An understanding of the relationship between arthritis, thrombocytopenia, and CD44 antibody treatment remains critical for continued development of CD44 antibody therapeutics.

Immunological Reactivity Using Monoclonal and Polyclonal Antibodies of Autoimmune Thyroid Target Sites with Dietary Proteins

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Datis Kharrazian

2017-01-01

Full Text Available Many hypothyroid and autoimmune thyroid patients experience reactions with specific foods. Additionally, food interactions may play a role in a subset of individuals who have difficulty finding a suitable thyroid hormone dosage. Our study was designed to investigate the potential role of dietary protein immune reactivity with thyroid hormones and thyroid axis target sites. We identified immune reactivity between dietary proteins and target sites on the thyroid axis that includes thyroid hormones, thyroid receptors, enzymes, and transport proteins. We also measured immune reactivity of either target specific monoclonal or polyclonal antibodies for thyroid-stimulating hormone (TSH receptor, 5′deiodinase, thyroid peroxidase, thyroglobulin, thyroxine-binding globulin, thyroxine, and triiodothyronine against 204 purified dietary proteins commonly consumed in cooked and raw forms. Dietary protein determinants included unmodified (raw and modified (cooked and roasted foods, herbs, spices, food gums, brewed beverages, and additives. There were no dietary protein immune reactions with TSH receptor, thyroid peroxidase, and thyroxine-binding globulin. However, specific antigen-antibody immune reactivity was identified with several purified food proteins with triiodothyronine, thyroxine, thyroglobulin, and 5′deiodinase. Laboratory analysis of immunological cross-reactivity between thyroid target sites and dietary proteins is the initial step necessary in determining whether dietary proteins may play a potential immunoreactive role in autoimmune thyroid disease.

Evidence Refuting the Existence of Autoimmune/Autoinflammatory Syndrome Induced by Adjuvants (ASIA)

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Ameratunga, Rohan; Gillis, David; Gold, Michael

2017-01-01

Autoimmune/autoinflammatory syndrome induced by adjuvants (ASIA) was described in 2011. Over time the condition and its triggers have broadened to include several autoimmune disorders, the macrophagic myofasciitis syndrome, the Gulf war syndrome, the sick building syndrome, siliconosis...

Patients with autoimmune hepatitis who have antimitochondrial antibodies need long-term follow-up to detect late development of primary biliary cirrhosis.

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Dinani, Amreen M; Fischer, Sandra E; Mosko, Jeff; Guindi, Maha; Hirschfield, Gideon M

2012-06-01

Patients with autoimmune hepatitis (AIH) who have antibodies against mitochondrial proteins (AMA positive) are believed to have an autoimmune syndrome that should be managed as AIH. Of patients with AMA-positive AIH, we report on 3 individuals to demonstrate how autoimmune liver disease can progress over time. Specific features of primary biliary cirrhosis (PBC) overlapped in time in these patients. Our observations indicate the importance of careful follow up of patients with AMA-positive AIH; health care professionals that treat such patients should therefore be aware of longitudinal clinical changes that might indicate development of PBC in this setting. Copyright © 2012 AGA Institute. Published by Elsevier Inc. All rights reserved.

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

International Nuclear Information System (INIS)

Santos Castro, M. dos.

1981-01-01

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

Autoimmune paediatric liver disease.

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Mieli-Vergani, Giorgina; Vergani, Diego

2008-06-07

Liver disorders with a likely autoimmune pathogenesis in childhood include autoimmune hepatitis (AIH), autoimmune sclerosing cholangitis (ASC), and de novo AIH after liver transplantation. AIH is divided into two subtypes according to seropositivity for smooth muscle and/or antinuclear antibody (SMA/ANA, type 1) or liver kidney microsomal antibody (LKM1, type 2). There is a female predominance in both. LKM1 positive patients tend to present more acutely, at a younger age, and commonly have partial IgA deficiency, while duration of symptoms before diagnosis, clinical signs, family history of autoimmunity, presence of associated autoimmune disorders, response to treatment, and long-term prognosis are similar in both groups. The most common type of paediatric sclerosing cholangitis is ASC. The clinical, biochemical, immunological, and histological presentation of ASC is often indistinguishable from that of AIH type 1. In both, there are high IgG, non-organ specific autoantibodies, and interface hepatitis. Diagnosis is made by cholangiography. Children with ASC respond to immunosuppression satisfactorily and similarly to AIH in respect to remission and relapse rates, times to normalization of biochemical parameters, and decreased inflammatory activity on follow up liver biopsies. However, the cholangiopathy can progress. There may be evolution from AIH to ASC over the years, despite treatment. De novo AIH after liver transplantation affects patients not transplanted for autoimmune disorders and is strikingly reminiscent of classical AIH, including elevated titres of serum antibodies, hypergammaglobulinaemia, and histological findings of interface hepatitis, bridging fibrosis, and collapse. Like classical AIH, it responds to treatment with prednisolone and azathioprine. De novo AIH post liver transplantation may derive from interference by calcineurin inhibitors with the intrathymic physiological mechanisms of T-cell maturation and selection. Whether this condition is a

Voltage gated potassium channel antibodies positive autoimmune encephalopathy in a child: A case report and literature review of an under-recognized condition

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Subramanian Ganesan

2013-01-01

Full Text Available Autoimmune limbic encephalitis (LE associated with voltage gated potassium channel antibodies (VGKC-Abs in children is more common than previously thought and is not always paraneoplastic. Non-neoplastic, autoimmune LE associated with VGKC-Abs has been described recently. However, only few case reports in children as the disease is predominantly described in the adult population. It is likely that this type of autoimmune encephalitis is currently under-diagnosed and hence, under-treated, especially in children. We present a 13-year-old previously fit and healthy African girl diagnosed with LE and we reviewed the literature for its current management.

Voltage gated potassium channel antibodies positive autoimmune encephalopathy in a child: A case report and literature review of an under-recognized condition

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Ganesan, Subramanian; Beri, Sushil; Khan, Beri; Hussain, Nahin

2013-01-01

Autoimmune limbic encephalitis (LE) associated with voltage gated potassium channel antibodies (VGKC-Abs) in children is more common than previously thought and is not always paraneoplastic. Non-neoplastic, autoimmune LE associated with VGKC-Abs has been described recently. However, only few case reports in children as the disease is predominantly described in the adult population. It is likely that this type of autoimmune encephalitis is currently under-diagnosed and hence, under-treated, especially in children. We present a 13-year-old previously fit and healthy African girl diagnosed with LE and we reviewed the literature for its current management. PMID:24339586

Mercury and autoimmunity: implications for occupational and environmental health

International Nuclear Information System (INIS)

Silbergeld, Ellen K.; Silva, Ines A.; Nyland, Jennifer F.

2005-01-01

Mercury (Hg) has long been recognized as a neurotoxicant; however, recent work in animal models has implicated Hg as an immunotoxicant. In particular, Hg has been shown to induce autoimmune disease in susceptible animals with effects including overproduction of specific autoantibodies and pathophysiologic signs of lupus-like disease. However, these effects are only observed at high doses of Hg that are above the levels to which humans would be exposed through contaminated fish consumption. While there is presently no evidence to suggest that Hg induces frank autoimmune disease in humans, a recent epidemiological study has demonstrated a link between occupational Hg exposure and lupus. In our studies, we have tested the hypothesis that Hg does not cause autoimmune disease directly, but rather that it may interact with triggering events, such as genetic predisposition, exposure to antigens, or infection, to exacerbate disease. Treatment of mice that are not susceptible to Hg-induced autoimmune disease with very low doses and short term exposures of inorganic Hg (20-200 μg/kg) exacerbates disease and accelerates mortality in the graft versus host disease model of chronic lupus in C57Bl/6 x DBA/2 mice. Furthermore, low dose Hg exposure increases the severity and prevalence of experimental autoimmune myocarditis (induced by immunization with cardiac myosin peptide in adjuvant) in A/J mice. To test our hypothesis further, we examined sera from Amazonian populations exposed to Hg through small-scale gold mining, with and without current or past malaria infection. We found significantly increased prevalence of antinuclear and antinucleolar antibodies and a positive interaction between Hg and malaria. These results suggest a new model for Hg immunotoxicity, as a co-factor in autoimmune disease, increasing the risks and severity of clinical disease in the presence of other triggering events, either genetic or acquired

Pegylated interferon de novo-induce autoimmune haemolytic anaemia in chronic hepatitis C patient

OpenAIRE

Said, Ashraf; Elbahrawy, Ashraf; Alfiomy, Mohamed; Abdellah, Mohamed; Shahat, Khaled; Salah, Mohamed; Mostafa, Sadek; Elwassief, Ahmed; Aboelfotoh, Attef; Abdelhafeez, Hafez; El-Sherif, Assem

2011-01-01

A 55-year-old Egyptian woman with chronic hepatitis C undergoing treatment with pegylated interferon (Peg-IFN) alfa-2a plus ribavirin was referred to our hospital on November 2010 with prolonged easy fatigability and an attack of syncope; she had no prior history of autoimmune disorders or allergy. Laboratory investigations documented the presence of Peg-IFN induced autoimmune haemolytic anaemia and autoimmune thyroiditis. Intravenous γ globulin (IVGG) failed to correct the autoimmune process...

[Autoimmune diseases of the thyroid gland].

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Allelein, S; Feldkamp, J; Schott, M

2017-01-01

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.

[Autoimmune Encephalitis Associated with Malignant Tumors].

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Inuzuka, Takashi

2016-09-01

Autoimmune encephalitis consists of limbic symptoms and signs associated with antibodies against neuronal cell-surface antigens or intracellular antigens. Some cases are known to be associated with anti-channel or anti-receptor-related molecule antibodies. Whether these cases are paraneoplastic depends on the kinds of antigens that the antibodies are produced against. Other cases due to well-characterized onco-neural antibodies are almost always paraneoplastic and are generally resistant to anti-tumor therapy and/or immunotherapy. An exception is anti-Ma2 antibody-positive encephalitis associated with a testicular tumor. Antibodies for intracellular antigens are considered not to be pathogenic. Rather, the T-cell response is thought to be responsible. These antibodies are useful markers for the diagnosis of paraneoplastic disorders and in the search for underlying cancer, as neurological symptoms often precede tumor diagnosis. There is a relationship among onco-neural antibodies, clinical features, tumor types, and response to immunotherapy. Here we describe the characteristics of autoimmune encephalitis cases with antibodies against different intracellular antigens, such as Hu, Ma2, CRMP5, or amphiphysin.

Autoimmune encephalitis and sleep disorders

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Yan HUANG

2017-10-01

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

Anetoderma: Is It a Sign of Autoimmunity?

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Hessa Al Buainain

2009-12-01

Full Text Available Anetoderma is a rare elastolytic disorder characterized by circumscribed areas of flaccid skin due to the loss of elastic tissue in the dermis. Primary anetoderma is frequently observed in patients with autoimmune diseases or abnormalities especially with antiphospholipid antibodies with or without antiphospholipid syndrome. In this case report we discuss a patient with primary anetoderma with positive antithyroid peroxidase antibodies, which is consistent with autoimmune thyroiditis.

[Autoimmune Associated Encephalitis and Dementia].

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Watanabe, Osamu

2016-04-01

Antibodies against various neural surface antigens induce cognitive impairments. Anti-VGKC (voltage gated potassium channel) complex antibodies are well known as one of the causative autoantibodies. An anti-VGKC antibody was identified as the autoantibody in acquired neuromyotonia (Isaacs' syndrome), which causes muscle cramps and difficulty in opening the palm of the hands. However, this antibody also tests positive in autoimmune limbic encephalitis, which has a subacute progress and causes poor memory or epilepsy attacks. Typical cases have a distinctive adult-onset, frequent, brief dystonic seizure semiology that predominantly affects the arms and ipsilateral face. It has now been termed faciobrachial dystonic seizures. In recent years, the true target antigens of the anti-VGKC antibody of this VGKC limbic encephalitis have been recognized as leucine rich glioma inactivated protein (LGI)-1 and others. These antibodies to amnesia-related LGI-1 in limbic encephalitis neutralize the LGI-1-ADAM22 (an anchor protein) interaction and reduce synaptic AMPA receptors. There have been reports of limbic encephalitis associated with anti-VGKC complex antibodies mimicking Creutzfeldt-Jakob disease (CJD). Less than 2% of the patients with sporadic CJD (sCJD) develop serum anti-VGKC complex antibodies and, when positive, only at low titres. Low titres of these antibodies occur only rarely in suspected patients with sCJD, and when present, should be interpreted with caution.

Stress proteins, autoimmunity, and autoimmune disease.

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Winfield, J B; Jarjour, W N

1991-01-01

At birth, the immune system is biased toward recognition of microbial antigens in order to protect the host from infection. Recent data suggest that an important initial line of defense in this regard involves autologous stress proteins, especially conserved peptides of hsp60, which are presented to T cells bearing gamma delta receptors by relatively nonpolymorphic class lb molecules. Natural antibodies may represent a parallel B cell mechanism. Through an evolving process of "physiological" autoreactivity and selection by immunodominant stress proteins common to all prokaryotes, B and T cell repertoires expand during life to meet the continuing challenge of infection. Because stress proteins of bacteria are homologous with stress proteins of the host, there exists in genetically susceptible individuals a constant risk of autoimmune disease due to failure of mechanisms for self-nonself discrimination. That stress proteins actually play a role in autoimmune processes is supported by a growing body of evidence which, collectively, suggests that autoreactivity in chronic inflammatory arthritis involves, at least initially, gamma delta cells which recognize epitopes of the stress protein hsp60. Alternate mechanisms for T cell stimulation by stress proteins undoubtedly also exist, e.g., molecular mimicry of the DR beta third hypervariable region susceptibility locus for rheumatoid arthritis by a DnaJ stress protein epitope in gram-negative bacteria. While there still is confusion with respect to the most relevant stress protein epitopes, a central role for stress proteins in the etiology of arthritis appears likely. Furthermore, insight derived from the work thus far in adjuvant-induced arthritis already is stimulating analyses of related phenomena in autoimmune diseases other than those involving joints. Only limited data are available in the area of humoral autoimmunity to stress proteins. Autoantibodies to a number of stress proteins have been identified in SLE and

Celiac disease in autoimmune cholestatic liver disorders.

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Volta, Umberto; Rodrigo, Luis; Granito, Alessandro; Petrolini, Nunzio; Muratori, Paolo; Muratori, Luigi; Linares, Antonio; Veronesi, Lorenza; Fuentes, Dolores; Zauli, Daniela; Bianchi, Francesco B

2002-10-01

In this study, serological screening for celiac disease (CD) was performed in patients with autoimmune cholestasis to define the prevalence of such an association and to evaluate the impact of gluten withdrawal on liver disease associated with gluten sensitive enteropathy. Immunoglobulin A endomysial, human and guinea pig tissue transglutaminase antibodies, and immunoglobulin A and G gliadin antibodies were sought in 255 patients with primary biliary cirrhosis, autoimmune cholangitis, and primary sclerosing cholangitis. Immunoglobulin A endomysial and human tissue transglutaminase antibodies were positive in nine patients (seven primary biliary cirrhosis, one autoimmune cholangitis, and one primary sclerosing cholangitis), whose duodenal biopsy results showed villous atrophy consistent with CD. Two of these patients had a malabsorption syndrome, and one had iron-deficiency anemia. Clinical and biochemical signs of cholestasis did not improve after gluten withdrawal in the three patients with severe liver disease. A longer follow-up of the six celiac patients with mild liver damage is needed to clarify whether gluten restriction can contribute to slow down the progression of liver disease. The high prevalence of CD (3.5%) in autoimmune cholestasis suggests that serological screening for CD should be routinely performed in such patients by immunoglobulin A endomysial or human tissue transglutaminase antibodies.

Primary biliary cirrhosis--autoimmune hepatitis overlap syndrome associated with dermatomyositis, autoimmune thyroiditis and antiphospholipid syndrome.

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Pamfil, Cristina; Candrea, Elisabeta; Berki, Emese; Popov, Horațiu I; Radu, Pompilia I; Rednic, Simona

2015-03-01

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.

Clearance of a monoclonal anti-DNA antibody following administration of DNA in normal and autoimmune mice

International Nuclear Information System (INIS)

Jones, F.S.; Pisetsky, D.S.; Kurlander, R.J.

1986-01-01

To study the assembly of DNA-anti-DNA complexes in vivo, we have measured the clearance from blood and organ localization of a murine IgG2a monoclonal anti-DNA antibody, called 6/0, following the infusion of DNA intravenously or intraperitoneally. Intraperitoneal DNA caused a profound acceleration of 6/0 anti-DNA clearance that was dose dependent and demonstrable after the infusion of as little as 1.9 microgram per gram of body weight of single-stranded DNA. The antibody was cleared primarily in the liver without increased deposition in the kidney. Intraperitoneal infusions of DNA also accelerated the clearance of 6/0 in autoimmune MRL-lpr/lpr mice. In contrast, intravenous DNA given in comparable doses caused only a slight increase in 6/0 antibody clearance; this accelerated clearance was seen only at low antigen doses and only during the first 10 min following DNA infusion. Using double-radiolabeling techniques, 6/0 and Cl.18, an IgG2ak myeloma protein without anti-DNA activity, were found to disappear from blood at a comparable rate in both B6D2 mice and MRL-lpr/lpr mice. These results suggest that the DNA-anti-DNA immune complexes can form in vivo but that this process is profoundly affected by the manner in which DNA enters the circulation. In addition, the results suggest that DNA-dependent clearance is not a major pathway for anti-DNA metabolism in normal or at least one strain of autoimmune mice

Antibodies to Lactobacilli and Bifidobacteria in young children with different propensity to develop islet autoimmunity.

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Talja, Ija; Kubo, Anna-Liisa; Veijola, Riitta; Knip, Mikael; Simell, Olli; Ilonen, Jorma; Vähä-Mäkilä, Mari; Sepp, Epp; Mikelsaar, Marika; Utt, Meeme; Uibo, Raivo

2014-01-01

The intestinal microbiota is essential to the maturation and homeostasis of the immune system. Immunoblot assays were used to establish the prevalence of serum IgG, IgM, and IgA antibodies specific for Bifidobacterium adolescentis, Bifidobacterium longum, and Lactobacillus rhamnosus GG proteins in young children presenting with or without type 1 diabetes (T1D). We demonstrated that children between the ages of 6 and 12 months had a substantial increase in the frequency of IgG antibodies specific for L. rhamnosus GG proteins. We measured IgG, IgM, and IgA class antibody reactivity against B. adolescentis DSM 20083, B. adolescentis DSM 20086, and B. longum DSM 20088 proteins demonstrating significantly higher IgA responses against B. adolescentis DSM 20083 strain proteins in children who developed islet autoimmunity and T1D later in life. B. adolescentis strains showed more IgM type antibodies in children who developed T1D later in life, but the difference was not statistically significant. B. longum proteins were recognized by IgG and IgA antibodies to a higher extent compared to other bacteria studied. These results confirm that differences in immune reactivity against some commensal strains in young children may represent a different risk factor for developing T1D.

Antibodies to filamentous actin (F-actin) in type 1 autoimmune hepatitis.

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Granito, A; Muratori, L; Muratori, P; Pappas, G; Guidi, M; Cassani, F; Volta, U; Ferri, A; Lenzi, M; Bianchi, F B

2006-03-01

To evaluate the diagnostic significance of anti-filamentous actin antibodies (A-FAA) assessed with a commercial ELISA in comparison with immunofluorescence reactivity and patterns of anti-smooth muscle antibodies (SMA); and to correlate A-FAA positivity with clinical, immunogenetic, laboratory, and histological features in patients with autoimmune hepatitis type 1 (AIH-1). We studied 78 consecutive untreated AIH-1 patients and 160 controls: 22 with autoimmune hepatitis type 2 (AIH-2), 51 with hepatitis C, 17 with coeliac disease (CD), 20 with primary biliary cirrhosis (PBC) and 50 blood donors. SMA was evaluated by indirect immunofluorescence (IIF) on frozen sections of rat tissues, and A-FAA with a modified commercial ELISA. SMA was detected by IIF in 61 (78%) of 78 AIH-1 patients, of whom 47 (60%) had the SMA-T/G and 14 (18%) the SMA-V pattern. Of the pathological controls, 32 (20%) had the SMA-V pattern (25 with hepatitis C, 2 with AIH-2, 2 with PBC, 3 with CD). A-FAA were present in 55 AIH-1 patients (70.5%; 46 with SMA-T/G, 7 with SMA-V, and 2 SMA-negative), and in 10 controls (6%), of whom five had hepatitis C, two AIH-2, two PBC and one CD. The association between A-FAA and the SMA-T/G pattern was statistically significant (p<0.0001). A-FAA levels were higher in SMA-T/G positive than SMA-V positive AIH-1 patients and controls (p<0.0001). A-FAA positivity was significantly associated with higher gamma-globulin and IgG levels, but did not correlate with other considered parameters. The modified A-FAA ELISA strictly correlates with the SMA-T/G pattern and is a reliable and operator independent assay for AIH-1. Detection of A-FAA, even if devoid of prognostic relevance, may be useful when interpretative doubts of standard IIF arise.

Antibodies to filamentous actin (F‐actin) in type 1 autoimmune hepatitis

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Granito, A; Muratori, L; Muratori, P; Pappas, G; Guidi, M; Cassani, F; Volta, U; Ferri, A; Lenzi, M; Bianchi, F B

2006-01-01

Aims To evaluate the diagnostic significance of anti‐filamentous actin antibodies (A‐FAA) assessed with a commercial ELISA in comparison with immunofluorescence reactivity and patterns of anti‐smooth muscle antibodies (SMA); and to correlate A‐FAA positivity with clinical, immunogenetic, laboratory, and histological features in patients with autoimmune hepatitis type 1 (AIH‐1). Methods We studied 78 consecutive untreated AIH‐1 patients and 160 controls: 22 with autoimmune hepatitis type 2 (AIH‐2), 51 with hepatitis C, 17 with coeliac disease (CD), 20 with primary biliary cirrhosis (PBC) and 50 blood donors. SMA was evaluated by indirect immunofluorescence (IIF) on frozen sections of rat tissues, and A‐FAA with a modified commercial ELISA. Results SMA was detected by IIF in 61 (78%) of 78 AIH‐1 patients, of whom 47 (60%) had the SMA‐T/G and 14 (18%) the SMA‐V pattern. Of the pathological controls, 32 (20%) had the SMA‐V pattern (25 with hepatitis C, 2 with AIH‐2, 2 with PBC, 3 with CD). A‐FAA were present in 55 AIH‐1 patients (70.5%; 46 with SMA‐T/G, 7 with SMA‐V, and 2 SMA‐negative), and in 10 controls (6%), of whom five had hepatitis C, two AIH‐2, two PBC and one CD. The association between A‐FAA and the SMA‐T/G pattern was statistically significant (p<0.0001). A‐FAA levels were higher in SMA‐T/G positive than SMA‐V positive AIH‐1 patients and controls (p<0.0001). A‐FAA positivity was significantly associated with higher γ‐globulin and IgG levels, but did not correlate with other considered parameters. Conclusion The modified A‐FAA ELISA strictly correlates with the SMA‐T/G pattern and is a reliable and operator independent assay for AIH‐1. Detection of A‐FAA, even if devoid of prognostic relevance, may be useful when interpretative doubts of standard IIF arise. PMID:16505279

Arthrogenicity of type II collagen monoclonal antibodies associated with complement activation and antigen affinity

OpenAIRE

Koobkokkruad, Thongchai; Kadotani, Tatsuya; Hutamekalin, Pilaiwanwadee; Mizutani, Nobuaki; Yoshino, Shin

2011-01-01

Abstract Background The collagen antibody-induced arthritis (CAIA) model, which employs a cocktail of monoclonal antibodies (mAbs) to type II collagen (CII), has been widely used for studying the pathogenesis of autoimmune arthritis. In this model, not all mAbs to CII are capable of inducing arthritis because one of the initial events is the formation of collagen-antibody immune complexes on the cartilage surface or in the synovium, and subsequent activation of the complement by the complexes...

Loss of Roquin induces early death and immune deregulation but not autoimmunity

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Bertossi, Arianna; Aichinger, Martin; Sansonetti, Paola; Lech, Maciej; Neff, Frauke; Pal, Martin; Wunderlich, F. Thomas; Anders, Hans-Joachim; Klein, Ludger

2011-01-01

The substitution of one amino acid in the Roquin protein by the sanroque mutation induces a dramatic autoimmune syndrome in mice. This is believed to occur through ectopic expression of inducible T cell co-stimulator (ICOS) and unrestrained differentiation of follicular T helper cells, which induce spontaneous germinal center reactions to self-antigens. In this study, we demonstrate that tissue-specific ablation of Roquin in T or B cells, in the entire hematopoietic system, or in epithelial cells of transplanted thymi did not cause autoimmunity. Loss of Roquin induced elevated expression of ICOS through T cell–intrinsic and –extrinsic mechanisms, which itself was not sufficient to break self-tolerance. Instead, ablation of Roquin in the hematopoietic system caused defined changes in immune homeostasis, including the expansion of macrophages, eosinophils, and T cell subsets, most dramatically CD8 effector–like T cells, through cell-autonomous and nonautonomous mechanisms. Germline Roquin deficiency led to perinatal lethality, which was partially rescued on the genetic background of an outbred strain. However, not even complete absence of Roquin resulted in overt self-reactivity, suggesting that the sanroque mutation induces autoimmunity through an as yet unknown mechanism. PMID:21844204

Low-level laser in the treatment of patients with hypothyroidism induced by chronic autoimmune thyroiditis: a randomized, placebo-controlled clinical trial.

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Höfling, Danilo B; Chavantes, Maria Cristina; Juliano, Adriana G; Cerri, Giovanni G; Knobel, Meyer; Yoshimura, Elisabeth M; Chammas, Maria Cristina

2013-05-01

Chronic autoimmune thyroiditis (CAT) is the most common cause of acquired hypothyroidism, which requires lifelong levothyroxine replacement therapy. Currently, no effective therapy is available for CAT. Thus, the objective of this study was to evaluate the efficacy of low-level laser therapy (LLLT) in patients with CAT-induced hypothyroidism by testing thyroid function, thyroid peroxidase antibodies (TPOAb), thyroglobulin antibodies (TgAb), and ultrasonographic echogenicity. A randomized, placebo-controlled trial with a 9-month follow-up was conducted from 2006 to 2009. Forty-three patients with a history of levothyroxine therapy for CAT-induced hypothyroidism were randomly assigned to receive either 10 sessions of LLLT (830 nm, output power of 50 mW, and fluence of 707 J/cm(2); L group, n=23) or 10 sessions of a placebo treatment (P group, n=20). The levothyroxine was suspended 30 days after the LLLT or placebo procedures. Thyroid function was estimated by the levothyroxine dose required to achieve normal concentrations of T3, T4, free-T4 (fT4), and thyrotropin after 9 months of postlevothyroxine withdrawal. Autoimmunity was assessed by measuring the TPOAb and TgAb levels. A quantitative computerized echogenicity analysis was performed pre- and 30 days postintervention. The results showed a significant difference in the mean levothyroxine dose required to treat the hypothyroidism between the L group (38.59 ± 20.22 μg/day) and the P group (106.88 ± 22.90 μg/day, Phypothyroidism.

Detection of anti-neutrophil antibodies in autoimmune neutropenia of infancy: a multicenter study.

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Sella, Ruti; Flomenblit, Lena; Goldstein, Itamar; Kaplinsky, Chaim

2010-02-01

Autoimmune neutropenia of infancy is caused by neutrophil-specific autoantibodies. Primary AIN is characterized by neutrophil count familial or congenital neutropenias. To further assure the quality of the new test, we retested six samples previously tested by the gold standard method. All medical files were screened and clinical outcomes were recorded. Our method showed specificity of 85%, sensitivity of 62.5%, and a positive predictive value of 91.8%, values quite similar to those obtained by more traditional methods. The new method showed high specificity for detection of anti-neutrophil antibodies in the appropriate clinical setting and could be an effective tool for clinical decision making.

Origin and pathogenesis of antiphospholipid antibodies

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C.M. Celli

1998-06-01

Full Text Available Antiphospholipid antibodies (aPL are a heterogeneous group of antibodies that are detected in the serum of patients with a variety of conditions, including autoimmune (systemic lupus erythematosus, infectious (syphilis, AIDS and lymphoproliferative disorders (paraproteinemia, myeloma, lymphocytic leukemias. Thrombosis, thrombocytopenia, recurrent fetal loss and other clinical complications are currently associated with a subgroup of aPL designating the antiphospholipid syndrome. In contrast, aPL from patients with infectious disorders are not associated with any clinical manifestation. These findings led to increased interest in the origin and pathogenesis of aPL. Here we present the clinical features of the antiphospholipid syndrome and review the origin of aPL, the characteristics of experimentally induced aPL and their historical background. Within this context, we discuss the most probable pathogenic mechanisms induced by these antibodies.

Association of autoimmune hepatitis and multiple sclerosis: a coincidence?

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Marta Sofia Mendes Oliveira

2015-09-01

Full Text Available Autoimmune hepatitis is a chronic liver inflammation resulting from deregulation of immune tolerance mechanisms. Multiple sclerosis is also an inflammatory disease in which the insulating covers of nerve cells in the brain and spinal cord are damaged. Here we present a case of an 18 year old female with multiple sclerosis was treated with glatiramer acetate and with interferon beta 1a at our hospital. Seven months after initiating treatment, liver dysfunction occurred. Clinical and laboratory findings were suggestive of drug-induced hepatitis, which led to discontinuation of treatment with interferon. Facing a new episode of acute hepatitis one year later, she was subjected to a liver biopsy, and the analysis of autoantibodies was positive for smooth muscle antibodies. Given the diagnosis of autoimmune hepatitis she started therapy with prednisolone and azathioprine, with good clinical and analytical response. Besides, the demyelinating lesions of multiple sclerosis became lower. In conclusion, there are only a few cases that describe the association of autoimmune hepatitis with multiple sclerosis, and there is a chance both diseases have the same autoimmune inflammatory origin.

Thyroid Autoimmunity in Girls with Turner Syndrome.

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Witkowska-Sędek, Ewelina; Borowiec, Ada; Kucharska, Anna; Chacewicz, Karolina; Rumińska, Małgorzata; Demkow, Urszula; Pyrżak, Beata

2017-01-01

Turner syndrome is associated with increased incidence of autoimmune diseases, especially those of the thyroid gland. The aim of this study was to assess the prevalence of thyroid autoimmunity among pediatric patients with Turner syndrome. The study was retrospective and included 41 girls with Turner syndrome aged 6-18 years. Free thyroxine (FT4), thyroid stimulating hormone (TSH), anti-thyroid peroxidase (TPO-Ab) antibodies, anti-thyroglobulin (TG-Ab) antibodies, and karyotype were investigated. The correlation between karyotype and incidence of thyroid autoimmunity was also examined. Eleven patients (26.8%) were positive for TPO-Ab and/or TG-Ab. Three girls from that subgroup were euthyroid, 5 had subclinical hypothyroidism, and 3 were diagnosed with overt hypothyroidism. Out of these 11 patients affected by thyroid autoimmunity, 6 girls had mosaic karyotype with X-isochromosome (n = 4) or with deletions (n = 2), and 5 had the 45,X karyotype. The study findings confirmed a high incidence of thyroid autoimmunity in girls with Turner syndrome, but we failed to observe an association between the incidence of thyroid autoimmunity and karyotype. We conclude that it is important to monitor thyroid function in patients with Turner syndrome because they are prone to develop hypothyroidism.

KADAR ANTIBODI-TIROPEROKSIDASE DAN ANTIBODI-TIROGLOBULIN PADA WANITA USIA SUBUR DI DAERAH ENDEMlS GAKI

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Agus Wibowo

2012-10-01

Full Text Available Background: Thyroid hormones play a critical role in human. Disorders of the thyroid gland result primary from autoimmune processes that either stimulate the over production of thyroid hormones (hyperthyroid or causes glandular destruction and hormones deficiency (hypothyroid. Autoimmune Thyroid Disease (AITD a common organ specific autoimmune disorder is seen mostly in women. AITD are complex disease that are caused by an interaction between susceptibility genes and environmental trigger such dietary iodine. The development of antibodies to Thyroid peroxidase (TPO and Thyroglobulin (TG is the main hall mark of AITD. Method: 'Thirty respondents from were analyzed. The blood were collected for TSH, FreeT4, Tyroglobulin Antibody and Tyroperoxidase Antibody analyzed and DNA isolation. Circulating TSH, FreeT4, autoantibodies to TPO and TG are measured by ELISA. Result: 50% respondent in normal thyroid hormones and 50% in hypothyroid and hyperthyroid status. TPO antibodies  and thyroglobulin antibodies found in all of respondent with thyroid disorder. Conclusion: Antibodies to TPO and TG is seen in respondent with thyroid disorder   Keywords: AITD, TSH, FreeT4, TPO antibodies, TG antibodies.

IgG4 autoantibodies are inhibitory in the autoimmune disease bullous pemphigoid.

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Zuo, Yagang; Evangelista, Flor; Culton, Donna; Guilabert, Antonio; Lin, Lin; Li, Ning; Diaz, Luis; Liu, Zhi

2016-09-01

The IgG4 subclass of antibodies exhibits unique characteristics that suggest it may function in an immunoregulatory capacity. The inhibitory function of IgG4 has been well documented in allergic disease by the demonstration of IgG4 blocking antibodies, but similar functions have not been explored in autoimmune disease. Bullous pemphigoid (BP) is a subepidermal autoimmune blistering disease characterized by autoantibodies directed against BP180 and an inflammatory infiltrate including eosinophils and neutrophils. Animal models have revealed that the NC16A region within BP180 harbors the critical epitopes necessary for autoantibody mediated disease induction. BP180 NC16A-specific IgG belong to the IgG1, IgG3, and IgG4 subclasses. The purpose of this study was to determine effector functions of different IgG subclasses of NC16A-specific autoantibodies in BP. We find that IgG4 anti-NC16A autoantibodies inhibit the binding of IgG1 and IgG3 autoantibodies to the NC16A region. Moreover, IgG4 anti-NC16A blocks IgG1 and IgG3 induced complement fixation, neutrophil infiltration, and blister formation clinically and histologically in a dose-dependent manner following passive transfer to humanized BP180-NC16A mice. These findings highlight the inhibitory role of IgG4 in autoimmune disease and have important implications for the treatment of BP as well as other antibody mediated inflammatory and autoimmune diseases. Copyright © 2016 Elsevier Ltd. All rights reserved.

AUTOIMMUNITY AS A POSSIBLE MECHANISM OF PROTACTIN-INDUCED PROSTATITIS

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AUTOIMMUNITY AS A POSSIBLE MECHANISM OF PROLACTIN-INDUCED PROSTATITIS. RW Luebke, CB Copeland, and LR Bishop. US EPA, Research Triangle Park, NCStoker et al. reported inflammation of the lateral prostate (LP) lobes in 120 day old Wistar rats after manipulation of prolac...

Novel biomarkers of mercury-induced autoimmune dysfunction: a Cross-sectional study in Amazonian Brazil

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Motts, Jonathan A.; Shirley, Devon L.; Silbergeld, Ellen K.; Nyland, Jennifer F.

2014-01-01

Mercury is an ubiquitous environmental contaminant, causing both neurotoxicity and immunotoxicity. Given its ability to amalgamate gold, mercury is frequently used in small-scale artisanal gold mining. We have previously reported that elevated serum titers of antinuclear autoantibodies (ANA) are associated with mercury exposures of miners in gold mining. The goal of this project was to identify novel serum biomarkers of mercury-induced immunotoxicity and autoimmune dysregulation. We conducted an analysis of serum samples from a cross-sectional epidemiological study on miners working in Amazonian Brazil. In proteomic screening analyses, samples were stratified based on mercury concentrations and ANA titer and a subset of serum samples (N=12) were profiled using Immune Response Biomarker Profiling ProtoArray protein microarray for elevated autoantibodies. Of the up-regulated autoantibodies in the mercury-exposed cohort, potential target autoantibodies were selected based on relevance to pro-inflammatory and macrophage activation pathways. ELISAs were developed to test the entire sample cohort (N=371) for serum titers to the highest of these autoantibodies (anti-glutathione S-transferase alpha, GSTA1) identified in the high mercury/high ANA group. We found positive associations between elevated mercury exposure and up-regulated serum titers of 3760 autoantibodies as identified by ProtoArray. Autoantibodies identified as potential novel biomarkers of mercury-induced immunotoxicity include antibodies to the following proteins: GSTA1, tumor necrosis factor ligand superfamily member 13, linker for activation of T cells, signal peptide peptidase like 2B, stimulated by retinoic acid 13, and interferon induced transmembrane protein. ELISA analyses confirmed that mercury-exposed gold miners had significantly higher serum titers of anti-GSTA1 autoantibody [unadjusted odds ratio = 89.6; 95% confidence interval: 27.2, 294.6] compared to emerald miners (referent population

[Auto-immune disorders as a possible cause of neuropsychiatric syndromes].

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Martinez-Martinez, P; Molenaar, P C; Losen, M; Hoffmann, C; Stevens, J; de Witte, L D; van Amelsvoort, T; van Os, J; Rutten, B P F

2015-01-01

Changes that occur in the behaviour of voltage-gated ion channels and ligand-gated receptor channels due to gene mutations or auto-immune attack are the cause of channelopathies in the central and peripheral nervous system. Although the relation between molecular channel defects and clinical symptoms has been explained in the case of many neuromuscular channelopathies, the pathophysiology of auto-immunity in neuropsychiatric syndromes is still unclear. To review recent findings regarding neuronal auto-immune reactions in severe neuropsychiatric syndromes. Using PubMed, we consulted the literature published between 1990 and August 2014 relating to the occurrence of auto-immune antibodies in severe and persistent neuropsychiatric syndromes. Auto-antibodies have only limited access to the central nervous system, but if they do enter the system they can, in some cases, cause disease. We discuss recent findings regarding the occurrence of auto-antibodies against ligand-activated receptor channels and potassium channels in neuropsychiatric and neurological syndromes, including schizophrenia and limbic encephalitis. Although the occurrence of several auto-antibodies in schizophrenia has been confirmed, there is still no proof of a causal relationship in the syndrome. We still have no evidence of the prevalence of auto-immunity in neuropsychiatric syndromes. The discovery that an antibody against an ion channel is associated with some neuropsychiatric disorders may mean that in future it will be possible to treat patients by means of immunosuppression, which could lead to an improvement in a patient's cognitive abilities.

Cutting-edge issues in autoimmune orchitis.

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

2012-04-01

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

Autoimmune encephalitis associated with voltage-gated potassium channels-complex and leucine-rich glioma-inactivated 1 antibodies

DEFF Research Database (Denmark)

Celicanin, Marko; Blaabjerg, M; Maersk-Moller, C

2017-01-01

BACKGROUND AND PURPOSE: The aim of this study was to describe clinical and paraclinical characteristics of all Danish patients who tested positive for anti-voltage-gated potassium channels (VGKC)-complex, anti-leucine-rich glioma-inactivated 1 (LGI1) and anti-contactin-associated protein-2......, electroencephalography and (18) F-fluorodeoxyglucose positron emission tomography scans were re-evaluated by experts in the field. RESULTS: A total of 28/192 patients tested positive for VGKC-complex antibodies by radioimmunoassay and indirect immunofluorescence; 17 had antibodies to LGI1 and 6/7 of the available....... CONCLUSIONS: Patients diagnosed with anti-LGI1 autoimmune encephalitis increased significantly from 2009 to 2014, probably due to increased awareness. In contrast to seropositive anti-VGKC-complex patients, all anti-LGI1-positive patients presented with a classical limbic encephalitis. The majority...

Autoimmune Cytopenias In Common Variable Immunodeficiency (CVID

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Roshini Sarah Abraham

2012-07-01

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.

Heterogeneous stock mice are susceptible to encephalomyelitis and antibody-initiated arthritis but not to collagen- and G6PI-induced arthritis.

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Klaczkowska, D; Raposo, B; Nandakumar, K S

2011-01-01

The strategy of using heterogeneous stock (HS) mice has proven to be successful in fine mapping of quantitative trait loci in complex diseases. However, whether these mice can be used for arthritis, encephalomyelitis and autoimmune phenotypes has not been addressed. Here, we screened the Northport HS mice for arthritis phenotypes using three different models: collagen-induced arthritis (CIA), using rat, bovine or chicken collagen type II (CII); recombinant human glucose-6-phosphate isomerase (G6PI)-induced arthritis; and collagen antibody-induced arthritis (CAIA). Irrespective of the origin of collagen, we found HS mice to be fairly resistant to CIA and G6PI-induced arthritis, despite the development of antibodies against the respective antigens. On the other hand, HS mice were found to be susceptible for CAIA. Similarly, these mice developed encephalomyelitis (EAE) induced either with mouse or rat spinal cord homogenate (SCH), or with recombinant rat myelin oligodendrocyte glycoprotein, with elevated antibody levels against CNS proteins. Accordingly, we conclude that the use of HS mice for fine mapping and positional cloning of gene(s) involved in CAIA and EAE is possible, but not for collagen- and G6PI-induced arthritis. © 2011 The Authors. Scandinavian Journal of Immunology © 2011 Blackwell Publishing Ltd.

Autoimmune hepatitis.

Science.gov (United States)

Vergani, D; Mieli-Vergani, G

2004-06-01

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

Rehabilitation or the death penalty: autoimmune B cells in the dock.

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Dahal, Lekh N; Cragg, Mark S

2015-03-01

CD20-based monoclonal antibodies have become established as treatments for lymphoma, rheumatoid arthritis, systemic lupus erythematosus, vasculitis and dermatomyositis, with the principle therapeutic mechanism relating to B-cell depletion through effector cell engagement. An article by Brühl et al. in this issue of the European Journal of Immunology [Eur. J. Immunol. 2015. 45: 705-715] reveals a fundamentally distinct mechanism of silencing autoimmune B-cell responses. Rather than B-cell depletion, the authors use anti-CD79b antibodies to induce B-cell tolerance and suppress humoral immune responses against collagen to prevent the development of arthritis in mice. Here we highlight the differences in the mechanisms used by anti-CD20 and anti-CD79b Ab therapy and discuss why depletion of B cells may not be required to treat autoimmune arthritis and other B-cell-associated pathologies. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Autoimmune liver disease in children.

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Mieli-Vergani, G; Vergani, D

2003-03-01

Autoimmune liver disorders are characterised by an inflammatory liver histology, circulating non-organ specific autoantibodies and increased levels of immunoglobulin G (IgG) in the absence of a known aetiology. They respond to immunosuppressive treatment, which should be instituted as soon as diagnosis is made. Liver disorders with a likely autoimmune pathogenesis include autoimmune hepatitis (AIH) and autoimmune sclerosing cholangitis (ASC). Two types of AIH are recognised according to seropositivity for smooth muscle and/or antinuclear antibody (SMA/ANA, type 1) or liver kidney microsomal antibody (LKM1, type 2). There is a female predominance in both. LKM1-positive patients tend to present more acutely, at a younger age, and commonly have immunoglobulin A (IgA) deficiency, while duration of symptoms before diagnosis, clinical signs, family history of autoimmunity, presence of associated autoimmune disorders, response to treatment and long-term prognosis are similar in both groups. The most common type of paediatric sclerosing cholangitis is ASC. The clinical, biochemical, immunological and histological presentation of ASC is often indistinguishable from that of AIH. In both, there are high IgG, non-organ specific autoantibodies and interface hepatitis. Diagnosis is made by cholangiography. Children with ASC respond to immunosuppression satisfactorily and similarly to AIH in respect to remission and relapse rates, times to normalisation of biochemical parameters and decreased inflammatory activity on follow-up liver biopsies. However, the cholangiopathy can progress and there may be an evolution from AIH to ASC over the years, despite treatment. Whether the juvenile autoimmune form of sclerosing cholangitis and AIH are 2 distinct entities, or different aspects of the same condition, remains to be elucidated.

Alpha-Methyldopa-Induced Autoimmune Hemolytic Anemia in the Third Trimester of Pregnancy

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Charalampos Grigoriadis

2013-01-01

Full Text Available Alpha-methyldopa has been demonstrated to be safe for use during pregnancy and is now used to treat gestational hypertension. In pregnancy, alpha-methyldopa-induced autoimmune hemolytic anemia does not have typical features and the severity of symptoms ranges from mild fatigue to dyspnea, respiratory failure, and death if left untreated. A case of alpha-methyldopa-induced autoimmune hemolytic anemia in a 36-year-old gravida 2, para 1 woman at 37+6 weeks of gestation is reported herein along with the differential diagnostic procedure and the potential risks to the mother and the fetus.

Anti-soluble liver antigen/liver-pancreas (SLA/LP) antibodies in pediatric patients with autoimmune hepatitis.

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Vitozzi, Susana; Djilali-Saiah, Idriss; Lapierre, Pascal; Alvarez, Fernando

2002-12-01

Antibodies against soluble liver antigen/liver-pancreas (SLA/LP) have been associated with severe autoimmune hepatitis (AIH) and poor outcome, but most of these reports have focused on adult patients. The aim of this study was to assess the prevalence and clinical significance of anti-SLA/LP antibodies in a pediatric population with AIH. We developed a quantitative enzyme-linked immunoassay (ELISA), a Western blot (WB) and an immunoprecipitation assay (IPA) based on recombinant cDNA from activated Jurkat cells. The specificity of these tests was validated by testing 200 serum samples from healthy subjects, and from patients with liver and non-liver diseases. Anti-SLA/LP antibodies were found in patients with type 1 and type 2 AIH. The prevalence of these antibodies in patients with type 1 AIH was: 42% when tested by ELISA, 15% by WB and 50% by IPA. In patients with type 2 AIH, the prevalence rates were 42% by ELISA, 18% by WB and 44% by IPA. The mean titer values for anti-SLA/LP antibodies was significantly higher in type 2 AIH (1:1,300 +/- 339) than in type 1 AIH (1:600 +/- 71; p LKM1) and anti-liver cytosol type 1 (LC1) antibodies in sera. The presence of anti-SLA/LP showed a significant female preponderance in type 1 and 2 AIH patients (p = 0.0003 and p = 0.003, respectively), and was significantly correlated with a lower age at diagnosis (p = 0.05) in type 1 AIH patients. In conclusion, anti-SLA/LP antibodies in pediatric patients are associated with both type 1 and 2 AIH.

Activation-induced cytidine deaminase deficiency causes organ-specific autoimmune disease.

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Koji Hase

Full Text Available Activation-induced cytidine deaminase (AID expressed by germinal center B cells is a central regulator of somatic hypermutation (SHM and class switch recombination (CSR. Humans with AID mutations develop not only the autosomal recessive form of hyper-IgM syndrome (HIGM2 associated with B cell hyperplasia, but also autoimmune disorders by unknown mechanisms. We report here that AID-/- mice spontaneously develop tertiary lymphoid organs (TLOs in non-lymphoid tissues including the stomach at around 6 months of age. At a later stage, AID-/- mice develop a severe gastritis characterized by loss of gastric glands and epithelial hyperplasia. The disease development was not attenuated even under germ-free (GF conditions. Gastric autoantigen -specific serum IgM was elevated in AID-/- mice, and the serum levels correlated with the gastritis pathological score. Adoptive transfer experiments suggest that autoimmune CD4+ T cells mediate gastritis development as terminal effector cells. These results suggest that abnormal B-cell expansion due to AID deficiency can drive B-cell autoimmunity, and in turn promote TLO formation, which ultimately leads to the propagation of organ-specific autoimmune effector CD4+ T cells. Thus, AID plays an important role in the containment of autoimmune diseases by negative regulation of autoreactive B cells.

Eosinophils in Autoimmune Diseases

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Daniela Čiháková

2017-04-01

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

Eosinophils in Autoimmune Diseases

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

2017-01-01

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

Antituberculosis Drug-Induced Liver Injury with Autoimmune Features: Facing Diagnostic and Treatment Challenges

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Maria Adriana Rangel

2017-01-01

Full Text Available The authors present a case report of antituberculosis drug-induced liver injury that offered diagnostic challenges (namely, the possibility of drug-induced autoimmune hepatitis and treatment difficulties.

A unique combination of autoimmune limbic encephalitis, type 1 diabetes, and Stiff person syndrome associated with GAD-65 antibody

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Chandra Mohan Sharma

2016-01-01

Full Text Available Antibodies to GAD-65 have been implicated in the pathogenesis of type 1 diabetes , limbic encephalitis and Stiff person syndrome, however these diseases rarely occur concurrently. We intend to present a rare case of 35 year old female who was recently diagnosed as having type 1 diabetes presented with 1½ month history of recurrent seizures, subacute onset gait ataxia, dysathria, psychiatric disturbance and cognitive decline. No tumor was found on imaging and the classic paraneoplastic panel was negative. Cerebrospinal fluid and blood was positive for GAD-65 antibodies.Patient showed significant improvement with immunomodulatory therapy. Association of GAD-65 antibodies has been found with various disorders including type 1 diabetes, limbic encephalitis, Stiff person syndrome,cerebellar ataxia and palatal myoclonus.This case presents with unique combination of type 1 diabetes, Stiff person syndrome and limbic encephalitis associated with GAD-65 antibodies that is responsive to immunotherapy. It also highlights the emerging concept of autoimmunity in the causation of various disorders and there associations.

Anti-synthetase syndrome associated with anti PL-12 and anti-Signal recognition particle antibodies and a necrotizing auto-immune myositis.

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Malkan, Ashish; Cappelen-Smith, Cecilia; Beran, Roy; Griffith, Neil; Toong, Catherine; Wang, Min-Xia; Cordato, Dennis

2015-02-01

We report a 37-year-old woman with a 2 month history of proximal muscle weakness and extremely high creatine kinase (21,808 U/L) due to necrotizing auto-immune myositis (NAM) in association with anti-synthetase syndrome. Myositis-specific auto-immune antibody panel was positive for anti-Signal recognition particle and anti-PL-12. CT scan of the chest confirmed interstitial lung disease. Prednisolone, intravenous immunoglobulin and cyclophosphamide therapy was given with gradual improvement. This patient is notable for the unusual combination of NAM and anti-synthetase syndrome with the rare finding of two myositis-specific autoantibodies, which directed testing for associated extramuscular features and management with more aggressive immunotherapy. Copyright © 2014 Elsevier Ltd. All rights reserved.

The Roles of the TSH Receptor Antibodies in Autoimmune Thyroid Diseases

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Koh, Chang Soon

1986-01-01

To evaluate the clinical and pathogenetic roles of TSH receptor antibodies in autoimmune thyroid diseases, TBII were measured by TSH-radioreceptor assay methods in 352 patients with Graves disease, 108 patients with other thyroid diseases and 69 normal persons. The normal range of TBII activity was less than 15%. The frequencies of detectable TBIl in 169 patients with untreated Graves disease, 31 patients with hyperthyroidism under treatment and 70 patients with euthyroidism under treatment were 92.4%, 87.1% and 54.3% respectively. However 12 (21.8%) out of 55 patients who have been in remission more than one year after discontinuation of antithyroid drugs treatment had detectable TBII activities in their sera. In 196 patients with untreated Graves disease, the frequency of TBII increased by increasing size of goiter and the frequency of proptosis was significantly high in patients whose TBII activities were more than 60%. TBll activities were roughly correlated with total T 3 ,T 4 and free T 4 , index but low γ 2 value(less than 0.1). In 67 patients with Graves' disease who were positive TB1I before antithyroid drugs treatment, TBII activities began to decrease from the third months and it was converted to negative in 35.8% of patients at 12 months after treatment. There were no significant differences of the declining and disappearing rates of TBII activities between high dose and conventional dose groups. TBII activities were significantly increased initially (2-4 months) and then began to decrease from 5-9 months after 131 I treatment. There were two groups, one whose TBII activities decreased gradually and the other did not change until 12 months after subtotal thyroidectomy. Although preoperative clinical and laboratory findings of both groups were not different, TBII activities of non-decreasing group were significantly higher than those of decreasing group(74.6+18.6% vs 39.2+15.2%; P(0.01). Thirty three(55.9%) out of 59 patients with Graves disease

The Role of Pathogenic Autoantibodies in Autoimmunity

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Merrill J. Rowley

2015-11-01

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.

Synthetic α subunit peptide 125-147 of human nicotinic acetylcholine receptor induces antibodies to native receptor

International Nuclear Information System (INIS)

McCormick, D.J.; Griesmann, G.E.; Huang, Z.; Lennon, V.A.

1986-01-01

A synthetic peptide corresponding to residues 125-147 of the Torpedo acetylcholine receptor (AChR) α subunit proved to be a major antigenic region of the AChR. Rats inoculated with 50 μg of peptide (T α 125-147) developed T cell immunity and antibodies to native AChR and signs of experimental autoimmune myasthenia gravis. They report the synthesis and preliminary testing of a disulfide-looped peptide comprising residues 125-147 of the human AChR α subunit. Peptide H α 125-147 differs from T α 125-147 at residues 139 (Glu for Gln) and 143 (Ser for Thr). In immunoprecipitation assays, antibodies to Torpedo AChR bound 125 I-labelled Hα 125-147 antibody bound Hα 125-147, but monoclonal antibodies to an immunodominant region of native AChR bound neither Hα 125-147 nor T α 125-147. Rats immunized with H α 125-147 produced anti-mammalian muscle AChR antibodies that induced modulation of AChRs from cultured human myotubes. Thus, region 125-147 of the human AChR α subunit is extracellular in muscle, and is both antigenic and immunogenic. It remains to be determined whether or not autoantibodies to this region may in part cause the weakness or myasthenia gravis in man

Severe hypoglycaemia in a person with insulin autoimmune syndrome accompanied by insulin receptor anomaly type B.

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Kato, T; Itoh, M; Hanashita, J; Itoi, T; Matsumoto, T; Ono, Y; Imamura, S; Hayakawa, N; Suzuki, A; Mizutani, Y; Uchigata, Y; Oda, N

2007-11-01

A rare case of the insulin autoimmune syndrome (IAS) accompanied by insulin receptor anomaly is reported. Antibodies to insulin and insulin receptor were determined in the patient with severe hypoglycaemia before and after the treatment with prednisolone. Titers of antibody to insulin and insulin receptors were 73.0% and 41.5%, respectively. Drug-induced lymphocyte stimulation tests were all negative for the suspicious drugs. Her HLA-DR was DRB1*0403/04051. Following steroid therapy, the formation of antibodies was suppressed and alleviated her symptoms. Scatchard analysis yielded findings specific to polyclonal antibodies. The changes in autoantibodies resulted in alleviation of the hypoglycemic symptoms as a result of steroid therapy.

[Autoimmune hepatitis].

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Färkkilä, Martti

2013-01-01

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

Celiac anti-type 2 transglutaminase antibodies induce phosphoproteome modification in intestinal epithelial Caco-2 cells.

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Gaetana Paolella

Full Text Available BACKGROUND: Celiac disease is an inflammatory condition of the small intestine that affects genetically predisposed individuals after dietary wheat gliadin ingestion. Type 2-transglutaminase (TG2 activity seems to be responsible for a strong autoimmune response in celiac disease, TG2 being the main autoantigen. Several studies support the concept that celiac anti-TG2 antibodies may contribute to disease pathogenesis. Our recent findings on the ability of anti-TG2 antibodies to induce a rapid intracellular mobilization of calcium ions, as well as extracellular signal-regulated kinase phosphorylation, suggest that they potentially act as signaling molecules. In line with this concept, we have investigated whether anti-TG2 antibodies can induce phosphoproteome modification in an intestinal epithelial cell line. METHODS AND PRINCIPAL FINDINGS: We studied phosphoproteome modification in Caco-2 cells treated with recombinant celiac anti-TG2 antibodies. We performed a two-dimensional electrophoresis followed by specific staining of phosphoproteins and mass spectrometry analysis of differentially phosphorylated proteins. Of 14 identified proteins (excluding two uncharacterized proteins, three were hypophosphorylated and nine were hyperphosphorylated. Bioinformatics analyses confirmed the presence of phosphorylation sites in all the identified proteins and highlighted their involvement in several fundamental biological processes, such as cell cycle progression, cell stress response, cytoskeletal organization and apoptosis. CONCLUSIONS: Identification of differentially phosphorylated proteins downstream of TG2-antibody stimulation suggests that in Caco-2 cells these antibodies perturb cell homeostasis by behaving as signaling molecules. We hypothesize that anti-TG2 autoantibodies may destabilize the integrity of the intestinal mucosa in celiac individuals, thus contributing to celiac disease establishment and progression. Since several proteins here

Antibodies against human cytochrome P-450db1 in autoimmune hepatitis type II.

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Zanger, U M; Hauri, H P; Loeper, J; Homberg, J C; Meyer, U A

1988-11-01

In a subgroup of children with chronic active hepatitis, circulating autoantibodies occur that bind to liver and kidney endoplasmic reticulum (anti-liver/kidney microsome antibody type I or anti-LKM1). Anti-LKM1 titers follow the severity of the disease and the presence of these antibodies serves as a diagnostic marker for this autoimmune hepatitis type II. We demonstrate that anti-LKM1 IgGs specifically inhibit the hydroxylation of bufuralol in human liver microsomes. Using two assay systems with different selectivity for the two cytochrome P-450 isozymes catalyzing bufuralol metabolism in human liver, we show that anti-LKM1 exclusively recognizes cytochrome P-450db1. Immunopurification of the LKM1 antigen from solubilized human liver microsomes resulted in an electrophoretically homogenous protein that had the same molecular mass (50 kDa) as purified P-450db1 and an identical N-terminal amino acid sequence. Recognition of both purified P-450db1 and the immunoisolated protein on western blots by several monoclonal antibodies confirmed the identity of the LKM1 antigen with cytochrome P-450db1. Cytochrome P-450db1 has been identified as the target of a common genetic polymorphism of drug oxidation. However, the relationship between the polymorphic cytochrome P-450db1 and the appearance of anti-LKM1 autoantibodies as well as their role in the pathogenesis of chronic active hepatitis remains speculative.

The clinical extremes of autoimmune cholangitis

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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.

Diabetic peripheral neuropathy, is it an autoimmune disease?

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Janahi, Noor M; Santos, Derek; Blyth, Christine; Bakhiet, Moiz; Ellis, Mairghread

2015-11-01

Autoimmunity has been identified in a significant number of neuropathies, such as, proximal neuropathies, and autonomic neuropathies associated with diabetes mellitus. However, possible correlations between diabetic peripheral neuropathy and autoimmunity have not yet been fully investigated. This study was conducted to investigate whether autoimmunity is associated with the pathogenesis of human diabetic peripheral neuropathy. A case-control analysis included three groups: 30 patients with diabetic peripheral neuropathy, 30 diabetic control patients without neuropathy, and 30 healthy controls. Blood analysis was conducted to compare the percentages of positive antinuclear antibodies (ANA) between the three groups. Secondary analysis investigated the correlations between the presence of autoimmune antibodies and sample demographics and neurological manifestations. This research was considered as a pilot study encouraging further investigations to take place in the near future. Antinuclear antibodies were significantly present in the blood serum of patients with diabetic peripheral neuropathy in comparison to the control groups (pneuropathy group were 50 times higher when compared to control groups. Secondary analysis showed a significant correlation between the presence of ANA and the neurological manifestation of neuropathy (Neuropathy symptom score, Neuropathy disability score and Vibration Perception Threshold). The study demonstrated for the first time that human peripheral diabetic neuropathy may have an autoimmune aetiology. The new pathogenic factors may lead to the consideration of new management plans involving new therapeutic approaches and disease markers. Copyright © 2015 Elsevier B.V. All rights reserved.

Interferin with thyroid scintigraphy: the effects of interferon alpha induced thyroid gland autoimmunity and dysfunction upon thyroid scintigraphy in patients with the hepatitis C virus

International Nuclear Information System (INIS)

Rome, S.P.; Karamoskos, P.; Schlicht, S.M.

2003-01-01

Full text: The incidence of hepatitis C virus (HCV) infection is increasing. Interferon alpha therapy is often used to treat patients who are HCV positive. Thyroid gland autoimmunity and dysfunction has been reported to occur with variable frequency during INF-alpha therapy in patients with the HCV. This study reviews the scintigraphic findings of thyroid scans in such patients in order to assess for the effects on thyroid scintigraphy. To our knowledge, there has been no comprehensive study of this important occurrence to date. There were a number of patients with the HCV being treated at our institution between 23/09/1996 and 09/08/2000. Some of them received INF-alpha therapy, certain were subsequently diagnosed with thyroid gland autoimmunity and/or dysfunction. Eight were imaged with thyroid scintigraphy and reviewed. The scintigraphic findings in the 8 patients fell into two broad categories; 4 demonstrated changes of Graves' disease, and 3 changes of thyroiditis (1 of these was sub-acute). One hypothyroid patient with anti-thyroglobulin antibodies had normal thyroid scintigraphy. Six patients were found to have antithyroid antibodies. One patient with thyroiditis tested negative to antithyroid antibodies. One patient was not tested for antithyroid antibodies. Interferon alpha induced thyroid gland autoimmunity and/or dysfunction can markedly affect the thyroid scintigraphic findings of patients with the hepatitis C virus. This hitherto undescribed occurrence on thyroid scintigraphy has important practical implications of which Nuclear Medicine Specialists need to be aware in order to correctly interpret thyroid scintigraphy studies in such patients. The clinical presentation and effects on imaging appearances are varied. The Nuclear Medicine Specialist can play a central role in establishing the causal link. Awareness of this occurrence enables the Nuclear Medicine Specialist to add value to the referral. This occurrence will become an increasingly common

A rare case of autoimmune limbic encephalitis: an uncharted territory!

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Ibrahim, Hatim; Al Jasser, Abdulelah N; Khan, Sonia A; Tlili, Kalthoum G

2017-10-01

Autoimmune encephalitis is rare. Several auto- antibodies are described in autoimmune encephalitis. We describe a case of autoimmune limbic encephalitis associated with positive voltage gated potassium channel (VGKC) antibodies and positive leucine-rich glioma inactivated protein 1 antibodies (LGI1). A 33-year-old Saudi housewife, she presented with 2 months history of cognitive deterioration and recurrent left facio-brachial dystonic seizures followed by generalized tonic clonic seizures. At times the seizures are preceded by rising epigastric aura and shortness of breath. The neurological examination was normal apart from upgoing left plantar reflex. She had borderline IQ of 76 with impaired verbal fluency and impaired visual and verbal memory. Magnetic resonance imaging of the brain showed right mesial temporal non-enhancing lesion. Cerebrospinal fluid examination was positive for LGI1 and VGKC. Optimal seizure control was achieved with immunotherapy.

Autoimmune gastritis: Pathologist's viewpoint.

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

2015-11-14

Western countries are seeing a constant decline in the incidence of Helicobacter pylori-associated gastritis, coupled with a rising epidemiological and clinical impact of autoimmune gastritis. This latter gastropathy is due to autoimmune aggression targeting parietal cells through a complex interaction of auto-antibodies against the parietal cell proton pump and intrinsic factor, and sensitized T cells. Given the specific target of this aggression, autoimmune gastritis is typically restricted to the gastric corpus-fundus mucosa. In advanced cases, the oxyntic epithelia are replaced by atrophic (and metaplastic) mucosa, creating the phenotypic background in which both gastric neuroendocrine tumors and (intestinal-type) adenocarcinomas may develop. Despite improvements in our understanding of the phenotypic changes or cascades occurring in this autoimmune setting, no reliable biomarkers are available for identifying patients at higher risk of developing a gastric neoplasm. The standardization of autoimmune gastritis histology reports and classifications in diagnostic practice is a prerequisite for implementing definitive secondary prevention strategies based on multidisciplinary diagnostic approaches integrating endoscopy, serology, histology and molecular profiling.

Autoimmune encephalitis with anti-leucine-rich glioma-inactivated 1 or anti-contactin-associated protein-like 2 antibodies (formerly called voltage-gated potassium channel-complex antibodies).

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Bastiaansen, Anna E M; van Sonderen, Agnes; Titulaer, Maarten J

2017-06-01

Twenty years since the discovery of voltage-gated potassium channel (VGKC)-related autoimmunity; it is currently known that the antibodies are not directed at the VGKC itself but to two closely associated proteins, anti-leucine-rich glioma-inactivated 1 (LGI1) and contactin-associated protein-like 2 (Caspr2). Antibodies to LGI1 and Caspr2 give well-described clinical phenotypes. Anti-LGI1 encephalitis patients mostly have limbic symptoms, and anti-Caspr2 patients have variable syndromes with both central and peripheral symptoms. A large group of patients with heterogeneous symptoms are VGKC positive but do not have antibodies against LGI1 or Caspr2. The clinical relevance of VGKC positivity in these 'double-negative' patients is questionable. This review focusses on these three essentially different subgroups. The clinical phenotypes of anti-LGI1 encephalitis and anti-Caspr2 encephalitis have been described in more detail including data on treatment and long-term follow-up. A specific human leukocyte antigen (HLA) association was found in nontumor anti-LGI1 encephalitis, but not clearly in those with tumors. There has been increasing interest in the VGKC patients without LGI1/Caspr2 antibodies questioning its relevance in clinical practice. Anti-LGI1 encephalitis and anti-Caspr2 encephalitis are separate clinical entities. Early recognition and treatment is necessary and rewarding. The term VGKC-complex antibodies, lumping patients with anti-LGI1, anti-Caspr2 antibodies or lacking both, should be considered obsolete.

Autoimmune polyglandular syndrome, type 2 associated with myasthenia gravis

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Pejin Radoslav

2012-01-01

Full Text Available Introduction. Autoimmune polyglandular syndrome type 2 is defined as adrenal insufficiency associated with autoimmune primary hypothyroidism and/or with autoimmune type 1 diabetes mellitus, but very rare with myasthenia gravis. Case report. We presented a case of an autoimmune polyglandular syndrome, type 2 associated with myasthenia gravis. A 49-year-old female with symptoms of muscle weakness and low serum levels of cortisol and aldosterone was already diagnosed with primary adrenal insufficiency. Primary hypothyroidism was identified with low values of free thyroxine 4 (FT4 and raised values of thyroidstumulating hormone (TSH. The immune system as a cause of hypothyroidism was confirmed by the presence of thyroid antibodies to peroxidase and TSH receptors. Myasthenia gravis was diagnosed on the basis of a typical clinical feature, positive diagnostic tests and an increased titre of antibodies against the acetylcholine receptors. It was not possible to confirm the immune nature of adrenal insufficiency by the presence of antibodies to 21- hydroxylase. The normal morphological finding of the adrenal glands was an indirect confirmation of the condition as well as the absence of other diseases that might have led to adrenal insufficiency and low levels of both serum cortisol and aldosterone. Hormone replacement therapy, anticholinergic therapy and corticosteroid therapy for myasthenia gravis improved the patient’s general state of health and muscle weakness. Conclusion. This case report indicates a need to examine each patient with an autoimmune disease carefully as this condition may be associated with another autoimmune diseases.

Autoimmune vitiligo in rheumatic disease in the mestizo Mexican population.

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Avalos-Díaz, Esperanza; Pérez-Pérez, Elena; Rodríguez-Rodríguez, Mayra; Pacheco-Tovar, María-Guadalupe; Herrera-Esparza, Rafael

2016-08-01

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.

Autoimmune hyperthyroidism due to secondary adrenal insufficiency: resolution with glucocorticoids.

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Skamagas, Maria; Geer, Eliza B

2011-01-01

To describe the course of autoimmune hyperthyroid disease in a patient with corticotropin (ACTH) deficiency treated with glucocorticoids. We report the clinical presentation, laboratory data, imaging studies, and management of a patient with weight loss, fatigue, apathy, hallucinations, and arthritis. Autoimmune hyperthyroidism (positive thyroperoxidase and thyroglobulin antibodies and borderline positive thyrotropin receptor antibody) was diagnosed in a 71-year-old woman. New psychotic symptoms prompted brain magnetic resonance imaging, which revealed a partially empty sella. Undetectable morning cortisol, undetectable ACTH, and failure to stimulate cortisol with synthetic ACTH (cosyntropin 250 mcg) secured the diagnosis of long-standing secondary adrenal insufficiency. Hydrocortisone replacement improved the patient's symptoms, resolved the thyroid disease, and decreased thyroid antibody titers. In retrospect, the patient recalled severe postpartum hemorrhage requiring blood transfusion at age 38 years. A Sheehan event probably occurred 33 years before the patient presented with corticotropin deficiency. Hyperthyroidism accelerated cortisol metabolism and provoked symptoms of adrenal insufficiency. The hypocortisolemic state may precipitate hyperimmunity and autoimmune thyroid disease. Rapid resolution of hyperthyroidism and decreased thyroid antibody titers with glucocorticoid treatment support this hypothesis.

Impact of positive thyroid autoimmunity on pregnant women with subclinical hypothyroidism.

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López-Tinoco, Cristina; Rodríguez-Mengual, Amparo; Lara-Barea, Almudena; Barcala, Julia; Larrán, Laura; Saez-Benito, Ana; Aguilar-Diosdado, Manuel

2018-03-01

The impact of subclinical hypothyroidism (SH) and thyroid autoimmunity on obstetric and perinatal complications continues to be a matter of interest and highly controversial. To assess the impact of SH and autoimmunity in early pregnancy on the obstetric and perinatal complications in our population. A retrospective cohort study in 435 women with SH (TSH ranging from 3.86 and 10 μIU/mL and normal FT4 values) in the first trimester of pregnancy. Epidemiological and clinical parameters were analyzed and were related to obstetric and perinatal complications based on the presence of autoimmunity (thyroid peroxidase antibodies [TPO] > 34 IU/mL). Mean age was 31.3 years (SD 5.2). Seventeen percent of patients had positive TPO antibodies. Presence of positive autoimmunity was associated to a family history of hypothyroidism (P=.04) and a higher chance of miscarriage (P=.009). In the multivariate analysis, positive TPO antibodies were associated to a 10.25-fold higher risk of miscarriage. No statistically significant associations were found with all other obstetric and perinatal complications. In our region, pregnant women with SH and thyroid autoimmunity had a higher risk of miscarriage but not of other obstetric and perinatal complications. Copyright © 2017 SEEN y SED. Publicado por Elsevier España, S.L.U. All rights reserved.

Selective loss of Purkinje cells in a patient with anti-gliadin-antibody-positive autoimmune cerebellar ataxia

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Hasegawa Akira

2011-02-01

Full Text Available Abstract The patient was an 84-year-old woman who had the onset of truncal ataxia at age 77 and a history of Basedow's disease. Her ataxic gait gradually deteriorated. She could not walk without support at age 81 and she was admitted to our hospital at age 83. Gaze-evoked nystagmus and dysarthria were observed. Mild ataxia was observed in all limbs. Her deep tendon reflex and sense of position were normal. IgA anti-gliadin antibody, IgG anti-gliadin antibody, anti-SS-A/Ro antibody, anti-SS-B/La antibody and anti-TPO antibody were positive. A conventional brain MRI did not show obvious cerebellar atrophy. However, MRI voxel based morphometry (VBM and SPECT-eZIS revealed cortical cerebellar atrophy and reduced cerebellar blood flow. IVIg treatment was performed and was moderately effective. After her death at age 85, the patient was autopsied. Neuropathological findings were as follows: selective loss of Purkinje cells; no apparent degenerative change in the efferent pathways, such as the dentate nuclei or vestibular nuclei; no prominent inflammatory reaction. From these findings, we diagnosed this case as autoimmune cerebellar atrophy associated with gluten ataxia. All 3 autopsies previously reported on gluten ataxia have noted infiltration of inflammatory cells in the cerebellum. In this case, we postulated that the infiltration of inflammatory cells was not found because the patient's condition was based on humoral immunity. The clinical conditions of gluten ataxia have not yet been properly elucidated, but are expected to be revealed as the number of autopsied cases increases.

Regulatory B and T cell responses in patients with autoimmune thyroid disease and healthy controls

DEFF Research Database (Denmark)

Kristensen, Birte

2016-01-01

Autoimmune diseases occur due to faulty self-tolerance. Graves' disease (GD) and Hashimoto's thyroiditis (HT) are classic examples of organ-specific autoimmune diseases. GD is an auto-antibody-mediated disease where autoantibodies are produced against the thyroid stimulating hormone receptor (TSHR...... (Bregs) and regulatory T cells (Tregs) were investigated in the context of GD and HT. First, we studied the role of the thyroid self-antigen, thyroglobulin (TG) in healthy donors. The self-antigen TG, but not the foreign recall antigen tetanus toxoid (TT), was able to induce interleukin 10 (IL-10......) secretion by B cells and CD4+ T cells. These IL-10 producing B cells (B10 cells) from healthy donors were enriched with the CD5+ and CD24hi phenotype. In addition, TG was able to induce IL-6 production by B cells. In contrast, TT induced production of Th1-type pro-inflammatory cytokines including interferon...

On immunological polymorphism of autoimmune thyroiditis

International Nuclear Information System (INIS)

Karachentsev, Yu.Yi.

1999-01-01

The study involved 46 persons. In the majority of patients the exposure dose was 0.155±0.01 Gy. Clinical, ultrasound, immunological, statistical and non-parametric methods were used. Considerable immunological polymorphism of autoimmune thyroiditis in the liquidators has been established; 1) with disturbances in the cellular immunity and low antithyroid antibody index, 2) without disturbances in the cellular immunity with positive indices of antithyroid antibodies, 3) with disturbances in cellular immunity and high indices of TH and MA antibodies

Hepatocyte growth factor limits autoimmune neuroinflammation via glucocorticoid-induced leucine zipper expression in dendritic cells.

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Benkhoucha, Mahdia; Molnarfi, Nicolas; Dunand-Sauthier, Isabelle; Merkler, Doron; Schneiter, Gregory; Bruscoli, Stefano; Riccardi, Carlo; Tabata, Yasuhiko; Funakoshi, Hiroshi; Nakamura, Toshikazu; Reith, Walter; Santiago-Raber, Marie-Laure; Lalive, Patrice H

2014-09-15

Autoimmune neuroinflammation, including multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE), a prototype for T cell-mediated autoimmunity, is believed to result from immune tolerance dysfunction leading to demyelination and substantial neurodegeneration. We previously showed that CNS-restricted expression of hepatocyte growth factor (HGF), a potent neuroprotective factor, reduced CNS inflammation and clinical deficits associated with EAE. In this study, we demonstrate that systemic HGF treatment ameliorates EAE through the development of tolerogenic dendritic cells (DCs) with high expression levels of glucocorticoid-induced leucine zipper (GILZ), a transcriptional repressor of gene expression and a key endogenous regulator of the inflammatory response. RNA interference-directed neutralization of GILZ expression by DCs suppressed the induction of tolerance caused by HGF. Finally, adoptive transfer of HGF-treated DCs from wild-type but not GILZ gene-deficient mice potently mediated functional recovery in recipient mice with established EAE through effective modulation of autoaggressive T cell responses. Altogether, these results show that by inducing GILZ in DCs, HGF reproduces the mechanism of immune regulation induced by potent immunomodulatory factors such as IL-10, TGF-β1, and glucocorticoids and therefore that HGF therapy may have potential in the treatment of autoimmune dysfunctions. Copyright © 2014 by The American Association of Immunologists, Inc.

Female Infertility and Serum Auto-antibodies: a Systematic Review.

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Deroux, Alban; Dumestre-Perard, Chantal; Dunand-Faure, Camille; Bouillet, Laurence; Hoffmann, Pascale

2017-08-01

On average, 10 % of infertile couples have unexplained infertility. Auto-immune disease (systemic lupus erythematosus, anti-phospholipid syndrome) accounts for a part of these cases. In the last 20 years, aspecific auto-immunity, defined as positivity of auto-antibodies in blood sample without clinical or biological criteria for defined diseases, has been evoked in a subpopulation of infertile women. A systematic review was performed (PUBMED) using the MESH search terms "infertility" and "auto-immunity" or "reproductive technique" or "assisted reproduction" or "in vitro fertilization" and "auto-immunity." We retained clinical and physiopathological studies that were applicable to the clinician in assuming joint management of both infertility associated with serum auto-antibodies in women. Thyroid auto-immunity which affects thyroid function could be a cause of infertility; even in euthyroidia, the presence of anti-thyroperoxydase antibodies and/or thyroglobulin are related to infertility. The presence of anti-phospholipid (APL) and/or anti-nuclear (ANA) antibodies seems to be more frequent in the population of infertile women; serum auto-antibodies are associated with early ovarian failure, itself responsible for fertility disorders. However, there exist few publications on this topic. The methods of dosage, as well as the clinical criteria of unexplained infertility deserve to be standardized to allow a precise response to the question of the role of serum auto-antibodies in these women. The direct pathogenesis of this auto-immunity is unknown, but therapeutic immunomodulators, prescribed on a case-by-case basis, could favor pregnancy even in cases of unexplained primary or secondary infertility.

Vaccines, adjuvants and autoimmunity.

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

2015-10-01

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

Autoimmune liver serology: current diagnostic and clinical challenges.

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Bogdanos, Dimitrios-P; Invernizzi, Pietro; Mackay, Ian-R; Vergani, Diego

2008-06-07

Liver-related autoantibodies are crucial 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 variants in adults and children. AIH-1 is specified by anti-nuclear antibody (ANA) and smooth muscle antibody (SMA). AIH-2 is specified by antibody to liver kidney microsomal antigen type-1 (anti-LKM1) and anti-liver cytosol type 1 (anti-LC1). SMA, ANA and anti-LKM antibodies can be present in de-novo AIH following liver transplantation. PBC is specified by antimitochondrial antibodies (AMA) reacting with enzymes of the 2-oxo-acid dehydrogenase complexes (chiefly pyruvate dehydrogenase complex E2 subunit) and disease-specific ANA mainly reacting with nuclear pore gp210 and nuclear body sp100. Sclerosing cholangitis presents as at least two variants, first the classical primary sclerosing cholangitis (PSC) mostly affecting adult men wherein the only (and non-specific) reactivity is an atypical perinuclear antineutrophil cytoplasmic antibody (p-ANCA), also termed perinuclear anti-neutrophil nuclear antibodies (p-ANNA) and second the childhood disease called autoimmune sclerosing cholangitis (ASC) with serological features resembling those of type 1 AIH. Liver diagnostic serology is a fast-expanding area of investigation as new purified and recombinant autoantigens, and automated technologies such as ELISAs and bead assays, become available to complement (or even compete with) traditional immunofluorescence procedures. We survey for the first time global trends in quality assurance impacting as it does on (1) manufacturers/purveyors of kits and reagents, (2) diagnostic service laboratories that fulfill clinicians' requirements, and (3) the end-user, the physician providing patient care, who must properly interpret test results in the overall clinical context.

Autoimmune gastritis: Pathologist’s viewpoint

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

2015-01-01

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

Hybrid kappa\\lambda antibody is a new serological marker to diagnose autoimmune pancreatitis and differentiate it from pancreatic cancer.

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Hao, Mingju; Li, Wenli; Yi, Lang; Yu, Songlin; Fan, Gaowei; Lu, Tian; Yang, Xin; Wang, Guojing; Zhang, Dong; Ding, Jiansheng; Zhang, Kuo; Zhang, Rui; Lin, Guigao; Han, Yanxi; Wang, Lunan; Li, Jinming

2016-06-08

The only generally accepted serological marker currently used for the diagnosis of autoimmune pancreatitis (AIP) is IgG4. Our aim was mainly to determine whether hybrid κ\\λ antibody can help to diagnose AIP and to differentiate it from pancreatic cancer. We established an enzyme-linked immunosorbent assay (ELISA) system to measure the levels of hybrid κ\\λ antibodies in human sera. Sera were obtained from 338 patients, including 61 with AIP, 74 with pancreatic cancer, 50 with acute pancreatitis, 40 with ordinary chronic pancreatitis, 15 with miscellaneous pancreatic diseases, and 98 with normal pancreas. Our study showed levels of hybrid κ\\λ antibodies in the AIP group were significantly higher than in the non-AIP group (P < 0.001). The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for the diagnosis of AIP were 80.3%, 91%, 66.2% and 95.5% respectively. Furthermore, the combined measurement of serum hybrid κ\\λ antibody and IgG4 tended to increase the sensitivity although the difference was not statistically significant (90.2% vs. 78.7%, P = 0.08), compared to measurement of IgG4 alone. Our findings suggest that hybrid κ\\λ antibody could be a new serological marker to diagnose AIP and differentiate it from pancreatic cancer.

Synthetic. cap alpha. subunit peptide 125-147 of human nicotinic acetylcholine receptor induces antibodies to native receptor

Energy Technology Data Exchange (ETDEWEB)

McCormick, D.J.; Griesmann, G.E.; Huang, Z.; Lennon, V.A.

1986-03-05

A synthetic peptide corresponding to residues 125-147 of the Torpedo acetylcholine receptor (AChR) ..cap alpha.. subunit proved to be a major antigenic region of the AChR. Rats inoculated with 50 ..mu..g of peptide (T ..cap alpha.. 125-147) developed T cell immunity and antibodies to native AChR and signs of experimental autoimmune myasthenia gravis. They report the synthesis and preliminary testing of a disulfide-looped peptide comprising residues 125-147 of the human AChR ..cap alpha.. subunit. Peptide H ..cap alpha.. 125-147 differs from T ..cap alpha.. 125-147 at residues 139 (Glu for Gln) and 143 (Ser for Thr). In immunoprecipitation assays, antibodies to Torpedo AChR bound /sup 125/I-labelled H..cap alpha.. 125-147 antibody bound H..cap alpha.. 125-147, but monoclonal antibodies to an immunodominant region of native AChR bound neither H..cap alpha.. 125-147 nor T ..cap alpha.. 125-147. Rats immunized with H ..cap alpha.. 125-147 produced anti-mammalian muscle AChR antibodies that induced modulation of AChRs from cultured human myotubes. Thus, region 125-147 of the human AChR ..cap alpha.. subunit is extracellular in muscle, and is both antigenic and immunogenic. It remains to be determined whether or not autoantibodies to this region may in part cause the weakness or myasthenia gravis in man.

Antiphosphatidylserine/prothrombin antibodies as biomarkers to identify severe primary antiphospholipid syndrome.

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Hoxha, Ariela; Mattia, Elena; Tonello, Marta; Grava, Chiara; Pengo, Vittorio; Ruffatti, Amelia

2017-05-01

Anti-phosphatidylserine/prothrombin (aPS/PT) antibodies have begun to be considered potentional biomarkers for antiphospholipid syndrome (APS). This cohort study investigate the role of aPS/PT antibodies as a risk factor for severe APS by evaluating the association between those antibodies and clinical/laboratory profiles of APS. Plasma/serum samples from 197 APS patients, 100 healthy subjects and 106 patients with autoimmune diseases were collected. IgG/IgM aPS/PT antibodies were assayed using commercial ELISA kit. Prevalences of IgG and IgM aPS/PT (pantiphospholipid antibody patients than in double and single positivity ones (p<0.0001 for all). APS/PT antibodies were associated to severe thrombosis, severe pregnancy complications inducing prematurity, and vascular microangiopathy, all generally associated to high risk APS forms requiring strong therapy.

Autoimmune Thyroiditis and Myasthenia Gravis

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Angela Lopomo

2017-07-01

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.

Autoimmune Thyroiditis and Myasthenia Gravis

Science.gov (United States)

Lopomo, Angela; Berrih-Aknin, Sonia

2017-01-01

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. PMID:28751878

Possible Role of Autoimmunity in Patients with Premature Ovarian Insuf f iciency

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Renata Košir Pogačnik

2014-01-01

Full Text Available Background: To evaluate the involvement of immune abnormality in patients with idiopathic premature ovarian insufficiency (POI. In addition to the known etiology, autoimmune disorders may be a pathologic mechanism for POI. Materials and Methods: Our study was a prospective controlled trial. Twenty women with POI, reasons other than autoimmune excluded, were enrolled in this study. The control group consisted of 17 healthy women. In both groups, family and personal history were taken and the levels of follicle stimulating hormone, luteinizing hormone, thyroid-stimulating hormone, prolactin, anti-Müllerian hormone, inhibin B, antithyroglobulin and antithyroid peroxidase antibodies were determined. Antiovarian antibodies and subpopulations of peripheral blood T-lymhocytes were also determined. Results: Participants in the study group exhibited hypergonadotropichypogonadism, while high levels of follicle stimulating hormone and low levels of inhibin B and anti- Müllerian hormone were observed. In 16 (80% patients, POI was associated in their personal and familial history with another autoimmune disease. Fifty percent of patients presented highly elevated antithyroid antibodies. The lymphocyte subset, especially B cells, was significantly higher (p=0.014, and peripheral regulatory lymphocytes CD25+ high were significantly lower (p=0.015 in the study group than in the control group. Antiovarian antibodies were detected in 20% of patients with POI. Conclusion: We presume that the presence of anti-ovarian antibodies together with abnormalities of cellular immunity may in some cases potentially represent the involvement of an autoimmune mechanism in idiopathic POI.

Autoimmune hemolytic anemia: transfusion challenges and solutions

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Barros MM

2017-03-01

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

Strategies for induction of catalytic antibodies toward HIV-1 glycoprotein gp120 in autoimmune prone mice.

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Durova, Oxana M; Vorobiev, Ivan I; Smirnov, Ivan V; Reshetnyak, Andrew V; Telegin, Georgy B; Shamborant, Olga G; Orlova, Nadezda A; Genkin, Dmitry D; Bacon, Andrew; Ponomarenko, Natalia A; Friboulet, Alain; Gabibov, Alexander G

2009-11-01

Tremendous efforts to produce an efficient vaccine for HIV infection have been unsuccessful. The ability of HIV to utilize sophisticated mechanisms to escape killing by host immune system rises dramatic problems in the development of antiviral therapeutics. The HIV infection proceeds by interaction of coat viral glycoprotein gp120 trimer with CD4(+) receptor of the lymphocyte. Thus this surface antigen may be regarded as a favorable target for immunotherapy. In the present study, we have developed three different strategies to produce gp120-specific response in autoimmune prone mice (SJL strain) as potential tools for production "catalytic vaccine". Therefore (i) reactive immunization by peptidylphosphonate, structural part of the coat glycoprotein, (ii) immunization by engineered fused epitopes of gp120 and encephalogenic peptide, a part of myelin basic protein, and (iii) combined vaccination by DNA and corresponding gp120 fragments incorporated into liposomes were investigated. In the first two cases monoclonal antibodies and their recombinant fragments with amidolytic and gp120-specific proteolytic activities were characterized. In the last case, catalytic antibodies with virus neutralizing activity proved in cell line models were harvested.

Characterization of pituitary cells targeted by antipituitary antibodies in patients with isolated autoimmune diseases without pituitary insufficiency may help to foresee the kind of future hypopituitarism.

Science.gov (United States)

De Bellis, A; Dello Iacovo, A; Bellastella, G; Savoia, A; Cozzolino, D; Sinisi, A A; Bizzarro, A; Bellastella, A; Giugliano, D

2014-10-01

Detection of antipituitary antibodies (APA) at high levels and with a particular immunofluorescence pattern in patients with autoimmune polyendocrine syndromes may indicate a possible future autoimmune pituitary involvement. This longitudinal study was aimed at characterizing in patients with a single organ-specific autoimmune disease the pituitary cells targeted by APA at start, verifying whether this characterization allows to foresee the kind of possible subsequent hypopituitarism. Thirty-six APA positive and 40 APA negative patients with isolated autoimmune diseases participated in the study. None of them had pituitary dysfunction at entry. Characterization by four-layer immunofluorescence of pituitary cells targeted by APA in APA positive patients at entry and study of pituitary function in all patients were performed every 6 months during a 5 year follow-up. Antipituitary antibodies immunostained selectively one type of pituitary-secreting cells in 21 patients (58.3 %, group 1), and several types of pituitary cells in the remaining 15 (41.7 %, group 2). All patients in group 1 showed subsequently a pituitary insufficiency, corresponding to the type of cells targeted by APA in 18 of them (85.7 %). Only 8 out of 15 patients in group 2 (53.3 %) showed a hypopituitarism, isolated in 7 and combined in the other one. None of APA negative patients showed hypopituitarism. The characterization of pituitary cells targeted by APA in patients with isolated autoimmune diseases, when the pituitary function is still normal, may help to foresee the kind of subsequent hypopituitarism, especially when APA immunostained selectively only one type of pituitary cells. A careful follow-up of pituitary function in these patients is advisable to allow an early diagnosis of hypopituitarism, even in subclinical phase and a consequent timely replacement therapy.

Hydralazine-induced constrictive pericarditis

NARCIS (Netherlands)

Franssen, CFC; ElGamal, MIH; Gans, ROB; Hoorntje, SJ

A 59-year-old man was diagnosed as having constrictive pericarditis 17 months after a typical hydralazine-induced autoimmune syndrome, This late complication of hydralazine has been reported only once. Ten years later the patient was found to have anti-neutrophil cytoplasmic antibodies directed

Exacerbation of Autoimmune Thyroiditis by CTLA-4 Blockade: A Role for IFNγ-Induced Indoleamine 2, 3-Dioxygenase.

Science.gov (United States)

Sharma, Rajni; Di Dalmazi, Giulia; Caturegli, Patrizio

2016-08-01

Cytotoxic T-lymphocyte associated protein 4 (CTLA-4) is a negative regulator of immune responses that suppresses the activity of effector T cells and contributes to the maintenance of self tolerance. When blocked therapeutically, CTLA-4 leads to an overall activation of T cells that has been exploited for cancer control, a control associated however with a variety of immune-related side effects such as autoimmune thyroiditis. To investigate the mechanism(s) underlying this form of thyroiditis, we used the NOD-H2(h4) mouse, a model that develops thyroiditis at very high incidence after addition of iodine to the drinking water. NOD-H2(h4) mice were started on drinking water supplemented with 0.05% sodium iodide when 8 weeks old and then injected with a hamster monoclonal antibody against mouse CTLA-4, polyclonal hamster immunoglobulins, or phosphate buffered saline when 11 weeks old. One month later (15 weeks of age), mice were sacrificed to assess thyroiditis, general immune responses in blood and spleen, and expression of indoleamine 2, 3-dioxygenase (IDO) in the thyroid and in isolated antigen-presenting cells after stimulation with interferon gamma. The study also analyzed IDO expression in four autopsy cases of metastatic melanoma who had received treatment with a CTLA-4 blocking antibody, and six surgical pathology Hashimoto thyroiditis controls. CTLA-4 blockade worsened autoimmune thyroiditis, as assessed by a greater incidence, a more aggressive mononuclear cell infiltration in thyroids, and higher thyroglobulin antibody levels when compared to the control groups. CTLA-4 blockade also expanded the proportion of splenic CD4+ effector T cells, as well as the production of interleukin (IL)-2, interferon gamma, IL-10, and IL-13 cytokines. Interestingly, CTLA-4 blockade induced a strong expression of IDO in mouse and human thyroid glands, an expression that could represent a counter-regulatory mechanism to protect against the inflammatory environment. This study

Exacerbation of Autoimmune Thyroiditis by CTLA-4 Blockade: A Role for IFNγ-Induced Indoleamine 2, 3-Dioxygenase

Science.gov (United States)

Sharma, Rajni; Di Dalmazi, Giulia

2016-01-01

Background: Cytotoxic T-lymphocyte associated protein 4 (CTLA-4) is a negative regulator of immune responses that suppresses the activity of effector T cells and contributes to the maintenance of self tolerance. When blocked therapeutically, CTLA-4 leads to an overall activation of T cells that has been exploited for cancer control, a control associated however with a variety of immune-related side effects such as autoimmune thyroiditis. To investigate the mechanism(s) underlying this form of thyroiditis, we used the NOD-H2h4 mouse, a model that develops thyroiditis at very high incidence after addition of iodine to the drinking water. Methods: NOD-H2h4 mice were started on drinking water supplemented with 0.05% sodium iodide when 8 weeks old and then injected with a hamster monoclonal antibody against mouse CTLA-4, polyclonal hamster immunoglobulins, or phosphate buffered saline when 11 weeks old. One month later (15 weeks of age), mice were sacrificed to assess thyroiditis, general immune responses in blood and spleen, and expression of indoleamine 2, 3-dioxygenase (IDO) in the thyroid and in isolated antigen-presenting cells after stimulation with interferon gamma. The study also analyzed IDO expression in four autopsy cases of metastatic melanoma who had received treatment with a CTLA-4 blocking antibody, and six surgical pathology Hashimoto thyroiditis controls. Results: CTLA-4 blockade worsened autoimmune thyroiditis, as assessed by a greater incidence, a more aggressive mononuclear cell infiltration in thyroids, and higher thyroglobulin antibody levels when compared to the control groups. CTLA-4 blockade also expanded the proportion of splenic CD4+ effector T cells, as well as the production of interleukin (IL)-2, interferon gamma, IL-10, and IL-13 cytokines. Interestingly, CTLA-4 blockade induced a strong expression of IDO in mouse and human thyroid glands, an expression that could represent a counter-regulatory mechanism to protect against the inflammatory

The Roles of the TSH Receptor Antibodies in Autoimmune Thyroid Diseases

Energy Technology Data Exchange (ETDEWEB)

Koh, Chang Soon [Seoul National University College of Medicine, Seoul (Korea, Republic of)

1986-09-15

To evaluate the clinical and pathogenetic roles of TSH receptor antibodies in autoimmune thyroid diseases, TBII were measured by TSH-radioreceptor assay methods in 352 patients with Graves disease, 108 patients with other thyroid diseases and 69 normal persons. The normal range of TBII activity was less than 15%. The frequencies of detectable TBIl in 169 patients with untreated Graves disease, 31 patients with hyperthyroidism under treatment and 70 patients with euthyroidism under treatment were 92.4%, 87.1% and 54.3% respectively. However 12 (21.8%) out of 55 patients who have been in remission more than one year after discontinuation of antithyroid drugs treatment had detectable TBII activities in their sera. In 196 patients with untreated Graves disease, the frequency of TBII increased by increasing size of goiter and the frequency of proptosis was significantly high in patients whose TBII activities were more than 60%. TBll activities were roughly correlated with total T{sub 3},T{sub 4} and free T{sub 4}, index but low gamma{sup 2} value(less than 0.1). In 67 patients with Graves' disease who were positive TB1I before antithyroid drugs treatment, TBII activities began to decrease from the third months and it was converted to negative in 35.8% of patients at 12 months after treatment. There were no significant differences of the declining and disappearing rates of TBII activities between high dose and conventional dose groups. TBII activities were significantly increased initially (2-4 months) and then began to decrease from 5-9 months after {sup 131}I treatment. There were two groups, one whose TBII activities decreased gradually and the other did not change until 12 months after subtotal thyroidectomy. Although preoperative clinical and laboratory findings of both groups were not different, TBII activities of non-decreasing group were significantly higher than those of decreasing group(74.6+18.6% vs 39.2+15.2%; P(0.01). Thirty three(55.9%) out of 59

Long-Term Follow-Up of a Child with Autoimmune Thyroiditis and Recurrent Hyperthyroidism in the Absence of TSH Receptor Antibodies

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Christopher Dunne

2014-01-01

Full Text Available Hashitoxicosis is an initial, transient, hyperthyroid phase that rarely affects patients with Hashimoto thyroiditis. We present here an unusual case of a child with Hashimoto thyroiditis and recurrent hyperthyroidism. A 4 yr 6/12 old male was diagnosed by us with autoimmune subclinical hypothyroidism (normal free T4, slightly elevated TSH, and elevated TG antibody titer. Two years and 6/12 later he experienced increased appetite and poor weight gain; a laboratory evaluation revealed suppressed TSH, elevated free T4, and normal TSI titer. In addition, an I123 thyroid uptake was borderline-low. A month later, the free T4 had normalized. After remaining asymptomatic for 3 years, the patient presented again with increased appetite, and he was found with low TSH and high free T4. Within the following 3 months, his free T4 and TSH normalized. At his most recent evaluation, his TSH was normal and the free T4 was borderline-high; the TG antibody titer was still elevated and the TSI titer was negative. To our knowledge, this is the first patient reported with Hashimoto thyroiditis and recurrent hyperthyroidism. This case exemplifies the variability of the manifestations and natural history of Hashimoto thyroiditis and supports the need for a long-term evaluation of patients with autoimmune thyroid disease.

Liver/kidney microsomal antibody type 1 and liver cytosol antibody type 1 concentrations in type 2 autoimmune hepatitis.

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Muratori, L; Cataleta, M; Muratori, P; Lenzi, M; Bianchi, F B

1998-05-01

Liver/kidney microsomal antibody type 1 (LKM1) and liver cytosol antibody type 1 (LC1) are the serological markers of type 2 autoimmune hepatitis (AIH). Since LKM1 and LC1 react against two distinct liver specific autoantigens (cytochrome P450IID6 (CYP2D6) and a 58 kDa cytosolic polypeptide respectively), the aim was to see whether LKM1 and LC1 concentrations correlate with liver disease activity. Twenty one patients with type 2 AIH were studied. All sera were tested by indirect immunofluorescence, counterimmunoelectrophoresis, and immunoblotting visualised by enhanced chemiluminescence. To evaluate LKM1 and LC1 levels, the 50 kDa microsomal reactivity (corresponding to CYP2D6) and the 58 kDa cytosolic reactivity were quantified by densitometric analysis. Seven patients were positive for LKM1, nine for LC1, and five for both. Serial serum samples at onset and during immunosuppressive treatment were analysed in 13 patients (four positive for LKM1, six positive for LC1 and three positive for both). During remission, LKM1 concentration remained essentially unchanged in six of seven patients, and decreased in only one. Conversely, in two of nine patients, LC1 was completely lost, and, in the remaining seven, LC1 concentration was reduced by more than 50%. After immunosuppression tapering or withdrawal, flare ups of liver necrosis ensued with increasing LC1 concentration, but not LKM1. LC1 concentration, at variance with that of LKM1, parallels liver disease activity, and its participation in the pathogenic mechanisms of liver injury can be hypothesised.

[Non-autoimmune thyroiditis].

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Rizzo, Leonardo F L; Mana, Daniela L; Bruno, Oscar D

2014-01-01

The term thyroiditis comprises a group of thyroid diseases characterized by the presence of inflammation, including autoimmune and non-autoimmune entities. It may manifest as an acute illness with severe thyroid pain (subacute thyroiditis and infectious thyroiditis), and conditions in which the inflammation is not clinically evident evolving without pain and presenting primarily thyroid dysfunction and/or goiter (drug-induced thyroiditis and Riedel thyroiditis). The aim of this review is to provide an updated approach on non-autoimmune thyroiditis and its clinical, diagnostic and therapeutic aspects.

Pulmonary aspergillosis and central nervous system hemorrhage as complications of autoimmune hemolytic anemia treated with corticosteroids.

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Cleri, Dennis J; Moser, Robert L; Villota, Francisco J; Wang, Yue; Husain, Syed A; Nadeem, Shahzinah; Anjari, Tarek; Sajed, Mohammad

2003-06-01

Warm, active antibody adult autoimmune hemolytic anemia is the most common form of hemolytic anemia not related to drug therapy. Mortality in adult autoimmune hemolytic anemia is related to the inability to successfully treat patients' underlying disease, or the infectious complications of splenectomy and prolonged steroid therapy. Predisposing factors for invasive aspergillosis are neutropenia and steroid therapy. We present a fatal case of aspergillosis complicating a nonneutropenic case of warm active antibody adult autoimmune hemolytic anemia treated with prolonged steroid therapy.

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

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Jun-ichi Sakai

1999-01-01

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

Autoimmune Syndrome Induced by Adjuvants (ASIA after Silicone Breast Augmentation Surgery

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Daniel Nunes e Silva, MD

2017-09-01

Full Text Available Summary:. Generally, the main complications of silicone implantation are local symptoms. However, some patients develop late-onset systemic symptoms often associated with a rare form of hyperactive immune response, as part of a syndrome known as autoimmune syndrome induced by adjuvants (ASIA. Reported cases of ASIA have shown resolution with explantation, but not with immunomodulatory therapy. In this report, we described a case of a previously healthy 23-year-old woman, who has undergone silicone breast implant augmentation, for aesthetic reasons, and developed localized cutaneous impairment 3 years postsurgery. She received a diagnosis of ASIA with a new presentation: Lupus-like manifestation through localized cutaneous impairment. This patient’s symptoms were managed without the need for surgical intervention, which has not been previously reported, because the patient did not want an explantation for aesthetic reasons. The patient was started on hydroxychloroquine, 400 mg per day, and remains asymptomatic after 2 years of treatment. The exact predisposition to ASIA is still unknown. Without implant explantation and with immunomodulatory treatment, this patient’s condition substantially improved. Based on our current understanding of this disease, it might not be prudent to indicate breast augmentation with silicone implants in patients with documented autoimmune reaction to an adjuvant, an established autoimmune condition, or genetic predisposition. However, if a patient does develop silicone-induced ASIA, explantation is no longer the only successfully reported option, as these symptoms can be managed with immune suppression.

[An evaluation of HLA class 2 alleles and anti-islet antibodies as evidence for non-autoimmune diabetes in Wolfram syndrome].

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Zmysłowska, Agnieszka; Borowiec, Maciej; Antosik, Karolina; Wyka, Krystyna; Cieślik-Heinrich, Agnieszka; Klich, Izabela; Młynarski, Wojciech

2010-01-01

A clinical criterion of the Wolfram syndrome is the coexistence of diabetes and optic atrophy recognized before the age of 15. Diabetes present in Wolfram syndrome is a result of the selective β cell loss and failed insulin secretion which is probably associated with non-autoimmune pathogenesis. The aim of the study was an evaluation of HLA subtypes and presence of β-cell autoantibodies in patients with molecularly confirmed Wolfram syndrome. 9 patients with Wolfram syndrome aged 10-24 years were examined. We also studied 218 patients with type 1 diabetes as a reference group. A control group of 176 healthy individuals was included in the study. Besides the clinical assessment the HLA typing by PCR-SSO was performed. Islet cell antibodies (ICA), antibodies to glutamic acid decarboxylase (GADA), thyrosine phosphatase antibodies (IA2A) and insulin antibodies (IAA) were also detected. In all nine patients the coexistence of diabetes with optic atrophy was observed and in 8/9 individuals additional symptoms were recognized. In patients with Wolfram syndrome a significantly lower age of diagnosis of diabetes (Me=5.0 years) than in type 1 diabetic children (Me=10.4; p=0.002) was observed. Studies of HLA subtypes demonstrated an increased prevalence of HLA-DQw1, DRB1⋅03 and/or 04 and DR2. A comparison of the frequency of the HLA alleles in patients with Wolfram syndrome with type 1 diabetic children showed a more frequent presence of the DRB1⋅1501 (p=0.03; OR=13.28 (2.44-72.12)) and DQB1⋅06 (p=0.016; OR=10.15 (2.49-41.35)) alleles in patients with Wolfram syndrome. Polish patients with Wolfram syndrome have a different profile of the HLA antigens with the presence of DR2, DQw1 and DRB3/4 allele and are negative for diabetes-related autoantibodies, which may confirm non-autoimmune β-cell destruction in this syndrome.

Helicobacter pylori and autoimmune disease: Cause or bystander

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Smyk, Daniel S; Koutsoumpas, Andreas L; Mytilinaiou, Maria G; Rigopoulou, Eirini I; Sakkas, Lazaros I; Bogdanos, Dimitrios P

2014-01-01

Helicobacter pylori (H. pylori) is the main cause of chronic gastritis and a major risk factor for gastric cancer. This pathogen has also been considered a potential trigger of gastric autoimmunity, and in particular of autoimmune gastritis. However, a considerable number of reports have attempted to link H. pylori infection with the development of extra-gastrointestinal autoimmune disorders, affecting organs not immediately relevant to the stomach. This review discusses the current evidence in support or against the role of H. pylori as a potential trigger of autoimmune rheumatic and skin diseases, as well as organ specific autoimmune diseases. We discuss epidemiological, serological, immunological and experimental evidence associating this pathogen with autoimmune diseases. Although over one hundred autoimmune diseases have been investigated in relation to H. pylori, we discuss a select number of papers with a larger literature base, and include Sjögrens syndrome, rheumatoid arthritis, systemic lupus erythematosus, vasculitides, autoimmune skin conditions, idiopathic thrombocytopenic purpura, autoimmune thyroid disease, multiple sclerosis, neuromyelitis optica and autoimmune liver diseases. Specific mention is given to those studies reporting an association of anti-H. pylori antibodies with the presence of autoimmune disease-specific clinical parameters, as well as those failing to find such associations. We also provide helpful hints for future research. PMID:24574735

Lupus erythematosus, thyroiditis, alopecia areata and vitiligo – A multiple autoimmune syndrome type 3 case presentation

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Alin Laurentiu Tatu

2017-04-01

Full Text Available The combination of at least three autoimmune diseases in the same patient has defined as multiple autoimmune syndrome (MAS. Abnormalities of T cell-mediated immunity and humoral immunity have been described previously in the literature. Aims of work were to investigate the 22 years old patient with lupus erythematosus for three years and autoimune thyroiditis for one year, regardind other possible autoimmune conditions and to establish a treatment to control the diseases. The clinical exam revealed some circular hairless patches on the beard appeared about three months ago and white depigmented disseminated areas started one month ago and the laboratory investigations were performed. The modified laboratory findings were total IgE 530 UI/mL, Anti-SSA (anti-RO antibodies> 200 IU/mL, SSB negative, Antinuclear antibodies (ANA positive and fine speckled, Lupus anticoagulant testing positive, Anti-thyroid peroxidase antibodies 951 UI/ml, TSH 4,7 µUI/mL. The diagnosis of multiple autoimmune syndrome(MAS type 3 including Lupus erythematosus, autoimune Thyroiditis, Alopecia Areata and Vitiligo was established. Endocrine autoimmunities are associated with autoantibodies that react to specific antigens, whereas patients with collagen diseases synthesize immunoglobulins that recognize nonorgan-specific cellular targets, such as nucleoproteins and nucleic acids. Cellular autoimmunity is important in the pathogenesis MAS. The existence of one autoimmune disorder helps lead to the discovery of other autoimmune conditions.

“The NET outcome”: are neutrophil extracellular traps of any relevance to the pathophysiology of autoimmune disorders in childhood?

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Stavros Giaglis

2016-09-01

Full Text Available Neutrophil extracellular trap (NET formation represents a form of cell death distinct from apoptosis or necrosis, by which invading pathogens are simultaneously entangled and potentially eliminated. Increased NET formation is observed in systemic lupus erythematosus (SLE, rheumatoid arthritis (RA, antineutrophil cytoplasmic antibody (ANCA-associated and small vessel vasculitis (SVV, antiphospholipid antibody syndrome (APS and psoriasis. NETs contribute to the pathogenesis of autoimmunity by exposing cryptic autoepitopes, which may facilitate the generation of autoantibodies, induce the production of interferons and activate the complement cascade. In SLE, augmented disease activity and renal disease are associated with increased NET formation, so that NETs could serve as a marker for the monitoring of disease activity. NETs can additionally cause endothelial cell damage and death and stimulate inflammation in atheromatous plaques, adding to the accelerated atherosclerosis witnessed in autoimmune disease. Since NETs induce production of interferons, assessing the extent of NET formation might facilitate the prediction of IFN-alpha levels and identification of SLE patients with presumably better responses to anti-IFN-alpha therapies or other novel therapeutic concepts, such as N-acetyl-cysteine and inhibitors of DNase 1, and peptidylarginine deiminase 4 (PAD4, which also target NETs. In summary, the study of NETs provides a novel approach to the understanding of autoimmune disease pathogenesis and opens new vistas in the development of sensitive disease markers and therapies.

Autoimmune pancreatitis in an 11-year-old boy

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Refaat, Rania; Harth, Marc; Proschek, Petra; Lindemayr, Sebastian; Vogl, Thomas J.

2009-01-01

We report a case of histopathologically proven autoimmune pancreatitis in an 11-year-old boy. Abdominal US and MRI showed a focal swelling of the pancreatic head, the latter also showing delayed contrast enhancement. There was diffuse irregular pancreatic duct narrowing, compression of the intrapancreatic common bile duct, and mild proximal biliary dilatation on MR cholangiopancreatography. Laboratory results revealed normal serum IgG and subclass 4 with negative autoimmune antibodies, and slightly elevated carbohydrate antigen 19-9. This highlights the differentiation of autoimmune pancreatitis from pancreatic head cancer and, to a lesser extent, other forms of pancreatitis in children. (orig.)

Autoimmune pancreatitis in an 11-year-old boy

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Refaat, Rania [Johann-Wolfgang-Goethe University, Department of Diagnostic and Interventional Radiology, Frankfurt am Main (Germany); Ain Shams University, Department of Diagnostic and Interventional Radiology, Cairo (Egypt); Harth, Marc; Proschek, Petra; Lindemayr, Sebastian; Vogl, Thomas J. [Johann-Wolfgang-Goethe University, Department of Diagnostic and Interventional Radiology, Frankfurt am Main (Germany)

2009-04-15

We report a case of histopathologically proven autoimmune pancreatitis in an 11-year-old boy. Abdominal US and MRI showed a focal swelling of the pancreatic head, the latter also showing delayed contrast enhancement. There was diffuse irregular pancreatic duct narrowing, compression of the intrapancreatic common bile duct, and mild proximal biliary dilatation on MR cholangiopancreatography. Laboratory results revealed normal serum IgG and subclass 4 with negative autoimmune antibodies, and slightly elevated carbohydrate antigen 19-9. This highlights the differentiation of autoimmune pancreatitis from pancreatic head cancer and, to a lesser extent, other forms of pancreatitis in children. (orig.)

Prevalence and clinical significance of nonorgan specific antibodies in patients with autoimmune thyroiditis as predictor markers for rheumatic diseases.

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Elnady, Basant M; Kamal, Naglaa M; Shaker, Raneyah H M; Soliman, Amal F; Hasan, Waleed A; Alghamdi, Hamed A; Algethami, Mohammed M; Jajah, Mohamed Bilal

2016-09-01

Autoimmune diseases are considered the 3rd leading cause of morbidity and mortality in the industrialized countries. Autoimmune thyroid diseases (ATDs) are associated with high prevalence of nonorgan-specific autoantibodies, such as antinuclear antibodies (ANA), antidouble-stranded deoxyribonucleic acid (anti-dsDNA), antiextractable-nuclear antigens (anti-ENAs), rheumatoid factor (RF), and anticyclic-citrullinated peptides (anti-CCP) whose clinical significance is unknown.We aimed to assess the prevalence of various nonorgan-specific autoantibodies in patients with ATD, and to investigate the possible association between these autoantibodies and occurrence of rheumatic diseases and, if these autoantibodies could be considered as predictor markers for autoimmune rheumatic diseases in the future.This study had 2 phases: phase 1; in which 61 ATD patients free from rheumatic manifestations were assessed for the presence of these nonorgan-specific autoantibodies against healthy 61 control group, followed by 2nd phase longitudinal clinical follow-up in which cases are monitored systematically to establish occurrence and progression of any rheumatic disease in association to these autoantibodies with its influences and prognosis.Regarding ATD patients, ANA, anti-dsDNA, Anti-ENA, and RF were present in a percentage of (50.8%), (18%), (21.3%), and (34.4%), respectively, with statistically significance difference (P rheumatic diseases, over 2 years follow-up. It was obvious that those with positive anti-dsDNA had higher risk (2.45 times) to develop rheumatic diseases than those without. There was a statistically significant positive linear relationship between occurrence of disease in months and (age, anti-dsDNA, anti-CCP, RF, and duration of thyroiditis). Anti-dsDNA and RF are the most significant predictors (P rheumatic diseases than previously thought. Anti-dsDNA, RF, and anti-CCP antibodies may be used as predictive screening markers of systemic lupus erythematosus

Immunomodulatory Effect of Agave tequilana Evaluated on an Autoimmunity Like-SLE Model Induced in Balb/c Mice with Pristane.

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Gutiérrez Nava, Zúlima Jannette; Jiménez-Aparicio, Antonio Ruperto; Herrera-Ruiz, Maribel Lucila; Jiménez-Ferrer, Enrique

2017-05-25

In this work, the immunomodulatory activity of the acetone extract and the fructans obtained from Agave tequilana were evaluated, on the systemic autoimmunity type-SLE model generated by the administration of 2,6,10,14-tetramethylpentadecane (TMPD, also known as pristane) on Balb/c female mice. The systemic autoimmunity type-SLE was observed seven months after the application of TMPD, in which the animals from the negative control group (animals with damage and without any other treatment) developed articular inflammation, proteinuria, an increment of the antinuclear antibody titters and tissue pro-inflammatory cytokines levels (IL-1β, IL-6, TNF-α e IFN-γ) as well as the anti-inflammatory cytokine IL-10. The administration of the different treatments and the extracts of A. tequilana , provoked the decrease of: articular inflammation, the development of proteinuria, ssDNA/dsDNA antinuclear antibody titters and cytokines IL-1β, IL-6, TNF-α, IFN-γ and IL-10. The phytochemical analysis of the acetone extract identified the presence of the following compounds: β-sitosterol glycoside; 3,7,11,15-tetramethyl-2-hexadecen-1-ol (phytol); octadecadienoic acid-2,3-dihydroxypropyl ester; stigmasta-3,5-dien-7-one; cycloartenone and cycloartenol. Therefore, A. tequilana contains active compounds with the capacity to modify the evolution of the systemic autoimmunity type-SLE on a murine model.

Immunomodulatory Effect of Agave tequilana Evaluated on an Autoimmunity Like-SLE Model Induced in Balb/c Mice with Pristane

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Zúlima Jannette Gutiérrez Nava

2017-05-01

Full Text Available In this work, the immunomodulatory activity of the acetone extract and the fructans obtained from Agave tequilana were evaluated, on the systemic autoimmunity type-SLE model generated by the administration of 2,6,10,14-tetramethylpentadecane (TMPD, also known as pristane on Balb/c female mice. The systemic autoimmunity type-SLE was observed seven months after the application of TMPD, in which the animals from the negative control group (animals with damage and without any other treatment developed articular inflammation, proteinuria, an increment of the antinuclear antibody titters and tissue pro-inflammatory cytokines levels (IL-1β, IL-6, TNF-α e IFN-γ as well as the anti-inflammatory cytokine IL-10. The administration of the different treatments and the extracts of A. tequilana, provoked the decrease of: articular inflammation, the development of proteinuria, ssDNA/dsDNA antinuclear antibody titters and cytokines IL-1β, IL-6, TNF-α, IFN-γ and IL-10. The phytochemical analysis of the acetone extract identified the presence of the following compounds: β-sitosterol glycoside; 3,7,11,15-tetramethyl-2-hexadecen-1-ol (phytol; octadecadienoic acid-2,3-dihydroxypropyl ester; stigmasta-3,5-dien-7-one; cycloartenone and cycloartenol. Therefore, A. tequilana contains active compounds with the capacity to modify the evolution of the systemic autoimmunity type-SLE on a murine model.

Interrelation specific autoimmune pathologies of a thyroid gland with inorganic autoimmune rheumatic diseases

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O V Paramonova

2012-03-01

Full Text Available The problem of a pathology of a thyroid gland at rheumatic diseases, in particular at rheumatoid arthritis, remains actual and to this day. The work purpose was studying antitelogenesis to thyroid hormones at patients with mixt autoimmune pathology. In whey of blood of patients with RA and autothyroid pathology are found out antibodies (AB to Т3 and Т4, their concentration correlates with activity of pathological process. It is shown, that level AB to Т3 and Т4 authentically differs from the maintenance of the given antibodies in whey of blood of healthy faces. Level of antibodies to thyroid hormones can be considered as the criterion predicting development of pathology of a thyroid gland at patients with RA.

Hypothalamic-Pituitary Autoimmunity and Traumatic Brain Injury

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Federica Guaraldi

2015-05-01

Full Text Available Background: Traumatic brain injury (TBI is a leading cause of secondary hypopituitarism in children and adults, and is responsible for impaired quality of life, disabilities and compromised development. Alterations of pituitary function can occur at any time after the traumatic event, presenting in various ways and evolving during time, so they require appropriate screening for early detection and treatment. Although the exact pathophysiology is unknown, several mechanisms have been hypothesized, including hypothalamic-pituitary autoimmunity (HP-A. The aim of this study was to systematically review literature on the association between HP-A and TBI-induced hypopituitarism. Major pitfalls related to the HP-A investigation were also discussed. Methods: The PubMed database was searched with a string developed for this purpose, without temporal or language limits, for original articles assessing the association of HP-A and TBI-induced hypopituitarism. Results: Three articles from the same group met the inclusion criteria. Anti-pituitary and anti-hypothalamic antibodies were detected using indirect immunofluorescence in a significant number of patients with acute and chronic TBI. Elevated antibody titer was associated with an increased risk of persistent hypopituitarism, especially somatotroph and gonadotroph deficiency, while no correlations were found with clinical parameters. Conclusion: HPA seems to contribute to TBI-induced pituitary damage, although major methodological issues need to be overcome and larger studies are warranted to confirm these preliminary data.

Is autoimmune thyroid dysfunction a risk factor for gestational diabetes?

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Pascual Corrales, Eider; Andrada, Patricia; Aubá, María; Ruiz Zambrana, Alvaro; Guillén Grima, Francisco; Salvador, Javier; Escalada, Javier; Galofré, Juan C

2014-01-01

Some recent studies have related autoimmune thyroid dysfunction and gestational diabetes (GD). The common factor for both conditions could be the existence of pro-inflammatory homeostasis. The study objective was therefore to assess whether the presence of antithyroid antibodies is related to the occurrence of GD. Fifty-six pregnant women with serum TSH levels ≥ 2.5 mU/mL during the first trimester were retrospectively studied. Antithyroid antibodies were measured, and an O'Sullivan test was performed. GD was diagnosed based on the criteria of the Spanish Group on Diabetes and Pregnancy. Positive antithyroid antibodies were found in 21 (37.50%) women. GD was diagnosed in 15 patients, 6 of whom (10.71%) had positive antibodies, while 9 (16.07%) had negative antibodies. Data were analyzed using exact logistic regression by LogXact-8 Cytel; no statistically significant differences were found between GD patients with positive and negative autoimmunity (OR = 1.15 [95%CI = 0.28-4.51]; P=1.00). The presence of thyroid autoimmunity in women with TSH above the recommended values at the beginning of pregnancy is not associated to development of GD. However, GD prevalence was higher in these patients as compared to the Spanish general population, suggesting the need for closer monitoring in pregnant women with TSH levels ≥ 2.5 mU/mL. Copyright © 2013 SEEN. Published by Elsevier Espana. All rights reserved.

High throughput screening for antibody induced complement-dependent cytotoxicity in early antibody discovery using homogeneous macroconfocal fluorescence imaging

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Gerritsen, Arnout F.; Bosch, Martijn; de Weers, Michel; van de Winkel, Jan G. J.; Parren, Paul W. H. I.

2010-01-01

Complement-dependent cytotoxicity (CDC) represents an important Fc-mediated effector function of antibodies and is a quality often sought in candidates for therapeutic antibody development in cancer. Antibodies inducing potent CDC are relatively rare as the ability to induce CDC is strongly

Association between antiphospholipid antibodies and recurrent fetal loss in women without autoimmune disease: a metaanalysis.

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Opatrny, Lucie; David, Michéle; Kahn, Susan R; Shrier, Ian; Rey, Evelyne

2006-11-01

To assess the strength of association between recurrent fetal loss (RFL) and presence of antiphospholipid antibodies (aPL) in women without autoimmune disease, and to examine whether magnitude of association varies according to type or titer of antibody and timing of fetal loss. We searched Medline and Current Contents for articles published between 1975 and 2003 with terms denoting early (less than 13 weeks) and late (less than 24 weeks) RFL associated with various aPL. Published case-control, cohort, and cross-sectional studies rated moderate or strong were included in our metaanalysis. Pooled odds ratios with 95% CI were generated using the random-effects models with Cochrane Review Manager software. Our analysis included 25 studies. Lupus anticoagulant (LAC) was associated with late RFL (OR 7.79, 95% CI 2.30-26.45); the association of LAC was stronger than that of any other aPL. IgG anticardiolipin antibodies (aCL), when combining all titers, were associated with both early (OR 3.56, 95% CI 1.48-8.59) and late RFL (OR 3.57, 95% CI 2.26-5.65). Restricting analysis to include only women with moderate to high titers increased the strength of association (OR 4.68, 95% CI 2.96-7.40). It was not possible to extract data on isolated low IgG aCL positivity. IgM aCL were associated with late RFL (OR 5.61, 95% CI 1.26-25.03). There was no association found between early RFL and anti-Beta2-glycoprotein I antibodies (OR 2.12, 95% CI 0.69-6.53). The magnitude of the association between aPL and RFL varies according to type of aPL. More data on the relationship between recurrent fetal loss and isolated IgM aCL as well as with low titer IgG aCL would be useful. The place of testing for anti-Beta2-glycoprotein I antibodies remains to be determined.

Protein adducts of malondialdehyde and 4-hydroxynonenal contribute to trichloroethene-mediated autoimmunity via activating Th17 cells: Dose– and time–response studies in female MRL+/+ mice

International Nuclear Information System (INIS)

Wang, Gangduo; Wang, Jianling; Fan, Xiuzhen; Ansari, G.A.S.; Khan, M. Firoze

2012-01-01

Highlights: ► TCE exposure led to dose- and time-related increases in MDA-/HNE-protein adducts and their antibodies. ► Increased MDA-/HNE-adducts were associated with increases in serum autoantibodies. ► MDA-/HNE-albumin adducts trigger greater release of IL-17 and IL-21 from splenocytes of TCE-treated mice. ► Results support that MDA-/HNE-modified proteins could contribute to an autoimmune response. -- Abstract: Trichloroethene (TCE), a common occupational and environmental toxicant, is known to induce autoimmunity. Previous studies in our laboratory showed increased oxidative stress in TCE-mediated autoimmunity. To further establish the role of oxidative stress and to investigate the mechanisms of TCE-mediated autoimmunity, dose– and time–response studies were conducted in MRL+/+ mice by treating them with TCE via drinking water at doses of 0.5, 1.0 or 2.0 mg/ml for 12, 24 or 36 weeks. TCE exposure led to dose-related increases in malondialdehyde (MDA)-/hydroxynonenal (HNE)-protein adducts and their corresponding antibodies in the sera and decreases in GSH and GSH/GSSG ratio in the kidneys at 24 and 36 weeks, with greater changes at 36 weeks. The increases in these protein adducts and decreases in GSH/GSSG ratio were associated with significant elevation in serum anti-nuclear- and anti-ssDNA-antibodies, suggesting an association between TCE-induced oxidative stress and autoimmune response. Interestingly, splenocytes from mice treated with TCE for 24 weeks secreted significantly higher levels of IL-17 and IL-21 than did splenocytes from controls after stimulation with MDA-mouse serum albumin (MSA) or HNE-MSA adducts. The increased release of these cytokines showed a dose-related response and was more pronounced in mice treated with TCE for 36 weeks. These studies provide evidence that MDA- and or HNE-protein adducts contribute to TCE-mediated autoimmunity, which may be via activation of Th17 cells.

Galectin-3 in autoimmunity and autoimmune diseases.

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

2015-08-01

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

Leucine-rich glioma inactivated-1 and voltage gated potassium channel autoimmune encephalitis associated with ischemic stroke; A Case Report

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Marisa Patryce McGinley

2016-05-01

Full Text Available Autoimmune encephalitis is associated with a wide variety of antibodies and clinical presentations. Voltage gated potassium channel (VGKC antibodies are a cause of autoimmune non-paraneoplastic encephalitis characterized by memory impairment, psychiatric symptoms, and seizures. We present a case of VGKC encephalitis likely preceding an ischemic stroke. Reports of autoimmune encephalitis associated with ischemic stroke are rare. Several hypothesizes linking these two disease processes are proposed.

Leucine-Rich Glioma Inactivated-1 and Voltage-Gated Potassium Channel Autoimmune Encephalitis Associated with Ischemic Stroke: A Case Report

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McGinley, Marisa; Morales-Vidal, Sarkis; Ruland, Sean

2016-01-01

Autoimmune encephalitis is associated with a wide variety of antibodies and clinical presentations. Voltage-gated potassium channel (VGKC) antibodies are a cause of autoimmune non-paraneoplastic encephalitis characterized by memory impairment, psychiatric symptoms, and seizures. We present a case of VGKC encephalitis likely preceding an ischemic stroke. Reports of autoimmune encephalitis associated with ischemic stroke are rare. Several hypotheses linking these two disease processes are proposed. PMID:27242653

Collagen-Induced Arthritis: A model for Murine Autoimmune Arthritis

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Pietrosimone, K. M.; Jin, M.; Poston, B.; Liu, P.

2015-01-01

Collagen-induced arthritis (CIA) is a common autoimmune animal model used to study rheumatoid arthritis (RA). The development of CIA involves infiltration of macrophages and neutrophils into the joint, as well as T and B cell responses to type II collagen. In murine CIA, genetically susceptible mice (DBA/1J) are immunized with a type II bovine collagen emulsion in complete Freund’s adjuvant (CFA), and receive a boost of type II bovine collagen in incomplete Freund’s adjuvant (IFA) 21 days aft...

High Prevalence of Neutrophil Cytoplasmic Autoantibodies in Infants with Food Protein-Induced Proctitis/Proctocolitis: Autoimmunity Involvement?

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Alena Sekerkova

2015-01-01

Full Text Available Background. Food protein-induced proctitis/proctocolitis (FPIP is the most common noninfectious colitis in children in the first year of life. Along with the overall clinical symptoms, diarrhoea and rectal bleeding are the main manifestations of the disease. There is no routine noninvasive test that would be specific for this type of colitis. The aim of our study was to find a noninvasive laboratory test or tests that may be helpful in differential diagnosis of food protein-induced proctitis/proctocolitis. Methods. ANA, ANCA, ASCA, a-EMA, a-tTg, specific IgE, total IgE, IgG, IgA, IgM, and concentration of serum calprotectin were measured in a group of 25 patients with colitis and 18 children with other diagnoses. Results. Atypical-pANCA antibodies of IgG isotype were detected in the sera of 24 patients by the method of indirect immunofluorescence, and 5 patients showed also the positivity of IgA isotype. In control samples these autoantibodies were not detected. Other autoantibodies were not demonstrated in either patient or control group. Conclusions. Of the parameters tested in noninfectious colitis, atypical-pANCA on ethanol-fixed granulocytes appears to be a suitable serological marker of food protein-induced proctitis/proctocolitis and suggests a possible involvement of an autoimmune mechanisms in the pathogenesis of this disease.

The role of parvovirus B19 in the pathogenesis of autoimmunity and autoimmune disease.

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Kerr, Jonathan R

2016-04-01

Human parvovirus B19 is a single-stranded DNA virus which preferentially targets the erythroblasts in the bone marrow. B19 infection commonly causes erythema infectiosum, arthralgia, fetal death, transient aplastic crisis in patients with shortened red cell survival, and persistent infection in people who are immunocompromised. Less common clinical manifestations include atypical skin rashes, neurological syndromes, cardiac syndromes, and various cytopenias. B19 infection has also been associated with development of a variety of different autoimmune diseases, including rheumatological, neurological, neuromuscular, cardiovascular, haematological, nephrological and metabolic. Production of a variety of autoantibodies has been demonstrated to occur during B19 infection and these have been shown to be key to the pathogenesis of the particular disease process in a significant number of cases, for example, production of rheumatoid factor in cases of B19-associated rheumatoid arthritis and production of anti-glutamic acid decarboxylase (GAD) in patients with B19-associated type 1 diabetes mellitus. B19 infection has also been associated with the development of multiple autoimmune diseases in 12 individuals. Documented mechanisms in B19-associated autoimmunity include molecular mimicry (IgG antibody to B19 proteins has been shown to cross react with a variety of recognised human autoantigens, including collagen II, keratin, angiotensin II type 1 receptor, myelin basic protein, cardiolipin, and platelet membrane glycoprotein IIb/IIIa), B19-induced apoptosis with presentation of self-antigens to T lymphocytes, and the phospholipase activity of the B19 unique VP1 protein. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Unusual pediatric co-morbility: autoimmune thyroiditis and cortico-resistant nephrotic syndrome in a 6-month-old Italian patient

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Urbano Flavia

2012-10-01

Full Text Available Abstract We report on a case of autoimmune thyroiditis in a 6-month-old patient with cortico-resistant nephrotic syndrome. Normal serum levels of thyroid hormons and thyroid-stimulating hormone were detected with high titers of circulant antithyroid antibodies and a dysomogeneous ultrasound appearance of the gland, typical of autoimmune thyroiditis. The research of maternal thyroid antibodies was negative. This is the first case of autoimmune thyroiditis found in such a young patient with pre-existing nephrotic syndrome ever described in literature. This association is random because nephrotic syndrome does not have an autoimmune pathogenesis and the genes involved in autoimmune thyroiditis are not related to those of nephrotic syndrome.

Autoimmune polyendocrinopathy and hypophysitis after Puumala hantavirus infection

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Marlene Tarvainen

2016-11-01

Full Text Available Puumala hantavirus (PUUV infection causes nephropathia epidemica (NE, a relatively mild form of haemorrhagic fever with renal syndrome (HFRS. Hypophyseal haemorrhage and hypopituitarism have been described in case reports on patients with acute NE. Chronic hypopituitarism diagnosed months or years after the acute illness has also been reported, without any signs of a haemorrhagic aetiology. The mechanisms leading to the late-onset hormonal defects remain unknown. Here, we present a case of NE-associated autoimmune polyendocrinopathy and hypopituitarism presumably due to autoimmune hypophysitis. Thyroid peroxidase antibody seroconversion occurred between 6 and 12 months, and ovarian as well as glutamate decarboxylase antibodies were found 18 months after acute NE. Brain MRI revealed an atrophic adenohypophysis with a heterogeneous, low signal intensity compatible with a sequela of hypophysitis. The patient developed central (or mixed central and peripheral hypothyroidism, hypogonadism and diabetes insipidus, all requiring hormonal replacement therapy. This case report suggests that late-onset hormonal defects after PUUV infection may develop by an autoimmune mechanism. This hypothesis needs to be confirmed by prospective studies with sufficient numbers of patients.

Impact of Autoantibodies against Glycolytic Enzymes on Pathogenicity of Autoimmune Retinopathy and Other Autoimmune Disorders

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Grazyna Adamus

2017-04-01

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.

Testicular tumors as a possible cause of antisperm autoimmune response.

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Paoli, Donatella; Gilio, Barbara; Piroli, Emanuela; Gallo, Mariagrazia; Lombardo, Francesco; Dondero, Franco; Lenzi, Andrea; Gandini, Loredana

2009-02-01

To evaluate the presence of antisperm antibodies in testicular cancer patients 1 month after orchiectomy and before radiotherapy or chemotherapy. Clinical study. Department of andrology and seminology at a university hospital. One hundred ninety patients with testicular cancer. Determination of semen parameters and autoimmune reaction evaluated on the sperm surface and in blood serum. Autoimmune reaction on the sperm surface by the direct immunobead test (IBT), and in blood serum by the indirect IBT and the gelatin agglutination test (GAT), was evaluated 1 month after orchiectomy and before beginning chemotherapy or radiotherapy. Of the 190 patients, 11 (5.8%) were positive for antisperm antibody by GAT. On indirect IBT, 3 of the 11 GAT-positive patients were positive to IgG class only, with values of 22%, 24%, and 40%. Of the 11 GAT-positive patients, 4 showed no antibody bound to the sperm surface, and 3 were positive to IgG class only (28%, 21%, and 38%), with binding exclusively on the tail. Direct IBT could not be performed in the remaining 4 patients. Our data support the hypothesis that testicular cancer might not be a possible cause of antisperm autoimmunization and infertility.

Preparation of monoclonal antibodies against radiation-induced protein

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Nozawa, R.; Tanaka, A.; Watanabe, H.; Kitayama, S.

1992-01-01

We obtained the 6 monoclonal antibodies against gamma-induced proteins of Deinococcus radiodurans, and these antibodies were designated as Mab-3F, 4B, 4D, 4F, 4G and 12G. Using these antibodies, we investigated the relations between gamma-induced proteins and other stress protein in strain R1, and the induction of proteins were compared among strain R1, resistant mutant (rec1) and radiosensitive mutant (rec30). We found new 6 proteins recognized by these monoclonal antibodies which were induced after gamma-irradiation especially in strain R1 and rec 1, but not induced in strain rec30. We suppose that these proteins participate in repair of DNA damages including double strand breaks caused by gamma-irradiation. One of them was around 46kDa protein band recognized by Mab-12G, and this protein was so induced in a large quantity after irradiation that the protein could detect by gold staining. In addition to this observation, we found some proteins which were induced in R1 and rec 1 by gamma-irradiation and other stress, but not in strain rec30, such as 31kDa protein band recognized by Mab-3F, 4B and 4G, and other 11 proteins which were especially induced in irradiated strain R1. The latter proteins might be reinforcement factor to radioresistance such as GroE and DnaK, or participant in repair of damage by gamma-irradiation in strain R1. (author)

Antibodies to autoantigen targets in myasthenia and their value in clinical practice

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S. I. Dedaev

2014-01-01

Full Text Available Myasthenia gravis is a classic autoimmune disease, which clinical manifestations in the form of weakness and abnormal muscle fatigue, due to the damaging effect of polyclonal antibodies to different structures of the neuromuscular synapse and muscles. The study of autoimmune substrate with myasthenia is routine in many clinics dealing with the problems of neuromuscular pathology, and the identification of high concentration of serum antibodies to a number of antigenic structures is the gold standard in diagnosis.Determination of serum antibodies to various autoimmune targets is an important tool in clinical practice. The majority of patients shows the high concentration of antibodies to AchR that gives the opportunity to use it as an important diagnostic criterion. The specificity of changes in the concentration of AchR-antibodies due to pathogenetic treatment allows to objectify the suppression of autoimmune aggression and evaluate the reliability of remission. However, the absence of AchR-antibodies when there are clear clinical and electromyography signs of myasthenia gravis suggests an autoimmune attack against a number of other targets, the most studied of which is the MuSK. On the contrary, patients with myasthenia gravis associated with thymoma, almost always have a higher level of AchR-antibodies. The presence of thymoma is accompanied by the generation of antibodies to titin and RyR, which is also observed in persons with late-onset myasthenia without thymoma. High concentration of antibodies to these structures can be interpreted as a reliable sign of thymoma in patients younger than 60 years.

Smooth muscle antibodies and type 1 autoimmune hepatitis.

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Muratori, Paolo; Muratori, Luigi; Agostinelli, Daniela; Pappas, Georgios; Veronesi, Lorenza; Granito, Alessandro; Cassani, Fabio; Terlizzi, Paolo; Lenzi, Marco; Bianchi, Francesco B

2002-12-01

Smooth muscle antibodies (SMA) characterize type 1 autoimmune hepatitis. Our aim was to evaluate sensitivity and specificity of different immunofluorescence substrates for the detection of SMA. Sera from 55 patients with type 1 AIH 20 with primary biliary cirrhosis, 20 with HCV-related chronic hepatitis and 25 blood donors were studied for SMA and anti-microfilaments reactivity by immunofluorescence on rat tissue sections, cultured fibroblasts and commercially available HEp-2 cells (collectively revealing the so called anti-actin pattern), and for the XR1 system by counterimmunoelectrophoresis. SMA was classified on the basis of its immunofluorescence pattern (V--vessels, G--glomerular, T--tubular). As further control group, we studied 26 patients with a diagnosis other than AIH, selected on the basis of a SMA-non-T/XR1 positivity. In patients with AIH the SMA-T pattern on rodent tissue, and anti-MF on fibroblasts and on HEp-2 cells were present in 80, 82 and 80%, respectively. Five out of 11 SMA-non T positive AIH patients were anti-MF positive. None of the pathological and healthy controls was positive for SMA-T or anti-MF reactivity. XR1 system was present in 84% of AIH patients and in 5% of pathological controls (p = 0.01). Two out of 26 SMA-non-T/XR1 positive sera were positive for anti-MF by fibroblasts and HEp-2 cells. A significant correlation was found between SMA-T pattern and anti-MF reactivity; no correlation was found between XR1 system and SMA-T pattern or anti-MF reactivity. SMA-T pattern is highly sensitive and specific first diagnostic test for type 1 AIH; anti-MF can be used as additional tool for the diagnosis, particularly when, despite the absence of the SMA-T pattern, AIH is strongly suspected.

Antiretinal antibody- proven autoimmune retinopathy

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Sharanya Abraham

2017-01-01

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.

Autoimmune hepatitis vs. pregnancy

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Olga Adamczyk-Gruszka

2017-07-01

Full Text Available Introduction Autoimmune hepatitis (AIH is a disease of unknown etiology. In pregnancy, it may have mild clinical course as well as can lead to liver failure, or exacerbation of clinical symptoms. In pregnant women the severity of symptoms is often observed between the second and third trimester, and in the puerperium. The disease is marked by enhanced activity of Th lymphocytes, which hepatocytes recognize as foreign antigens. This results in interleukin production activating B lymphocytes, and the production of specific antibodies attacking and destroying the hepatocytes. Case report A 35-year old patient, CII PII, 7 Hbd, with autoimmune hepatitis reported for a check-up. Her first pregnancy was 18 years ago, without history of underlying disease, carried to term without complications. The woman gave birth to a baby-son weighing 3,280g, 10 points Apgar. The delivery was spontaneous and uneventful. The patient got pregnant after an 18-year break. When she twice-tested positively for pregnancy, the treatment with azathioprine was switched to prednisolone. Over the pregnancy the patient was hospitalized 4 times, in 25, 29, 35, and 37 week of gestation due to a threat of preterm delivery, and pregnancy-related cholestasis associated with AIH. In 37 week of gestation, delivery was induced, and she gave birth to a healthy male, weighing 2,650 g, body height of 49 cm, 10 points Apgar scale. The liver function improved and stabilized after the delivery. Treatment with prednisolone has been continued, and the patient’s condition is still controlled. Pregnant patients with autoimmune hepatitis often experience exacerbation of the disease, especially in the third trimester, and in the postpartum period. This case shows that with proper care it is possible to continue and terminate pregnancy safely for the mother and her newly born baby.

Autoimmune Polyendocrine Syndrome 3 Onset with Severe Ketoacidosis in a 74-Year-Old Woman

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Stefano Benedini

2015-01-01

Full Text Available Type 1 diabetes mellitus (T1D, autoimmune thyroid disease, and autoimmune gastritis often occur together forming the so-called autoimmune polyendocrine syndrome type 3 (APS3. We here report a clinical case of a 74-year-old woman who presented for the first time with severe hyperglycemia and ketoacidosis diagnosed as T1D. Further clinical investigations revealed concomitant severe hypothyroidism with autoimmune thyroid disease and severe cobalamin deficiency due to chronic atrophic gastritis. The diagnosis of type 1 diabetes mellitus was confirmed by the detection of autoantibodies against glutamic acid decarboxylase 65, islet cell antibodies, and anti-insulin autoantibodies. Anti-thyroperoxidase, anti-thyroglobulin, and anti-gastric parietal cell antibodies were also clearly positive. The case emphasized that new onset diabetic ketoacidosis, hypothyroidism, and cobalamin deficiency may simultaneously occur, and one disease can mask the features of the other, thereby making diagnosis difficult. It is noteworthy that an APS3 acute episode occurred in an asymptomatic elder woman for any autoimmune diseases.

A Distinct Class of Antibodies May Be an Indicator of Gray Matter Autoimmunity in Early and Established Relapsing Remitting Multiple Sclerosis Patients

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Ann J. Ligocki

2015-10-01

Full Text Available * These authors contributed equally to the work in this manuscript.We have previously identified a distinct class of antibodies expressed by B cells in the cerebrospinal fluid (CSF of early and established relapsing remitting multiple sclerosis (RRMS patients that is not observed in healthy donors. These antibodies contain a unique pattern of mutations in six codons along VH4 antibody genes that we termed the antibody gene signature (AGS. In fact, patients who have such B cells in their CSF are identified as either having RRMS or developing RRMS in the future. As mutations in antibody genes increase antibody affinity for particular antigens, the goal for this study was to investigate whether AGS+ antibodies bind to brain tissue antigens. Single B cells were isolated from the CSF of 10 patients with early or established RRMS. We chose 32 of these B cells that expressed antibodies enriched for the AGS for further study. We generated monoclonal full-length recombinant human antibodies (rhAbs and used both immunological assays and immunohistochemistry to investigate the capacity of these AGS+ rhAbs to bind brain tissue antigens. AGS+ rhAbs did not recognize myelin tracts in the corpus callosum. Instead, AGS+ rhAbs recognized neuronal nuclei and/or astrocytes, which are prevalent in the cortical gray matter. This pattern was unique to the AGS+ antibodies from early and established RRMS patients, as AGS+ antibodies from an early neuromyelitis optica patient did not display the same reactivity. Prevalence of CSF-derived B cells expressing AGS+ antibodies that bind to these cell types may be an indicator of gray matter-directed autoimmunity in early and established RRMS patients.

Hapten-Induced Contact Hypersensitivity, Autoimmune Reactions, and Tumor Regression: Plausibility of Mediating Antitumor Immunity

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Dan A. Erkes

2014-01-01

Full Text Available Haptens are small molecule irritants that bind to proteins and elicit an immune response. Haptens have been commonly used to study allergic contact dermatitis (ACD using animal contact hypersensitivity (CHS models. However, extensive research into contact hypersensitivity has offered a confusing and intriguing mechanism of allergic reactions occurring in the skin. The abilities of haptens to induce such reactions have been frequently utilized to study the mechanisms of inflammatory bowel disease (IBD to induce autoimmune-like responses such as autoimmune hemolytic anemia and to elicit viral wart and tumor regression. Hapten-induced tumor regression has been studied since the mid-1900s and relies on four major concepts: (1 ex vivo haptenation, (2 in situ haptenation, (3 epifocal hapten application, and (4 antigen-hapten conjugate injection. Each of these approaches elicits unique responses in mice and humans. The present review attempts to provide a critical appraisal of the hapten-mediated tumor treatments and offers insights for future development of the field.

Autoimmune Addison's disease.

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Napier, Catherine; Pearce, Simon H S

2012-12-01

Addison's disease is a rare autoimmune disorder. In the developed world, autoimmune adrenalitis is the commonest cause of primary adrenal insufficiency, where the majority of patients have circulating antibodies against the key steroidogenic enzyme 21-hydroxylase. A complex interplay of genetic, immunological and environmental factors culminates in symptomatic adrenocortical insufficiency, with symptoms typically developing over months to years. Biochemical evaluation and further targeted investigations must confirm primary adrenal failure and establish the underlying aetiology. The diagnosis of adrenocortical insufficiency will necessitate lifelong glucocorticoid and mineralocorticoid replacement therapy, aiming to emulate physiological patterns of hormone secretion to achieve well-being and good quality of life. Education of patients and healthcare professionals is essential to minimise the risk of a life-threatening adrenal crisis, which must be promptly recognised and aggressively managed when it does occur. This article provides an overview of our current understanding of the natural history and underlying genetic and immunological basis of this condition. Future research may reveal novel therapeutic strategies for patient management. Until then, optimisation of pharmacological intervention and continued emphasis on education and empowerment of patients should underpin the management of individuals with autoimmune Addison's disease. Copyright © 2012. Published by Elsevier Masson SAS.

Identification of anti-CD98 antibody mimotopes for inducing antibodies with antitumor activity by mimotope immunization.

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Saito, Misa; Kondo, Masahiro; Ohshima, Motohiro; Deguchi, Kazuki; Hayashi, Hideki; Inoue, Kazuyuki; Tsuji, Daiki; Masuko, Takashi; Itoh, Kunihiko

2014-04-01

A mimotope is an antibody-epitope-mimicking peptide retrieved from a phage display random peptide library. Immunization with antitumor antibody-derived mimotopes is promising for inducing antitumor immunity in hosts. In this study, we isolated linear and constrained mimotopes from HBJ127, a tumor-suppressing anti-CD98 heavy chain mAb, and determined their abilities for induction of antitumor activity equal to that of the parent antibody. We detected elevated levels of antipeptide responses, but failed to detect reactivity against native CD98-expressing HeLa cells in sera of immunized mice. Phage display panning and selection of mimotope-immunized mouse spleen-derived antibody Fab library showed that HeLa cell-reactive Fabs were successfully retrieved from the library. This finding indicates that native antigen-reactive Fab clones represented an undetectable minor population in mimotope-induced antibody repertoire. Functional and structural analysis of retrieved Fab clones revealed that they were almost identical to the parent antibody. From these results, we confirmed that mimotope immunization was promising for retrieving antitumor antibodies equivalent to the parent antibody, although the co-administration of adjuvant compounds such as T-cell epitope peptides and Toll-like receptor 4 agonist peptides is likely to be necessary for inducing stronger antitumor immunity than mimotope injection alone. © 2014 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.

Anti‑livin antibodies in Hashimoto thyroiditis.

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Baumann-Antczak, Aleksandra; Kosowicz, Jerzy; Zamysłowska, Hanna; Ruchała, Marek

2012-01-01

Livin belongs to the family of apoptosis inhibitors. High livin expression is observed in malignancies of the gastrointestinal tract, lungs, breast, and kidneys, but it is not present in differentiated adult tissues. In some malignant processes, anti‑livin antibodies are present. The aim of the study was to evaluate the prevalence of anti‑livin antibodies in Hashimoto thyroiditis, a disease characterized by rapid and widespread thyrocyte apoptosis. The study comprised 65 women with Hashimoto thyroiditis and the control group of 40 healthy women. In the majority of the patients, clinical manifestations of hypothyroidism were observed; all patients had high levels of serum antithyroid peroxidase antibodies. A solid‑phase radioimmunoassay in livin‑coated polyethylene tubes using 125I-labeled protein A was used to determine anti-livin antibodies. Significant amounts of anti-livin antibodies were reported in 18 patients (26.8%); 3 patients (4.6%) had borderline antibody levels; while in controls only 1 patient was positive (2.5%, P Hashimoto thyroiditis, an autoimmune process is more general and involves numerous autoantibodies including an antibody against apoptosis inhibitor - livin. Anti‑livin antibodies cannot serve only as a marker of malignancy because they are also present in autoimmune processes.

The role of the autoimmunity laboratory in autoimmune diseases

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SS Hasson

2012-04-01

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.

Vitiligo: How do oxidative stress-induced autoantigens trigger autoimmunity?

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Xie, Heng; Zhou, Fubo; Liu, Ling; Zhu, Guannan; Li, Qiang; Li, Chunying; Gao, Tianwen

2016-01-01

Vitiligo is a common depigmentation disorder characterized by a loss of functional melanocytes and melanin from epidermis, in which the autoantigens and subsequent autoimmunity caused by oxidative stress play significant roles according to hypotheses. Various factors lead to reactive oxygen species (ROS) overproduction in the melanocytes of vitiligo: the exogenous and endogenous stimuli that cause ROS production, low levels of enzymatic and non-enzymatic antioxidants, disturbed antioxidant pathways and polymorphisms of ROS-associated genes. These factors synergistically contribute to the accumulation of ROS in melanocytes, finally leading to melanocyte damage and the production of autoantigens through the following ways: apoptosis, accumulation of misfolded peptides and cytokines induced by endoplasmic reticulum stress as well as the sustained unfolded protein response, and an 'eat me' signal for phagocytic cells triggered by calreticulin. Subsequently, autoantigens presentation and dendritic cells maturation occurred mediated by the release of antigen-containing exosomes, adenosine triphosphate and melanosomal autophagy. With the involvement of inducible heat shock protein 70, cellular immunity targeting autoantigens takes the essential place in the destruction of melanocytes, which eventually results in vitiligo. Several treatments, such as narrow band ultraviolet, quercetin and α-melanophore-stimulating hormone, are reported to be able to lower ROS thereby achieving repigmentation in vitiligo. In therapies targeting autoimmunity, restore of regulatory T cells is absorbing attention, in which narrow band ultraviolet also plays a role. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Seizure semiology: an important clinical clue to the diagnosis of autoimmune epilepsy.

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Lv, Rui-Juan; Ren, Hai-Tao; Guan, Hong-Zhi; Cui, Tao; Shao, Xiao-Qiu

2018-02-01

The purpose of this study is to analyze the seizure semiologic characteristics of patients with autoimmune epilepsy (AE) and describe the investigation characteristics of AE using a larger sample size. This observational retrospective case series study was conducted from a tertiary epilepsy center between May 2014 and March 2017. Cases of new-onset seizures were selected based on laboratory evidence of autoimmunity. At the same time, typical mesial temporal lobe epilepsy (MTLE) patients with hippocampal sclerosis (HS) were recruited as the control group from the subjects who underwent presurgical evaluation during the same period. A total of 61 patients with AE were identified. Specific autoimmune antibodies were detected in 39 patients (63.93%), including anti-VGKC in 23 patients (37.70%), anti-NMDA-R in 9 patients (14.75%), anti-GABA B -R in 6 patients (9.84%), and anti-amphiphysin in 1 patient (1.64%). Regarding the seizure semiology, no significant differences were noted between AE patients with autoantibody and patients with suspected AE without antibody. Compared to typical MTLE patients with HS, both AE patients with autoantibody and patients with suspected AE without antibody had the same seizure semiologic characteristics, including more frequent SPS or CPS, shorter seizure duration, rare postictal confusion, and common sleeping SGTC seizures. This study highlights important seizure semiologic characteristics of AE. Patients with autoimmune epilepsy had special seizure semiologic characteristics. For patients with autoimmune epilepsy presenting with new-onset seizures in isolation or with a seizure-predominant neurological disorder, the special seizure semiologic characteristics may remind us to test neuronal nuclear/cytoplasmic antibodies early and initiate immunomodulatory therapies as soon as possible. Furthermore, the absence of neural-specific autoantibodies does not rule out AE.

Diagnostic accuracy of atypical p-ANCA in autoimmune hepatitis using ROC- and multivariate regression analysis.

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Terjung, B; Bogsch, F; Klein, R; Söhne, J; Reichel, C; Wasmuth, J-C; Beuers, U; Sauerbruch, T; Spengler, U

2004-09-29

Antineutrophil cytoplasmic antibodies (atypical p-ANCA) are detected at high prevalence in sera from patients with autoimmune hepatitis (AIH), but their diagnostic relevance for AIH has not been systematically evaluated so far. Here, we studied sera from 357 patients with autoimmune (autoimmune hepatitis n=175, primary sclerosing cholangitis (PSC) n=35, primary biliary cirrhosis n=45), non-autoimmune chronic liver disease (alcoholic liver cirrhosis n=62; chronic hepatitis C virus infection (HCV) n=21) or healthy controls (n=19) for the presence of various non-organ specific autoantibodies. Atypical p-ANCA, antinuclear antibodies (ANA), antibodies against smooth muscles (SMA), antibodies against liver/kidney microsomes (anti-Lkm1) and antimitochondrial antibodies (AMA) were detected by indirect immunofluorescence microscopy, antibodies against the M2 antigen (anti-M2), antibodies against soluble liver antigen (anti-SLA/LP) and anti-Lkm1 by using enzyme linked immunosorbent assays. To define the diagnostic precision of the autoantibodies, results of autoantibody testing were analyzed by receiver operating characteristics (ROC) and forward conditional logistic regression analysis. Atypical p-ANCA were detected at high prevalence in sera from patients with AIH (81%) and PSC (94%). ROC- and logistic regression analysis revealed atypical p-ANCA and SMA, but not ANA as significant diagnostic seromarkers for AIH (atypical p-ANCA: AUC 0.754+/-0.026, odds ratio [OR] 3.4; SMA: 0.652+/-0.028, OR 4.1). Atypical p-ANCA also emerged as the only diagnostically relevant seromarker for PSC (AUC 0.690+/-0.04, OR 3.4). None of the tested antibodies yielded a significant diagnostic accuracy for patients with alcoholic liver cirrhosis, HCV or healthy controls. Atypical p-ANCA along with SMA represent a seromarker with high diagnostic accuracy for AIH and should be explicitly considered in a revised version of the diagnostic score for AIH.

21 CFR 866.5100 - Antinuclear antibody immunological test system.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Antinuclear antibody immunological test system....5100 Antinuclear antibody immunological test system. (a) Identification. An antinuclear antibody... the autoimmune antibodies in serum, other body fluids, and tissues that react with cellular nuclear...

Association of Cytotoxic T-Lymphocyte Antigen 4 (CTLA4) and Thyroglobulin (TG) Genetic Variants with Autoimmune Hypothyroidism

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Patel, Hinal; Mansuri, Mohmmad Shoab; Singh, Mala; Begum, Rasheedunnisa; Shastri, Minal; Misra, Ambikanandan

2016-01-01

Autoimmune hypothyroidism is known to be caused by immune responses related to the thyroid gland and its immunological feature includes presence of autoimmune antibodies. Therefore the aim was to analyze presence of anti-TPO antibodies in hypothyroidism patients in Gujarat. Cytotoxic T-Lymphocyte Antigen 4 (CTLA4) is one of the susceptibility genes for various autoimmune diseases. Hence, exon1 +49A/G and 3’UTR CT60A/G single nucleotide polymorphisms (SNPs) in CTLA4 and its mRNA expression levels were investigated in autoimmune hypothyroidism patients. Thyroglobulin (TG) is known to be associated with autoimmune thyroid disorders and thus exon 33 (E33) SNP in TG was investigated. We analyzed the presence of anti-TPO antibodies in the plasma samples of 84 hypothyroidism patients and 62 controls by ELISA. PCR-RFLP technique was used for genotyping of polymorphisms. sCTLA4 and flCTLA4 mRNA expression levels were assessed by real time PCR. 59.52% of hypothyroid patients had anti-TPO antibodies in their circulation. The genotype and allele frequencies differed significantly for +49A/G (p = 0.0004 for +49AG, p = 0.0019 for +49GG & p = 0.0004 for allele), CT60 (p = 0.0110 for CT60AG, p = 0.0005 for CT60GG & phypothyroidism when adjusted for age and gender. Our results suggest +49A/G and CT60 polymorphism of CTLA4 and E33 polymorphism of TG may be genetic risk factors for autoimmune hypothyroidism susceptibility and down regulation of both forms of CTLA4 advocates the crucial role of CTLA4 in pathogenesis of autoimmune hypothyroidism. PMID:26963610

[Maternal autoimmune thyroid disease: relevance for the newborn].

Science.gov (United States)

Temboury Molina, M Carmen; Rivero Martín, M José; de Juan Ruiz, Jesús; Ares Segura, Susana

2015-04-08

Autoimmune thyroid disease is amongst the most frequent endocrine disorders during pregnancy. It is associated with an increase in perinatal morbidity, congenital defects, neurological damage, fetal and neonatal thyroid dysfunction. Maternal thyroid hormones play a key role in child neurodevelopment. We aimed to evaluate the thyroid function and the clinical course of neonates born from mothers with autoimmune thyroid disease during the first months of life in order to define the follow-up. We monitored thyroid function and clinical status during the first months in 81 newborns of mothers with autoimmune thyroid disease; 16 had Graves disease and 65 autoimmune thyroiditis. A percentage of 4.93 newborns had congenital defects, and 8.64% neonates showed an increase in thyrotropin (TSH) (>9.5 μUI/mL 2 times) and required thyroxin within the first month of life. A 85.7% of these showed a negative newborn screening (due to a later increase of TSH). A higher TSH value in the newborn was related to an older age of the mother, higher levels of thyroid peroxidase (TPO) antibody during pregnancy and lower birth weight. A higher free thyroxine (FT4) value in the newborn was related to fewer days of life and mothers with Graves disease. We recommend the evaluation of TSH, T4 and TPO antibodies before 10 weeks in all pregnant women with follow-up if maternal thyroid autoimmunity or disorders is detected. It is also recommended to test children's serum TSH and FT4 at 48 h of life in newborns of mothers with autoimmune thyroid disease and repeat them between the 2nd and 4th week in children with TSH>6 μUI/mL. Careful endocrine follow-up is advised in pregnant women and children if hyperthyroidism is detected. Copyright © 2013 Elsevier España, S.L.U. All rights reserved.

Frequently relapsing anti-glomerular basement membrane antibody disease with changing clinical phenotype and antibody characteristics over time

OpenAIRE

Gu, Bobby; Magil, Alex B.; Barbour, Sean J.

2016-01-01

Anti-glomerular basement membrane (GBM) antibody disease is a typically monophasic autoimmune disease with severe pulmonary and renal involvement. We report an atypical case of frequently relapsing anti-GBM antibody disease with both anti-GBM antibody?positive flares with pulmonary and renal involvement, and anti-GBM antibody?negative flares that were pulmonary limited with no histologic renal disease. This is the first report of alternating disease phenotype and anti-GBM antibody status over...

Auto-immune Haemolytic Anaemia and Paroxys

African Journals Online (AJOL)

who presented with an acute auto-immune haemolytic anaemia. In addition to a persistently positive Coombs test, with specific red cell auto-antibodies, the acidified serum test and the sucrose haemolysis test were repeatedly positive. CASE REPORT. A 24-year-old Indian woman was admitted to hospital in. July 1969.

Immune responses to Epstein-Barr virus in individuals with systemic and organ specific autoimmune disorders

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Kannangai R

2010-01-01

Full Text Available Purpose: Autoimmune diseases usually manifest in genetically predisposed individuals following an environmental trigger. There are several viral infections including Epstein-Barr virus (EBV implicated in the pathogenesis of autoimmune disorders. The aim of this study was to look at the antibody pattern to EBV proteins in the plasma of both systemic and organ specific autoimmune disorders, estimate pro-inflammatory plasma cytokines (IL-8 and TNF-α among these autoimmune patients and compare the observations with those in normal healthy controls. Materials and Methods: Samples from 44 rheumatoid arthritis patients, 25 Hashimoto′s thyroiditis patients, appropriately age and sex matched healthy controls were tested for EBV IgM antibodies by an immunoblot assay and two cytokines (IL-8 and TNF-α by commercial assays. Results: Among the rheumatoid arthritis patients, 23 (52% were positive for EBNA1 antibody, while 13 (52% of the Hashimoto′s thyroiditis patients and 12 (30% of the healthy controls showed similar bands. The intensity of the bands was high in the autoimmune patients when compared to the bands seen in control samples. The difference in the EBNA1 reactivity between rheumatoid arthritis patients and controls were significant (P = 0.038. There was a significant difference in the IgM reactivity to VCAp19 protein between patients and controls (P = 0.011. Conclusion: Our study showed an increased EBV activation among the autoimmune patient groups compared to the normal healthy controls. Further studies are required to delineate the association between the aetiology of autoimmune disorders and EBV.

[Treatment of autoimmune hepatic diseases].

Science.gov (United States)

Bueverov, A O

2004-01-01

The immunosuppresive drugs, primarily glucocorticosteroids, serve as the basis for the pathogenetic treatment of autoimmune diseases of the liver. In autoimmune hepatitis, immunosuppressive therapy induces and maintains persistent remission in most patients while in primary biliary cirrhosis and primary sclerosing cholangitis, its capacities are substantially limited. Ursodeoxycholic acid is used as the basic drug in predominantly occurring intrahepatic cholestasis. The treatment of cross autoimmune syndromes generally requires the choice of a combination of drugs.

The relevance of VGKC positivity in the absence of LGI1 and Caspr2 antibodies.

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van Sonderen, Agnes; Schreurs, Marco W J; de Bruijn, Marienke A A M; Boukhrissi, Sanae; Nagtzaam, Mariska M P; Hulsenboom, Esther S P; Enting, Roelien H; Thijs, Roland D; Wirtz, Paul W; Sillevis Smitt, Peter A E; Titulaer, Maarten J

2016-05-03

To assess the clinical relevance of a positive voltage-gated potassium channel (VGKC) test in patients lacking antibodies to LGI1 and Caspr2. VGKC-positive patients were tested for LGI1 and Caspr2 antibodies. Patients lacking both antibodies were matched (1:2) to VGKC-negative patients. Clinical and paraclinical criteria were used to blindly determine evidence for autoimmune inflammation in both groups. Patients with an inconclusive VGKC titer were analyzed in the same way. A total of 1,455 patients were tested by VGKC radioimmunoassay. Fifty-six patients tested positive, 50 of whom were available to be included. Twenty-five patients had antibodies to LGI1 (n = 19) or Caspr2 (n = 6) and 25 patients lacked both antibodies. Evidence for autoimmune inflammation was present in 7 (28%) of the VGKC-positive patients lacking LGI1 and Caspr2, compared to 9 (18%) of the VGKC-negative controls (p = 0.38). Evidence for autoimmune inflammation was mainly found in patients with limbic encephalitis/encephalomyelitis (57%), but not in other clinical phenotypes (5%, p VGKC titers were significantly higher in patients with antibodies to LGI1 or Caspr2 (p VGKC titer, while many VGKC-positive patients had no evidence for autoimmune inflammation. VGKC positivity in the absence of antibodies to LGI1 and Caspr2 is not a clear marker for autoimmune inflammation and seems not to contribute in clinical practice. No cutoff value for the VGKC titer was appropriate to discriminate between patients with and without autoimmune inflammation. © 2016 American Academy of Neurology.

Predictive value of antinuclear antibodies in autoimmune diseases classified by clinical criteria: Analytical study in a specialized health institute, one year follow-up

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María Elena Soto

2015-01-01

Full Text Available Introduction: Determination of antinuclear antibodies (ANA by indirect immunofluorescence (IIF is usually the initial test for the diagnosis of systemic rheumatic diseases (SRD. Assigning predictive values to positive and negative results of the test is vital because lack of knowledge about ANAs and their usefulness in classification criteria of SRD leads to inappropriate use. Methods: Retrospective study, ANA tests requested by different specialties, correlation to patients' final diagnosis. Results: The prevalence of autoimmune disease was relatively low in our population yielding a low PPV and a high NPV for the ANA test. 40% of the patients had no clinical criteria applied prior to test. Coexistence of two or more autoimmune disorders affects prevalence and predictive values. Conclusion: Application of the test after careful evaluation for clinical criteria remarkably improves the positive likelihood ratio for the diagnosis.

Ameliorating Role Exerted by Al-Hijamah in Autoimmune Diseases: Effect on Serum Autoantibodies and Inflammatory Mediators

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Baghdadi, Hussam; Abdel-Aziz, Nada; Ahmed, Nagwa Sayed; Mahmoud, Hany Salah; Barghash, Ayman; Nasrat, Abdullah; Nabo, Manal Mohamed Helmy; El Sayed, Salah Mohamed

2015-01-01

Autoimmune diseases have common properties characterized by abnormal blood chemistry with high serum autoimmune antibodies, and inflammatory mediators. Those causative pathological substances (CPS) cannot be excreted by physiological mechanisms. Current treatments for autoimmune diseases involve steroids, cytotoxic drugs, plasmapheresis and monoclonal antibodies. Wet cupping therapy (WCT) of prophetic medicine is called Al-hijamah that treats numerous diseases having different etiology and pathogenesis via a pressure-dependent and size-dependent non-specific filtration then excretion of CPS causing clearance of blood and interstitial fluids. Al-hijamah clears blood passing through the fenestrated skin capillaries. Medical bases of Al-hijamah were reported in the evidence-based Taibah mechanism (Taibah theory). Al-hijamah was reported to be an excellent treatment for rheumatoid arthritis that improved patients’ blood chemistry and induced significant clinical improvement and pharmacological potentiation. Al-hijamah improved the natural immunity and suppressed the pathological immunity through decreasing the serum level of autoantibodies, inflammatory mediators, and serum ferritin (a key player in autoimmunity). Al-hijamah reduced significantly pain severity, number of swollen joints and disease activity with no significant side effects. Main steps of Al-hijamah are skin suction (cupping), scarification (sharatmihjam in Arabic) and second suction (triple S technique) that is better therapeutically than the traditional WCT (double S technique). Whenever an excess noxious substance is to be removed from patients’ blood and interstitial fluids, Al-hijamah is indicated. Shartatmihjam is a curative treatment in prophetic teachings according to the prophetic hadeeth: “Cure is in three: in shartatmihjam, oral honey and cauterization. I do not recommend my nation to cauterize”. Al-hijamah may have better therapeutic benefits than plasmapheresis. Al-hijamah may be

Prostaglandin D2 Receptor DP1 Antibodies Predict Vaccine-induced and Spontaneous Narcolepsy Type 1: Large-scale Study of Antibody Profiling

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Helle Sadam

2018-03-01

Full Text Available Background: Neuropathological findings support an autoimmune etiology as an underlying factor for loss of orexin-producing neurons in spontaneous narcolepsy type 1 (narcolepsy with cataplexy; sNT1 as well as in Pandemrix influenza vaccine-induced narcolepsy type 1 (Pdmx-NT1. The precise molecular target or antigens for the immune response have, however, remained elusive. Methods: Here we have performed a comprehensive antigenic repertoire analysis of sera using the next-generation phage display method - mimotope variation analysis (MVA. Samples from 64 children and adolescents were analyzed: 10 with Pdmx-NT1, 6 with sNT1, 16 Pandemrix-vaccinated, 16 H1N1 infected, and 16 unvaccinated healthy individuals. The diagnosis of NT1 was defined by the American Academy of Sleep Medicine international criteria of sleep disorders v3. Findings: Our data showed that although the immunoprofiles toward vaccination were generally similar in study groups, there were also striking differences in immunoprofiles between sNT1 and Pdmx-NT1 groups as compared with controls. Prominent immune response was observed to a peptide epitope derived from prostaglandin D2 receptor (DP1, as well as peptides homologous to B cell lymphoma 6 protein. Further validation confirmed that these can act as true antigenic targets in discriminating NT1 diseased along with a novel epitope of hemagglutinin of H1N1 to delineate exposure to H1N1. Interpretation: We propose that DP1 is a novel molecular target of autoimmune response and presents a potential diagnostic biomarker for NT1. DP1 is involved in the regulation of non-rapid eye movement (NREM sleep and thus alterations in its functions could contribute to the disturbed sleep regulation in NT1 that warrants further studies. Together our results also show that MVA is a helpful method for finding novel peptide antigens to classify human autoimmune diseases, possibly facilitating the design of better therapies. Keywords: Narcolepsy type 1

Genetic disassociation of autoimmunity and resistance to costimulation blockade-induced transplantation tolerance in nonobese diabetic mice.

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Pearson, Todd; Markees, Thomas G; Serreze, David V; Pierce, Melissa A; Marron, Michele P; Wicker, Linda S; Peterson, Laurence B; Shultz, Leonard D; Mordes, John P; Rossini, Aldo A; Greiner, Dale L

2003-07-01

Curing type 1 diabetes by islet transplantation requires overcoming both allorejection and recurrent autoimmunity. This has been achieved with systemic immunosuppression, but tolerance induction would be preferable. Most islet allotransplant tolerance induction protocols have been tested in nonobese diabetic (NOD) mice, and most have failed. Failure has been attributed to the underlying autoimmunity, assuming that autoimmunity and resistance to transplantation tolerance have a common basis. Out of concern that NOD biology could be misleading in this regard, we tested the hypothesis that autoimmunity and resistance to transplantation tolerance in NOD mice are distinct phenotypes. Unexpectedly, we observed that (NOD x C57BL/6)F(1) mice, which have no diabetes, nonetheless resist prolongation of skin allografts by costimulation blockade. Further analyses revealed that the F(1) mice shared the dendritic cell maturation defects and abnormal CD4(+) T cell responses of the NOD but had lost its defects in macrophage maturation and NK cell activity. We conclude that resistance to allograft tolerance induction in the NOD mouse is not a direct consequence of overt autoimmunity and that autoimmunity and resistance to costimulation blockade-induced transplantation tolerance phenotypes in NOD mice can be dissociated genetically. The outcomes of tolerance induction protocols tested in NOD mice may not accurately predict outcomes in human subjects.

NK cell autoreactivity and autoimmune diseases

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Alessandro ePoggi

2014-02-01

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.

Inducible tertiary lymphoid structures, autoimmunity and exocrine dysfunction in a novel model of salivary gland inflammation in C57BL/6 mice§

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Bombardieri, Michele; Barone, Francesca; Lucchesi, Davide; Nayar, Saba; van den Berg, Wim B; Proctor, Gordon; Buckley, Christopher D; Pitzalis, Costantino

2012-01-01

Salivary glands in patients with Sjögren’s syndrome (SS) develop ectopic lymphoid structures (ELS) characterized by B/T cell compartmentalization, the formation of high endothelial venules (HEV), follicular dendritic cell networks (FDCs), functional B cell activation with expression of activation-induced cytidine deaminase (AID) as well as local differentiation of autoreactive plasma cells. The mechanisms triggering ELS formation, autoimmunity and exocrine dysfunction in SS are largely unknown. Here we present a novel model of inducible ectopic lymphoid tissue formation, breach of humoral self-tolerance and salivary hypofunction following delivery of a replication-deficient adenovirus-5 (AdV5) in submandibular glands of C57BL/6 mice through retrograde excretory duct cannulation. In this model, inflammation rapidly and consistently evolves from diffuse infiltration towards the development of SS-like periductal lymphoid aggregates within 2 weeks from AdV delivery. These infiltrates progressively acquire ELS features and support functional GL7+/AID+ germinal centers. Formation of ELS is preceded by ectopic expression of lymphoid chemokines CXCL13, CCL19 and lymphotoxin-β and is associated with development of anti-nuclear antibodies in up to 75% of mice. Finally, reduction in salivary flow was observed over 3 weeks post AdV infection consistent with exocrine gland dysfunction as a consequence of the inflammatory response. This novel model has the potential to unravel the cellular and molecular mechanisms regulating ELS formation and their role in exocrine dysfunction and autoimmunity in SS. PMID:22942425

Nanorobotic investigation identifies novel visual, structural and functional correlates of autoimmune pathology in a blistering skin disease model.

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Kristina Seiffert-Sinha

Full Text Available There remain major gaps in our knowledge regarding the detailed mechanisms by which autoantibodies mediate damage at the tissue level. We have undertaken novel strategies at the interface of engineering and clinical medicine to integrate nanoscale visual and structural data using nanorobotic atomic force microscopy with cell functional analyses to reveal previously unattainable details of autoimmune processes in real-time. Pemphigus vulgaris is a life-threatening autoimmune blistering skin condition in which there is disruption of desmosomal cell-cell adhesion structures that are associated with the presence of antibodies directed against specific epithelial proteins including Desmoglein (Dsg 3. We demonstrate that pathogenic (blister-forming anti-Dsg3 antibodies, distinct from non-pathogenic (non-blister forming anti-Dsg3 antibodies, alter the structural and functional properties of keratinocytes in two sequential steps--an initial loss of cell adhesion and a later induction of apoptosis-related signaling pathways, but not full apoptotic cell death. We propose a "2-Hit" model for autoimmune disruption associated with skin-specific pathogenic autoantibodies. These data provide unprecedented details of autoimmune processes at the tissue level and offer a novel conceptual framework for understanding the action of self-reactive antibodies.

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.

2017-01-01

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 OBOR OECD: Immunology Impact factor: 3.172, year: 2016

The Genetics of Autoimmune Thyroiditis: the first decade

Science.gov (United States)

Rose, Noel R.

2011-01-01

Most of our current understanding of the genetic predisposition to autoimmune disease can be traced to experiments performed in the decade from 1971 to 1981. Chella David was a key contributor to this research. Many of these early steps came from studies of experimental autoimmune thyroiditis. This model has been especially valuable because essentially the same disease can occur spontaneously in selected strains of animals or can be induced by deliberate immunization. From a genetic point of view, the disease has been investigated in three different species: mice, rats and chickens. The same antigen, thyroglobulin, initiates the disease in all three species. Among the main discoveries were the relationship of autoimmune disease to the major histocompatibility complex (MHC), the interplay of different subregions within the MHC in promoting or retarding development of disease, the differing roles of MHC class II and MHC I class genes in induction and effector phases, respectively, and the cumulative effect of non-MHC genes, each of which represents a small addition to overall susceptibility. Other experiments revealed that genetic differences in thyroglobulin allotypes influence susceptibility to thyroiditis. Thyroid glands differed in different strains in vulnerability to passive transfer of antibody. The first evidence of modulatory genes on the sex-related X chromosome emerged. All of these genetic findings were concurrently translated to the human disease, Hashimoto’s thyroiditis, where thyroglobulin is also the initiating antigen. PMID:21683550

Autoimmune and immunogenetic profile of patients with optic neuritis in a population-based cohort

DEFF Research Database (Denmark)

Soelberg, K.; Nilsson, A. C.; Nielsen, C.

2018-01-01

Background: Optic neuritis (ON) is an inflammatory optic neuropathy, where the genetic and autoimmune dependency remains poorly characterized. Objective: To investigate autoimmune and immunogenetic aspects of ON. Method: In a prospective population-based cohort 51 patients with ON were included...... antibodies. Coexisting neural autoantibodies were detected in two patients and in 12 patients other systemic autoantibodies were found. Four (8%) had other autoimmune disorders. A family history of autoimmunity was observed in 12 (24%) and of demyelinating disease in six patients (12%). In MS-ON patients...

Multiple Autoimmune Propensity and B-Non-Hodgkin Lymphoma: Cause or Effect?

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E. Koumati

2011-01-01

Full Text Available We report a case of multiple autoimmunity consisting of the presence of autoimmune haemolytic anaemia (AIHA, antimitochondrial antibodies (AMAs, and antiphospholipid antibodies (APLAbs as the presenting manifestations of an extrahepatic B-non-Hodgkin lymphoma (B-NHL in a 63-year-old woman. The patient presented with fatigue attributed to severe AIHA. Due to increased serum IgM and -GT levels, an investigation for AMA was performed, which proved positive with anti-M2 specificity. A prolongation of activated partial thromboplastin time (aPTT led to the determination of APLAbs (lupus anticoagulant and other APLAbs which were also positive. Bone marrow biopsy in combination with immmunohistochemical studies established the diagnosis of lymphoplasmacytic B-NHL. Ten months later, B-NHL was in remission while AMA and APLAbs were still positive. In conclusion, we documented the coexistence of multiple autoimmune reactions together with B-NHL highlighting the possible common pathogenetic pathways of the two entities.

Palivizumab Exposure and the Risk of Autoimmune Disease

DEFF Research Database (Denmark)

Haerskjold, Ann; Linder, Marie; Henriksen, Lonny

2016-01-01

of autoimmune disease were diagnosed among palivizumab-exposed children during the period of observation. Among the children exposed to palivizumab, one child in Denmark developed inflammatory bowel disease; in Sweden, children developed juvenile arthritis (one child), diabetes mellitus (two children), celiac......BACKGROUND: Treatment with biologic pharmaceuticals may be associated with an increased risk of immune-mediated disease. Palivizumab is a humanized monoclonal antibody designed to provide passive immunity against respiratory syncytial virus infection. Palivizumab is primarily used in preterm...... children known to be immunologically immature. The long-term effect of palivizumab in terms of autoimmune diseases has not yet been investigated. AIM: Our objective was to investigate whether exposure to palivizumab was associated with the development of autoimmune diseases in children. METHODS...

"PREVALENCE OF AUTOANTIBODIES TO THYROID PEROXIDASE AND AUTOIMMUNE THYROID DISEASE IN TYPE I DIABETES MELLITUS"

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H. Moayeri A. Rabbani

2004-09-01

Full Text Available Type I diabetes mellitus (DM is frequently associated with autoimmune thyroid disease (ATD. Association of ATD and type I DM has been described with varying frequencies but there is still debate about the situation in the Iranian population. We investigated the prevalence of anti thyroid peroxidase (anti-TPO antibodies and ATD in children and adolescents with type I DM. A total of 145 patients with type I DM were participated in this study. They were screened for anti-TPO antibodies and TSH levels. Signs and symptoms of hypothyroidism and hyperthyroidism and the presence of goiter were sought. A group of 50 healthy unrelated girls and boys aged 11-16 years served as controls. Anti-TPO antibodies were found in 34 (23.4% diabetic patients and 1 subject (2% in the control group (P<0.001. Frequency of anti TPO antibodies was significantly higher in girls than boys (P<0.05. We failed to show any significant correlation between thyroid autoimmunity and duration of DM. We found that younger patients at diagnosis are more likely to be anti-TPO negative (P<0.001. Out of 145 diabetic patients, 32 (22% had visible goiter. Subclinical hypothyroidism, hypothyroidism and thyrotoxicosis occurred in 1, 9 and 1 patients, respectively. Visible goiter was found in 2 subjects (4% of the control group, but all of them were euthyroid. In conclusion, the evaluation of thyroid autoimmunity in type I diabetic patients may improve the diagnosis of thyroid disease in early stages. Yearly examination of anti-TPO antibodies allows identifying diabetic patients with thyroid autoimmunity.

Effects of the PPAR-β agonist GW501516 in an in vitro model of brain inflammation and antibody-induced demyelination

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Honegger Paul

2009-05-01

Full Text Available Abstract Background Brain inflammation plays a central role in numerous brain pathologies, including multiple sclerosis (MS. Microglial cells and astrocytes are the effector cells of neuroinflammation. They can be activated also by agents such as interferon-γ (IFN-γ and lipopolysaccharide (LPS. Peroxisome proliferator-associated receptor (PPAR pathways are involved in the control of the inflammatory processes, and PPAR-β seems to play an important role in the regulation of central inflammation. In addition, PPAR-β agonists were shown to have trophic effects on oligodendrocytes in vitro, and to confer partial protection in experimental autoimmune encephalomyelitis (EAE, an animal model of MS. In the present work, a three-dimensional brain cell culture system was used as in vitro model to study antibody-induced demyelination and inflammatory responses. GW 501516, a specific PPAR-β agonist, was examined for its capacity to protect from antibody-mediated demyelination and to prevent inflammatory responses induced by IFN-γ and LPS. Methods Aggregating brain cells cultures were prepared from embryonal rat brain, and used to study the inflammatory responses triggered by IFN-γ and LPS and by antibody-mediated demyelination induced by antibodies directed against myelin-oligodendrocyte glycoprotein (MOG. The effects of GW 501516 on cellular responses were characterized by the quantification of the mRNA expression of tumor necrosis factor-α (TNF-α, interleukin-6 (IL-6, inducible NO synthase (i-NOS, PPAR-β, PPAR-γ, glial fibrillary acidic protein (GFAP, myelin basic protein (MBP, and high molecular weight neurofilament protein (NF-H. GFAP expression was also examined by immunocytochemistry, and microglial cells were visualized by isolectin B4 (IB4 and ED1 labeling. Results GW 501516 decreased the IFN-γ-induced up-regulation of TNF-α and iNOS in accord with the proposed anti-inflammatory effects of this PPAR-β agonist. However, it increased IL

Design of Peptide Immunotherapies for MHC Class-II-Associated Autoimmune Disorders

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Masha Fridkis-Hareli

2013-01-01

Full Text Available Autoimmune disorders, that occur when autoreactive immune cells are induced to activate their responses against self-tissues, affect one percent of the world population and represent one of the top 10 leading causes of death. The major histocompatibility complex (MHC is a principal susceptibility locus for many human autoimmune diseases, in which self-tissue antigens providing targets for pathogenic lymphocytes are bound to HLA molecules encoded by disease-associated alleles. In spite of the attempts to design strategies for inhibition of antigen presentation targeting the MHC-peptide/TCR complex via generation of blocking antibodies, altered peptide ligands (APL, or inhibitors of costimulatory molecules, potent therapies with minimal side effects have yet to be developed. Copaxone (glatiramer acetate, GA is a random synthetic amino acid copolymer that reduces the relapse rate by about 30% in relapsing-remitting multiple sclerosis (MS patients. Based on the elucidated binding motifs of Copaxone and of the anchor residues of the immunogenic myelin basic protein (MBP peptide to HLA-DR molecules, novel copolymers have been designed and proved to be more effective in suppressing MS-like disease in mice. In this report, we describe the rationale for design of second-generation synthetic random copolymers as candidate drugs for a number of MHC class-II-associated autoimmune disorders.

Age impact on autoimmune thyroid disease in females

Science.gov (United States)

Stoian, Dana; Craciunescu, Mihalea; Timar, Romulus; Schiller, Adalbert; Pater, Liana; Craina, Marius

2013-10-01

Thyroid autoimmune disease, a widespread phenomenon in female population, impairs thyroid function during pregnancy. Identifying cases, which will develop hypothyroidism during pregnancy, is crucial in the follow-up process. The study group comprised 108 females, with ages between 20-40 years; with known inactive autoimmune thyroid disease, before pregnancy that became pregnant in the study follow-up period. They were monitored by means of clinical, hormonal and immunological assays. Supplemental therapy with thyroid hormones was used, where needed. Maternal age and level of anti-thyroid antibodies were used to predict thyroid functional impairment.

Porous silicon biosensor for the detection of autoimmune diseases

Science.gov (United States)

Jane, Andrew O.; Szili, Endre J.; Reed, Joanne H.; Gordon, Tom P.; Voelcker, Nicolas H.

2007-12-01

Advances in porous silicon (pSi) technology have led to the development of new sensitive biosensors. The unique optical properties of pSi renders the material a perfect candidate for optical transducers exploiting photoluminescence or white light interference effects. The ability of biosensors exploiting these transduction mechanisms to quickly and accurately detect biological target molecules affords an alternative to current bioassays such as enzyme-linked immunosorbent assays (ELISAs). Here, we present a pSi biosensor that was developed to detect antibodies against the autoimmune protein La. This protein is associated with autoimmune diseases including rheumatic disorders, systematic lupus erythematosus (SLE) and Sjogren's syndrome (SS). A fast and sensitive detection platform such as the one described here can be applied to the rapid diagnosis of these debilitating autoimmune diseases. The immobilisation of the La protein onto pSi films gave a protein receptor-decorated sensor matrix. A cascade of immunological reactions was then initiated to detect anti-La antibody on the functionalised pSi surface. In the presence of o-phenylenediamine (OPD), horseradish peroxidase (HRP)/H IIO II catalysed the formation of an oxidised radical species that accelerated pSi corrosion. pSi corrosion was detected as a blue-shift in the generated interference pattern, corresponding to a decrease in the effective optical thickness (EOT) of the pSi film. Compared to an ELISA, the pSi biosensor could detect the anti-La antibody at a similar concentration (500 - 125 ng/ml). Furthermore, we found that the experimental process can be significantly shortened resulting in detection of the anti-La antibody in 80 minutes compared to a minimum of 5 hours required for ELISA.

ROLE OF IL-6 IN EXPERIMENTAL ARTHRITIS CAUSED BY TRANSFER OF ARTHRITOGENIC ANTIBODIES

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M. S. Drutskaya

2016-01-01

Full Text Available Interleukin-6 (IL-6 exerts important functions on immune regulation. In case of high expression, IL-6 may promote autoimmune disorders, e.g., arthritis. Systemic IL-6 blockers based on monoclonal antibodies against IL-6, or its specific receptor subunit, are already used in clinical settings, adding to a range of known biological drugs, such as, TNF blockers. Rheumatic disorders and their experimental therapy are reproducible in mice. This study revealed systemically increased levels of IL-6 in developing arthritis caused by transfer of pathogenic antibodies, as well as the effects of IL-6 neutralization by monoclonal antibodies against murine IL-6. Our results suggest a pathogenic role of the two cytokines, TNF and IL-6, in experimental arthritis induced by passive transfer of anti-collagen antibodies.

Organ-specific autoimmunity in type 1 diabetes mellitus: Screening with respect to glycemic control

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Mohamed Ghada A

2016-01-01

Full Text Available Type 1 diabetes (T1D is a tissue-specific autoimmune disease and often associated with other autoimmune diseases; so our study aimed to define the occurrence of thyroid peroxidase antibody (TPOAb and thyroglobulin antibody (TGAb in autoimmune thyroid disease (AIT, tissue transglutaminase antibody (TTGAb in celiac disease, And to evaluate the relationship between the presence of these antibodies and glycemic control. Our retrospective study included 60 Kuwaiti patients with T1D who attended and follow in Diabetes outpatient clinics of Kuwait primary health care centers during the period of 2014-2015. For them, recorded data for age, sex, duration of diabetes, Body Mass Index (BMI, HbA1c was reviewed. Patients were screened for the presence of Specific antibodies to islet antigens (ICAb, glutamic acid decarboxylase autoantibodies (GADAb, insulin autoantibodies (IAA, TPOAb, TGAb, TTGAb and also thyroid stimulating hormone (TSH were measured by ELISA. Of the total 60 patients (20 men, 40women, mean age was17.95 ± (5.44 y; the mean duration of diabetes was 6.63 ± (4.27 y; mean HbA1c was 10.41± (1.96 %. Only 58 (96.7% wer e positive for GADAb, 32 (53.3% were positive for ICAb, and 48 (80% were positive for IAA, 14 (23.3% patients were positive for TPOAb, 11 (18.3% were positive for TGAb, 10 (16.7 % were positive for both TPOAb and TGAb; furthermore 8 (13.3% patients were positive for TTGAb. Neither organ-specific autoimmune disease (AIT and celiac disease nor pancreatic β cells autoantibodies had a significant association with the glycemic control. In our study, we confirmed the high prevalence of a second organ-specific autoimmune disease in individuals with type 1 diabetes. Also Subclinical forms of these disorders have no influence on diabetes control. Further research will be necessary to test these relationships in a prospective follow-up study

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

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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; Hadzic, Nedim

2017-11-03

Paediatric autoimmune liver disease is characterised 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 (ASC), and de novo AIH after liver transplantation. Two types of paediatric AIH are recognized according to seropositivity for smooth muscle and/or antinuclear antibody (SMA/ANA, AIH-1) or liver kidney microsomal type 1 and/or anti-liver cytosol type 1 antibodies (anti-LKM-1/anti-LC-1; AIH-2).Pertinent issues addressing the diagnosis, treatment and long term follow up were formulated by a core group of ESPGHAN members. They have commissioned the first authors with execution of this project. Initially, they have performed a systematic literature search on MEDLINE, ResearchGate and Mendeley databases over the last 30 years and produced a document focusing on prospective and retrospective studies in children. The ESPGHAN core group and ESPGHAN Hepatology Committee members voted on each recommendation, using a formal voting technique.

LKM3 autoantibodies in hepatitis C cirrhosis: a further phenomenon of the HCV-induced autoimmunity.

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Csepregi, A; Nemesánszky, E; Luettig, B; Obermayer-Straub, P; Manns, M P

2001-03-01

Chronic hepatitis C is frequently associated with laboratory markers-including LKM1 autoantibodies--of autoimmunity. A 62-yr-old woman with hepatitis C cirrhosis presented autoantibodies against liver and kidney microsomal proteins. By further evaluation of autoantibodies using ELISA and immunoblotting LKM1 and LKM3 autoantibodies could be revealed. The target antigen of LKM3 autoantibodies proved to be UGT-1.1 isoenzyme. In the absence of chronic hepatitis D infection or autoimmune hepatitis type 2, this is the first case that reports the occurrence of LKM3 autoantibodies in HCV-induced chronic liver disease.

Management of phenytoin-induced gingival enlargement in a patient with antiphospholipid antibody syndrome: A rare case report

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Shilpa Sarvesh Urolagin

2016-01-01

Full Text Available Antiphospholipid antibody (APLA syndrome is a noninflammatory autoimmune disease, with innumerable clinical manifestations ranging from recurrent thrombosis and pregnancy morbidity to valvular lesions, transverse myelitis, thrombocytopenia, and hemolytic anemia. APLAs in antiphospholipid syndrome (APS are well-known risk factors for cerebrovascular accidents. Stroke is the most common manifestation of APS in the central nervous system. Gingival enlargement is a known side effect of phenytoin which is an antiepileptic drug. This can have a significant effect on the quality of life as well as increasing the oral bacterial load by generating plaque retention sites. The management of gingival overgrowth seems to be directed at controlling gingival inflammation through a good oral hygiene regimen. Thus, this case report aims to describe the conservative management of phenytoin-induced gingival enlargement combined with inflammatory enlargement in a patient with APLA syndrome.

Human neutrophils in auto-immunity.

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

2016-04-01

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

Predicting post-vaccination autoimmunity: who might be at risk?

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Soriano, Alessandra; Nesher, Gideon; Shoenfeld, Yehuda

2015-02-01

Vaccinations have been used as an essential tool in the fight against infectious diseases, and succeeded in improving public health. However, adverse effects, including autoimmune conditions may occur following vaccinations (autoimmune/inflammatory syndrome induced by adjuvants--ASIA syndrome). It has been postulated that autoimmunity could be triggered or enhanced by the vaccine immunogen contents, as well as by adjuvants, which are used to increase the immune reaction to the immunogen. Fortunately, vaccination-related ASIA is uncommon. Yet, by defining individuals at risk we may further limit the number of individuals developing post-vaccination ASIA. In this perspective we defined four groups of individuals who might be susceptible to develop vaccination-induced ASIA: patients with prior post-vaccination autoimmune phenomena, patients with a medical history of autoimmunity, patients with a history of allergic reactions, and individuals who are prone to develop autoimmunity (having a family history of autoimmune diseases; asymptomatic carriers of autoantibodies; carrying certain genetic profiles, etc.). Copyright © 2014 Elsevier Ltd. All rights reserved.

[Animal models of autoimmune prostatitis and their evaluation criteria].

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Shen, Jia-ming; Lu, Jin-chun; Yao, Bing

2016-03-01

Chronic prostatitis is a highly prevalent disease of unclear etiology. Researches show that autoimmune reaction is one cause of the problem. An effective animal model may help a lot to understand the pathogenesis and find proper diagnostic and therapeutic strategies of the disease. Currently used autoimmune prostatitis-related animal models include those of age-dependent spontaneous prostatitis, autoimmune regulator-dependent spontaneous prostatitis, self antigen-induced prostatitis, and steroid-induced prostatitis. Whether an animal model of autoimmune prostatitis is successfully established can be evaluated mainly from the five aspects: histology, morphology, specific antigens, inflammatory factors, and pain intensity.

Identification of Novel Genetic Loci Associated with Thyroid Peroxidase Antibodies and Clinical Thyroid Disease

NARCIS (Netherlands)

M. Medici (Marco); E. Porcu (Eleonora); G. Pistis (Giorgio); A. Teumer (Alexander); S.J. Brown (Stephen); R.A. Jensen (Richard); R. Rawal (R.); G.L. Roef (Greet); T.S. Plantinga (Theo S.); S.H.H.M. Vermeulen (Sita); J. Lahti (Jari); M.C. Simmonds (Mark); L.L.N. Husemoen (Lise Lotte); R.M. Freathy (Rachel); B.M. Shields (Beverley); D. Pietzner (Diana); R. Nagy (Rebecca); L. Broer (Linda); L. Chaker (Layal); T.I.M. Korevaar (Tim); M.G. Plia (Maria Grazia); C. Sala (Cinzia); U. Völker (Uwe); J.B. Richards (Brent); F.C. Sweep (Fred); C. Gieger (Christian); T. Corre (Tanguy); E. Kajantie (Eero); L. Thuesen (Leif); Y.E. Taes (Youri); W.E. Visser (Wil Edward); A.T. Hattersley (Andrew); J. Kratzsch (Jürgen); A. Hamilton (Amy); W. Li (Wei); G. Homuth (Georg); M. Lobina (Monia); S. Mariotti (Stefano); N. Soranzo (Nicole); M. Cocca (Massimiliano); M. Nauck (Matthias); C. Spielhagen (Christin); H.A. Ross (Alec); A.M. Arnold (Alice); M. van de Bunt (Martijn); S. Liyanarachchi (Sandya); M. Heier (Margit); H.J. Grabe (Hans Jörgen); C. Masciullo (Corrado); T.E. Galesloot (Tessel); E.M. Lim (Ee Mun); G. Reischl (Gunilla); P.J. Leedman (Peter); S. Lai (Sandra); A. Delitala (Alessandro); A. Bremner (Alexandra); D.I.W. Philips (David I.); J.P. Beilby (John); A. Mulas (Antonella); M. Vocale (Matteo); G.R. Abecasis (Gonçalo); T. Forsen (Tom); A. James (Alan); E. Widen (Elisabeth); J. Hui (Jennie); H. Prokisch (Holger); E.E. Rietzschel (Ernst); A. Palotie (Aarno); W. Feddema (Wouter); S.J. Fletcher (Stephen); K. Schramm (Katharina); J.I. Rotter (Jerome); A. Kluttig (Alexander); D. Radke (Dörte); M. Traglia (Michela); G. Surdulescu (Gabriela); H. He (Hao); J.A. Franklyn (Jayne); D. Tiller (Daniel); B. Vaidya (Bijay); T. Meyer (Thorsten); T. Jorgensen (Torben); K. Hagen (Knut); P.C. O'Leary (Peter); E. Wichmann (Eric); A.R.M.M. Hermus (Ad); B.M. Psaty (Bruce); T. Ittermann (Till); A. Hofman (Albert); E. Bosi (Emanuele); D. Schlessinger (David); H. Wallaschofski (Henri); N. Pirastu (Nicola); Y.S. Aulchenko (Yurii); A. de la Chapelle (Albert); R.T. Netea-Maier (Romana ); J.E. Gough (Julie); H. Meyer zu Schwabedissen (Henriette); T.M. Frayling (Timothy); J.-M. Kaufman (Jean-Marc); A. Linneberg (Allan); K. Räikkönen (Katri); J.W.A. Smit (Jan); L.A.L.M. Kiemeney (Bart); F. Rivadeneira Ramirez (Fernando); A.G. Uitterlinden (André); J.P. Walsh (John); C. Meisinger (Christa); M. den Heijer (Martin); T.J. Visser (Theo); T.D. Spector (Timothy); S.G. Wilson (Scott); H. Völzke (Henry); A.R. Cappola (Anne); D. Toniolo (Daniela); S. Sanna (Serena); S. Naitza (Silvia); R.P. Peeters (Robin)

2014-01-01

textabstractAutoimmune thyroid diseases (AITD) are common, affecting 2-5% of the general population. Individuals with positive thyroid peroxidase antibodies (TPOAbs) have an increased risk of autoimmune hypothyroidism (Hashimoto's thyroiditis), as well as autoimmune hyperthyroidism (Graves'

Selenium Supplementation does not Decrease Thyroid Peroxidase Antibody Concentration in Children and Adolescents with Autoimmune Thyroiditis

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W. Bonfig

2010-01-01

Full Text Available In adults, selenium supplementation decreases thyroid peroxidase antibody (TPO Ab concentrations in patients with autoimmune thyroiditis (AIT. Our aim in this study was to investigate if selenium supplementation decreased TPO Ab and thyroglobulin antibody (Tg Ab concentrations in children with AIT. Forty-nine patients (33 females with newly diagnosed AIT and hypothyroidism were randomized to daily oral therapy with levothyroxine alone (group A, n = 18, levothyroxine plus 100 µg sodium-selenite (group B, n = 13, or levothyroxine plus 200 µg sodium-selenite (group C, n = 18. Mean age at diagnosis was 12.2 ± 2.2 years. All 49 patients needed a mean levothyroxine dose of 1.6 ± 0.5 µg/kg body weight to lower TSH to the treatment goal of 1–2 µU/ml, with no significant difference between groups. At study entry and after 12 months, TPO Ab concentrations were comparable in all three groups. Tg Ab concentrations decreased significantly after 12 months in group A and group C (p = 0.03 and p = 0.01, but not in group B (p = 0.06. It is our conclusion that selenium supplementation with sodium-selenite does not decrease TPO Ab concentrations in children and adolescents, neither given in the reduced dose of 100 µg daily nor given in the “adult” supplementation dose of 200 µg daily.

Free radical theory of autoimmunity

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Kannan Subburaj

2006-06-01

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

Pathologically confirmed autoimmune encephalitis in suspected Creutzfeldt-Jakob disease

NARCIS (Netherlands)

Maat, P.; de Beukelaar, J.W.; Jansen, C.; Schuur, M.; van Duijn, C.M.; van Coevorden, M.H.; de Graaff, E.; Titulaer, E.; Rozemuller, A.J.M.; Sillevis Smitt, P.

2015-01-01

Objective: To determine the clinical features and presence in CSF of antineuronal antibodies in patients with pathologically proven autoimmune encephalitis derived from a cohort of patients with suspected Creutzfeldt-Jakob disease (CJD). Methods: The Dutch Surveillance Centre for Prion Diseases

Does Autoimmunity have a Role in Myoclonic Astatic Epilepsy? A Case Report of Voltage Gated Potassium Channel Mediated Seizures.

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Sirsi, Deepa; Dolce, Alison; Greenberg, Benjamin M; Thodeson, Drew

2016-01-01

There is expanding knowledge about the phenotypic variability of patients with voltage gated potassium channel complex (VGKC) antibody mediated neurologic disorders. The phenotypes are diverse and involve disorders of the central and peripheral nervous systems. The central nervous system manifestations described in the literature include limbic encephalitis, status epilepticus, and acute encephalitis. We report a 4.5 year-old boy who presented with intractable Myoclonic Astatic Epilepsy (MAE) or Doose syndrome and positive VGKC antibodies in serum. Treatment with steroids led to resolution of seizures and electrographic normalization. This case widens the spectrum of etiologies for MAE to include autoimmunity, in particular VGKC auto-antibodies and CNS inflammation, as a primary or contributing factor. There is an evolving understanding of voltage gated potassium channel complex mediated autoimmunity in children and the role of inflammation and autoimmunity in MAE and other intractable pediatric epilepsy syndromes remains to be fully defined. A high index of suspicion is required for diagnosis and appropriate management of antibody mediated epilepsy syndromes.

Prevalence and clinical features of celiac disease in patients with autoimmune thyroiditis: cross-sectional study

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Aline Ventura

Full Text Available CONTEXT AND OBJECTIVE: Celiac disease is an autoimmune disorder with an average prevalence of 1% in Europe and the United States. Because of strong European ancestry in southern Brazil, this study aimed to evaluate the seroprevalence of celiac disease among autoimmune thyroiditis patients.DESIGN AND SETTING: Cross-sectional study in a public university hospital.METHODS: This cross-sectional prevalence study included autoimmune thyroiditis patients who were tested for anti-endomysial and anti-transglutaminase antibodies between August 2010 and July 2011.RESULTS: Fifty-three patients with autoimmune thyroiditis were included; 92.5% were women, with mean age of 49.0 ± 13.5 years. Five patients (9.3% were serologically positive for celiac disease: three of them (5.6% were reactive for anti-endomysial antibodies and two (3.7% for anti-transglutaminase. None of them exhibited anemia and one presented diarrhea. Endoscopy was performed on two patients: one with normal histology and the other with lymphocytic infiltrate and villous atrophy.CONCLUSION: The prevalence of celiac disease among patients with autoimmune thyroid disease was 9.3%; one patient complained of diarrhea and none presented anemia. Among at-risk populations, like autoimmune thyroiditis patients, the presence of diarrhea or anemia should not be used as a criterion for indicating celiac disease investigation. This must be done for all autoimmune thyroiditis patients because of its high prevalence.

[Allergy and autoimmunity: Molecular diagnostics, therapy, and presumable pathogenesis].

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Arefieva, A S; Smoldovskaya, O V; Tikhonov, A A; Rubina, A Yu

2017-01-01

Allergic and autoimmune diseases represent immunopathological reactions of an organism to antigens. Despite that the allergy is a result of exaggerated immune response to foreign antigens (allergens) and autoimmune diseases are characterized by the pathological response to internal antigens (autoantigens), the underlying mechanisms of these diseases are probably common. Thus, both types of diseases represent variations in the hypersensitivity reaction. A large percentage of both the adult and pediatric population is in need of early diagnostics of these pathologies of the immune system. Considering the diversity of antibodies produced in allergic and autoimmune disease and the difficulties accompanying clinical diagnosing, molecular diagnostics of these pathological processes should be carried out in several stages, including screening and confirmatory studies. In this review, we summarize the available data on the molecular diagnostics and therapy of allergic and autoimmune diseases and discuss the basic similarities and differences in the mechanisms of their development.

Identification of novel genetic Loci associated with thyroid peroxidase antibodies and clinical thyroid disease

NARCIS (Netherlands)

Medici, M.; Porcu, E.; Pistis, G.; Teumer, A.; Brown, S.J.; Jensen, R.A.; Rawal, R.; Roef, G.L.; Plantinga, T.S.; Vermeulen, S.; Lahti, J.; Simmonds, M.J.; Husemoen, L.L.; Freathy, R.M.; Shields, B.M.; Pietzner, D.; Nagy, R.; Broer, L.; Chaker, L.; Korevaar, T.I.; Plia, M.G.; Sala, C.; Volker, U.; Richards, J.B.; Sweep, F.C.; Gieger, C.; Corre, T.; Kajantie, E.; Thuesen, B.; Taes, Y.E.; Visser, W.E.; Hattersley, A.T.; Kratzsch, J.; Hamilton, A.; Li, W.; Homuth, G.; Lobina, M.; Mariotti, S.; Soranzo, N.; Cocca, M.; Nauck, M.; Spielhagen, C.; Ross, A.; Arnold, A.; Bunt, M. van de; Liyanarachchi, S.; Heier, M.; Grabe, H.J.; Masciullo, C.; Galesloot, T.E.; Lim, E.M.; Reischl, E.; Leedman, P.J.; Lai, S.; Delitala, A.; Bremner, A.P.; Philips, D.I.; Beilby, J.P.; Mulas, A.; Vocale, M.; Abecasis, G.; Forsen, T.; James, A.; Widen, E.; Hui, J.; Prokisch, H.; Rietzschel, E.E.; Palotie, A.; Feddema, P.; Fletcher, S.J.; Schramm, K.; Rotter, J.I.; Kluttig, A.; Radke, D.; Traglia, M.; Surdulescu, G.L.; He, H.; Franklyn, J.A.; Tiller, D.; Vaidya, B.; Meyer, T.; Jorgensen, T.; Eriksson, J.G.; O'Leary, P.C.; Wichmann, E.; Hermus, A.R.M.M.; Psaty, B.M.; Ittermann, T.; Hofman, A.; Bosi, E.; Schlessinger, D.; Wallaschofski, H.; Pirastu, N.; Aulchenko, Y.S.; Chapelle, A. dela; Netea-Maier, R.T.; Gough, S.C.; Meyer Zu Schwabedissen, H.; Frayling, T.M.; Kaufman, J.M.; Smit, J.W.; Kiemeney, B.; et al.,

2014-01-01

Autoimmune thyroid diseases (AITD) are common, affecting 2-5% of the general population. Individuals with positive thyroid peroxidase antibodies (TPOAbs) have an increased risk of autoimmune hypothyroidism (Hashimoto's thyroiditis), as well as autoimmune hyperthyroidism (Graves' disease). As the

Identification of Novel Genetic Loci Associated with Thyroid Peroxidase Antibodies and Clinical Thyroid Disease

NARCIS (Netherlands)

Medici, M.; Porcu, E.; Pistis, G.; Teumer, A.; Brown, S.J.; Jensen, R.A.; Rawal, R.; Roef, G.L.; Plantinga, T.S.; Vermeulen, S.H.; Lahti, J.; Simmonds, M.J.; Husemoen, L.L.N.; Freathy, R.M.; Shields, B.M.; Pietzner, D.; Nagy, R.; Broer, L.; Chaker, L.; Korevaar, T.I.M.; Plia, M.G.; Sala, C.; Volker, U.; Richards, J.B.; Sweep, F.C.; Gieger, C.; Corre, T.; Kajantie, E.; Thuesen, B.; Taes, Y.E.; Visser, W.E.; Hattersley, A.T.; Kratzsch, J.; Hamilton, A.; Li, W.; Homuth, G.; Lobina, M.; Mariotti, S.; Soranzo, N.; Cocca, M.; Nauck, M.; Spielhagen, C.; Ross, A.; Arnold, A.; van de Bunt, M.; Liyanarachchi, S.; Heier, M.; Grabe, H.J.; Masciullo, C.; Galesloot, T.E.; Lim, E.M.; Reischl, E.; Leedman, P.J.; Lai, S.; Delitala, A.; Bremner, A.P.; Philips, D.I.W.; Beilby, J.P.; Mulas, A.; Vocale, M.; Abecasis, G.; Forsen, T.; James, A.; Widen, E.; Hui, J.; Prokisch, H.; Rietzschel, E.E.; Palotie, A.; Feddema, P.; Fletcher, S.J.; Schramm, K.; Rotter, J.I.; Kluttig, A.; Radke, D.; Traglia, M.; Surdulescu, G.L.; He, H.L.; Franklyn, J.A.; Tiller, D.; Vaidya, B.; Meyer, T.; Jorgensen, T.; Eriksson, J.G.; O'Leary, P.C.; Wichmann, E.; Hermus, A.R.; Psaty, B.M.; Ittermann, T.; Hofman, A.; Bosi, E.; Schlessinger, D.; Wallaschofski, H.; Pirastu, N.; Aulchenko, Y.S.; de la Chapelle, A.; Netea-Maier, R.T.; Gough, S.C.L.; Meyer zu Schwabedissen, H.; Frayling, T.M.; den Heijer, M.; Naitza, S.; Peeters, R.P.

2014-01-01

Autoimmune thyroid diseases (AITD) are common, affecting 2-5% of the general population. Individuals with positive thyroid peroxidase antibodies (TPOAbs) have an increased risk of autoimmune hypothyroidism (Hashimoto's thyroiditis), as well as autoimmune hyperthyroidism (Graves' disease). As the

Sarcoidosis and Thyroid Autoimmunity

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Piera Fazzi

2017-08-01

Full Text Available Most of the studies have shown a higher risk for subclinical and clinical hypothyroidism, antithyroid autoantibodies [overall antithyroid peroxidase antibodies (TPOAb], and in general, thyroid autoimmunity, overall in the female gender in patients with sarcoidosis (S. A significantly higher prevalence of clinical hypothyroidism and Graves’ disease was also described in female S patients with respect to controls. Gallium-67 (Ga-67 scyntigraphy in S patients, in the case of thyroid uptake, suggests the presence of aggressive autoimmune thyroiditis and hypothyroidism. For this reason, ultrasonography and thyroid function should be done in the case of Ga-67 thyroid uptake. In conclusion, thyroid function, TPOAb measurement, and ultrasonography should be done to assess the clinical profile in female S patients, and the ones at high risk (female individuals, with TPOAb positivity, and hypoechoic and small thyroid should have periodically thyroid function evaluations and suitable treatments.

[Detection and the production mechanism of antinuclear antibodies (ANA) and anti-liver/kidney microsomal tpe 1 antibodies (anti-LKM1) in patients with chronic hepatitis C].

Science.gov (United States)

Bai, Li; Lu, Hai-Ying; Feng, Zhen-Ru; Yu, Min; Li, Wen-Gang; Gong, Wei-Bo; Zhao, Nu-en-ji-ya; Xu, Xiao-Yuan

2009-08-01

To investigate the prevalence of antinuclear antibodies (ANA) and anti-liver/ kidney microsomal type 1 antibodies (anti-LKM1) in patients with chronic hepatitis C (CHC)and to explore the mechanism of production of these autoantibodies. Serum samples were collected from 360 patients with CHC (case group), 69 patients with chronic hepatitis B (CHB) and 69 patients with autoimmune hepatitis (AIH) (control group). Serum ANA and anti-LKM1 were detected by indirect immunofluorescence (HF) technique and enzyme-linked immunosorbent assay (ELISA), respectively. Multi-factor analysis was performed to explore the correlations of the production of autoantibodies with some factors such as age, sex, viral loads, HCV genotype, biochemical parameters and clinical characteristics. Fifty-four (15%) of 360 patients infected with HCV were positive in autoantibodies. The prevalence of ANA and anti-LKM1 were 12.5% (45/360) and 2.5% (9/ 360), respectively. The positive rate of autoantibodies in patients with CHC was significantly higher than that in patients with CHB (15% vs 2.9%, P = 0.006), but significantly lower than that in patients with AIH (15% vs 47.9%, P 0.05). Autoantibodies related to AIH can be detected in CHC patients; interferon may not induce the production of autoantibodies; it is very likely that HCV infection induces the autoimmune reaction and the production of autoantibodies.

Autoimmune Arthritides, Rheumatoid Arthritis, Psoriatic Arthritis, or Peripheral Spondyloarthritis Following Lyme Disease.

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Arvikar, Sheila L; Crowley, Jameson T; Sulka, Katherine B; Steere, Allen C

2017-01-01

To describe systemic autoimmune joint diseases that develop following Lyme disease, and to compare their clinical features with those of Lyme arthritis (LA). We reviewed records of all adult patients referred to our LA clinic over a 13-year period, in whom we had diagnosed a systemic autoimmune joint disease following Lyme disease. For comparison, records of patients enrolled in our LA cohort over the most recent 2-year period were analyzed. Levels of IgG antibodies to Borrelia burgdorferi and to 3 Lyme disease-associated autoantigens were measured. We identified 30 patients who had developed a new-onset systemic autoimmune joint disorder a median of 4 months after Lyme disease (usually manifested by erythema migrans [EM]). Fifteen had rheumatoid arthritis (RA), 13 had psoriatic arthritis (PsA), and 2 had peripheral spondyloarthritis (SpA). The 30 patients typically had polyarthritis, and those with PsA or SpA often had previous psoriasis, axial involvement, or enthesitis. In the comparison group of 43 patients with LA, the usual clinical picture was monoarticular knee arthritis, without prior EM. Most of the patients with systemic autoimmune joint disorders were positive for B burgdorferi IgG antibodies, as detected by enzyme-linked immunosorbent assay, but had significantly lower titers and lower frequencies of Lyme disease-associated autoantibodies than patients with LA. Prior to our evaluation, these patients had often received additional antibiotics for presumed LA, without benefit. We prescribed antiinflammatory agents, most commonly disease-modifying antirheumatic drugs, resulting in improvement. Systemic autoimmune joint diseases (i.e., RA, PsA, SpA) may follow Lyme disease. Development of polyarthritis after antibiotic-treated EM, previous psoriasis, or low-titer B burgdorferi antibodies may provide insight into the correct diagnosis. © 2016, American College of Rheumatology.

CD8 Follicular T Cells Promote B Cell Antibody Class Switch in Autoimmune Disease.

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Valentine, Kristen M; Davini, Dan; Lawrence, Travis J; Mullins, Genevieve N; Manansala, Miguel; Al-Kuhlani, Mufadhal; Pinney, James M; Davis, Jason K; Beaudin, Anna E; Sindi, Suzanne S; Gravano, David M; Hoyer, Katrina K

2018-05-09

CD8 T cells can play both a protective and pathogenic role in inflammation and autoimmune development. Recent studies have highlighted the ability of CD8 T cells to function as T follicular helper (Tfh) cells in the germinal center in the context of infection. However, whether this phenomenon occurs in autoimmunity and contributes to autoimmune pathogenesis is largely unexplored. In this study, we show that CD8 T cells acquire a CD4 Tfh profile in the absence of functional regulatory T cells in both the IL-2-deficient and scurfy mouse models. Depletion of CD8 T cells mitigates autoimmune pathogenesis in IL-2-deficient mice. CD8 T cells express the B cell follicle-localizing chemokine receptor CXCR5, a principal Tfh transcription factor Bcl6, and the Tfh effector cytokine IL-21. CD8 T cells localize to the B cell follicle, express B cell costimulatory proteins, and promote B cell differentiation and Ab isotype class switching. These data reveal a novel contribution of autoreactive CD8 T cells to autoimmune disease, in part, through CD4 follicular-like differentiation and functionality. Copyright © 2018 by The American Association of Immunologists, Inc.

Quantitation of autoantibodies in systemic autoimmune diseases : clinically useful?

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Kallenberg, C. G. M.; Stegeman, C. A.; Bootsma, H.; Biji, M.; Limburg, P. C.

2006-01-01

Serial assessment of levels of autoantibodies has been proposed as being clinically useful in certain systemic autoimmune diseases. In particular, attention has been given to anti-dsDNA antibodies in systemic lupus erythematosus (SLE) and ANCA in the ANCA-associated vasculitides (AAV). Much

Intraocular inflammation in autoimmune diseases.

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Pras, Eran; Neumann, Ron; Zandman-Goddard, Gisele; Levy, Yair; Assia, Ehud I; Shoenfeld, Yehuda; Langevitz, Pnina

2004-12-01

The uveal tract represents the vascular organ of the eye. In addition to providing most of the blood supply to the intraocular structures, it acts as a conduit for immune cells, particularly lymphocytes, to enter the eye. Consequently, the uveal tract is represented in many intraocular inflammatory processes. Uveitis is probably a misnomer unless antigens within the uvea are the direct targets of the inflammatory process. A better term of the condition is "intraocular inflammation" (IOI). To review the presence of IOI in autoimmune diseases, the immunopathogenic mechanisms leading to disease, and treatment. We reviewed the English medical literature by using MEDLINE (1984-2003) employing the terms "uveitis," "intraocular inflammation," and "autoimmune diseases." An underlying autoimmune disease was identified in up to 40% of patients with IOI, and included spondyloarthropathies, Behcets disease, sarcoidosis, juvenile chronic arthritis, Vogt-Koyanagi-Harada syndrome (an inflammatory syndrome including uveitis with dermatologic and neurologic manifestations), immune recovery syndrome, and uveitis with tubulointerstitial disease. The immunopathogenesis of IOI involves enhanced T-cell response. Recently, guidelines for the use of immunosuppressive drugs for inflammatory eye disease were established and include: corticosteroids, azathioprine, methotrexate, mycophenolate mofetil, cyclosporine, tacrolimus, cyclophosphamide, and chlorambucil. New therapies with limited experience include the tumor necrosis factor alpha inhibitors, interferon alfa, monoclonal antibodies against lymphocyte surface antigens, intravenous immunoglobulin (IVIG), and the intraocular delivery of immunosuppressive agents. An underlying autoimmune disease was identified in up to 40% of patients with IOI. Immunosuppressive drugs, biologic agents, and IVIG are employed for the treatment of IOI in autoimmune diseases.

Update on antiphospholipid antibody syndrome.

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Lopes, Michelle Remião Ugolini; Danowski, Adriana; Funke, Andreas; Rêgo, Jozelia; Levy, Roger; Andrade, Danieli Castro Oliveira de

2017-11-01

Antiphospholipid syndrome (APS) is an autoimmune disease characterized by antiphospholipid antibodies (aPL) associated with thrombosis and/or pregnancy morbidity. Most APS events are directly related to thrombotic events, which may affect small, medium or large vessels. Other clinical features like thrombocytopenia, nephropathy, cardiac valve disease, cognitive dysfunction and skin ulcers (called non-criteria manifestations) add significant morbidity to this syndrome and represent clinical situations that are challenging. APS was initially described in patients with systemic lupus erythematosus (SLE) but it can occur in patients without any other autoimmune disease. Despite the autoimmune nature of this syndrome, APS treatment is still based on anticoagulation and antiplatelet therapy.

Autoimmunity due to molecular mimicry as a cause of neurological disease.

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Levin, Michael C; Lee, Sang Min; Kalume, Franck; Morcos, Yvette; Dohan, F Curtis; Hasty, Karen A; Callaway, Joseph C; Zunt, Joseph; Desiderio, Dominic; Stuart, John M

2002-05-01

One hypothesis that couples infection with autoimmune disease is molecular mimicry. Molecular mimicry is characterized by an immune response to an environmental agent that cross-reacts with a host antigen, resulting in disease. This hypothesis has been implicated in the pathogenesis of diabetes, lupus and multiple sclerosis (MS). There is limited direct evidence linking causative agents with pathogenic immune reactions in these diseases. Our study establishes a clear link between viral infection, autoimmunity and neurological disease in humans. As a model for molecular mimicry, we studied patients with human T-lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP), a disease that can be indistinguishable from MS (refs. 5,6,7). HAM/TSP patients develop antibodies to neurons. We hypothesized these antibodies would identify a central nervous system (CNS) autoantigen. Immunoglobulin G isolated from HAM/TSP patients identified heterogeneous nuclear ribonuclear protein-A1 (hnRNP-A1) as the autoantigen. Antibodies to hnRNP-A1 cross-reacted with HTLV-1-tax, the immune response to which is associated with HAM/TSP (refs. 5,9). Immunoglobulin G specifically stained human Betz cells, whose axons are preferentially damaged. Infusion of autoantibodies in brain sections inhibited neuronal firing, indicative of their pathogenic nature. These data demonstrate the importance of molecular mimicry between an infecting agent and hnRNP-A1 in autoimmune disease of the CNS.

Antiphospholipid Antibody Induced by Nivolumab

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Ahmed Aburahma

2018-01-01

Full Text Available Nivolumab is a monoclonal antibody against the programmed death protein 1 and is used for patients with advanced melanoma. It is associated with potentially immune-related adverse events, including disorders of the skin, GI tract, and the thyroid; these disorders were successfully treated with prednisone and infliximab. Other immunotherapeutic agents were observed to induce the formation of antiphospholipid antibody (APA including α-interferon and interleukin-2. We present a case of APA development after the third dose of nivolumab in a 71-year-old male with advanced melanoma. The APA was detected after finding a prolonged aPTT; the lupus anticoagulant assay tested positive. The patient was treated with prednisone but, unfortunately, he expired a few days later.

Regulatory B and T cell responses in patients with autoimmune thyroid disease and healthy controls

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Kristensen, Birte; Hegedüs, Laszlo

2016-01-01

). HT is primarily a T-cell mediated disease, and whether B cells play a pathogenic role in the pathogenesis is still unclear. Both GD and HT are characterized by infiltration of the thyroid gland by self-reactive T cells and B cells. In the first paper of this thesis, the role of regulatory B cells...... (Bregs) and regulatory T cells (Tregs) were investigated in the context of GD and HT. First, we studied the role of the thyroid self-antigen, thyroglobulin (TG) in healthy donors. The self-antigen TG, but not the foreign recall antigen tetanus toxoid (TT), was able to induce interleukin 10 (IL-10......Autoimmune diseases occur due to faulty self-tolerance. Graves' disease (GD) and Hashimoto's thyroiditis (HT) are classic examples of organ-specific autoimmune diseases. GD is an auto-antibody-mediated disease where autoantibodies are produced against the thyroid stimulating hormone receptor (TSHR...

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

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2013-01-01

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

Antibody-Mediated Extreme Insulin Resistance: A Report of Three Cases.

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Kim, Han Na; Fesseha, Betiel; Anzaldi, Laura; Tsao, Allison; Galiatsatos, Panagis; Sidhaye, Aniket

2018-01-01

Type 2 diabetes mellitus is characterized by relative insulin deficiency and insulin resistance. Features suggesting severe insulin resistance include acanthosis nigricans, hyperandrogenism, weight loss, and recurrent hospital admissions for diabetic ketoacidosis. In rare circumstances, hyperglycemia persists despite administration of massive doses of insulin. In these cases, it is important to consider autoimmune etiologies for insulin resistance, such as type B insulin resistance and insulin antibody-mediated extreme insulin resistance, which carry high morbidity and mortality if untreated. Encouragingly, immunomodulatory regimens have recently been published that induce remission at high rates. We describe 3 cases of extreme insulin resistance mediated by anti-insulin receptor autoantibodies or insulin autoantibodies. All cases were effectively treated with an immunomodulatory regimen. Although cases of extreme insulin resistance are rare, it is important to be aware of autoimmune causes, recognize suggestive signs and symptoms, and pursue appropriate diagnostic evaluation. Prompt treatment with immunomodulators is key to restoring euglycemia in patients with autoimmune etiologies of insulin resistance. Copyright © 2018 Elsevier Inc. All rights reserved.

Different Mechanisms of Inflammation Induced in Virus and Autoimmune-Mediated Models of Multiple Sclerosis in C57BL6 Mice

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Abhinoy Kishore

2013-01-01

Full Text Available Multiple sclerosis (MS is an inflammatory demyelinating disease of the human central nervous system (CNS. Neurotropic demyelinating strain of MHV (MHV-A59 or its isogenic recombinant strain RSA59 induces MS-like disease in mice mediated by microglia, along with a small population of T cells. The mechanism of demyelination is at least in part due to microglia-mediated myelin stripping, with some direct axonal injury. Immunization with myelin oligodendrocyte glycoprotein (MOG induces experimental autoimmune encephalomyelitis (EAE, a mainly CD4+ T-cell-mediated disease, although CD8+ T cells may play a significant role in demyelination. It is possible that both autoimmune and nonimmune mechanisms such as direct viral toxicity may induce MS. Our study directly compares CNS pathology in autoimmune and viral-induced MS models. Mice with viral-induced and EAE demyelinating diseases demonstrated similar patterns and distributions of demyelination that accumulated over the course of the disease. However, significant differences in acute inflammation were noted. Inflammation was restricted mainly to white matter at all times in EAE, whereas inflammation initially largely involved gray matter in acute MHV-induced disease and then is subsequently localized only in white matter in the chronic disease phase. The presence of dual mechanisms of demyelination may be responsible for the failure of immunosuppression to promote long-term remission in many MS patients.

Genotoxic effect and antigen binding characteristics of SLE auto-antibodies to peroxynitrite-modified human DNA.

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Khan, Md Asad; Alam, Khursheed; Mehdi, Syed Hassan; Rizvi, M Moshahid A

2017-12-01

Systemic lupus erythematosus (SLE) is an inflammatory autoimmune disease characterized by auto-antibodies against native deoxyribonucleic acid after modification and is one of the reasons for the development of SLE. Here, we have evaluated the structural perturbations in human placental DNA by peroxynitrite using spectroscopy, thermal denaturation and high-performance liquid chromatography (HPLC). Peroxynitrite is a powerful potent bi-functional oxidative/nitrative agent that is produced both endogenously and exogenously. In experimental animals, the peroxynitrite-modified DNA was found to be highly immunogenic. The induced antibodies showed cross-reactions with different types of DNA and nitrogen bases that were modified with peroxynitrite by inhibition ELISA. The antibody activity was inhibited by approximately 89% with its immunogen as the inhibitor. The antigen-antibodies interaction between induced antibodies with peroxynitrite-modified DNA showed retarded mobility as compared to the native form. Furthermore, significantly increased binding was also observed in SLE autoantibodies with peroxynitrite-modified DNA than native form. Moreover, DNA isolated from lymphocyte of SLE patients revealed significant recognition of anti-peroxynitrite-modified DNA immunoglobulin G (IgG). Our data indicates that DNA modified with peroxynitrite presents unique antigenic determinants that may induce autoantibody response in SLE. Copyright © 2017 Elsevier Inc. All rights reserved.

Immunization with Clinical HIV-1 Env Proteins Induces Broad Antibody Dependent Cellular Cytotoxicity-Mediating Antibodies in a Rabbit Vaccination Model.

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Karlsson, Ingrid; Borggren, Marie; Jensen, Sanne Skov; Heyndrickx, Leo; Stewart-Jones, Guillaume; Scarlatti, Gabriella; Fomsgaard, Anders

2017-11-17

The induction of both neutralizing antibodies and non-neutralizing antibodies with effector functions, for example, antibody-dependent cellular cytotoxicity (ADCC), is desired in the search for effective vaccines against HIV-1. In the pursuit of novel immunogens capable of inducing an efficient antibody response, rabbits were immunized with selected antigens using different prime-boost strategies. We immunized 35 different groups of rabbits with Env antigens from clinical HIV-1 subtypes A and B, including immunization with DNA alone, protein alone, and DNA prime with protein boost. The rabbit sera were screened for ADCC activity using a GranToxiLux-based assay with human peripheral blood mononuclear cells as effector cells and CEM.NKR CCR5 cells coated with HIV-1 envelope as target cells. The groups with the highest ADCC activity were further characterized for cross-reactivity between HIV-1 subtypes. The immunogen inducing the most potent and broadest ADCC response was a trimeric gp140. The ADCC activity was highest against the HIV-1 subtype corresponding to the immunogen. The ADCC activity did not necessarily reflect neutralizing activity in the pseudovirus-TZMbl assay, but there was an overall correlation between the two antiviral activities. We present a rabbit vaccination model and an assay suitable for screening HIV-1 vaccine candidates for the induction of ADCC-mediating antibodies in addition to neutralizing antibodies. The antigens and/or immunization strategies capable of inducing antibodies with ADCC activity did not necessarily induce neutralizing activity and vice versa. Nevertheless, we identified vaccine candidates that were able to concurrently induce both types of responses and that had ADCC activity that was cross-reactive between different subtypes. When searching for an effective vaccine candidate, it is important to evaluate the antibody response using a model and an assay measuring the desired function.

Multiple endocrinopathies (growth hormone deficiency, autoimmune hypothyroidism and diabetes mellitus in Kearns-Sayre syndrome

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A. Berio

2013-06-01

Full Text Available Kearns-Sayre syndrome is characterized by onset before 20 years, chronic progressive external opthalmoplegia, pigmentary retinal degeneration, and ataxia (and/or hearth block, and/or high protein content in the cerebrospinal fluid in the presence of mtDNA rearrangements. Multiple endocrine dysfunction associated with this syndrome was rarely reported. In this paper, the Authors report on a female patient with Kearns-Sayre syndrome with large heteroplasmic mtDNA deletion, absence of cytochrome c oxidase in many muscle fibers, partial GH deficiency, hypothyroidism and subsequently insulin dependent diabetes mellitus (IDDM. Anti-thyroid peroxidase and antithyreoglobulin antibodies were present in high titer in serum while anti-islet cell antibodies were absent. The patient developed thyroiditis with Hashimoto encephalopathy. The presence of GH deficiency, autoimmune thyroiditis with hypothyroidism and IDDM distinguishes this case from others and confirms the association of Kearns-Sayre syndrome with multiple endocrine dysfunction. Hashimoto encephalopathy and anti-thyroideal antibodies suggest that in this patient, predisposed by a genetic factor (a mitochondrial deletion anti-thyroideal antibodies may have contributed to the hypothyroidism and, by interfering with cerebral mitochondrial function, may have caused the encephalopathy. GH deficiency and IDDM can be attributed to oxidative phosphorylation deficiency but the autoimmunity may also have played a role in the production of glandular insufficiencies. It seems important to search for endocrine autoimmunity in every case of KSS.

Properdin-dependent activation and control of immune-homeostasis and autoimmunity

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O'Flynn, Joseph

2014-01-01

The complement system has been shown to have a role in various systemic autoimmune (AI) diseases which have a renal component. This includes systemic lupus erythematosus (SLE), goodpastures syndrome and anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitides. In particular the classical

Shwachman-Diamond syndrome with autoimmune-like liver disease and enteropathy mimicking celiac disease.

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Veropalumbo, Claudio; Campanozzi, Angelo; De Gregorio, Fabiola; Correra, Antonio; Raia, Valeria; Vajro, Pietro

2015-02-01

Liver abnormalities that normalize during infancy as well an enteropathy are reported in Shwachman-Diamond syndrome (SDS). The pathogenesis of both conditions is unknown. We report two SDS cases with autoimmune-like (antismooth muscle and/or antinuclear antibody positivity) liver disease and antigliadin antibody positive inflammatory enteropathy. Hypertransaminasemia did not resolve after immunosuppressive therapy and/or a gluten-free diet. These transient autoimmune phenomena and gut-liver axis perturbations may have played a role in transient SDS hepatopathy and enteropathy. Our report may stimulate other studies to define the relationship between the SDS genetic defect and intestinal permeability as the pathogenic mechanism underlying SDS related liver and intestinal inflammation. Copyright © 2014. Published by Elsevier Masson SAS.

Challenges in interpretation of thyroid function tests in pregnant women with autoimmune thyroid disease

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Feldt-Rasmussen, Ulla; Bliddal, Sofie; Rasmussen, Åse Krogh

2011-01-01

Physiological changes during gestation are important to be aware of in measurement and interpretation of thyroid function tests in women with autoimmune thyroid diseases. Thyroid autoimmune activity is decreasing in pregnancy. Measurement of serum TSH is the first-line screening variable....... Measurement of antithyroperoxidase and/or TSH receptor antibodies adds to the differential diagnosis of autoimmune and nonautoimmune thyroid diseases....... for thyroid dysfunction also in pregnancy. However, using serum TSH for control of treatment of maternal thyroid autoimmunity infers a risk for compromised foetal development. Peripheral thyroid hormone values are highly different among laboratories, and there is a need for laboratory-specific gestational age...

[VGKC-complex antibodies].

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Watanabe, Osamu

2013-04-01

Various antibodies are associated with voltage-gated potassium channels (VGKCs). Representative antibodies to VGKCs were first identified by radioimmunoassays using radioisotope-labeled alpha-dendrotoxin-VGKCs solubilized from rabbit brain. These antibodies were detected only in a proportion of patients with acquired neuromyotonia (Isaacs' syndrome). VGKC antibodies were also detected in patients with Morvan's syndrome and in those with a form of autoimmune limbic encephalitis. Recent studies indicated that the "VGKC" antibodies are mainly directed toward associated proteins (for example LGI-1 and CASPR-2) that complex with the VGKCs themselves. The "VGKC" antibodies are now commonly known as VGKC-complex antibodies. In general, LGI-1 antibodies are most commonly detected in patients with limbic encephalitis with syndrome of inappropriate secretion of antidiuretic hormone. CASPR-2 antibodies are present in the majority of patients with Morvan's syndrome. These patients develop combinations of CNS symptoms, autonomic dysfunction, and peripheral nerve hyperexcitability. Furthermore, VGKC-complex antibodies are tightly associated with chronic idiopathic pain. Hyperexcitability of nociceptive pathways has also been implicated. These antibodies may be detected in sera of some patients with neurodegenerative diseases (for example, amyotrophic lateral sclerosis and Creutzfeldt-Jakob disease).

Segmental vitiligo with segmental morphea: An autoimmune link?

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Pravesh Yadav

2014-01-01

Full Text Available An 18-year old girl with segmental vitiligo involving the left side of the trunk and left upper limb with segmental morphea involving the right side of trunk and right upper limb without any deeper involvement is illustrated. There was no history of preceding drug intake, vaccination, trauma, radiation therapy, infection, or hormonal therapy. Family history of stable vitiligo in her brother and a history of type II diabetes mellitus in the father were elicited. Screening for autoimmune diseases and antithyroid antibody was negative. An autoimmune link explaining the co-occurrence has been proposed. Cutaneous mosiacism could explain the presence of both the pathologies in a segmental distribution.

THYROID AUTOIMMUNITY IN AN IODINE-REPLETE POPULATION: A RESEARCH ARTICLE

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Peter Manoharan

2016-05-01

Full Text Available INTRODUCTION In recent times, the incidence and prevalence of thyroid disorders has been increasing in the Indian population. Autoimmune thyroiditis or Hashimoto’s thyroiditis is one of the most common causes of thyroid disease. Antithyroid antibodies rarely develop before 20 years of age, but they may be a prelude to the development of subsequent hypothyroidism. It is universally known that iodine deficiency causes hypothyroidism. However, sustained unnecessary iodine supplementation may be harmful. Goitre, thyroid dysfunction (both hypo- and hyperthyroidism and thyroid autoimmunity have been reported as a result of sustained supplementation in the iodine-replete state. Data on the impact of iodisation on thyroid function in adults is sparse. A study was conducted with an objective to estimate the problem of thyroid autoimmunity in patients who presented to the OPD. PATIENTS AND METHODS Patients who presented to the surgical OPD with clinical features of thyroid disease were included in the study after obtaining informed consent. Demographic details and clinical features of thyroid disease were noted. Thyroid status was estimated with the help of serum levels of thyroid stimulating hormone (TSH, free l-thyroxine (FT4, and free tri-iodothyronine (FT3. Autoantibodies to thyroid peroxidase (Anti-TPO were estimated. Findings were tabulated and analysed. RESULTS AND CONCLUSION The prevalence of antibody positivity was 69.7% (209 out of the 300 patients in this study. Among age-groups, the maximum prevalence was found in the third decade of life (75/99 patients, 75.8%. Among those who were antibody-positive, 69.9% were euthyroid, 26.8% were hypothyroid and 3.3% were thyrotoxic. Hypothyroidism (elevated S. TSH had a significant positive correlation (r = 0.324, p = 0.003 with antibody-positivity (elevated S. AMA.

Breaking Tolerance to Thyroid Antigens: Changing Concepts in Thyroid Autoimmunity

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Rapoport, Basil

2014-01-01

Thyroid autoimmunity involves loss of tolerance to thyroid proteins in genetically susceptible individuals in association with environmental factors. In central tolerance, intrathymic autoantigen presentation deletes immature T cells with high affinity for autoantigen-derived peptides. Regulatory T cells provide an alternative mechanism to silence autoimmune T cells in the periphery. The TSH receptor (TSHR), thyroid peroxidase (TPO), and thyroglobulin (Tg) have unusual properties (“immunogenicity”) that contribute to breaking tolerance, including size, abundance, membrane association, glycosylation, and polymorphisms. Insight into loss of tolerance to thyroid proteins comes from spontaneous and induced animal models: 1) intrathymic expression controls self-tolerance to the TSHR, not TPO or Tg; 2) regulatory T cells are not involved in TSHR self-tolerance and instead control the balance between Graves' disease and thyroiditis; 3) breaking TSHR tolerance involves contributions from major histocompatibility complex molecules (humans and induced mouse models), TSHR polymorphism(s) (humans), and alternative splicing (mice); 4) loss of tolerance to Tg before TPO indicates that greater Tg immunogenicity vs TPO dominates central tolerance expectations; 5) tolerance is induced by thyroid autoantigen administration before autoimmunity is established; 6) interferon-α therapy for hepatitis C infection enhances thyroid autoimmunity in patients with intact immunity; Graves' disease developing after T-cell depletion reflects reconstitution autoimmunity; and 7) most environmental factors (including excess iodine) “reveal,” but do not induce, thyroid autoimmunity. Micro-organisms likely exert their effects via bystander stimulation. Finally, no single mechanism explains the loss of tolerance to thyroid proteins. The goal of inducing self-tolerance to prevent autoimmune thyroid disease will require accurate prediction of at-risk individuals together with an antigen

Possible role of anti-SSA/Ro antibodies in the pathogenesis of pulmonary hypertension

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Kelsey Guerreso

2016-01-01

Conclusion: It is known that pulmonary hypertension has association with autoimmune diseases, however no clear markers yet exist. Anti-SSA/Ro antibodies have been rarely described in cases of pulmonary disease, and less so in pulmonary hypertension. This case describes a unique association between isolated pulmonary hypertension and anti-SSA/Ro antibody, thereby illustrating the need to investigate this autoantibody and others in the pathogenesis of autoimmune pulmonary hypertension.

CD4+ CD25+ cells in type 1 diabetic patients with other autoimmune manifestations

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Dalia S. Abd Elaziz

2014-11-01

Full Text Available The existence of multiple autoimmune disorders in diabetics may indicate underlying primary defects of immune regulation. The study aims at estimation of defects of CD4+ CD25+high cells among diabetic children with multiple autoimmune manifestations, and identification of disease characteristics in those children. Twenty-two cases with type 1 diabetes associated with other autoimmune diseases were recruited from the Diabetic Endocrine and Metabolic Pediatric Unit (DEMPU, Cairo University along with twenty-one normal subjects matched for age and sex as a control group. Their anthropometric measurements, diabetic profiles and glycemic control were recorded. Laboratory investigations included complete blood picture, glycosylated hemoglobin, antithyroid antibodies, celiac antibody panel and inflammatory bowel disease markers when indicated. Flow cytometric analysis of T-cell subpopulation was performed using anti-CD3, anti-CD4, anti-CD8, anti-CD25 monoclonal antibodies. Three cases revealed a proportion of CD4+ CD25+high below 0.1% and one case had zero counts. However, this observation did not mount to a significant statistical difference between the case and control groups neither in percentage nor absolute numbers. Significant statistical differences were observed between the case and the control groups regarding their height, weight centiles, as well as hemoglobin percentage, white cell counts and the absolute lymphocytic counts. We concluded that, derangements of CD4+ CD25+high cells may exist among diabetic children with multiple autoimmune manifestations indicating defects of immune controllers.

Heparin- induced thrombocytopenia (HIT: a case report of CABG patient

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Alireza Jahangirifard

2016-08-01

Full Text Available Heparin- induced thrombocytopenia (HIT is an antibody mediated adverse effect of heparin therapy which is classified into two subtypes, HITI which is non-immune, spontaneously reversible thrombocytopenia and; HITII which is an autoimmune-mediated adverse effect of heparin therapy. In this case report, we described a 65-year old male patient with HITII after coronary artery bypass grafting.Key words: Heparin- induced thrombocytopenia, Heparin- induced thrombosis, coronary artery bypass grafting.

Natural and cross-inducible anti-SIV antibodies in Mauritian cynomolgus macaques.

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Hongzhao Li

Full Text Available Cynomolgus macaques are an increasingly important nonhuman primate model for HIV vaccine research. SIV-free animals without pre-existing anti-SIV immune responses are generally needed to evaluate the effect of vaccine-induced immune responses against the vaccine epitopes. Here, in order to select such animals for vaccine studies, we screened 108 naïve female Mauritian cynomolgus macaques for natural (baseline antibodies to SIV antigens using a Bio-Plex multiplex system. The antigens included twelve 20mer peptides overlapping the twelve SIV protease cleavage sites (-10/+10, respectively (PCS peptides, and three non-PCS Gag or Env peptides. Natural antibodies to SIV antigens were detected in subsets of monkeys. The antibody reactivity to SIV was further confirmed by Western blot using purified recombinant SIV Gag and Env proteins. As expected, the immunization of monkeys with PCS antigens elicited anti-PCS antibodies. However, unexpectedly, antibodies to non-PCS peptides were also induced, as shown by both Bio-Plex and Western blot analyses, while the non-PCS peptides do not share sequence homology with PCS peptides. The presence of natural and vaccine cross-inducible SIV antibodies in Mauritian cynomolgus macaques should be considered in animal selection, experimental design and result interpretation, for their best use in HIV vaccine research.

AUTOIMMUNE DISEASE DURING PREGNANCY AND THE MICROCHIMERISM LEGACY OF PREGNANCY

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Adams Waldorf, Kristina M.; Nelson, J. Lee

2009-01-01

Pregnancy has both short-term effects and long-term consequences. For women who have an autoimmune disease and subsequently become pregnant, pregnancy can induce amelioration of the mother’s disease, such as in rheumatoid arthritis, while exacerbating or having no effect on other autoimmune diseases like systemic lupus erythematosus. That pregnancy also leaves a long-term legacy has recently become apparent by the discovery that bi-directional cell trafficking results in persistence of fetal cells in the mother and of maternal cells in her offspring for decades after birth. The long-term persistence of a small number of cells (or DNA) from a genetically disparate individual is referred to as microchimerism. While microchimerism is common in healthy individuals and is likely to have health benefits, microchimerism has been implicated in some autoimmune diseases such as systemic sclerosis. In this paper, we will first discuss short-term effects of pregnancy on women with autoimmune disease. Pregnancy-associated changes will be reviewed for selected autoimmune diseases including rheumatoid arthritis, systemic lupus erythematosus and autoimmune thyroid disease. The pregnancy-induced amelioration of rheumatoid arthritis presents a window of opportunity for insights into both immunological mechanisms of fetal-maternal tolerance and pathogenic mechanisms in autoimmunity. A mechanistic hypothesis for the pregnancy-induced amelioration of rheumatoid arthritis will be described. We will then discuss the legacy of maternal-fetal cell transfer from the perspective of autoimmune diseases. Fetal and maternal microchimerism will be reviewed with a focus on systemic sclerosis (scleroderma), autoimmune thyroid disease, neonatal lupus and type I diabetes mellitus. PMID:18716941

A Tandem Repeat in Decay Accelerating Factor 1 Is Associated with Severity of Murine Mercury-Induced Autoimmunity

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David M. Cauvi

2014-01-01

Full Text Available Decay accelerating factor (DAF, a complement-regulatory protein, protects cells from bystander complement-mediated lysis and negatively regulates T cells. Reduced expression of DAF occurs in several systemic autoimmune diseases including systemic lupus erythematosus, and DAF deficiency exacerbates disease in several autoimmune models, including murine mercury-induced autoimmunity (mHgIA. Daf1, located within Hmr1, a chromosome 1 locus associated in DBA/2 mice with resistance to mHgIA, could be a candidate. Here we show that reduced Daf1 transcription in lupus-prone mice was not associated with a reduction in the Daf1 transcription factor SP1. Studies of NZB mice congenic for the mHgIA-resistant DBA/2 Hmr1 locus suggested that Daf1 expression was controlled by the host genome and not the Hmr1 locus. A unique pentanucleotide repeat variant in the second intron of Daf1 in DBA/2 mice was identified and shown in F2 intercrosses to be associated with less severe disease; however, analysis of Hmr1 congenics indicated that this most likely reflected the presence of autoimmunity-predisposing genetic variants within the Hmr1 locus or that Daf1 expression is mediated by the tandem repeat in epistasis with other genetic variants present in autoimmune-prone mice. These studies argue that the effect of DAF on autoimmunity is complex and may require multiple genetic elements.

Autoimmune Diabetes and Thyroiditis Complicating Treatment with Nivolumab

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Li Li

2017-03-01

Full Text Available Programmed cell death-1 (PD-1 ligand inhibitors have gained popularity in the treatment of advanced non-small-cell lung cancer. The immune system is regulated by stimulatory and inhibitory signaling and aims to achieve the balance between activation and inhibition. Treatment with immune checkpoint inhibitors enhances immune response, but is also known to diminish immune tolerance and increase autoimmune toxicity. Here we present a case of a patient with advanced squamous cell lung cancer who developed type I diabetes and thyroiditis after treatment with PD-1 checkpoint inhibitor nivolumab. The presence of autoimmune diabetes mellitus and thyroiditis were confirmed by markedly elevated titers of the glutamic acid decarboxylase autoantibody and thyroid peroxidase antibody, respectively. This report serves to heighten awareness of potential autoimmune toxicities related to anti-PD-1 therapy, especially as these toxicities are manageable if identified in a timely manner.

Identification of a novel myositis-associated antibody directed against cortactin.

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Labrador-Horrillo, Moisés; Martínez, Maria Angeles; Selva-O'Callaghan, Albert; Trallero-Araguás, Ernesto; Grau-Junyent, Josep M; Vilardell-Tarrés, Miquel; Juarez, Candido

2014-10-01

The aim of this study is to describe a novel myositis-associated autoantibody (anti-cortactin antibody) and assess related clinical and immunological manifestations and its clinical significance. Adult patients with myositis (dermatomyositis, polymyositis, immune-mediated necrotizing myopathy, and inclusion body myositis), as well as patients with other autoimmune diseases and non-inflammatory myopathies were analyzed for the presence of anti-cortactin antibody using in-house developed ELISA and immunoblotting techniques with a commercial source of purified cortactin. The cut-off for positive status was determined in a group of healthy volunteers. Antibody against cortactin was positive in 7/34 (20%) polymyositis patients, 9/117 (7.6%) dermatomyositis, 2/7 (26%) immune-mediated necrotizing myopathy, and none of the 4 patients with inclusion body myositis. The antibody also tested positive in 3/101 patients with other autoimmune diseases (2 systemic sclerosis and 1 systemic lupus erythematosus), and in 1/29 patients with non-inflammatory myopathy. No relevant association with specific clinical features was found in patients with these antibodies. Anti-cortactin antibody was more frequently positive in patients with polymyositis and immune-mediated necrotizing myopathy than in the remaining myositis patients, and was the only myositis autoantibody found in sera of 3 patients from these groups. Our data indicate that cortactin is a novel target antigen in patients with autoimmune diseases, especially patients with polymyositis or immune-mediated necrotizing myopathy. Anti-cortactin can be considered a new myositis-associated antibody. Copyright © 2014 Elsevier B.V. All rights reserved.

Pathogenic and Epiphenomenal Anti-DNA Antibodies in SLE

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Mirjana Pavlovic

2010-01-01

Full Text Available The discoveries of natural and the development of manufactured highly efficient catalytic antibodies (abzymes opens the door to many practical applications. One of the most fascinating is the use of such antibodies in human therapy and prevention (vaccination, of cancer, AIDS, autoimmune diseases. A special entity of naturally occurring DNA hydrolytic anti-DNA antibodies is emerging within past decades linked to autoimmune and lymphoproliferative disorders, such as systemic lupus erythematosus (SLE, multiple sclerosis (MS, Sjogren Syndrome (SS, B - Chronic lymphocytic leucosis (B-CLL, and Multiple Myeloma (MM. The origin of the antibodies is unknown. The underlying mechanisms of these activities are suggested to be penetration into the living cells and translocation in the nucleus, with recognition of the specific binding sites at particular (ss or ds DNA. There are controversies in the literature whether hydrolysis is a sequence-specific event. The interplay between anti-DNA antibodies and DNA is not yet elucidated. This molecular “twist” also suggests that anti-DNA antibodies with DNA hydrolytic capacity could be the organism's immune response to a microbial attack, with microbial DNA, or specific genes within microbial DNA sequence, as a target for neutralization. The catalytic antibody-based approach can become a key tool in selective chemotherapeutic strategies.

Intramuscular Immunisation with Chlamydial Proteins Induces Chlamydia trachomatis Specific Ocular Antibodies.

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Alexander Badamchi-Zadeh

Full Text Available Ocular infection with Chlamydia trachomatis can cause trachoma, which is the leading cause of blindness due to infection worldwide. Despite the large-scale implementation of trachoma control programmes in the majority of countries where trachoma is endemic, there remains a need for a vaccine. Since C. trachomatis infects the conjunctival epithelium and stimulates an immune response in the associated lymphoid tissue, vaccine regimens that enhance local antibody responses could be advantageous. In experimental infections of non-human primates (NHPs, antibody specificity to C. trachomatis antigens was found to change over the course of ocular infection. The appearance of major outer membrane protein (MOMP specific antibodies correlated with a reduction in ocular chlamydial burden, while subsequent generation of antibodies specific for PmpD and Pgp3 correlated with C. trachomatis eradication.We used a range of heterologous prime-boost vaccinations with DNA, Adenovirus, modified vaccinia Ankara (MVA and protein vaccines based on the major outer membrane protein (MOMP as an antigen, and investigated the effect of vaccine route, antigen and regimen on the induction of anti-chlamydial antibodies detectable in the ocular lavage fluid of mice.Three intramuscular vaccinations with recombinant protein adjuvanted with MF59 induced significantly greater levels of anti-MOMP ocular antibodies than the other regimens tested. Intranasal delivery of vaccines induced less IgG antibody in the eye than intramuscular delivery. The inclusion of the antigens PmpD and Pgp3, singly or in combination, induced ocular antigen-specific IgG antibodies, although the anti-PmpD antibody response was consistently lower and attenuated by combination with other antigens.If translatable to NHPs and/or humans, this investigation of the murine C. trachomatis specific ocular antibody response following vaccination provides a potential mouse model for the rapid and high throughput

Antibody-Based Cancer Therapy : Successful Agents and Novel Approaches

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Hendriks, D; Choi, G; de Bruyn, M; Wiersma, V R; Bremer, E; Galluzi, Lorenzo; Vitale, Ilio

2017-01-01

Since their discovery, antibodies have been viewed as ideal candidates or "magic bullets" for use in targeted therapy in the fields of cancer, autoimmunity, and chronic inflammatory disorders. A wave of antibody-dedicated research followed, which resulted in the clinical approval of a first

Anti-soluble liver antigen (SLA) antibodies in chronic HCV infection.

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Vitozzi, Susana; Lapierre, Pascal; Djilali-Saiah, Idriss; Marceau, Gabriel; Beland, Kathie; Alvarez, Fernando

2004-05-01

Hepatitis C infection is associated with autoimmune disorders, such as the production of autoantibodies. Anti-LKM1 and anti-LC1, immunomarkers of type 2 autoimmune hepatitis, have been previously associated with a HCV infection. Anti-Soluble-Liver-Antigen autoantibodies (SLA) are specifically associated with type 1 and type 2 autoimmune hepatitis and more closely related to patients who relapse after steroid therapy. The recent molecular cloning of the soluble liver antigen provides the opportunity to develop more specific tests for the detection of antibodies against it. The aim of this work is to characterize anti-soluble-liver autoantibodies in sera from patients chronically infected by HCV. A recombinant cDNA from activated Jurkat cells coding for the full length tRNP(Ser)Sec/SLA antigen was obtained. ELISA, Western Blot and immunoprecipitation tests were developed and used to search for linear and conformational epitopes recognized by anti-SLA antibodies in sera from patients chronically infected by HCV. Anti-soluble liver antigen antibodies were found in sera from 10.4% of HCV-infected patients. The prevalence was significantly increased to 27% when anti-LKM1 was also present. Most anti-SLA reactivity was directed against conformational epitopes on the antigen. The means titers by ELISA were lower than those obtained in type 2 AIH. The result of autoantibody isotyping showed a subclass restriction to IgG1 and also IgG4. This study shows the presence of anti-SLA antibodies in approximately 10% of HCV infected patients. The prevalence of SLA autoantibodies in HCV infected patients increases when LKM1 autoantibodies are also present. The relationship between the prevalence of this characteristic autoimmune hepatitis autoantibody and the implication of an autoimmune phenomenon in the liver injury of patients chronically infected by HCV needs further investigation.

Immunization with Clinical HIV-1 Env Proteins Induces Broad Antibody Dependent Cellular Cytotoxicity-Mediating Antibodies in a Rabbit Vaccination Model

DEFF Research Database (Denmark)

Karlsson, Ingrid; Borggren, Marie; Jensen, Sanne Skov

2018-01-01

The induction of both neutralizing antibodies and non-neutralizing antibodies with effector functions, for example, antibody-dependent cellular cytotoxicity (ADCC), is desired in the search for effective vaccines against HIV-1. In the pursuit of novel immunogens capable of inducing an efficient a...

Autoimmune hemolytic anemia, as part of Evans' syndrome, caused by cold reactive IgG autoantibodies

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Jaarsma, AS; Muis, N; DeGraaf, SSN

1996-01-01

We describe a boy with Evans' syndrome, consisting of immune thrombocytopenic purpura at age 2 and autoimmune hemolytic anemia (AIHA) at age 4. AIHA was caused by cold Ige autoantibodies. This is unusual because AIHA is generally associated with either warm IgG antibodies or cold IgM antibodies.

Comparison of the human gastric microbiota in hypochlorhydric states arising as a result of Helicobacter pylori-induced atrophic gastritis, autoimmune atrophic gastritis and proton pump inhibitor use.

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Bryony N Parsons

2017-11-01

Full Text Available Several conditions associated with reduced gastric acid secretion confer an altered risk of developing a gastric malignancy. Helicobacter pylori-induced atrophic gastritis predisposes to gastric adenocarcinoma, autoimmune atrophic gastritis is a precursor of type I gastric neuroendocrine tumours, whereas proton pump inhibitor (PPI use does not affect stomach cancer risk. We hypothesised that each of these conditions was associated with specific alterations in the gastric microbiota and that this influenced subsequent tumour risk. 95 patients (in groups representing normal stomach, PPI treated, H. pylori gastritis, H. pylori-induced atrophic gastritis and autoimmune atrophic gastritis were selected from a cohort of 1400. RNA extracted from gastric corpus biopsies was analysed using 16S rRNA sequencing (MiSeq. Samples from normal stomachs and patients treated with PPIs demonstrated similarly high microbial diversity. Patients with autoimmune atrophic gastritis also exhibited relatively high microbial diversity, but with samples dominated by Streptococcus. H. pylori colonisation was associated with decreased microbial diversity and reduced complexity of co-occurrence networks. H. pylori-induced atrophic gastritis resulted in lower bacterial abundances and diversity, whereas autoimmune atrophic gastritis resulted in greater bacterial abundance and equally high diversity compared to normal stomachs. Pathway analysis suggested that glucose-6-phospahte1-dehydrogenase and D-lactate dehydrogenase were over represented in H. pylori-induced atrophic gastritis versus autoimmune atrophic gastritis, and that both these groups showed increases in fumarate reductase. Autoimmune and H. pylori-induced atrophic gastritis were associated with different gastric microbial profiles. PPI treated patients showed relatively few alterations in the gastric microbiota compared to healthy subjects.

Comparison of the human gastric microbiota in hypochlorhydric states arising as a result of Helicobacter pylori-induced atrophic gastritis, autoimmune atrophic gastritis and proton pump inhibitor use

Science.gov (United States)

Eccles, Richard; Duckworth, Carrie A.; Varro, Andrea

2017-01-01

Several conditions associated with reduced gastric acid secretion confer an altered risk of developing a gastric malignancy. Helicobacter pylori-induced atrophic gastritis predisposes to gastric adenocarcinoma, autoimmune atrophic gastritis is a precursor of type I gastric neuroendocrine tumours, whereas proton pump inhibitor (PPI) use does not affect stomach cancer risk. We hypothesised that each of these conditions was associated with specific alterations in the gastric microbiota and that this influenced subsequent tumour risk. 95 patients (in groups representing normal stomach, PPI treated, H. pylori gastritis, H. pylori-induced atrophic gastritis and autoimmune atrophic gastritis) were selected from a cohort of 1400. RNA extracted from gastric corpus biopsies was analysed using 16S rRNA sequencing (MiSeq). Samples from normal stomachs and patients treated with PPIs demonstrated similarly high microbial diversity. Patients with autoimmune atrophic gastritis also exhibited relatively high microbial diversity, but with samples dominated by Streptococcus. H. pylori colonisation was associated with decreased microbial diversity and reduced complexity of co-occurrence networks. H. pylori-induced atrophic gastritis resulted in lower bacterial abundances and diversity, whereas autoimmune atrophic gastritis resulted in greater bacterial abundance and equally high diversity compared to normal stomachs. Pathway analysis suggested that glucose-6-phospahte1-dehydrogenase and D-lactate dehydrogenase were over represented in H. pylori-induced atrophic gastritis versus autoimmune atrophic gastritis, and that both these groups showed increases in fumarate reductase. Autoimmune and H. pylori-induced atrophic gastritis were associated with different gastric microbial profiles. PPI treated patients showed relatively few alterations in the gastric microbiota compared to healthy subjects. PMID:29095917

Brain-Reactive Antibodies and Disease

OpenAIRE

Diamond, B.; Honig, G.; Mader, S.; Brimberg, L.; Volpe, B.T.

2013-01-01

Autoimmune diseases currently affect 5–7% of the world's population; in most diseases there are circulating autoantibodies. Brain-reactive antibodies are present in approximately 2–3% of the general population but do not usually contribute to brain pathology. These antibodies penetrate brain tissue only early in development or under pathologic conditions. This restriction on their pathogenicity and the lack of correlation between serum titers and brain pathology have, no doubt, contributed to...

Bioinformatics analysis of the factors controlling type I IFN gene expression in autoimmune disease and virus-induced immunity

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Di eFeng

2013-09-01

Full Text Available Patients with systemic lupus erythematosus (SLE and Sjögren's syndrome (SS display increased levels of type I IFN-induced genes. Plasmacytoid dendritic cells (PDCs are natural interferon producing cells and considered to be a primary source of IFN-α in these two diseases. Differential expression patterns of type I IFN inducible transcripts can be found in different immune cell subsets and in patients with both active and inactive autoimmune disease. A type I IFN gene signature generally consists of three groups of IFN-induced genes - those regulated in response to virus-induced type I IFN, those regulated by the IFN-induced mitogen-activated protein kinase/extracellular-regulated kinase (MAPK/ERK pathway, and those by the IFN-induced phosphoinositide-3 kinase (PI-3K pathway. These three groups of type I IFN-regulated genes control important cellular processes such as apoptosis, survival, adhesion, and chemotaxis, that when dysregulated, contribute to autoimmunity. With the recent generation of large datasets in the public domain from next-generation sequencing and DNA microarray experiments, one can perform detailed analyses of cell type-specific gene signatures as well as identify distinct transcription factors that differentially regulate these gene signatures. We have performed bioinformatics analysis of data in the public domain and experimental data from our lab to gain insight into the regulation of type I IFN gene expression. We have found that the genetic landscape of the IFNA and IFNB genes are occupied by transcription factors, such as insulators CTCF and cohesin, that negatively regulate transcription, as well as IRF5 and IRF7, that positively and distinctly regulate IFNA subtypes. A detailed understanding of the factors controlling type I IFN gene transcription will significantly aid in the identification and development of new therapeutic strategies targeting the IFN pathway in autoimmune disease.

Combined short-term immunotherapy for experimental autoimmune myasthenia gravis

International Nuclear Information System (INIS)

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

1983-01-01

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

Nongoitrous autoimmune thyroiditis with facial palsy

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Hyung Jik Lee

2013-12-01

Full Text Available We report a case of severe hypothyroidism with nongoitrous, autoimmune thyroiditis and pituitary hyperplasia in a 13-year-old boy, who presented with sudden palsy on the left side of his face. Prednisolone and antiviral medication was administered. However, the facial palsy did not improve completely. The medications were replaced with thyroxine, and the facial palsy recovered. Endocrinological testing showed severe hypothyroidism as follows: thyroid stimulating hormone (TSH level >100 µIU/mL, T4 of 1.04 µg/dL, T3 of 0.31 ng/mL, and free T4 of 0.07 ng/dL. Level of serum antithyroid peroxidase antibodies was 1,933.39 IU/mL, and that of antithyroglobulin antibodies was 848.16 IU/mL. Level of TSH receptor antibodies was >40 IU/L. Bioassay result for TSH receptor stimulating antibodies was negative. Thyroid sonography revealed no increase in the size or vascularity of the bilateral gland. Thyroid scintigraphy with 99mTc showed decreased uptake, and magnetic resonance imaging demonstrated an enlarged pituitary gland.

Autoimmune thyroiditis in antinuclear antibody positive children without rheumatologic disease

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Arkachaisri Thaschawee

2010-05-01

Full Text Available Abstract Background Children are commonly referred to a pediatric rheumatology center for the laboratory finding of an Anti-nuclear antibody (ANA of undetermined significance. Previous studies regarding adult rheumatology patients have supported an association between ANA and anti-thyroid antibodies, with the prevalence of thyroid antibodies being significantly higher in patients referred to a rheumatology center for an ANA without evidence of connective tissue disease compared to the general population. The purpose of the present study was to determine the frequency of thyroid antibodies in children referred to a pediatric rheumatology center for a positive ANA without evidence of a connective tissue disease. Methods A retrospective chart review was performed on children who were referred to our pediatric rheumatology center between August 2003 and March 2007 for positive ANA with concurrent thyroid antibody and thyroid function tests performed who did not fulfill criteria for a specific connective tissue disease. Laboratory and clinical features were recorded and analyzed. Mean and standard deviation were used to describe continuous data. Chi-square or Fisher's exact tests were used to compare proportions between variables. Results One-hundred and four ANA-positive patients with concurrent thyroid studies were evaluated (88% female, 93% Caucasian, mean age 11.9 ± 4.0 years. Half of patients had an ANA titer ≥ 1:320. The ANA pattern was speckled in 60% of the patients. Thyroid antibodies were detected in 30% of the patients. Anti-Thyroglobulin (ATG was detected in 29% and Anti-thyroid peroxidase (ATPO in 21% of the patients; of these children, 14% had hypothyroidism. ANA pattern and titer were not associated with anti-thyroid antibody positivity. Conclusion Thyroid antibodies associated with chronic lymphocytic thyroiditis, ATG and ATPO, were detected significantly higher in ANA-positive children without a rheumatologic condition (30% as

Acute Cerebellar Ataxia Induced by Nivolumab

OpenAIRE

Kawamura, Reina; Nagata, Eiichiro; Mukai, Masako; Ohnuki, Yoichi; Matsuzaki, Tomohiko; Ohiwa, Kana; Nakagawa, Tomoki; Kohno, Mitsutomo; Masuda, Ryota; Iwazaki, Masayuki; Takizawa, Shunya

2017-01-01

A 54-year-old woman with adenocarcinoma of the lung and lymph node metastasis experienced nystagmus and cerebellar ataxia 2 weeks after initiating nivolumab therapy. An evaluation for several autoimmune-related antibodies and paraneoplastic syndrome yielded negative results. We eventually diagnosed the patient with nivolumab-induced acute cerebellar ataxia, after excluding other potential conditions. Her ataxic gait and nystagmus resolved shortly after intravenous steroid pulse therapy follow...

Effects of latent toxoplasmosis on autoimmune thyroid diseases in pregnancy.

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Kaňková, Šárka; Procházková, Lucie; Flegr, Jaroslav; Calda, Pavel; Springer, Drahomíra; Potluková, Eliška

2014-01-01

Toxoplasmosis, one of the most common zoonotic diseases worldwide, can induce various hormonal and behavioural alterations in infected hosts, and its most common form, latent toxoplasmosis, influences the course of pregnancy. Autoimmune thyroid diseases (AITD) belong to the well-defined risk factors for adverse pregnancy outcomes. The aim of this study was to investigate whether there is a link between latent toxoplasmosis and maternal AITD in pregnancy. Cross-sectional study in 1248 consecutive pregnant women in the 9-12th gestational weeks. Serum thyroid-stimulating hormone (TSH), thyroperoxidase antibodies (TPOAb), and free thyroxine (FT4) were assessed by chemiluminescence; the Toxoplasma status was detected by the complement fixation test (CFT) and anti-Toxoplasma IgG enzyme-linked immunosorbent assay (ELISA). Overall, 22.5% of the women were positive for latent toxoplasmosis and 14.7% were screened positive for AITD. Women with latent toxoplasmosis had more often highly elevated TPOAb than the Toxoplasma-negative ones (p = 0.004), and latent toxoplasmosis was associated with decrease in serum TSH levels (p = 0.049). Moreover, we found a positive correlation between FT4 and the index of positivity for anti-Toxoplasma IgG antibodies (p = 0.033), which was even stronger in the TPOAb-positive Toxoplasma-positive women, (p = 0.014), as well as a positive correlation between FT4 and log2 CFT (p = 0.009). Latent toxoplasmosis was associated with a mild increase in thyroid hormone production in pregnancy. The observed Toxoplasma-associated changes in the parameters of AITD are mild and do not seem to be clinically relevant; however, they could provide new clues to the complex pathogenesis of autoimmune thyroid diseases.

Statin-Associated Autoimmune Myopathy: A Systematic Review of 100 Cases.

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Nazir, Salik; Lohani, Saroj; Tachamo, Niranjan; Poudel, Dilliram; Donato, Anthony

2017-04-01

Statins are a group of drugs that reduce the levels of triglycerides and cholesterol in blood by inhibiting HMG-CoA reductase, an enzyme involved in rate limiting step in cholesterol synthesis. About 2-20% patients on statins develop toxic myopathies, which usually resolve on discontinuation of statin. More recently, an immune-mediated necrotizing myopathy has been found to be associated with statin use which in most cases requires treatment with immunosuppressants. To perform a systematic review on published case reports and case series of statin-associated autoimmune myopathy. A comprehensive search of PUBMED, EMBASE, Cochrane library and ClinicalTrials.gov databases was performed for relevant articles from inception until March 19, 2016 to identify cases of statin-associated necrotizing myopathy and characterize their symptoms, evaluation and response to treatment. A total of 16 articles describing 100 patients with statin-associated autoimmune myopathy were identified. The mean age of presentation was 64.72 years, and 54.44% were males. The main presenting clinical feature was proximal muscle weakness, which was symmetric in 83.33% of patients. The mean creatine kinase (CK) was 6853 IU/l. Anti-HMG-CoA reductase antibody was positive in all cases tested (n = 57/57, 100%). In patients with no anti-HMG-CoA antibody results, diagnosis was established by findings of necrotizing myopathy on biopsy. Among the 83 cases where muscle biopsy information was available, 81.48% had necrosis, while 18.51% had combination of necrosis and inflammation. Most (83.82%) patients received two or more immunosuppressants to induce remission. Ninety-one percent had resolution of symptoms after treatment. Statin-associated necrotizing myopathy is a symmetric proximal muscle weakness associated with extreme elevations of CK. It is common in males and can occur after months of statin use. It is associated with necrosis on muscle biopsy and the presence of anti-HMG-CoA reductase antibodies

Thyroid disorders and the prevalence of antithyroid antibodies in Shiraz population.

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Karimi, Fariba; Kalantarhormozi, Mohammad Reza; Dabbaghmanesh, Mohammad Hossein; Ranjbar Omrani, Gholamhossein

2014-05-01

Thyroid dysfunction is a common health problem affecting millions of patients worldwide. Autoimmune thyroid disorders are among the most common autoimmune disorders. In this population-based study, we assessed the prevalence of abnormal thyroid function, antithyroid antibodies and the probable relationship between them in Shiraz, southern Iran. Serum thyrotropin (TSH) was determined in 981 subjects (66.8% female and 33.2% male; mean age: 39.1 ± 14.3 years), who were selected with stratified random sampling. Because of the preponderance of females over males, we performed the statistical analyses using sex-weighted data (50% for each sex). Also, antithyroid peroxidase antibodies (TPOAb), and antithyroglobulin antibodies (TgAb) were measured in two random subgroups of 376 and 537 patients respectively). Thyromegaly detected on physical examination. In this cross-sectional study, 8.1% of participants had elevated serum TSH level and 3.4% had low serum TSH level. A statistically significant relationship was found between gender and thyromegaly and TSH values. Positive TPOAb and positive TgAb were detected in 17% and 5.1% of participants respectively. In addition, a significant relationship was observed between elevated TSH levels and positive results for both antibodies. Detectable levels of thyroid antibodies correlated with female sex, while no correlation was observed between detectable levels of thyroid antibodies and thyromegaly. Thyroid disorders, especially elevated TSH level, are common. It seems that autoimmune mechanisms are strongly involved in the etiology of hypothyroidism in this area.

Clinical analysis of thyroglobulin antibody and thyroid peroxidase antibody and their association with vitiligo

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Yifen Yang

2014-01-01

Full Text Available Background: Recently, the abnormal presence of thyroglobulin antibody (TG-Ab and thyroid peroxidase antibody (TPO-Ab has been reported in vitiligo patients, but presence of TG-Ab and TPO-Ab in patients of different ages and gender, and its association with vitiligo and thyroid autoimmunity has rarely been reported. The aim of our research was to determine whether vitiligo was associated with thyroid autoimmunity and figure out its relationship with age and gender. Materials and Methods: We analyzed TG-Ab, TPO-Ab in age and gender matched 87 vitiligo patients and 90 healthy controls, the patients of vitiligo who were positive for the presence of TG-Ab and TPO-Ab were followed up to confirm autoimmune thyroid disease subsequently. Results: Results showed that the frequencies of TG-Ab (23.0%, 20/87 positivity and TPO-AB (24.1%, 21/87 in vitiligo patients were significantly higher than that in healthy controls (P < 0.05. Moreover, The positivity for of TG-Ab and TPO-Ab was higher in 11-20-year age group and 21-40-year age group than that in age matched healthy controls. We found female patients with vitiligo had higher positive frequencies of TG-Ab and TPO-Ab than healthy female controls. (34.1% vs. 8.8% and 34.1% vs. 11.1%, P = 0.000 and P = 0.011. When 20 patients with TG-Ab and TPO-Ab positivity were followed up for three monthes, 14 of them (70% were diagnosed as having autoimmune thyroid disease compared with age-matched healthy controls (16.7%, χ 2 = 5.4, P = 0.02. Conclusion: TG-Ab and TPO-Ab are likely to be found in female teenagers with vitiligo, and are relevant with respect to subsequent development autoimmune thyroid disease.

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

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

1988-11-01

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

Concurrent autoimmune hepatitis and grave's disease in hepatitis C during pegylated interferon α-2a and ribavirin therapy.

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Trikudanathan, Guru V; Ahmad, Imad; Israel, Jonathan L

2011-01-01

Classical interferon-α has been shown to be associated with the development of a variety of autoimmune disorders. A 34-year-old white woman with chronic hepatitis C virus infection who was treated with pegylated interferon α-2a and ribavirin, developed Grave's disease and autoimmune hepatitis (AIH) at 32 and 44 weeks, respectively, following initiation of the therapy. The diagnosis of AIH was made based on the new development of anti-smooth muscle antibodies, anti-mitochondrial antibodies, and liver biopsy findings. It was confirmed by positive response to steroid challenge and was assessed according to the international AIH scoring system. Based on the previous case reports, we review the existing literature. Clinicians should be aware of the possibility of multiple autoimmune disorders during interferon-based therapy for chronic hepatitis.

Frequency and prognostic impact of antibodies to aquaporin-4 in patients with optic neuritis

DEFF Research Database (Denmark)

Jarius, Sven; Frederiksen, Jette Lautrup Battistini; Waters, Patrick

2010-01-01

Antibodies to aquaporin-4 (AQP4-Ab) are found in 60-80% of patients with neuromyelitis optica (NMO), a severely disabling inflammatory CNS disorder of putative autoimmune aetiology, which predominantly affects the optic nerves and spinal cord.......Antibodies to aquaporin-4 (AQP4-Ab) are found in 60-80% of patients with neuromyelitis optica (NMO), a severely disabling inflammatory CNS disorder of putative autoimmune aetiology, which predominantly affects the optic nerves and spinal cord....

Anti-PIT-1 antibody syndrome; a novel clinical entity leading to hypopituitarism.

Science.gov (United States)

Bando, Hironori; Iguchi, Genzo; Yamamoto, Masaaki; Hidaka-Takeno, Ryoko; Takahashi, Yutaka

2015-03-01

Various hypothalamic-pituitary diseases cause hypopituitarism. Inflammation related to autoimmunity also causes hypopituitarism. Hypophysitis is a representative disease caused by autoimmunity. Generally, anterior pituitary hormones are non-specifically impaired in this condition, but specific hormone defects have been reported in some cases. Anti-PIT-1 (pituitary-specific transcription factor 1) antibody syndrome is a novel clinical entity that presents an acquired combined pituitary hormone deficiency characterized by a specific defect in growth hormone, prolactin, and thyroid-stimulating hormone. Circulating anti-PIT-1 antibody along with various autoantibodies are detected with multiple endocrine organopathy, meeting the definition of autoimmune polyglandular syndrome. Mechanistically, cytotoxic T lymphocytes that specifically react with PIT-1 protein play an important role in the development of this syndrome.

Screening Immunomodulators To Skew the Antigen-Specific Autoimmune Response.

Science.gov (United States)

Northrup, Laura; Sullivan, Bradley P; Hartwell, Brittany L; Garza, Aaron; Berkland, Cory

2017-01-03

Current therapies to treat autoimmune diseases often result in side effects such as nonspecific immunosuppression. Therapies that can induce antigen-specific immune tolerance provide an opportunity to reverse autoimmunity and mitigate the risks associated with global immunosuppression. In an effort to induce antigen-specific immune tolerance, co-administration of immunomodulators with autoantigens has been investigated in an effort to reprogram autoimmunity. To date, identifying immunomodulators that may skew the antigen-specific immune response has been ad hoc at best. To address this need, we utilized splenocytes obtained from mice with experimental autoimmune encephalomyelitis (EAE) in order to determine if certain immunomodulators may induce markers of immune tolerance following antigen rechallenge. Of the immunomodulatory compounds investigated, only dexamethasone modified the antigen-specific immune response by skewing the cytokine response and decreasing T-cell populations at a concentration corresponding to a relevant in vivo dose. Thus, antigen-educated EAE splenocytes provide an ex vivo screen for investigating compounds capable of skewing the antigen-specific immune response, and this approach could be extrapolated to antigen-educated cells from other diseases or human tissues.

Homeostatic T Cell Expansion to Induce Anti-Tumor Autoimmunity in Breast Cancer

National Research Council Canada - National Science Library

Baccala, Roberto

2007-01-01

... that (a) homeostatic T-cell proliferation consistently elicits anti-tumor responses; (b) irradiation is more effective than Tcell depletion by antibodies in inducing anti-tumor responses mediated by homeostatic T-cell proliferation...

AUTOIMMUNE CYTOPENIAS IN CHRONIC LYMPHOCYTIC LEUKEMIA, FACTS AND MYTHS

Directory of Open Access Journals (Sweden)

Pavankumar Tandra

2013-11-01

Full Text Available CLL has been defined as presence of more than 5000 small mature appearing monoclonal B lymphocytes with a specific immunophenotype in peripheral blood. It is a well-known fact that CLL is associated with autoimmune cytopenias. CLL cells are CD5+ B lymphocytes, and usually are not the “guilty” cells which produce autoantibodies. T cell defect is another characteristic of CLL and the total number of T cells is increased, and there is inversion of the CD4/CD8 ratio. Autoimmune hemolytic anemia (AIHA is the most common autoimmune complication of CLL and has been reported in 10-25% of CLL patients. However, the stage-adjusted estimated rate of AIHA in CLL is about 5%. Conversely, CLL is three times more common in patients who present with AIHA. Direct agglutinin test (DAT is positive in 7-14% of CLL patients but AIHA may also occur in DAT negative patients. Autoimmune thrombocytopenia (AIT is the second most common complication of CLL and has been reported in 2-3% of patients. DAT is positive in AIT but presence of antiplatelet antibodies is neither diagnostic nor reliable. Autoimmune neutropenia (AIN and pure red cell aplasia (PRCA are very rare complications of CLL and like other autoimmune complications of CLL may occur at any clinical stage. It is believed that most case reports of AIN and PRCA in CLL actually belong to large granular lymphocytic leukemia (LGL. Non-hematologic autoimmune complications of CLL including cold agglutinin disease (CAD, paraneoplastic pemphigus (PNP, acquired angioedema, and anti-myelin associated globulin are rare. Before starting any treatment, clinicians should distinguish between autoimmune cytopenias and massive bone marrow infiltration since autoimmune complications of CLL are not necessarily equal to advanced disease with poor prognosis. According to IWCLL guideline, steroids are the mainstay of treatment of simple autoimmunity. Intravenous immunoglobulin (IVIg, cyclosporine, and rituximab are used in

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

International Nuclear Information System (INIS)

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

1987-01-01

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

Psoriasis, Psoriatic Arthritis, and Thyroid Autoimmunity

Directory of Open Access Journals (Sweden)

Ilaria Ruffilli

2017-06-01

Full Text Available Psoriasis (PsO is a chronic relapsing/remitting autoimmune skin disease, associated with an increased risk of other autoimmune disorders. Psoriatic arthritis (PsA is a chronic inflammatory arthritis occurring approximately in 30% of PsO patients. Sporadic cases of association between PsO and autoimmune thyroid disorders (AITDs have been reported. However, two different recent studies did not find any association between them. In patients with PsO and PsA, an association with AITD has been shown by most of the studies in adults, but not in the juvenile form. In PsA women and men, thyroid autoimmunity [positive antithyroid peroxidase (AbTPO antibodies, hypoechoic thyroid pattern] and subclinical hypothyroidism were more prevalent than in the general population. An association has been shown also in patients with PsO, arthritis, and inflammatory bowel disease, who have more frequently AITD. A Th1 immune predominance has been shown in early PsO, and PsA, with high serum CXCL10 (Th1 prototype chemokine, overall in the presence of autoimmune thyroiditis. This Th1 immune predominance might be the immunopathogenetic base of the association of these disorders. A raised incidence of new cases of hypothyroidism, thyroid dysfunction, positive AbTPO, and appearance of a hypoechoic thyroid pattern in PsA patients, especially in women, has been shown recently, suggesting to evaluate AbTPO levels, thyroid function, and thyroid ultrasound, especially in PsA women. Thyroid function follow-up and suitable treatments should be performed regularly in PsA female patients at high risk (thyroid-stimulating hormone within the normal range but at the higher limit, positive AbTPO, hypoechoic, and small thyroid.

Radioimmunological proof of thyroglobulin antibodies in humans by the use of a double antibody method

International Nuclear Information System (INIS)

Waller, V.

1982-01-01

Thyroid antibodies, especially thyroglobulin antibodies, allow themselves to be proven with the double antibody method, in competitive radio binding assays and with the solid phase technique. These methods offer advantages relative to sensitivity and quantifiability. In this work a sensitive radioimmunoassay as a double antibody method was worked out whereby a 125 I-thyroglobulin/thyroglobulin antibody immune complex was precipitated out using anti-human immunoglobulin. The measured results from the radioimmunoassay show a good correlation with the results of the immune histological findings. A high to very high Tg antibody level occurs with autoimmune thyroiditis (80%), primary hypothyroidism (74%) and hyperthyroidism (70%). The control values with healthy people came to less than 5% specific binding. In correlation with the results of other authors this method is advantageous relative to test start and evaluation procedures. (orig.) [de

Lack of antibodies to NMDAR or VGKC-complex in GAD and cardiolipin antibody-positive refractory epilepsy.

Science.gov (United States)

Liimatainen, Suvi; Peltola, Jukka; Hietaharju, Aki; Sabater, Lidia; Lang, Bethan

2014-03-01

Over the last few years autoantibodies against neuronal proteins have been identified in several forms of autoimmune encephalitis and epilepsy. NMDA receptor (NMDAR) and voltage gated potassium channel (VGKC) complex antibodies are mainly associated with limbic encephalitis (LE) whereas glutamic acid decarboxylase antibodies (GADA) and anticardiolipin (ACL) antibodies are more commonly detected in patients with chronic epilepsy. Clinical features vary between these antibodies suggesting the specificity of different neuronal antibodies in seizures. Serum samples of 14 GADA positive and 24 ACL positive patients with refractory epilepsy were analyzed for the presence of VGKC or NMDAR antibodies. No positive VGKC or NMDAR antibodies were found in these patients. The results confirm the different significance of these neuronal antibodies in seizure disorders. Different autoantibodies have different significance in seizures and probably have different pathophysiological mechanisms of actions. Copyright © 2014 Elsevier B.V. All rights reserved.

Antithyroglobulin Antibodies and Antimicrosomal Antibodies in Various Thyroid Diseases

International Nuclear Information System (INIS)

Lee, Gwon Jun; Hong, Key Sak; Choi, Kang Won; Lee, Kyu; Koh, Chang Soon; Lee, Mun Ho; Park, Sung Hoe; Chi, Je Geun; Lee, Sang Kook

1979-01-01

The authors investigated the incidence of antithyroglobulin antibodies and antibodies and antimicrosomal antibodies measured by tanned red cell hemagglutination method in subjects suffering from various thyroid disorders. 1) In 15 normal patients, neither suffering from any thyroid diseases nor from any other autoimmune disorders, the antithyroglobulin antibodies were all negative, but the antimicrosomal antibody was positive only in one patient (6.7%). 2) The antithyroglobulin antibodies were positive in 31.5% (34 patients) of 108 patients with various thyroid diseases, and the antimicrosomal antibodies were positive in 37.0% (40 patients). 3) of the 25 patients with Graves' diseases, 7 patients (28.0%) showed positive for the antithyroglobulin antibodies, and 9 (36.0%) for the antimicrosomal antibodies. There was no definite differences in clinical and thyroid functions between the groups with positive and negative results. 4) Both antibodies were positive in 16 (88.9%) and 17 (94.4%) patients respectively among 18 patients with Hashimoto's thyroiditis, all of them were diagnosed histologically. 5) Three out of 33 patients with thyroid adenoma showed positive antibodies, and 3 of 16 patients with thyroid carcinoma revealed positive antibodies. 6) TRCH antibodies demonstrated negative results in 2 patients with subacute thyroiditis, but positive in one patient with idiopathic primary myxedema. 7) The number of patients with high titers(>l:802) was 16 for antithyroglobulin antibody, and 62.5% (10 patients) of which was Hashimoto's thyroiditis. Thirteen (65.0) of 20 patients with high titers (>l:802) for antimicrosomal antibody was Hashimoto's thyroiditis. TRCH test is a simple, sensitive method, and has high reliability and reproducibility. The incidences and titers of antithyroglobulin antibody and antimicrosomal antibody are especially high in Hashimoto's thyroiditis.

Celiac disease and endocrine autoimmunity.

Science.gov (United States)

Kahaly, George J; Schuppan, Detlef

2015-01-01

Celiac disease (CD) is a small-intestinal inflammatory disease that is triggered by the ingestion of the storage proteins (gluten) of wheat, barley and rye. Endocrine autoimmunity is prevalent in patients with CD and their relatives. The genes that predispose to endocrine autoimmune diseases, e.g. type 1 diabetes, autoimmune thyroid diseases, and Addison's disease, i.e. DR3-DQ2 and DR4-DQ8, are also the major genetic determinants of CD, which is the best understood HLA-linked disease. Thus, up to 30% of first-degree relatives both of patients with CD and/or endocrine autoimmunity are affected by the other disease. In CD, certain gluten proteins bind with high affinity to HLA-DQ2 or -DQ8 in the small-intestinal mucosa, to activate gluten-specific T cells which are instrumental in the destruction of the resorptive villi. Here, the autoantigen tissue transglutaminase increases the T cell response by generating deamidated gluten peptides that bind more strongly to DQ2 or DQ8. Classical symptoms such as diarrhea and consequences of malabsorption like anemia and osteoporosis are often absent in patients with (screening-detected) CD, but this absence does not significantly affect these patients' incidence of endocrine autoimmunity. Moreover, once autoimmunity is established, a gluten-free diet is not able to induce remission. However, ongoing studies attempt to address how far a gluten-free diet may prevent or retard the development of CD and endocrine autoimmunity in children at risk. The close relationship between CD and endocrine autoimmunity warrants a broader immune genetic and endocrine screening of CD patients and their relatives. © 2015 S. Karger AG, Basel.

Autoimmune encephalitis associated with voltage-gated potassium channels-complex and leucine-rich glioma-inactivated 1 antibodies - a national cohort study.

Science.gov (United States)

Celicanin, M; Blaabjerg, M; Maersk-Moller, C; Beniczky, S; Marner, L; Thomsen, C; Bach, F W; Kondziella, D; Andersen, H; Somnier, F; Illes, Z; Pinborg, L H

2017-08-01

The aim of this study was to describe clinical and paraclinical characteristics of all Danish patients who tested positive for anti-voltage-gated potassium channels (VGKC)-complex, anti-leucine-rich glioma-inactivated 1 (LGI1) and anti-contactin-associated protein-2 antibodies in the serum/cerebrospinal fluid between 2009 and 2013 with follow-up interviews in 2015 and 2016. We evaluated antibody status, symptoms leading to testing, course of disease, suspected diagnosis and time of admission as well as diagnosis and treatment. All magnetic resonance imaging, electroencephalography and 18 F-fluorodeoxyglucose positron emission tomography scans were re-evaluated by experts in the field. A total of 28/192 patients tested positive for VGKC-complex antibodies by radioimmunoassay and indirect immunofluorescence; 17 had antibodies to LGI1 and 6/7 of the available cerebrospinal fluids from these patients were seropositive. These 17 patients all had a clinical phenotype appropriate to LGI1 antibodies. The remaining 11 were LGI1 negative (n = 4) or not tested (n = 7). Of these, two had a phenotype consistent with limbic encephalitis. The remaining phenotypes were Guillain-Barré syndrome, Creutzfeldt-Jakob disease, neuromyotonia and anti-N-methyl-D-aspartate receptor encephalitis. Magnetic resonance imaging abnormalities were demonstrated in 69% of the LGI1-positive patients. Two patients with normal magnetic resonance imaging demonstrated temporal lobe hypermetabolism using 18 F-fluorodeoxyglucose positron emission tomography. Abnormal electroencephalography recordings were found in 86% of the patients. Upon follow-up (median 3.2 years), the median modified Rankin Scale score of anti-LGI1-positive patients was 2 and only two patients reported seizures in the past year. Patients diagnosed with anti-LGI1 autoimmune encephalitis increased significantly from 2009 to 2014, probably due to increased awareness. In contrast to seropositive anti-VGKC-complex patients, all anti-LGI1

Thyroid Autoimmunity and Behçet’s Disease: Is There a Significant Association?

Directory of Open Access Journals (Sweden)

Filiz Cebeci

2013-01-01

Full Text Available Background. Behcet’s disease (BD could be regarded as an autoimmune disease in many aspects. Autoimmune thyroid disease (ATD is frequently accompanied by other various autoimmune diseases. Nevertheless, there is not still enough data showing the association between BD and ATD. In addition, no controlled study is present in the PubMed, which evaluates thyroidal autoimmunity using antithyroid peroxidase antibody in a large series of patients with BD. Methods. We aimed to investigate the frequency of ATD in patients with BD. The study included 124 patients with BD and 99 age- and sex-matched healthy volunteers. Results. Autoimmune thyroiditis was noted in 21 cases (16.9% with BD. In the control group, 22 cases (22.22% were diagnosed as autoimmune thyroiditis. There was no difference between the groups in respect to thyroid autoantibodies (. There were no statistically significant differences between baseline TSH levels of the BD patients and of the controls (. Statistically, the mean serum free T4 levels of the patients with BD were higher than those of the controls (. Conclusions. No association could be found between BD and ATD. Therefore, it is not of significance to investigate thyroid autoimmunity in BD.

GAD antibody-associated limbic encephalitis in a young woman with APECED

Directory of Open Access Journals (Sweden)

Anna Kopczak

2017-05-01

Full Text Available The autoimmune polyendocrinopathy–candidiasis–ectodermal dystrophy (APECED syndrome is a genetic disorder caused by a mutation in the autoimmune regulator (AIRE gene. Immune deficiency, hypoparathyroidism and Addison’s disease due to autoimmune dysfunction are the major clinical signs of APECED. We report on a 21-year-old female APECED patient with two inactivating mutations in the AIRE gene. She presented with sudden onset of periodic nausea. Adrenal insufficiency was diagnosed by means of the ACTH stimulation test. Despite initiation of hormone replacement therapy with hydrocortisone and fludrocortisone, nausea persisted and the patient developed cognitive deficits and a loss of interest which led to the diagnosis of depression. She was admitted to the psychiatric department for further diagnostic assessment. An EEG showed a focal epileptic pattern. Glutamic acid decarboxylase (GAD antibodies, which had been negative eight years earlier, were now elevated in serum and in the cerebrospinal fluid. Oligoclonal bands were positive indicating an inflammatory process with intrathecal antibody production in the central nervous system (CNS. The periodic nausea was identified as dialeptic seizures, which clinically presented as gastrointestinal aura followed by episodes of reduced consciousness that occurred about 3–4 times per day. GAD antibody-associated limbic encephalitis (LE was diagnosed. Besides antiepileptic therapy, an immunosuppressive treatment with corticosteroids was initiated followed by azathioprine. The presence of nausea and vomiting in endocrine patients with autoimmune disorders is indicative of adrenal insufficiency. However, our case report shows that episodic nausea may be a symptom of epileptic seizures due to GAD antibodies-associated LE in patients with APECED.

Immune cell-derived c3 is required for autoimmune diabetes induced by multiple low doses of streptozotocin.

Science.gov (United States)

Lin, Marvin; Yin, Na; Murphy, Barbara; Medof, M Edward; Segerer, Stephan; Heeger, Peter S; Schröppel, Bernd

2010-09-01

The complement system contributes to autoimmune injury, but its involvement in promoting the development of autoimmune diabetes is unknown. In this study, our goal was to ascertain the role of complement C3 in autoimmune diabetes. Susceptibility to diabetes development after multiple low-dose streptozotocin treatment in wild-type (WT) and C3-deficient mice was analyzed. Bone marrow chimeras, luminex, and quantitative reverse transcription PCR assays were performed to evaluate the phenotypic and immunologic impact of C3 in the development of this diabetes model. Coincident with the induced elevations in blood glucose levels, we documented alternative pathway complement component gene expression within the islets of the diabetic WT mice. When we repeated the experiments with C3-deficient mice, we observed complete resistance to disease, as assessed by the absence of histologic insulitis and the absence of T-cell reactivity to islet antigens. Studies of WT chimeras bearing C3-deficient bone marrow cells showed that bone marrow cell-derived C3, and not serum C3, is involved in the induction of diabetes in this model. The data reveal a key role for immune cell-derived C3 in the pathogenesis of murine multiple low-dose streptozotocin-induced diabetes and support the concept that immune cell mediated diabetes is in part complement-dependent.

[Neuroimmunological diseases associated with VGKC complex antibodies].

Science.gov (United States)

Watanabe, Osamu

2013-05-01

Antibodies to voltage-gated potassium channels(VGKC) were first identified by radioimmunoassay of radioisotope labeled alpha-dendrotoxin-VGKCs solubilized from rabbit brain. These antibodies were found only in a proportion of patients with acquired neuromyotonia (Isaacs' syndrome). VGKC antibodies were also detected in Morvan's syndrome and in a form of autoimmune limbic encephalitis. Recent studies indicated that the "VGKC" antibodies are mainly directed toward associated proteins(for example LGI-1, Caspr-2) that complex with the VGKCs themselves. The "VGKC" antibodies are now usually known as VGKC-complex antibodies. In general, LGI-1 antibodies are most common in limbic encephalitis with SIADH. Caspr-2 antibodies are present in the majority of patients with Morvan's syndrome. These patients develop combinations of CNS symptoms, autonomic dysfunction, and peripheral nerve hyperexcitability.

Combined short-term immunotherapy for experimental autoimmune myasthenia gravis

Energy Technology Data Exchange (ETDEWEB)

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

1983-08-01

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

[Autoimmune thyroid disease and other non-endocrine autoimmune diseases].

Science.gov (United States)

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

2011-01-01

Autoimmune diseases are chronic conditions initiated by the loss of immunological tolerance to self-antigens. They constitute heterogeneous group of disorders, in which multiple alterations in the immune system result in a spectrum of syndromes that either target specific organs or affect the body systematically. Recent epidemiological studies have shown a possible shift of one autoimmune disease to another or the fact that more than one autoimmune disease may coexist in a single patient or in the same family. Numerous autoimmune diseases have been shown to coexist frequently with thyroid autoimmune diseases. AUTOIMMNUNE THYROID DISEASE AND OTHER ORGAN SPECIFIC NON-ENDOCRINE AUTOIMMUNE DISEASES: This part of the study reviews the prevalence of autoimmune thyroid disease coexisting with: pernicious anaemia, vitiligo, celiac disease, autoimmune liver disease, miastenia gravis, alopecia areata and sclerosis multiplex, and several recommendations for screening have been given. AUTOIMMUNE THYROID DISEASE AND OTHER ORGAN NON-SPECIFIC NON-ENDOCRINE AUTOIMMUNE DISEASES: Special attention is given to the correlation between autoimmune thyroid disease and rheumatoid arthritis, systemic lupus erythematosus, syndrome Sjögren, systemic sclerosis and mixed connective tissue disease. Screening for autoimmune thyroid diseases should be recommended in everyday clinical practice, in patients with primary organ-specific or organ non-specific autoimmune disease. Otherwise, in patients with primary thyroid autoimmune disease, there is no good reason of seeking for all other autoimmune diseases, although these patients have a greater risk of developing other autoimmune disease. Economic aspects of medicine require further analyzing of these data, from cost/benefit point of view to justified either mandatory screening or medical practitioner judgment.

Rate of positive autoimmune markers in Human T lymphotropic virus type 1 carriers: a case-control study from Iran.

Science.gov (United States)

Ahmadi Ghezeldasht, Sanaz; Hedayati-Moghaddam, Mohammad Reza; Habibi, Meysam; Mollahosseini, Farzad; Rafatpanah, Houshang; Miri, Rahele; Hatef Fard, MohammadReza; Sahebari, Maryam

2018-01-01

Human T lymphotropic virus type 1 (HTLV-1) infection with high prevalence in the north-east of Iran, particularly in Mashhad, can lead to adult T-cell leukemia (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and a variety of autoimmune diseases. The aim of the study was to examine the presence of autoimmune markers in HTLV carries. Serum samples were obtained from blood donors in Mashhad, northeastern Iran. One hundred and five HTLV-1 positive (cases) and 104 age- and sex-matched HTLV-1 negative donors (controls) were assessed for presence of serum autoimmune markers by enzyme-linked immunosorbent assay. The mean ages of cases and controls were 40.8 ± 9.4 and 41.5 ± 9.3 years, respectively (P = 0.5). In the case group, 81.9% and in the control group 83.7% were male (P = 0.74). The frequency of positive antinuclear antibodies and anticyclic citrullinated peptide antibodies in the serum of the two groups were not significantly different (P = 0.68 and P = 0.62, respectively). Only one antineutrophil cytoplasmic antibody-positive case (1%) was observed in the group and no anti-phospholipid immunoglobulin G positivity was observed. The frequency of rheumatoid factor (RF) was greater in case group than in the control group, although the difference was not significant (P = 0.08). The amount of RF in all 12 RF positive sera were higher than normal levels (33-37 IU/mL). Because we failed to detect any significant relation between serum autoimmune markers and HTLV-1 infection, and because of the relatively low prevalence of autoimmune diseases, it could be concluded that healthy HTLV-1 carriers do not produce rheumatologic-related auto-antibodies more than the healthy population. © 2017 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.

Detection of LGI1 and CASPR2 antibodies with a commercial cell-based assay in patients with very high VGKC-complex antibody levels.

Science.gov (United States)

Yeo, T; Chen, Z; Chai, J Y H; Tan, K

2017-07-15

The presence of VGKC-complex antibodies, without LGI1/CASPR2 antibodies, as a standalone marker for neurological autoimmunity remains controversial. Additionally, the lack of an unequivocal VGKC-complex antibody cut-off level defining neurological autoimmunity makes it important to test for monospecific antibodies. We aim to determine the performance characteristics of a commercial assay (Euroimmun, Lübeck, Germany) for LGI1/CASPR2 antibody detection in patients with very high VGKC-complex antibody levels and report their clinico-serological associations. We identified 8 patients in our cohort with the highest VGKC-complex antibody levels (median 2663.5pM, range 933-6730pM) with VGKC-complex antibody related syndromes (Group A). Two other groups were identified; 1 group with suspected neuronal surface antibody syndromes and negative for VGKC-complex antibodies (Group B, n=8), and another group with cerebellar ataxia and negative for onconeuronal antibodies (Group C, n=8). Seven out of 8 patients (87.5%) in Group A had LGI1 and/or CASPR2 antibodies. One Group B patient had LGI1 antibodies but was negative on re-testing with a live cell assay. No Group C patients had monospecific antibodies. Inter-rater reliability was high; combining Groups A and B patients, the kappa statistic was 0.87 and 1.0 for LGI1 and CASPR2 antibodies respectively. We demonstrated that a high proportion of patients with very high VGKC-complex antibody levels and relevant clinical syndromes have LGI1 and/or CASPR2 antibodies detected by the commercial assay. Our findings lend support to the use of the assay for rapid and reliable detection of LGI1 and CASPR2 antibodies. Copyright © 2017 Elsevier B.V. All rights reserved.

Rheumatic Disease Autoantibodies in Autoimmune Liver Diseases.

Science.gov (United States)

Utiyama, Shirley R R; Zenatti, Katiane B; Nóbrega, Heloisa A J; Soares, Juliana Z C; Skare, Thelma L; Matsubara, Caroline; Muzzilo, Dominique A; Nisihara, Renato M

2016-08-01

Autoimmune liver diseases (ALDs) are known to be associated with systemic autoimmune rheumatic diseases (SARDs) and their autoantibodies. We aimed to study the prevalence of SARDs and related autoantibodies, as well as their prognostic implications in a group of patients with ALDs. This was a cross-sectional study. Sixty patients with ALDs (38.3% with autoimmune hepatitis; 11.7% with primary biliary cirrhosis; 25% with primary sclerosing cholangitis and 25% with overlap syndrome) were studied for the presence of SARDs and their autoantibodies. There was autoimmune rheumatic disease in 20% of the studied sample. Systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) were the commonest (11.6% and 5%, respectively). Antinuclear antibodies (ANAs) were present in 35% of the patients, followed by anti-Ro (20.0%); anti-nucleosome (18.3%); rheumatoid factor (10%) anti-CCP (8.3%); anti-RNP (8.3%); anti-ds-DNA (6.6%); anti-La (3.3%); anti-Sm (3.3%), anti-ribosomal P (3.3%). Anti-Ro (p = 0.0004), anti-La (p = 0.03), anti-RNP (p = 0.04) and anti-Sm (p = 0.03) were commonly found in patients with SARD, but not anti-DNA, anti-nucleosome and anti-ribosomal P. No differences were found in liver function tests regarding to the presence of autoantibodies. There was a high prevalence of SARD and their autoantibodies in ALD patients. Anti-Ro, anti-La, anti-RNP and anti-Sm positivity points to an association with systemic autoimmune rheumatic diseases. The presence of autoantibodies was not related to liver function tests.

Antithyroid Antibodies Are Implicated in Epileptogenesis of Adult Patients With Epilepsy

OpenAIRE

Tsai, Meng-Han; Fu, Ting-Ying; Chen, Nai-Ching; Shih, Fu-Yuan; Lu, Yan-Ting; Cheng, Mei-Yun; Chuang, Hung-Yi; Chuang, Yao-Chung

2015-01-01

Abstract Antithyroid antibodies (Abs) are associated with epilepsy in steroid-responsive encephalopathy, but have been rarely studied in unselected epilepsy patients. This study aimed to characterize the prevalence and associated factors of antithyroid Abs and other auto-Abs in adult patients with epilepsy. Epilepsy patients without autoimmune disorders were surveyed for antinuclear antibody (ANA), anti-?2 glycoprotein 1 antibody (a?2GP1), anticardiolipin IgG Ab, antimicrosomal antibody (AMA)...

A phase III randomized trial comparing glucocorticoid monotherapy versus glucocorticoid and rituximab in patients with autoimmune haemolytic anaemia

DEFF Research Database (Denmark)

Birgens, Henrik Sverre; Frederiksen, Henrik; Hasselbalch, Hans C

2013-01-01

The impact of first-line treatment with the anti-CD 20 chimeric monoclonal antibody rituximab in patients with warm-antibody reactive autoimmune haemolytic anaemia (WAIHA) is unknown. We report the first randomized study of 64 patients with newly diagnosed WAIHA who received prednisolone and ritu...

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

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

2017-08-01

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

Designing two-in-one antibodies.

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Valladares, Ignacio Garcia; Espinoza, Luis R

2009-09-01

Evaluation of: Bostrom J, Shang-Fan Y, Kan D et al.: Variants of the antibody Herceptin that interact with HER2 and VEGF at the antigen binding site. Science 323, 1610-1614 (2009). The longstanding held notion that one antibody equals one antigen and, hence, one function has been challenged in recent years. Improved technology in antibody production, especially the accumulation of sequence data of immunoglobulin genes and the advent of PCR have made it possible to clone antibody gene repertoires. The current paper provides further challenge to the notion of one antibody = one antigen by developing 'two-in-one' antibodies with an antigen-binding site that binds two distinct proteins with high affinity. A therapeutic variant antibody of Herceptin (Genentech, CA, USA) was isolated that binds the human EGF receptor (HER)2 and also to VEGF. This development may represent a breakthrough discovery and may have significant implications in the therapy of malignant, infectious, allergic and autoimmune disorders.

Antibody-Induced Internalization of the Human Respiratory Syncytial Virus Fusion Protein.

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Leemans, A; De Schryver, M; Van der Gucht, W; Heykers, A; Pintelon, I; Hotard, A L; Moore, M L; Melero, J A; McLellan, J S; Graham, B S; Broadbent, L; Power, U F; Caljon, G; Cos, P; Maes, L; Delputte, P

2017-07-15

Respiratory syncytial virus (RSV) infections remain a major cause of respiratory disease and hospitalizations among infants. Infection recurs frequently and establishes a weak and short-lived immunity. To date, RSV immunoprophylaxis and vaccine research is mainly focused on the RSV fusion (F) protein, but a vaccine remains elusive. The RSV F protein is a highly conserved surface glycoprotein and is the main target of neutralizing antibodies induced by natural infection. Here, we analyzed an internalization process of antigen-antibody complexes after binding of RSV-specific antibodies to RSV antigens expressed on the surface of infected cells. The RSV F protein and attachment (G) protein were found to be internalized in both infected and transfected cells after the addition of either RSV-specific polyclonal antibodies (PAbs) or RSV glycoprotein-specific monoclonal antibodies (MAbs), as determined by indirect immunofluorescence staining and flow-cytometric analysis. Internalization experiments with different cell lines, well-differentiated primary bronchial epithelial cells (WD-PBECs), and RSV isolates suggest that antibody internalization can be considered a general feature of RSV. More specifically for RSV F, the mechanism of internalization was shown to be clathrin dependent. All RSV F-targeted MAbs tested, regardless of their epitopes, induced internalization of RSV F. No differences could be observed between the different MAbs, indicating that RSV F internalization was epitope independent. Since this process can be either antiviral, by affecting virus assembly and production, or beneficial for the virus, by limiting the efficacy of antibodies and effector mechanism, further research is required to determine the extent to which this occurs in vivo and how this might impact RSV replication. IMPORTANCE Current research into the development of new immunoprophylaxis and vaccines is mainly focused on the RSV F protein since, among others, RSV F-specific antibodies are

Non-Celiac Gluten Sensitivity and Autoimmunity. A Case Report.

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Carlos Isasi

2014-12-01

Full Text Available Introduction, objective: To present a case report in which the finding of non-coeliac gluten sensitivity was decisive for the treatment of a complex autoimmune disease. Materials and methods: A 43-year-old woman with polyarthritis, psoriatic features, anti-SSA/Ro and anti-cyclic citrullinated peptide antibodies, with refractory course, was evaluated for gluten sensitivity despite negative serology for coeliac disease. Results: The patient carried the HLA DQ2 haplotype and duodenal biopsy showed lymphocytic enteritis. A gluten-free diet resolved the clinical picture and permitted tapering of immunosuppressive therapy. Conclusion: Non-coeliac gluten sensitivity can be associated with autoimmunity despite the absence of the specific autoantibodies of coeliac disease.

Autoimmune features caused by dengue fever: a case report

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Denis Leonardo Fontes Jardim

Full Text Available Dengue virus is the most important mosquito-borne viral disease in the world. Co-circulation of the four types of dengue viruses and expansion of dengue epidemic gave rise to infection enhancement and a big expansion of clinical aspects of the disease. Herein we report a case of a 25-year-old white woman with dengue fever and numerous associated autoimmune features. Our patient had proteinuria, an extensive right pleural effusion, a thin pericardial effusion and ascites. She had a low C3 level and positive antinuclear antibody; cryoglobulins were also positive. The numerous autoimmune features of this patient were a diagnostic challenge, since she was a young woman and could be easily mistaken for a rheumatologic patient in a newly open disease. Dengue infection probably was a triggering event causing an abnormal immune response. Therefore, dengue should be suspected in patients with hematological disorders and autoimmune features in endemic regions or those who have travelled to those regions.

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

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Wechsler, Janine

2018-02-01

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

Addison's disease in a patient with hypothyroidism: autoimmune polyglandular syndrome type 2.

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Bain, Anna; Stewart, Munro; Mwamure, Peter; Nirmalaraj, Kingsley

2015-08-03

A 57-year-old Caucasian woman with known autoimmune hypothyroidism diagnosed in 2006 presented to hospital with flu-like symptoms and circulatory collapse. She reported weight loss and gradual increase in her skin pigmentation over a 1-year period. Aggressive fluid resuscitation was instituted. Hormonal tests showed primary adrenal insufficiency. Appropriate steroid replacement was started with rapid clinical response. Subsequent antibody tests confirmed the diagnosis of autoimmune polyglandular type 2 (Schmidt's) syndrome. The adrenal crisis had been precipitated by influenza virus type B infection. 2015 BMJ Publishing Group Ltd.

The Epidemiologic Evidence Linking Autoimmune Diseases and Psychosis

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Benros, Michael E; Eaton, William W; Mortensen, Preben B

2014-01-01

diseases involve multiple organs and general dysfunction of the immune system, which could affect the brain and induce psychiatric symptoms. Most studies have been cross-sectional, observing an increased prevalence of a broad number of autoimmune diseases in people with psychotic disorders. Furthermore......, there is some evidence of associations of psychosis with a family history of autoimmune disorders and vice versa. Additionally, several autoimmune diseases, individually and in aggregate, have been identified as raising the risk for psychotic disorders in longitudinal studies. The associations have been...

Vaccination of horses with Lyme vaccines for dogs induces short-lasting antibody responses.

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Guarino, Cassandra; Asbie, Sanda; Rohde, Jennifer; Glaser, Amy; Wagner, Bettina

2017-07-24

Borrelia burgdorferi can induce Lyme disease. Approved Lyme vaccines for horses are currently not available. In an effort to protect horses, veterinarians are using Lyme vaccines licensed for dogs. However, data to assess the response of horses to, or determine the efficacy of this off-label vaccine use are missing. Here, antibodies against outer surface protein A (OspA), OspC, and OspF were quantified in diagnostic serum submissions from horses with a history of vaccination with canine Lyme vaccines. The results suggested that many horses respond with low and often short-lasting antibody responses. Subsequently, four experimental vaccination trials were performed. First, we investigated antibody responses to three canine vaccines in B. burgdorferi-naïve horses. One killed bacterin vaccine induced antibodies against OspC. OspA antibodies were low for all three vaccines and lasted less than 16weeks. The second trial tested the impact of the vaccine dose using the OspA/OspC inducing bacterin vaccine in horses. A 2mL dose produced higher OspA and OspC antibody values than a 1mL dose. However, the antibody response again quickly declined, independent of dose. Third, the horses were vaccinated with 2 doses of a recombinant OspA vaccine. Previous vaccination and/or environmental exposure enhanced the magnitude and longevity of the OspA antibody response to about 20weeks. Last, the influence of intramuscular versus subcutaneous vaccine administration was investigated for the recombinant OspA vaccine. OspA antibody responses were not influenced by injection route. The current work highlights that commercial Lyme vaccines for dogs induce only transient antibody responses in horses which can also be of low magnitude. Protection from infection with B. burgdorferi should not be automatically assumed after vaccinating horses with Lyme vaccines for dogs. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Intravenous Immunoglobulins: Mode of Action and Indications in Autoimmune and Inflammatory Dermatoses

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Lyubomir A. Dourmishev

2016-01-01

Full Text Available Intravenous immunoglobulins (IVIGs, a mixture of variable amounts of proteins (albumin, IgG, IgM, IgA, and IgE antibodies, as well as salt, sugar, solvents, and detergents, are successfully used to treat a variety of dermatological disorders. For decades, IVIGs have been administered for treatment of infectious diseases and immune deficiencies, since they contain natural antibodies that represent a first-line defense against pathogens. Today their indication has expanded, including the off-label therapy for a variety of autoimmune and inflammatory diseases. In dermatology, IVIGs are administered for treatment of different disorders at different therapeutic regimens, mostly with higher doses then those administered for treatment of infectious diseases. The aim of this prospective review is to highlight the indications, effectiveness, side effects, and perspectives of the systemic treatment with IVIGs for patients with severe, life-threatening, and resistant to conventional therapies autoimmune or inflammatory dermatoses.

Autoantibodies and their antigens in autoimmune hepatitis.

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Bogdanos, Dimitrios P; Mieli-Vergani, Giorgina; Vergani, Diego

2009-08-01

Autoantibody detection assists in the diagnosis and allows differentiation of autoimmune hepatitis (AIH) type 1 (AIH-1), characterized by antinuclear antibody (ANA) and/or smooth muscle antibody (SMA), and type 2 (AIH-2), distinguished by the presence of antibodies to liver-kidney microsome type 1 (anti-LKM1) and/or antibodies to liver cytosol type 1 (anti-LC1). Detection of atypical perinuclear antineutrophil cytoplasmic antibodies (pANCA) and anti-soluble liver antigen (SLA) antibodies can act as an additional pointer toward the diagnosis of AIH, particularly in the absence of the conventional autoantibodies. Routine autoantibody testing by indirect immunofluorescence has been recently complemented by molecular assays based on purified or recombinant antigens. Although the AIH-1-specific ANA and SMA targets need better definition, those of anti-LKM1 and anti-LC1 in AIH-2 have been clearly identified; the fine specificity of antibody reactivity and its clinical relevance to disease pathogenesis are the focus of ongoing investigation. This article critically discusses the current knowledge of the diagnostic and clinical significance of AIH-related autoantibody reactivities, focusing on key issues that the physician needs to be aware of to be able to request the appropriate testing and to interpret correctly the laboratory results within the clinical context of the patient. Copyright Thieme Medical Publishers.

Antithyroglobulin Antibodies and Antimicrosomal Antibodies in Various Thyroid Diseases

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Lee, Gwon Jun; Hong, Key Sak; Choi, Kang Won; Lee, Kyu; Koh, Chang Soon; Lee, Mun Ho; Park, Sung Hoe; Chi, Je Geun; Lee, Sang Kook [Seoul National University College of Medicine, Seoul (Korea, Republic of)

1979-03-15

The authors investigated the incidence of antithyroglobulin antibodies and antibodies and antimicrosomal antibodies measured by tanned red cell hemagglutination method in subjects suffering from various thyroid disorders. 1) In 15 normal patients, neither suffering from any thyroid diseases nor from any other autoimmune disorders, the antithyroglobulin antibodies were all negative, but the antimicrosomal antibody was positive only in one patient (6.7%). 2) The antithyroglobulin antibodies were positive in 31.5% (34 patients) of 108 patients with various thyroid diseases, and the antimicrosomal antibodies were positive in 37.0% (40 patients). 3) of the 25 patients with Graves' diseases, 7 patients (28.0%) showed positive for the antithyroglobulin antibodies, and 9 (36.0%) for the antimicrosomal antibodies. There was no definite differences in clinical and thyroid functions between the groups with positive and negative results. 4) Both antibodies were positive in 16 (88.9%) and 17 (94.4%) patients respectively among 18 patients with Hashimoto's thyroiditis, all of them were diagnosed histologically. 5) Three out of 33 patients with thyroid adenoma showed positive antibodies, and 3 of 16 patients with thyroid carcinoma revealed positive antibodies. 6) TRCH antibodies demonstrated negative results in 2 patients with subacute thyroiditis, but positive in one patient with idiopathic primary myxedema. 7) The number of patients with high titers(>l:802) was 16 for antithyroglobulin antibody, and 62.5% (10 patients) of which was Hashimoto's thyroiditis. Thirteen (65.0) of 20 patients with high titers (>l:802) for antimicrosomal antibody was Hashimoto's thyroiditis. TRCH test is a simple, sensitive method, and has high reliability and reproducibility. The incidences and titers of antithyroglobulin antibody and antimicrosomal antibody are especially high in Hashimoto's thyroiditis.

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

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Grau, Rafael G

2015-12-01

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

Insulin autoimmune syndrome: case report

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Rodrigo Oliveira Moreira

Full Text Available CONTEXT: Insulin autoimmune syndrome (IAS, Hirata disease is a rare cause of hypoglycemia in Western countries. It is characterized by hypoglycemic episodes, elevated insulin levels, and positive insulin antibodies. Our objective is to report a case of IAS identified in South America. CASE REPORT: A 56-year-old Caucasian male patient started presenting neuroglycopenic symptoms during hospitalization due to severe trauma. Biochemical evaluation confirmed hypoglycemia and abnormally high levels of insulin. Conventional imaging examinations were negative for pancreatic tumor. Insulin antibodies were above the normal range. Clinical remission of the episodes was not achieved with verapamil and steroids. Thus, a subtotal pancreatectomy was performed due to the lack of response to conservative treatment and because immunosuppressants were contraindicated due to bacteremia. Histopathological examination revealed diffuse hypertrophy of beta cells. The patient continues to have high insulin levels but is almost free of hypoglycemic episodes.

METABOLIC AND AUTOIMMUNE RISK FACTORS FOR CORONARY ARTERY DISEASE (CAD IN HEART TRANSPLANT RECIPIENTS

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T. A. Khalilulin

2010-01-01

Full Text Available One of the most essential autoimmunity risk factors for development of CAD are increasing level of anticardiolipin antibodies and homocystein. This report presents retrospective analyses of 39 heart transplant recipients with maximal follow up over 16 years. Our results showed that hyperhomocystenemia and high levels of anticardiolipin antibodies play great value in development of CAD. Thus relative risks for development of CAD in presence both high levels of anticardiolipin antibodies and homocysteine are higher, than in traditional nonimmune risk factors. 

Autoimmune Thyroid Diseases in Patients Treated with Alemtuzumab for Multiple Sclerosis: An Example of Selective Anti-TSH-Receptor Immune Response

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Mario Rotondi

2017-09-01

Full Text Available Alemtuzumab, a humanized anti-CD52 monoclonal antibody, is approved for the treatment of active relapsing-remitting multiple sclerosis (MS. Alemtuzumab induces a rapid and prolonged depletion of lymphocytes from the circulation, which results in a profound immuno-suppression status followed by an immune reconstitution phase. Secondary to reconstitution autoimmune diseases represent the most common side effect of Alemtuzumab treatment. Among them, Graves’ disease (GD is the most frequent one with an estimated prevalence ranging from 16.7 to 41.0% of MS patients receiving Alemtuzumab. Thyrotropin (TSH receptor (R-reactive B cells are typically observed in GD and eventually present this autoantigen to T-cells, which, in turn, secrete several pro-inflammatory cytokines and chemokines. Given that reconstitution autoimmunity is more frequently characterized by autoantibody-mediated diseases rather than by destructive Th1-mediated disorders, it is not surprising that GD is the most commonly reported side effect of Alemtuzumab treatment in patients with MS. On the other hand, immune reconstitution GD was not observed in a large series of patients with rheumatoid arthritis treated with Alemtuzumab. This negative finding supports the view that patients with MS are intrinsically more at risk for developing Alemtuzumab-related thyroid dysfunctions and in particular of GD. From a clinical point of view, Alemtuzumab-induced GD is characterized by a surprisingly high rate of remission, both spontaneous and after antithyroid drugs, as well as by a spontaneous shift to hypothyroidism, which is supposed to result from a change from stimulating to blocking TSH-receptor antibodies. These immune and clinical peculiarities support the concept that antithyroid drugs should be the first-line treatment in Alemtuzumab-induced Graves’ hyperthyroidism.

Prevalence of coeliac disease among adult patients with autoimmune hypothyroidism in Jordan.

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Farahid, O H; Khawaja, N; Shennak, M M; Batieha, A; El-Khateeb, M; Ajlouni, K

2014-02-11

The prevalence of coeliac disease among patients with autoimmune hypothyroidism has not been studied before in Jordan and other Arab countries. A cross-sectional record-based review was made of all adult autoimmune hypothyroidism patients who attended a referral centre in Jordan, during an 8-month period. Coeliac disease in these patients was diagnosed by the attending physician based on positive serological tests for anti-endomysial antibodies IgA and IgG followed by duodenal biopsy to confirm the diagnosis of coeliac disease. Of 914 patients recruited, 117 (12.8%) were seropositive for coeliac disease. Of 87 seropositive patients who underwent duodenal biopsy, 39 had positive histological findings of coeliac disease (44.8%). Extrapolating from these findings the overall rate of coeliac disease among autoimmune hypothyroidism patients was estimated to be 5.7%. In multivariate logistic regression coeliac disease was significantly associated with older age (> 40 years), presence of other autoimmune diseases, vitamin B12 deficiency and anaemia.

Anti-DNA antibodies: Sequencing, cloning, and expression

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Barry, M.M.

1992-01-01

To gain some insight into the mechanism of systemic lupus erythematosus, and the interactions involved in proteins binding to DNA four anti-DNA antibodies have been investigated. Two of the antibodies, Hed 10 and Jel 242, have previously been prepared from female NZB/NZW mice which develop an autoimmune disease resembling human SLE. The remaining two antibodies, Jel 72 and Jel 318, have previously been produced via immunization of C57BL/6 mice. The isotypes of the four antibodies investigated in this thesis were determined by an enzyme-linked-immunosorbent assay. All four antibodies contained [kappa] light chains and [gamma]2a heavy chains except Jel 318 which contains a [gamma]2b heavy chain. The complete variable regions of the heavy and light chains of these four antibodies were sequenced from their respective mRNAs. The gene segments and variable gene families expressed in each antibody were identified. Analysis of the genes used in the autoimmune anti-DNA antibodies and those produced by immunization indicated no obvious differences to account for their different origins. Examination of the amino acid residues present in the complementary-determining regions of these four antibodies indicates a preference for aromatic amino acids. Jel 72 and Jel 242 contain three arginine residues in the third complementary-determining region. A single-chain Fv and the variable region of the heavy chain of Hed 10 were expressed in Escherichia coli. Expression resulted in the production of a 26,000 M[sub r] protein and a 15,000 M[sub r] protein. An immunoblot indicated that the 26,000 M[sub r] protein was the Fv for Hed 10, while the 15,000 M[sub r] protein was shown to bind poly (dT). The contribution of the heavy chain to DNA binding was assessed.

Sialyl-Tn vaccine induces antibody-mediated tumour protection in a relevant murine model

DEFF Research Database (Denmark)

Julien, S; Picco, G; Sewell, R

2009-01-01

challenge. We show that synthetic STn coupled to keyhole limpet haemocyanin (Theratope), induced antibodies to STn that recognised the glycan carried on a number of glycoproteins and in these mice a significant delay in tumour growth was observed. The protection was dependent on STn being expressed...... by the tumour and was antibody mediated. Affinity chromatography of the STn-expressing tumour cell line, followed by mass spectrometry, identified osteopontin as a novel STn-carrying glycoprotein which was highly expressed by the tumours. These results suggest that if antibodies can be induced to a number...

Predictive models in the diagnosis and treatment of autoimmune epilepsy.

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Dubey, Divyanshu; Singh, Jaysingh; Britton, Jeffrey W; Pittock, Sean J; Flanagan, Eoin P; Lennon, Vanda A; Tillema, Jan-Mendelt; Wirrell, Elaine; Shin, Cheolsu; So, Elson; Cascino, Gregory D; Wingerchuk, Dean M; Hoerth, Matthew T; Shih, Jerry J; Nickels, Katherine C; McKeon, Andrew

2017-07-01

To validate predictive models for neural antibody positivity and immunotherapy response in epilepsy. We conducted a retrospective study of epilepsy cases at Mayo Clinic (Rochester-MN; Scottsdale-AZ, and Jacksonville-FL) in whom autoimmune encephalopathy/epilepsy/dementia autoantibody testing profiles were requested (06/30/2014-06/30/2016). An Antibody Prevalence in Epilepsy (APE) score, based on clinical characteristics, was assigned to each patient. Among patients who received immunotherapy, a Response to Immunotherapy in Epilepsy (RITE) score was assigned. Favorable seizure outcome was defined as >50% reduction of seizure frequency at the first follow-up. Serum and cerebrospinal fluid (CSF) from 1,736 patients were sent to the Mayo Clinic Neuroimmunology Laboratory for neural autoantibody evaluation. Three hundred eighty-seven of these patients met the diagnostic criteria for epilepsy. Central nervous system (CNS)-specific antibodies were detected in 44 patients. Certain clinical features such as new-onset epilepsy, autonomic dysfunction, viral prodrome, faciobrachial dystonic seizures/oral dyskinesia, inflammatory CSF profile, and mesial temporal magnetic resonance imaging (MRI) abnormalities had a significant association with positive antibody results. A significantly higher proportion of antibody-positive patients had an APE score ≥4 (97.7% vs. 21.6%, p < 0.01). Sensitivity and specificity of an APE score ≥4 to predict presence of specific neural auto-antibody were 97.7% and 77.9%, respectively. In the subset of patients who received immunotherapy (77), autonomic dysfunction, faciobrachial dystonic seizures/oral dyskinesia, early initiation of immunotherapy, and presence of antibodies targeting plasma membrane proteins (cell-surface antigens) were associated with favorable seizure outcome. Sensitivity and specificity of a RITE score ≥7 to predict favorable seizure outcome were 87.5% and 83.8%, respectively. APE and RITE scores can aid diagnosis

Development of Autoimmune Overt Hypothyroidism Is Highly Associated With Live Births and Induced Abortions but Only in Premenopausal Women

DEFF Research Database (Denmark)

Carle, Allan; Pedersen, Inge Buelow; Knudsen, Nils

2014-01-01

: In conditional multivariate logistic regression models, we analyzed the associations between the development of autoimmune hypothyroidism and age at menarche/menopause, years of menstruations, pregnancies, spontaneous and induced abortions, live births, and years on oral contraceptives and postmenopausal hormone...

MRI findings in glutamic acid decarboxylase associated autoimmune epilepsy

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Fredriksen, Jason R.; Carr, Carrie M.; Koeller, Kelly K.; Verdoorn, Jared T.; Kotsenas, Amy L. [Mayo Clinic, Department of Radiology, Rochester, MN (United States); Gadoth, Avi; Pittock, Sean J. [Mayo Clinic, Department of Neurology, Rochester, MN (United States)

2018-03-15

Glutamic acid decarboxylase (GAD65) has been implicated in a number of autoimmune-associated neurologic syndromes, including autoimmune epilepsy. This study categorizes the spectrum of MRI findings in patients with a clinical diagnosis of autoimmune epilepsy and elevated serum GAD65 autoantibodies. An institutional database search identified patients with elevated serum GAD65 antibodies and a clinical diagnosis of autoimmune epilepsy who had undergone brain MRI. Imaging studies were reviewed by three board-certified neuroradiologists and one neuroradiology fellow. Studies were evaluated for cortical/subcortical and hippocampal signal abnormality, cerebellar and cerebral volume loss, mesial temporal sclerosis, and parenchymal/leptomeningeal enhancement. The electronic medical record was reviewed for relevant clinical information and laboratory markers. A study cohort of 19 patients was identified. The majority of patients were female (84%), with a mean age of onset of 27 years. Serum GAD65 titers ranged from 33 to 4415 nmol/L (normal < 0.02 nmol/L). The most common presentation was medically intractable, complex partial seizures with temporal lobe onset. Parenchymal atrophy was the most common imaging finding (47%), with a subset of patients demonstrating cortical/subcortical parenchymal T2 hyperintensity (37%) or abnormal hippocampal signal (26%). No patients demonstrated abnormal parenchymal/leptomeningeal enhancement. The most common MRI finding in GAD65-associated autoimmune epilepsy is disproportionate parenchymal atrophy for age, often associated with abnormal cortical/subcortical T2 hyperintensities. Hippocampal abnormalities are seen in a minority of patients. This constellation of findings in a patient with medically intractable epilepsy should raise the possibility of GAD65 autoimmunity. (orig.)

Purpura fulminans and anticardiolipin antibodies in a patient with Grave's disease.

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Ligier, Sophie; Pham, Cuong D; Watters, A Kevin; Kassis, Jeannine; Fortin, Paul R

2002-01-01

We describe a patient with Grave's discase who developed purpura fulminans and who was found to have anticardiolipin antibodies after being started on propylthiouracil (PTU). We discuss the potential role of the antiphospholipid antibody in this woman's presentation, and its association to both PTU and autoimmune thyroid disease.

Differential Immuno-Reactivity to Genomic DNA, RNA and Mitochondrial DNA is Associated with Auto-Immunity

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Vilena V. Ivanova

2014-12-01

Full Text Available Background: Circulating auto-reactive antibodies are hallmark features of auto-immune diseases, however little is known with respect to the specificity of such bio-markers. In the present study, we investigated the specificity of anti-nucleic acid antibodies in the blood of subjects with systemic lupus erythematosus (SLE and healthy controls. Methods: Sera from 12 SLE cases and 8 controls were evaluated for immuno-reactivity to purified RNA, DNA and mitochondrial DNA (mtDNA by enzyme-linked immuno-sorbent assay (ELISA. Results: As expected, immuno-reactivity to total nucleic acids was significantly higher in subjects with SLE when compared to healthy controls, however a clear distinction was observed among the various nucleic acid sub-types, with sera from SLE subjects displaying the greatest immuno-reactivity to RNA followed by mtDNA and then total DNA. Conclusion: The identification of auto-reactive antibodies can serve as highly sensitive biomarkers, although their specificity may not always allow diagnostic certainty. The knowledge that auto-antibodies in subjects with SLE display differential immuno-reactivity may help to improve existing diagnostics and may lead to a better understanding of the pathogenesis of auto-immune disorders.

Nuclear antigen expression by ultraviolet light irradiation - a contribution to the UV-induced autoimmunity

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Wollina, U

1986-05-01

A review is given of nuclear antigen expression due to UVB, UVA, and PUVA. UVB alters DNA resulting in strong immunogenic UVDNA and complementary antibodies. Antibodies to UVDNA cross react with double-stranded DNA. UVDNA plays a (hypothetical) role in the induction of cutaneous lesions in lupus erythematosus (LE). Investigations of SS-A/Ro expression due to UVB seem to be more important under this view. Antibodies against SS-A/Ro are related to an increased photosensitivity in LE. PUVA and UVA are able to induce antinuclear antibodies of unknown specificity. It is likely that PUVA enhances SS-A/Ro expression in vitro. The results are discussed in sense of LE photobiology and unwanted side effects of photo(chemo)therapy in psoriasis. 54 references.

Nuclear antigen expression by ultraviolet light irradiation - a contribution to the UV-induced autoimmunity

International Nuclear Information System (INIS)

Wollina, U.

1986-01-01

A review is given about nuclear antigen expression due to UVB, UVA, and PUVA. UVB alters DNA resulting in strong immunogenic UVDNA and complementary antibodies. Antibodies to UVDNA cross react with double-stranded DNA. UVDNA plays a (hypothetical) role in the induction of cutaneous lesions in lupus erythematosus (LE). Investigations about SS-A/Ro expression due to UVB seem to be more important under this view. Antibodies against SS-A/Ro are related to an increased photosensitivity in LE. PUVA and UVA are able to induce antinuclear antibodies of unknown specificity. It is likely that PUVA enhances SS-A/Ro expression in vitro. The results are discussed in sense of LE photobiology and unwanted side effects of photo(chemo)therapy in psoriasis. (author)

Chemo-enzymatic production of O-glycopeptides for the detection of serum glycopeptide antibodies

DEFF Research Database (Denmark)

Nøstdal, Alexander; Wandall, Hans H

2013-01-01

Protein microarray is a highly sensitive tool for antibody detection in serum. Monitoring of patients' antibody titers to specific antigens is increasingly employed in the diagnosis of several conditions, ranging from infectious diseases, allergies, autoimmune diseases, and cancer. In this protoc...

A murine model of type 2 autoimmune hepatitis: Xenoimmunization with human antigens.

Science.gov (United States)

Lapierre, Pascal; Djilali-Saiah, Idriss; Vitozzi, Susana; Alvarez, Fernando

2004-04-01

Autoimmune hepatitis (AIH) is characterized by an immune-mediated injury of the hepatic parenchyma of unknown pathogenesis. Type 2 AIH is identified by the presence of anti-liver-kidney microsomes type 1 (anti-LKM1) and anti-liver cytosol type 1 (anti-LC1) autoantibodies. The current study shows that a murine model of AIH can be generated by DNA immunization against type 2 AIH self-antigens (P450 2D6 and formiminotransferase-cyclodeaminase). A pCMV plasmid containing the N-terminal region of mouse CTLA-4 and the antigenic region of human CYP2D6 (672-1,377 bp) and human formiminotransferase cyclodeaminase (FTCD; 1,232-1,668 bp) was used for DNA immunization of C57BL/6 female mice. Immunized mice showed elevated levels of alanine aminotransferase (ALT), with peaks at 4 and 7 months postinjection. Periportal, portal, and intralobular liver inflammatory infiltrates were observed at histology. Mainly CD4+ lymphocytes, but also CD8+ and B lymphocytes, were found in the liver. Cytotoxic-specific T cells were found in both the liver and spleen of these animals. Mice developed anti-LKM1 and anti-LC1 antibodies of immunoglobulin G2 (IgG2) subclass, against specific mouse autoantigens. The ALT levels correlated with both the presence of anti-LKM1/anti-LC1 antibodies and the presence of liver necroinflammation. In conclusion, in mice, DNA immunization against human autoantigens breaks tolerance and induces an autoimmune liver disease. Molecular mimicry between foreign and self-antigens explains the liver injury. This model of AIH resembles human type 2 AIH and will be helpful for the study of its pathogenesis.

Low birth weight is not associated with thyroid autoimmunity

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Brix, Thomas Heiberg; Hansen, Pia Skov; Rudbeck, Annette Beck

2006-01-01

CONTEXT: Low birth weight has been proposed as a risk factor for the development of antibodies toward thyroid peroxidase (TPOAb) and thyroglobulin (TgAb) in adult life. However, the association could also be due to genetic or environmental factors affecting both birth weight and the development...... of thyroid autoantibodies. The effect of these confounders can be minimized through investigation of twin pairs. OBJECTIVE AND DESIGN: To examine the impact of low birth weight on the development of thyroid autoimmunity, we studied whether within-twin-cohort and within-twin-pair differences in birth weight......, gestational age, TSH, and smoking) did not change the findings of nonsignificant regression coefficients. CONCLUSION: Low birth weight per se has no evident role in the etiology of thyroid autoimmunity....

Study on serum thyroid peroxidase antibody levels in autoimmune thyroid disease

International Nuclear Information System (INIS)

Zhang Zhixiang; Zheng Lan; Xu Shujin; Guan Jinghua

2008-01-01

Objective: To investigate the clinical significance of changes of serum thyroid peroxidase antibody (TPO-Ab) in patients with hyperthyroidism, hypothyroidism and simple goiter. Methods: Serum TPO-Ab, TMA,TGA and FT 3 , FT 4 , TSH levels were measured with radioimmunoassay(RIA) in 69 patients with hyperthyroidism, 53 patients with hypothyroidism, 45 patients with simple goiter and 20 controls. Results: The positive rate of thyroid peroxidase antibody (TPO-Ab) (82%-92.5%) was higher than that of thyroidglobulim antibody(TGA) (44.2%) and thyroid microsome antibody(TMA) (60.4-69.8%) in all patients with AICD. Conclusion: TPO-Ab could be taken as an important indicator in assessment of treatment and prognosis in patients with auto- immune thyroid diseases. (authors)

Frequency of autoimmune disorders and autoantibodies in patients with neuromyelitis optica.

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Pereira, Wildéa Lice de Carvalho Jennings; Reiche, Edna Maria Vissoci; Kallaur, Ana Paula; Oliveira, Sayonara Rangel; Simão, Andréa Name Colado; Lozovoy, Marcell Alysson Batisti; Schiavão, Lucas José Vaz; Rodrigues, Paula Raquel do Vale Pascoal; Alfieri, Daniela Frizon; Flauzino, Tamires; Kaimen-Maciel, Damacio Ramón

2017-06-01

The aim of this study was to report the frequency of autoimmune disorders and autoantibodies in 22 patients with neuromyelitis optica (NMO), as well as whether the seropositivity for autoantibodies differs between anti-aquaporin 4 (AQP4) positive and AQP4 negative NMO patients. Demographic, medical records, and a profile of autoantibodies were evaluated in 22 NMO patients, including AQP4, anti-thyroid-stimulating hormone receptor, antinuclear antibodies (ANA), anti-thyroperoxidase (anti-TPO), anti-thyroglobulin (anti-Tg), anti-double-stranded DNA, anti-neutrophil cytoplasmic, anti-cyclic citrullinate peptide, rheumatoid factor, anti-SSA/Ro, anti-SSB/La, anti-Smith antibodies (anti-Sm), anti-ribonucleoprotein, anti-nucleosome, and anti-Scl70. Thyroid-stimulating hormone and free thyroxin were measured. The frequency of women was higher than men (95.5% vs. 4.5%) and 68.2% were Afro-Brazilians. Six (27.3%) patients presented other autoimmune disorders, such as Hashimoto thyroiditis (n=2), Graves' disease (n=1), juvenile idiopathic arthritis (n=1), systemic lupus erythematosus and systemic sclerosis (n=1), and Raynaud's phenomenon (n=1). The most frequent autoantibodies were anti-AQP4 (54.5%), anti-nucleosome (31.8%), ANA (27.3%), anti-TPO (22.7%), and anti-Tg (22.7%). Difference was not observed in the frequency of autoimmune disorders when the patients were compared according to their anti-AQP4 status. The results of the present study underscored that the NMO patients present high frequency of autoantibodies against cellular antigens and the presence of autoimmune disorders. Further studies with large number of NMO patients may contribute to advances in the understanding of NMO disease mechanisms.

Etiology and pathogenesis of antisperm antibody

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farhad Shahsavar

2011-06-01

Full Text Available Antisperm antibodies (ASA occur in men and women and may significantly impair fertility. In this case, the testis is an immunologically privileged site where germ cell antigens are protected from autoimmune attack. However, due to disruption of the blood-testis barrier occurring from testicular injury, or as a consequence of trauma to the epididymis or vas deferens many testicular proteins get autoantigenic during immunological challenges resulting in the formation of ASA in the blood serum, seminal plasma or located on the sperm membrane. ASA have also been reported to be associated with inflammation, cryptorchidism, varicocele and surgical intervention in the genital organs. ASA may interfere with different sperm functions, which are essential for the fertilization process.This review article will help to increase our understanding of the specific mechanisms that elicit the autoimmune response to sperm and of the pathogenesis of ASA that leads to an antibody-mediated infertility.

Antismooth muscle and antiactin antibodies are indirect markers of histological and biochemical activity of autoimmune hepatitis.

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Couto, Claudia A; Bittencourt, Paulo L; Porta, Gilda; Abrantes-Lemos, Clarice P; Carrilho, Flair J; Guardia, Bianca D; Cançado, Eduardo L R

2014-02-01

Reactivity and titers of autoantibodies vary during the course of autoimmune hepatitis (AIH), and some autoantibodies have been associated with disease activity and adverse outcomes after treatment. The aim of this study was to assess the autoantibody behavior in AIH and its significance as predictors of biochemical and histological remission. A total of 117 patients with AIH (mean age 18.6 [4-69] years) were evaluated and tested for autoantibodies at disease onset and successively (mean 3.2 [2-6] times) after a mean follow-up evaluation of 70 [20-185] months. Antismooth muscle (ASMA), antiliver kidney microsome type 1 (anti-LKM1), antiliver cytosol type 1 (anti-LC1), antimitochondrial, antinuclear (ANA), and antiactin antibodies (AAA) were determined at disease onset and 379 other times during the follow-up evaluation through indirect immunofluorescence in rodent tissues, HEp-2 cells, and human fibroblasts. Anti-SLA/LP were assessed 45 times in the follow-up evaluation of 19 patients using enzyme-linked immunosorbent assay (ELISA). Upon admission, AIH types 1 and 2 were observed in 95 and 17 patients, respectively. Five subjects had AIH with anti-SLA/LP as the sole markers. Patients initially negative for AAA did not develop these antibodies thereafter. ANA were detected de novo in six and three subjects with AIH types 1 and 2, respectively. After treatment, only ASMA (>1:80) and AAA (>1:40) were significantly associated with biochemical (76.9% and 79.8%) and histological features (100% and 100%) of disease activity (P < 0.001). With the exception of ANA, the autoantibody profile does not markedly vary in the course of AIH. The persistence of high titers of ASMA and/or AAA in patients with AIH is associated with disease activity. © 2013 by the American Association for the Study of Liver Diseases.

Mast cells are important modifiers of autoimmune disease: With so much evidence, why is there controversy?

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Melissa Ann Brown

2012-06-01

Full Text Available There is abundant evidence that mast cells are active participants in events that mediate tissue damage in autoimmune disease. Disease-associated increases in mast cell numbers accompanied by mast cell degranulation and elaboration of numerous mast cell mediators at sites of inflammation are commonly observed in many human autoimmune diseases including multiple sclerosis, rheumatoid arthritis and bullous pemphigoid. In animal models, treatment with mast cell stabilizing drugs or mast cell ablation can result in diminished disease. A variety of receptors including those engaged by antibody, complement, pathogens and intrinsic danger signals are implicated in mast cell activation in disease. Similar to their role as first responders in infection settings, mast cells likely orchestrate early recruitment of immune cells, including neutrophils, to the sites of autoimmune destruction. This co-localization promotes cellular crosstalk and activation and results in the amplification of the local inflammatory response thereby promoting and sustaining tissue damage. Despite the evidence, there is still a debate regarding the relative role of mast cells in these processes. However, by definition, mast cells can only act as accessory cells to the self-reactive T and/or antibody driven autoimmune responses. Thus, when evaluating mast cell involvement using existing and somewhat imperfect animal models of disease, their importance is sometimes obscured. However, these potent immune cells are undoubtedly major contributors to autoimmunity and should be considered as important targets for therapeutic disease intervention.

Autoimmune connective tissue diseases and vaccination

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Ewa Więsik-Szewczyk

2015-12-01

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.

Frequency and significance of antibodies to liver/kidney microsome type 1 in adults with chronic active hepatitis.

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Czaja, A J; Manns, M P; Homburger, H A

1992-10-01

To assess the frequency of antibodies to liver/kidney microsome type 1 (anti-LKM1) in patients with chronic active hepatitis, 131 such patients were tested by an indirect immunofluorescence assay. Of 62 patients with type 1 autoimmune hepatitis, none were seropositive. In contrast, 3 of 11 patients with autoimmune hepatitis and antimitochondrial antibodies (27%) were seropositive for anti-LKM1. Each had responded to corticosteroid therapy, and retesting of sera confirmed that each had been misclassified as antimitochondrial antibody positive. None of the patients with chronic active hepatitis B (14 patients) or C (24 patients) had anti-LKM1. Similarly, none of the 20 patients with cryptogenic disease had these antibodies. It is concluded that anti-LKM1 is specific for type 2 autoimmune hepatitis and is infrequent in adult patients seen at a referral center in the United States for chronic active hepatitis. Anti-LKM1 reactivity may be misinterpreted as antimitochondrial antibody reactivity by indirect immunofluorescence. Chronic hepatitis B and C virus infections are not important stimuli for the production of anti-LKM1, and testing for anti-LKM 1 is unlikely to clarify the nature of cryptogenic disease.

Ionizing radiation and autoimmunity: Induction of autoimmune disease in mice by high dose fractionated total lymphoid irradiation and its prevention by inoculating normal T cells

International Nuclear Information System (INIS)

Sakaguchi, N.; Sakaguchi, S.; Miyai, K.

1992-01-01

Ionizing radiation can functionally alter the immune system and break self-tolerance. High dose (42.5 Gy), fractionated (2.5 Gy 17 times) total lymphoid irradiation (TLI) on mice caused various organ-specific autoimmune diseases, such as gastritis, thyroiditis, and orchitis, depending on the radiation dosages, the extent of lymphoid irradiation, and the genetic background of the mouse strains. Radiation-induced tissue damage is not the primary cause of the autoimmune disease because irradiation of the target organs alone failed to elicit the autoimmunity and shielding of the organs from irradiation was unable to prevent it. In contrast, irradiation of both the thymus and the peripheral lymphoid organs/tissues was required for efficient induction of autoimmune disease by TLI. TLI eliminated the majority of mature thymocytes and the peripheral T cells for 1 mo, and inoculation of spleen cell, thymocyte, or bone marrow cell suspensions (prepared from syngeneic nonirradiated mice) within 2 wk after TLI effectively prevented the autoimmune development. Depletion of T cells from the inocula abrogated the preventive activity. CD4 + T cells mediated the autoimmune prevention but CD8 + T cells did not. CD4 + T cells also appeared to mediate the TLI-induced autoimmune disease because CD4 + T cells from disease-bearing TLI mice adoptively transferred the autoimmune disease to syngeneic naive mice. Taken together, these results indicate that high dose, fractionated ionizing radiation on the lymphoid organs/tissues can cause autoimmune disease by affecting the T cell immune system, rather than the target self-Ags, presumably by altering T cell-dependent control of self-reactive T cells. 62 refs., 9 figs., 2 tabs

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

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

1991-04-01

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

Thyroid Dysfunction and Autoimmune Thyroid Diseases Among Atomic Bomb Survivors Exposed in Childhood.

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Imaizumi, Misa; Ohishi, Waka; Nakashima, Eiji; Sera, Nobuko; Neriishi, Kazuo; Yamada, Michiko; Tatsukawa, Yoshimi; Takahashi, Ikuno; Fujiwara, Saeko; Sugino, Keizo; Ando, Takao; Usa, Toshiro; Kawakami, Atsushi; Akahoshi, Masazumi; Hida, Ayumi

2017-07-01

The risk of thyroid cancer increases and persists for decades among individuals exposed to ionizing radiation in childhood, although the long-term effects of childhood exposure to medium to low doses of radiation on thyroid dysfunction and autoimmune thyroid diseases have remained unclear. To evaluate radiation dose responses for the prevalence of thyroid dysfunction and autoimmune thyroid disease among atomic bomb survivors exposed in childhood. Hiroshima and Nagasaki atomic bomb survivors who were younger than 10 years old at exposure underwent thyroid examinations at the Radiation Effects Research Foundation between 2007 and 2011, which was 62 to 66 years after the bombing. Data from 2668 participants (mean age, 68.2 years; 1455 women) with known atomic bomb thyroid radiation doses (mean dose, 0.182 Gy; dose range, 0 to 4.040 Gy) were analyzed. Dose-response relationships between atomic bomb radiation dose and the prevalence of hypothyroidism, hyperthyroidism (Graves' disease), and positive for antithyroid antibodies. Prevalences were determined for hypothyroidism (129 cases, 7.8%), hyperthyroidism (32 cases of Graves' disease, 1.2%), and positive for antithyroid antibodies (573 cases, 21.5%). None of these was associated with thyroid radiation dose. Neither thyroid antibody-positive nor -negative hypothyroidism was associated with thyroid radiation dose. Additional analyses using alternative definitions of hypothyroidism and hyperthyroidism found that radiation dose responses were not significant. Radiation effects on thyroid dysfunction and autoimmune thyroid diseases were not observed among atomic bomb survivors exposed in childhood, at 62 to 66 years earlier. The cross-sectional design and survival bias were limitations of this study. Copyright © 2017 Endocrine Society

ER stress proteins in autoimmune and inflammatory diseases

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Daisuke eMorito

2012-03-01

Full Text Available Over the past two decades, heat shock proteins (HSPs have been implicated in inflammatory responses and autoimmunity. HSPs were originally believed to maintain protein quality control in the cytosol. However, they also exist extracellularly and appear to act as inflammatory factors. Recently, a growing body of evidence suggested that the other class of stress proteins such as, endoplasmic reticulum (ER stress proteins, which originally act as protein quality control factors in the secretory pathway and are induced by ER stress in inflammatory lesions, also participate in inflammation and autoimmunity. The immunoglobulin heavy-chain binding protein (Bip/glucose-regulated protein 78 (Grp78, homocysteine-induced ER protein (Herp, calnexin, calreticulin, glucose-regulated protein 94 (Grp94/gp96, oxygen-regulated protein 150 (ORP150 and heat shock protein 47 (Hsp47/Serpin H1, which are expressed not only in the ER but also occasionally at the cell surface play pathophysiological roles in autoimmune and inflammatory diseases as pro- or anti-inflammatory factors. Here we describe the accumulating evidence of the participation of ER stress proteins in autoimmunity and inflammation and discuss the critical differences between the two classes of stress proteins.

Sjögren syndrome and neuromyelitis optica spectrum disorder co-exist in a common autoimmune milieu

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Diogo C. Carvalho

2014-06-01

Full Text Available The relationship between Sjögren’s syndrome (SS and neuromyelitis optica spectrum disorder (NMOSD is not completely understood. We report two patients with both conditions and review 47 other previously reported cases meeting currently accepted diagnostic criteria, from 17 articles extracted from PubMed. Out of 44 patients whose gender was informed, 42 were females. Mean age at onset of neurological manifestation was 36.2 years (10-74. Serum anti-AQP4-IgG was positive in 32 patients, borderline in 1, and negative in 4. Our Case 1 was seronegative for AQP4-IgG and had no non-organ-specific autoantibodies other than anti-SSB antibodies. Our Case 2 had serum anti-AQP4, anti-SSA/SSB, anti-thyreoglobulin and anti-acethylcholine-receptor antibodies, as well as clinical hypothyreoidism, but no evidence of myasthenia gravis. Our Cases and others, as previously reported in literature, with similar heterogeneous autoimmune response to aquaporin-4, suggest that SS and NMO co-exist in a common autoimmune milieu which is not dependent on aquaporin-4 autoimmunity.

Anticuerpos anti 21 hidroxilasa séricos en pacientes con anticuerpos antifracción microsomal: Síndrome poliendocrino autoinmune Seric 21- hydroxilase antibodies in patients with anti-microsomal fraction antibodies: Autoimmune polyendocrine syndrome

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Silvia Botta

2007-04-01

these are induced by autoantibodies. Alopecia, vitiligo, myasthenia and other manifestations can be minor components. We sought to establish the prevalence of seric a21-OH in patients with positive anti-microsomal fraction autoantibodies, autoimmune thyroid disease and/or non-endocrine autoimmune diseases. We also aimed to diagnose incomplete forms of APS and to follow up patients at risk of progression to complete forms of APS. A population of 72 patients and another of 60 controls with negative anti-microsomal fraction autoantibodies were studied. Elevated seric a21-OH were found in two patients. Patient A with 47 U/ml had autoimmune hypothyroidism and myasthenia; and patient B with 8.75 U/ml had autoimmune hypothyrodism and vitiligo; they both lacked adrenal insufficiency. Seric a21-OH had a prevalence of 2.8%. Regarding the adrenal component, patients A and B had an incomplete and latent APS type 2. Considering a21-OH as markers of latent endocrine autoimmune diseases and taking into account the eventual risk of developing clinical manifestations, periodic biochemical and clinical follow-ups are recommended.

Mercury exposure, serum antinuclear/antinucleolar antibodies, and serum cytokine levels in mining populations in Amazonian Brazil: a cross-sectional study.

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Gardner, Renee M; Nyland, Jennifer F; Silva, Ines A; Ventura, Ana Maria; de Souza, Jose Maria; Silbergeld, Ellen K

2010-05-01

Mercury is an immunotoxic substance that has been shown to induce autoimmune disease in rodent models, characterized by lymphoproliferation, overproduction of immunoglobulin (IgG and IgE), and high circulating levels of auto-antibodies directed at antigens located in the nucleus (antinuclear auto-antibodies, or ANA) or the nucleolus (antinucleolar auto-antibodies, or ANoA). We have reported elevated levels of ANA and ANoA in human populations exposed to mercury in artisanal gold mining, though other confounding variables that may also modulate ANA/ANoA levels were not well controlled. The goal of this study is to specifically test whether occupational and environmental conditions (other than mercury exposure) that are associated with artisanal gold mining affect the prevalence of markers of autoimmune dysfunction. We measured ANA, ANoA, and cytokine concentrations in serum and compared results from mercury-exposed artisanal gold miners to those from diamond and emerald miners working under similar conditions and with similar socio-economic status and risks of infectious disease. Mercury-exposed gold miners had higher prevalence of detectable ANA and ANoA and higher titers of ANA and ANoA as compared to diamond and emerald miners with no occupational mercury exposure. Also, mercury-exposed gold miners with detectable ANA or ANoA in serum had significantly higher concentrations of pro-inflammatory cytokines IL-1beta, TNF-alpha, and IFN-gamma in serum as compared to the diamond and emerald miners. This study provides further evidence that mercury exposure may lead to autoimmune dysfunction and systemic inflammation in affected populations. Copyright 2010 Elsevier Inc. All rights reserved.

Antagonist Anti-CD28 Therapeutics for the Treatment of Autoimmune Disorders

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Bernard Vanhove

2017-11-01

Full Text Available The effector functions of T lymphocytes are responsible for most autoimmune disorders and act by directly damaging tissues or by indirectly promoting inflammation and antibody responses. Co-stimulatory and co-inhibitory T cell receptor molecules are the primary pharmacological targets that enable interference with immune-mediated diseases. Among these, selective CD28 antagonists have drawn special interest, since they tip the co-stimulation/co-inhibition balance towards efficiently inhibiting effector T cells while promoting suppression by pre-existing regulatory T-cells. After having demonstrated outstanding therapeutic efficacy in multiple models of autoimmunity, inflammation and transplantation, and safety in phase-I studies in humans, selective CD28 antagonists are currently in early clinical development for the treatment of systemic lupus erythematous and rheumatoid arthritis. Here, we review the available proof of concept studies for CD28 antagonists in autoimmunity, with a special focus on the mechanisms of action.

Antibodies to the α-subunit of insulin receptor from eggs of immunized hens

International Nuclear Information System (INIS)

Song, C.; Yu, J.; Bai, D.H.; Hester, P.Y.; Kim, K.

1985-01-01

Simple methods for the generation, purification, and assay of antibodies to the α-subunit of insulin receptor from eggs of immunized hen have been described. Chicken antibodies against the α-subunit inhibit insulin binding to the receptor and stimulate glucose oxidation as well as autophosphorylation of the β-subunit. Thus the properties of chicken antibodies are very similar to those of antibodies found in human autoimmune diseases and different from rabbit antibodies obtained against the same antigen

Is autoimmune thyroiditis part of the genetic vulnerability (or an endophenotype) for bipolar disorder?

NARCIS (Netherlands)

Vonk, Ronald; van der Schot, Astrid C.; Kahn, Rene S.; Nolen, Willem A.; Drexhage, Hemmo A.

2007-01-01

Background: Both genetic and environmental factors are involved in the etiology of bipolar disorder; however, biological markers for the transmission of the bipolar genotype ("endophenotypes") have not been found. Autoimmune thyroiditis with raised levels of thyroperoxidase antibodies (TPO-Abs) is

Study of the prevalence of familial autoimmune myasthenia gravis in a Spanish cohort.

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Salvado, Maria; Canela, Merce; Ponseti, Jose Maria; Lorenzo, Laura; Garcia, Cecilia; Cazorla, Sonia; Gili, Gisela; Raguer, Nuria; Gamez, Josep

2016-01-15

Myasthenia gravis (MG) is an autoimmune disease caused by a failure of neuromuscular transmission. Familial clustering has been reported despiteMG usually manifesting as a sporadic condition presumed not to be inherited. Our study investigated the prevalence of FAMG in a Spanish cohort, characterizing their phenotype,antibody titres and thymus findings. We investigated the presence of familial cases in 462 MG patients, characterizing by age and MGFA class at debut, quantitative MG score, antibody titres, MGFA post-intervention status and thymus pathology. Sixteen cases from8 unrelated pedigrees were identified. The prevalence of FAMG caseswas 3.46%.Mean age at onset was 57.8 ± 17.4 years (range=23–82). Distribution at debut was: 6 ocular, 4 IIa, 4IIb, 1 IIIa and 1 IIIb. Thymoma was identified in two of the 7 thymectomized individuals. The prevalence of FAMG in Spain is similar to other populations. Post-intervention status did not differ from sporadic autoimmune MG. As in other neuromuscular disorders, phenotype and inheritance heterogeneity are present in FAMG. In addition to the interfamilial heterogeneity observed, members of the same family affected with FAMG may even present different ages of onset, severity and thymus involvement. Further studies are necessary to clarify the role of genetic risk factors in this form of autoimmune MG.

Primary Biliary Cirrhosis Is a Generalized Autoimmune Epithelitis

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Jun Gao

2015-03-01

Full Text Available Primary biliary cirrhosis (PBC is a chronic progressive autoimmune cholestatic liver disease characterized by highly specific antimitochondrial antibodies (AMAs and the specific immune-mediated injury of small intrahepatic bile ducts. Unique apoptotic feature of biliary epithelial cells (BECs may contribute to apotope presentation to the immune system, causing unique tissue damage in PBC. Perpetuation of inflammation may result in senescence of BECs, contributing to irreversible loss of bile duct. In addition to the classic liver manifestations, focal inflammation and tissue damage are also seen in salivary glands and urinary tract in a significant proportion of PBC patients. These findings provide potent support to the idea that molecular mimicry may be involved in the breakdown of autoimmune tolerance and mucosal immunity may lead to a systematic epithelitis in PBC patients. Thus, PBC is considered a generalized epithelitis in clinical practice.

The role of melatonin in autoimmune and atopic diseases

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J.R. Calvo

2016-04-01

Full Text Available Melatonin is the main secretory product synthesized and secreted by the pineal gland during the night. Melatonin is a pleitropic molecule with a wide distribution within phylogenetically distant organisms and has a great functional versatility, including the regulation of circadian and seasonal rhythms and antioxidant and anti-inflammatory properties. It also possesses the capacity to modulate immune responses by regulation of the TH1/TH2 balance and cytokine production. Immune system eradicates infecting organisms without serious injury to host tissues, but sometimes these responses are inadequately controlled, giving rise to called hypersensitivity diseases, or inappropriately targeted to host tissues, causing the autoimmune diseases. In clinical medicine, the hypersensitivity diseases include the allergic or atopic diseases and the hallmarks of these diseases are the activation of TH2 cells and the production of IgE antibody. Regarding autoimmunity, at the present time we know that the key events in the development of autoimmunity are a failure or breakdown of the mechanisms normally responsible for maintaining self-tolerance in B lymphocytes, T lymphocytes, or both, the recognition of self-antigens by autoreactive lymphocytes, the activation of these cells to proliferate and differentiate into effector cells, and the tissue injury caused by the effector cells and their products. Melatonin treatment has been investigated in atopic diseases, in several animal models of autoimmune diseases, and has been also evaluated in clinical autoimmune diseases. This review summarizes the role of melatonin in atopic diseases (atopic dermatitis and asthma and in several autoimmune diseases, such as arthritis rheumatoid, multiple sclerosis, systemic lupus erythematosus, type 1 diabetes mellitus, and inflammatory bowel diseases.

Clonal relationships between thyroid-stimulating hormone receptor-stimulating antibodies illustrate the effect of hypermutation on antibody function

DEFF Research Database (Denmark)

Padoa, Carolyn J; Larsen, Sanne L; Hampe, Christiane S

2009-01-01

relationship and derivation from a single precursor B-cell clone. The IGHV-region genes of the two mAbs underwent high degrees of somatic hypermutation by sharing numerous mutations before diverging, while the IGLV genes evolved separately. Interestingly, the mutations were present in both the complementarity......, in experimentally immunized mice, multiple pathogenic antibodies to TSHR can arise from a single clone by a series of somatic mutations in the V-region genes and may give an insight into how such antibodies develop spontaneously in autoimmune Graves' disease....

Immune complex-mediated autoimmunity in a patient With Smith-Magenis syndrome (del 17p11.2).

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Yang, Jianying; Chandrasekharappa, Settara C; Vilboux, Thierry; Smith, Ann C M; Peterson, Erik J

2014-08-01

Smith-Magenis syndrome (SMS) is a sporadic congenital disorder involving multiple organ systems caused by chromosome 17p11.2 deletions. Smith-Magenis syndrome features craniofacial and skeletal anomalies, cognitive impairment, and neurobehavioral abnormalities. In addition, some SMS patients may exhibit hypogammaglobulinemia. We report the first case of SMS-associated autoimmunity in a woman who presented with adult onset of multiple autoimmune disorders, including systemic lupus erythematosus, antiphospholipid antibody syndrome, and autoimmune hepatitis. Molecular analysis using single-nucleotide polymorphism array confirmed a de novo 3.8-Mb deletion (breakpoints, chr17: 16,660,721-20,417,975), resulting in haploinsufficiency for TACI (transmembrane activator and CAML interactor). Our data are consistent with potential loss of function for the BAFF (B cell-activating factor) receptor TACI as a contributing factor to human autoimmune phenomena.

LIPOPOLYSACCHARIDE INDUCES THE PRODUCTION OF DIAGNOSTIC MONOCLONAL ANTIBODY BY HYBRIDOMA CELLS AGAINST CONGENITAL ADRENAL HYPERPLASIA

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GEK KEE CHUA

2017-11-01

Full Text Available The purpose of this research is to screen and identify the potential inducers in maximizing the production of monoclonal antibody by hybridoma 192 cell line for Congenital Adrenal Hyperplasia diagnostic. There are nine inducers used in this research, namely lysozyme, aldolase, sodium butyrate, sodium phosphate, potassium phosphate, dimethyl sulfoxide, lipopolysaccharide, essential amino acids, and nonessential amino acids. Hybridoma 192 cell was cultured in 5% CO2 incubator at 37°C and ˃80% humidity in the medium with different concentrations of inducer agents. The inducers were added at the beginning of the culture and the samples were taken after 72 h of culture. The performance of these inducer agents was assessed based on the maximum monoclonal antibody titer achieved using Enzyme-linked Immunosorbent Assay. Lipopolysaccharide was found to increase the maximum monoclonal antibody titer when supplemented at 8 to 12 µg/mL. After optimization using one-factor central composite design at this range, the optimum point was determined to be 8 µg/mL. Verification experiments shows that lipopolysaccharide enhanced the average specific monoclonal antibody production rate by 56% relative to control. In conclusion, lipopolysaccharide at 8 µg/mL is able to increase the monoclonal antibody specific production of hybridoma 192 cell line.

The first childhood case with coexisting Hashimoto thyroiditis, vitiligo and autoimmune hepatitis.

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Keskin, Melikşah; Savaş-Erdeve, Şenay; Özbay-Hoşnut, Ferda; Kurnaz, Erdal; Çetinkaya, Semra; Aycan, Zehra

2016-01-01

Hashimoto thyroiditis (HT) is the most common pediatric autoimmune endocrine disorder. It results in autoimmune-mediated thyroid gland destruction and is an organ-specific, typical autoimmune disease. The presence of antithyroid antibodies and the typical pattern on ultrasonography indicate the diagnosis. It is also frequently seen together with other autoimmune disorders including type 1 insulin-dependent diabetes, celiac disease, alopecia and vitiligo. Autoimmune hepatitis (AIH) is a chronic type of liver injury with an immune etiology that can frequently cause end-stage liver disease if left untreated. Autoimmune hepatitis patients may present with hepatitis, and the laboratory tests in the absence of other etiology usually reveal a positive immune serology together with elevated immunoglobulins and abnormal liver histology. It is interesting that HT and AIH are rarely seen together although both have an autoimmune etiology. 14-year-old male who was being followed-up for vitiligo presented with symptoms of a swelling at the neck and fatigue. He was diagnosed with HT after the tests and the liver enzymes were found to be high. The patient was also diagnosed with AIH after tests revealed that the liver enzyme elevation had continued for longer than six months. The thyroid functions and liver enzymes returned to normal and the symptoms decreased after sodium L-thyroxine replacement together with steroid and azathioprine treatment. We present this case as we believe it is the first pediatric patient diagnosed with HT, AIH and vitiligo.

Experimental models of autoimmune inflammatory ocular diseases

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Fabio Gasparin

2012-04-01

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

Epigenetics of peripheral B cell differentiation and the antibody response

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Hong eZan

2015-12-01

Full Text Available Epigenetic modifications, such as histone post-translational modifications, DNA methylation, and alteration of gene expression by non-coding RNAs, including microRNAs (miRNAs and long non-coding RNAs (lncRNAs, are heritable changes that are independent from the genomic DNA sequence. These regulate gene activities and, therefore, cellular functions. Epigenetic modifications act in concert with transcription factors and play critical roles in B cell development and differentiation, thereby modulating antibody responses to foreign- and self-antigens. Upon antigen encounter by mature B cells in the periphery, alterations of these lymphocytes epigenetic landscape are induced by the same stimuli that drive the antibody response. Such alterations instruct B cells to undergo immunoglobulin class switch DNA recombination (CSR and somatic hypermutation (SHM, as well as differentiation to memory B cells or long-lived plasma cells for the immune memory. Inducible histone modifications, together with DNA methylation and miRNAs modulate the transcriptome, particularly the expression of activation-induced cytidine deaminase (AID, which is essential for CSR and SHM, and factors central to plasma cell differentiation, such as B lymphocyte-induced maturation protein-1 (Blimp-1. These inducible B cell-intrinsic epigenetic marks guide the maturation of antibody responses. Combinatorial histone modifications also function as histone codes to target CSR and, possibly, SHM machinery to the Ig loci by recruiting specific adaptors that can stabilize CSR/SHM factors. In addition, lncRNAs, such as recently reported lncRNA-CSR and an lncRNA generated through transcription of the S region that form G-quadruplex structures, are also important for CSR targeting. Epigenetic dysregulation in B cells, including the aberrant expression of non-coding RNAs and alterations of histone modifications and DNA methylation, can result in aberrant antibody responses to foreign antigens

Dissection of antibody specificities induced by yellow fever vaccination.

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Oksana Vratskikh

Full Text Available The live attenuated yellow fever (YF vaccine has an excellent record of efficacy and one dose provides long-lasting immunity, which in many cases may last a lifetime. Vaccination stimulates strong innate and adaptive immune responses, and neutralizing antibodies are considered to be the major effectors that correlate with protection from disease. Similar to other flaviviruses, such antibodies are primarily induced by the viral envelope protein E, which consists of three distinct domains (DI, II, and III and is presented at the surface of mature flavivirions in an icosahedral arrangement. In general, the dominance and individual variation of antibodies to different domains of viral surface proteins and their impact on neutralizing activity are aspects of humoral immunity that are not well understood. To gain insight into these phenomena, we established a platform of immunoassays using recombinant proteins and protein domains that allowed us to dissect and quantify fine specificities of the polyclonal antibody response after YF vaccination in a panel of 51 vaccinees as well as determine their contribution to virus neutralization by serum depletion analyses. Our data revealed a high degree of individual variation in antibody specificities present in post-vaccination sera and differences in the contribution of different antibody subsets to virus neutralization. Irrespective of individual variation, a substantial proportion of neutralizing activity appeared to be due to antibodies directed to complex quaternary epitopes displayed on the virion surface only but not on monomeric E. On the other hand, DIII-specific antibodies (presumed to have the highest neutralizing activity as well as broadly flavivirus cross-reactive antibodies were absent or present at very low titers. These data provide new information on the fine specificity as well as variability of antibody responses after YF vaccination that are consistent with a strong influence of individual

Atypical presentation of probable Creutzfeldt-Jakob disease associated with anti-Zic4 antibody: Literature review of neuronal antibodies in Creutzfeldt-Jakob disease.

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Salazar, Richard

2018-05-01

Sporadic Creutzfeldt-Jakob disease is a prion disease characterized by rapidly progressive dementia, ataxia and myoclonus. Atypical phenotype masquerading as stroke, movement disorders or autoimmune encephalitis have been described. Here, I report a probable case of sCJD with an atypical presentation associated with anti-Zic4 antibody and review the literature of neuronal antibodies in CJD. A 70 year-old gentleman is admitted with a 2-month history of recurrent stroke-like symptoms associated with behavioral disturbances, gait ataxia and rapidly progressive dementia. His initial examination demonstrated akinetic mutism, diffuse rigidity, dysautononia, and Cheyne-Stokes respiration. Over the following weeks his condition progressed to profound coma. A comprehensive infectious, metabolic, inflammatory and autoimmune work-up yielded negative results. Empiric immunosuppressive therapy ensued. He expired three months after symptoms onset. Autopsy was not performed. After his demise, prion tests came back abnormal for elevated 14-3-3 protein, total tau and positive RTQuIC. Later on, anti-Zic4 antibodies were found in serum. This case underscores the importance of a high index of suspicion for CJD even in case of atypical features or the concurrence of neuronal antibodies. Further larger prospective studies on the prevalence of these neuronal antibodies in CJD and the contribution of these autoantibodies to disease pathophysiology are necessary. Copyright © 2018 Elsevier B.V. All rights reserved.

Association of STAT4 polymorphisms with susceptibility to type-1 autoimmune hepatitis in the Japanese population.

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Migita, Kiyoshi; Nakamura, Minoru; Abiru, Seigo; Jiuchi, Yuka; Nagaoka, Shinya; Komori, Atsumasa; Hashimoto, Satoru; Bekki, Shigemune; Yamasaki, Kazumi; Komatsu, Tatsuji; Shimada, Masaaki; Kouno, Hiroshi; Hijioka, Taizo; Kohjima, Motoyuki; Nakamuta, Makoto; Kato, Michio; Yoshizawa, Kaname; Ohta, Hajime; Nakamura, Yoko; Takezaki, Eiichi; Nishimura, Hideo; Sato, Takeaki; Ario, Keisuke; Hirashima, Noboru; Oohara, Yukio; Naganuma, Atsushi; Muro, Toyokichi; Sakai, Hironori; Mita, Eiji; Sugi, Kazuhiro; Yamashita, Haruhiro; Makita, Fujio; Yatsuhashi, Hiroshi; Ishibashi, Hiromi; Yasunami, Michio

2013-01-01

Recent studies demonstrated an association of STAT4 polymorphisms with autoimmune diseases including systemic lupus erythematosus and rheumatoid arthritis, indicating multiple autoimmune diseases share common susceptibility genes. We therefore investigated the influence of STAT4 polymorphisms on the susceptibility and phenotype of type-1 autoimmune hepatitis in a Japanese National Hospital Organization (NHO) AIH multicenter cohort study. Genomic DNA from 460 individuals of Japanese origin including 230 patients with type-1 autoimmune hepatitis and 230 healthy controls was analyzed for two single nucleotide polymorphisms in the STAT4 gene (rs7574865, rs7582694). The STAT4 rs7574865T allele conferred risk for type-1 autoimmune hepatitis (OR = 1.61, 95% CI = 1.23-2.11; P = 0.001), and patients without accompanying autoimmune diseases exhibited an association with the rs7574865T allele (OR = 1.50, 95%CI = 1.13-1.99; P = 0.005). Detailed genotype-phenotype analysis of type-1 autoimmune hepatitis patients with (n = 44) or without liver cirrhosis (n = 186) demonstrated that rs7574865 was not associated with the development of liver cirrhosis and phenotype (biochemical data and the presence of auto-antibodies). This is the first study to show a positive association between a STAT4 polymorphism and type-1 autoimmune hepatitis, suggesting that autoimmune hepatitis shares a gene commonly associated with risk for other autoimmune diseases.

sirt1-null mice develop an autoimmune-like condition

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Sequeira, Jedon; Boily, Gino; Bazinet, Stephanie; Saliba, Sarah; He Xiaohong; Jardine, Karen; Kennedy, Christopher; Staines, William; Rousseaux, Colin; Mueller, Rudi; McBurney, Michael W.

2008-01-01

The sirt1 gene encodes a protein deacetylase with a broad spectrum of reported substrates. Mice carrying null alleles for sirt1 are viable on outbred genetic backgrounds so we have examined them in detail to identify the biological processes that are dependent on SIRT1. Sera from adult sirt1-null mice contain antibodies that react with nuclear antigens and immune complexes become deposited in the livers and kidneys of these animals. Some of the sirt1-null animals develop a disease resembling diabetes insipidus when they approach 2 years of age although the relationship to the autoimmunity remains unclear. We interpret these observations as consistent with a role for SIRT1 in sustaining normal immune function and in this way delaying the onset of autoimmune disease

Bone loss and aggravated autoimmune arthritis in HLA-DRβ1-bearing humanized mice following oral challenge with Porphyromonas gingivalis.

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Sandal, Indra; Karydis, Anastasios; Luo, Jiwen; Prislovsky, Amanda; Whittington, Karen B; Rosloniec, Edward F; Dong, Chen; Novack, Deborah V; Mydel, Piotr; Zheng, Song Guo; Radic, Marko Z; Brand, David D

2016-10-26

The linkage between periodontal disease and rheumatoid arthritis is well established. Commonalities among the two are that both are chronic inflammatory diseases characterized by bone loss, an association with the shared epitope susceptibility allele, and anti-citrullinated protein antibodies. To explore immune mechanisms that may connect the two seemingly disparate disorders, we measured host immune responses including T-cell phenotype and anti-citrullinated protein antibody production in human leukocyte antigen (HLA)-DR1 humanized C57BL/6 mice following exposure to the Gram-negative anaerobic periodontal disease pathogen Porphyromonas gingivalis. We measured autoimmune arthritis disease expression in mice exposed to P. gingivalis, and also in arthritis-resistant mice by flow cytometry and multiplex cytokine-linked and enzyme-linked immunosorbent assays. We also measured femoral bone density by microcomputed tomography and systemic cytokine production. Exposure of the gingiva of DR1 mice to P. gingivalis results in a transient increase in the percentage of Th17 cells, both in peripheral blood and cervical lymph nodes, a burst of systemic cytokine activity, a loss in femoral bone density, and the generation of anti-citrullinated protein antibodies. Importantly, these antibodies are not produced in response to P. gingivalis treatment of wild-type C57BL/6 mice, and P. gingivalis exposure triggered expression of arthritis in arthritis-resistant mice. Exposure of gingival tissues to P. gingivalis has systemic effects that can result in disease pathology in tissues that are spatially removed from the initial site of infection, providing evidence for systemic effects of this periodontal pathogen. The elicitation of anti-citrullinated protein antibodies in an HLA-DR1-restricted fashion by mice exposed to P. gingivalis provides support for the role of the shared epitope in both periodontal disease and rheumatoid arthritis. The ability of P. gingivalis to induce disease

Epigenetics of Autoantigens: New Opportunities for Therapy of Autoimmune Diseases

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Marko Radic

2013-01-01

Full Text Available The field of epigenetics requires that traditional divisions between scientific disciplines give way to cross-fertilization of concepts and ideas from different areas of investigation. Such is the case with research in autoimmunity. Recent discoveries of stimuli that induce autoimmunity reveal that epigenetic marks of autoantigens are recognized by autoreactive B and T cell receptors. Thus, insights into the initiation of autoimmunity, its prevention and therapy will arise from understanding the biochemistry, cell biology and microbiology of autoantigen epigenetics. Here, we highlight potential benefits from the inhibition of a histone modifying enzyme and the administration of a phosphorylated, spliceosome-derived peptide, in the treatment of autoimmunity.

CD8+ T-Cell Deficiency, Epstein-Barr Virus Infection, Vitamin D Deficiency, and Steps to Autoimmunity: A Unifying Hypothesis

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Michael P. Pender

2012-01-01

Full Text Available CD8+ T-cell deficiency is a feature of many chronic autoimmune diseases, including multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus, Sjögren's syndrome, systemic sclerosis, dermatomyositis, primary biliary cirrhosis, primary sclerosing cholangitis, ulcerative colitis, Crohn's disease, psoriasis, vitiligo, bullous pemphigoid, alopecia areata, idiopathic dilated cardiomyopathy, type 1 diabetes mellitus, Graves' disease, Hashimoto's thyroiditis, myasthenia gravis, IgA nephropathy, membranous nephropathy, and pernicious anaemia. It also occurs in healthy blood relatives of patients with autoimmune diseases, suggesting it is genetically determined. Here it is proposed that this CD8+ T-cell deficiency underlies the development of chronic autoimmune diseases by impairing CD8+ T-cell control of Epstein-Barr virus (EBV infection, with the result that EBV-infected autoreactive B cells accumulate in the target organ where they produce pathogenic autoantibodies and provide costimulatory survival signals to autoreactive T cells which would otherwise die in the target organ by activation-induced apoptosis. Autoimmunity is postulated to evolve in the following steps: (1 CD8+ T-cell deficiency, (2 primary EBV infection, (3 decreased CD8+ T-cell control of EBV, (4 increased EBV load and increased anti-EBV antibodies, (5 EBV infection in the target organ, (6 clonal expansion of EBV-infected autoreactive B cells in the target organ, (7 infiltration of autoreactive T cells into the target organ, and (8 development of ectopic lymphoid follicles in the target organ. It is also proposed that deprivation of sunlight and vitamin D at higher latitudes facilitates the development of autoimmune diseases by aggravating the CD8+ T-cell deficiency and thereby further impairing control of EBV. The hypothesis makes predictions which can be tested, including the prevention and successful treatment of chronic autoimmune diseases by controlling EBV infection.

Protective roles of natural IgM antibodies

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Caroline eGrönwall

2012-04-01

Full Text Available Antibodies are a vital part of the armentarium of the adaptive immune system for the fine-tuning of the recognition and response to foreign threats. However, in health there are some types of antibodies that instead recognize self-antigens for the enhancement of primitive innate functions. The repertoire of natural IgM antibodies is postulated to have been selected during immune evolution for their contributions to critical immunoregulatory and housekeeping properties. The clearance of dying cells is one of the most essential responsibilities of the immune system, which is essential to prevent uncontrolled inflammation and autoimmunity. In the murine immune system, natural IgM antibodies that recognize apoptotic cells have been shown to enhance the phagocytic clearance of dead and dying cells and to suppress innate immune signaling pathways. In the mouse, natural IgM are often the products of B-1 cell clones that arise during immune development without an absolute requirement for exogenous antigenic stimulation. In patients with systemic lupus erythemtosus, IgM autoantibodies, which bind to neo-epitopes on apoptotic cells, have been demonstrated to be present at significantly higher levels in patients with lower disease activity and with less severe organ damage. While certain specificities of IgM autoantibodies correlate with protection from lupus renal disease, others may convey protective properties from lupus-associated atherosclerotic cardiovascular disease. New unexpected insights into the functional roles of IgM antibodies are still emerging, especially regarding the functions of natural antibodies. Herein, we review recent progress in our understanding of the potential roles of natural IgM autoantibodies in the regulation of immune homeostasis and for protection from autoimmune and inflammatory diseases.

The relationship between the increased frequency of serum antineuronal antibodies and the severity of autism in children.

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Mostafa, Gehan Ahmed; Al-Ayadhi, Laila Yousef

2012-09-01

Autism may involve an autoimmune pathogenesis. Immunotherapy may have a role in autistic children who have brain auto-antibodies. This study aimed to investigate the frequency of serum antineuronal auto-antibodies, as indicators of the presence of autoimmunity to brain, in a group of autistic children. We are the first to measure the relationship between these antibodies and the degree of the severity of autism. Serum antineuronal antibodies were measured, by indirect immunofluorescence technique, in 80 autistic children, aged between 6 and 12 years, in comparison to 80 healthy-matched children. The severity of autism was assessed by using the Childhood Autism Rating Scale. Autistic children had significantly higher percent positivity of serum antineuronal antibodies (62.5%) than healthy controls (5%), P<0.001. The frequency of the positivity of serum antineuronal antibodies was significantly higher in children with severe autism (87.5%) than children with mild to moderate autism (25%), P<0.001. Similarly, the frequency of the positivity of these antibodies was significantly higher in female children with autism (90%) than male autistic children (53.3%), P=0.001. Serum antineuronal antibodies were found in a subgroup of autistic children and they were significantly correlated to the severity of autism. Thus, autism may be, in part, one of the pediatric autoimmune neuropsychiatric disorders. Further wide-scale studies are warranted to shed light on the etiopathogenic role of antineuronal antibodies in autism. The role of immunotherapy in autistic patients, who are seropositive for antineuronal antibodies, should also be studied. Copyright © 2011 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

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

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Lei Wang

2017-11-01

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

Protective effects of Punica granatum (pomegranate) peel extract on concanavalin A-induced autoimmune hepatitis in mice.

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Wang, Tingting; Men, Ruoting; Hu, Mingxing; Fan, Xiaoli; Yang, Xiaoxue; Huang, Xiaojun; Ye, Tinghong; Yang, Li

2018-04-01

Autoimmune hepatitis (AIH) is a chronic inflammatory liver disease of an unknown etiology, glucocorticoid therapy is currently recognized as an effective treatment for AIH, but conventional application and patient compliance are both hindered by its side effects. The exploration of the AIH pathogenesis and the searching for the new candidate drugs that exert potential activity and low toxicity are urgently needed. Pomegranate peel extract (PoPx) is a natural extract of Punica granatum and has been reported to have anti-inflammatory and antioxidative properties. The present study aimed to clarify the effect of PoPx on the concanavalin A (ConA)-induced autoimmune hepatitis in a mouse model that is well established at 12h after tail vein injection with a dose of 20 mg/kg of ConA. C57BL/6 female mice were pretreated with PoPx (250 mg/kg, once daily for 3 days) followed by a ConA challenge. Pretreatment with PoPx significantly alleviated ConA-induced liver injury by down-regulating the levels of plasma alanine transaminase (ALT), aspartate transaminase (AST) and cytokine, including TNF-α, interferon (IFN) -γ and interleukin (IL)-6. Moreover, liver hematoxylin and eosin (H&E) staining displayed a lighter inflammatory infiltration around the portal area in the PoPx-pretreated mice. In addition, the flow cytometry (FCM) data showed that the immune response in the liver was died down in the PoPx-pretreated condition. Specially, pretreatment with PoPx reduced the infiltration of activated CD4 + and CD8 + T cells in the liver. Taken together, these findings contributed to a better understanding of the actions of PoPx against acute AIH and indicated that PoPx might be a potential compound in treating T cell-mediated autoimmune liver injury. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Hyperthyroidism from autoimmune thyroiditis in a man with type 1 diabetes mellitus: a case report

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Hirsch Irl B

2011-07-01

Full Text Available Abstract Introduction The presentation, diagnosis, clinical course and treatment of a man with hyperthyroidism secondary to autoimmune thyroiditis in the setting of type 1 diabetes mellitus has not previously been described. Case presentation A 32-year-old European-American man with an eight-year history of type 1 diabetes mellitus presented with an unintentional 22-pound weight loss but an otherwise normal physical examination. Laboratory studies revealed a suppressed thyroid-stimulating hormone concentration and an elevated thyroxine level, which are consistent with hyperthyroidism. His anti-thyroid peroxidase antibodies were positive, and his thyroid-stimulating immunoglobulin test was negative. Uptake of radioactive iodine by scanning was 0.5% at 24 hours. The patient was diagnosed with autoimmune thyroiditis. Six weeks following his initial presentation he became clinically and biochemically hypothyroid and was treated with thyroxine. Conclusion This report demonstrates that autoimmune thyroiditis presenting as hyperthyroidism can occur in a man with type 1 diabetes mellitus. Autoimmune thyroiditis may be an isolated manifestation of autoimmunity or may be part of an autoimmune polyglandular syndrome. Among patients with type 1 diabetes mellitus who present with hyperthyroidism, Graves' disease and other forms of hyperthyroidism need to be excluded as autoimmune thyroiditis can progress quickly to hypothyroidism, requiring thyroid hormone replacement therapy.

Depigmented Allergoids Reveal New Epitopes with Capacity to Induce IgG Blocking Antibodies

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L?pez-Matas, M. Angeles; Gallego, Mayte; Iraola, V?ctor; Robinson, Douglas; Carn?s, Jer?nimo