Journal of Autoimmune Diseases - Most accessed articles

Immunogenetics of Hashimoto's thyroiditis

Dimitry Chistiakov — 2005-03-11T00:00:00Z

Hashimoto's thyroiditis (HT) is an organ-specific T-cell mediated disease. It is a complex disease, with a strong genetic component. To date, significant progress has been made towards the identification and functional characterization of HT susceptibility genes. In this review, we will summarize the recent advances in our understanding of the genetic input to the pathogenesis of HT.

The revised international autoimmune hepatitis score in chronic liver diseases including autoimmune hepatitis/overlap syndromes and autoimmune hepatitis with concurrent other liver disorders

Panagiotis Papamichalis — 2007-06-29T00:00:00Z

Background: We conducted a study in order to determine the usefulness and diagnostic value of International Autoimmune Hepatitis Group (IAHG) score in non-autoimmune hepatitis (AIH) hepatic disorders as well as in AIH/overlap syndromes and in cases with coexistence of AIH and other liver diseases. Methods: We applied the IAHG score in 423 patients with liver diseases excluding patients with AIH, AIH/overlap syndromes and AIH with concurrent other liver disease namely, patients with chronic hepatitis B (n = 109), chronic hepatitis C (n = 95), chronic hepatitis D (n = 4), alchoholic liver disease (n = 28), non-alcoholic fatty liver disease (n = 55), autoimmune cholestatic liver diseases (n = 77), liver disorders of undefined origin (n = 32) and with miscellaneous hepatic disorders (n = 23). 24 patients with AIH associated with any kind of liver disorder including 10 patients with AIH/overlap syndromes and 14 AIH with concurrent other liver disease were also investigated. 43 patients with AIH consisted the control group. Results: The specificity of the score was 98.1% while the sensitivity in unmasking AIH in patients with either AIH/overlap syndromes or AIH with concurrent other liver diseases was only 50% and 78.6%. In the binary logistic regression model, the presence of other autoimmune diseases (p < 0.001), the total histological score (p < 0.001) and positivity for autoantibodies (p < 0.05) were identified as independent predictors for the presnce of AIH/ovea syndromes o AI with concurren other liver diseass. Conclusion: The IAHG scoring system has very good specificity for excluding AIH in patients with chronic liver diseases but not that sensitivity in order to unmask AIH/overlap syndromes or AIH with concurrent other liver diseases. The presence of other autoimmune diseases or autoantibody markers in the absence of hepatitis viral markers should alarm physicians for the possible presence of AIH either as "pure" AIH or in association with other liver disorders (AIH/overlap syndromes or AIH with concurrent other liver diseases). Under these conditions, liver histology seems essential and it must always be included in the work up of hepatic patients.

Co-occurrence of autoimmune thyroid disease in a multiple sclerosis cohort

Scott Sloka — 2005-11-09T00:00:00Z

Background: Multiple sclerosis (MS), Hashimoto's disease and Graves' disease are autoimmune diseases that may share similar pathogenic mechanisms. The co-occurrence rates and demographic characteristics of Graves' disease and Hashimoto's disease (HT) in our MS population are compared with the general population. Methods: The prevalence of thyroid disease in our MS patients was determined by chart review and survey. Previous diagnosis of thyroid disease, age at diagnosis, treatment used, and about the use of disease modifying medications used to treat their MS were asked. Chart reviews were used to estimate the population prevalence of Graves' disease and Hashimoto's disease and to estimate the demographics of patients with thyroid disease. Results: A significant co-occurrence of Graves' disease with MS (p = 0.002), and a non-significant co-occurrence of Hashimoto's disease were noted (p = 0.097). No difference in the age of onset or gender of thyroid disease in MS patients compared to the general population was found. Conclusion: There is a significant co-occurrence in patients with MS and Graves' disease, and a trend to co-occurrence in patients with MS and Hashimoto's disease. There are no differences in the demographics of patients with thyroid disease in our MS patients compared to the general population.

Autoantibodies and autoantigens in autoimmune hepatitis: important tools in clinical practice and to study pathogenesis of the disease

Kalliopi Zachou — 2004-10-15T00:00:00Z

Autoimmune hepatitis (AIH) is a chronic necroinflammatory disease of the liver characterized by hypergammaglobulinemia, characteristic autoantibodies, association with HLA DR3 or DR4 and a favorable response to immunosuppressive treatment. The etiology is unknown. The detection of non-organ and liver-related autoantibodies remains the hallmark for the diagnosis of the disease in the absence of viral, metabolic, genetic, and toxic etiology of chronic hepatitis or hepatic injury. The current classification of AIH and the several autoantibodies/target-autoantigens found in this disease are reported. Current aspects on the significance of these markers in the differential diagnosis and the study of pathogenesis of AIH are also stated. AIH is subdivided into two major types; AIH type 1 (AIH-1) and type 2 (AIH-2). AIH-1 is characterized by the detection of smooth muscle autoantibodies (SMA) and/or antinuclear antibodies (ANA). Determination of antineutrophil cytoplasmic autoantibodies (ANCA), antibodies against the asialoglycoprotein receptor (anti-ASGP-R) and antibodies against to soluble liver antigens or liver-pancreas (anti-SLA/LP) may be useful for the identification of patients who are seronegative for ANA/SMA. AIH-2 is characterized by the presence of specific autoantibodies against liver and kidney microsomal antigens (anti-LKM type 1 or infrequently anti-LKM type 3) and/or autoantibodies against liver cytosol 1 antigen (anti-LC1). Anti-LKM-1 and anti-LKM-3 autoantibodies are also detected in some patients with chronic hepatitis C (HCV) and chronic hepatitis D (HDV). Cytochrome P450 2D6 (CYP2D6) has been documented as the major target-autoantigen of anti-LKM-1 autoantibodies in both AIH-2 and HCV infection. Recent convincing data demonstrated the expression of CYP2D6 on the surface of hepatocytes suggesting a pathogenetic role of anti-LKM-1 autoantibodies for the liver damage. Family 1 of UDP-glycuronosyltransferases has been identified as the target-autoantigen of anti-LKM-3. For these reasons the distinction between AIH and chronic viral hepatitis (especially of HCV) is of particular importance. Recently, the molecular target of anti-SLA/LP and anti-LC1 autoantibodies were identified as a 50 kDa UGA-suppressor tRNA-associated protein and a liver specific enzyme, the formiminotransferase cyclodeaminase, respectively. Anti-ASGP-R and anti-LC1 autoantibodies appear to correlate closely with disease severity and response to treatment suggesting a pathogenetic role of these autoantibodies for the hepatocellular injury. In general however, autoantibodies should not be used to monitor treatment, predict AIH activity or outcome. Finally, the current aspects on a specific form of AIH that may develop in some patients with a rare genetic syndrome, the autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome (APECED) are also given. Autoantibodies against liver microsomes (anti-LM) are the specific autoantibodies detected in AIH as a disease component of APECED but also in cases of dihydralazine-induced hepatitis. Cytochrome P450 1A2 has been identified as the target-autoantigen of anti-LM autoantibodies in both APECED-related AIH and dihydralazine-induced hepatitis. The latter may indicate that similar autoimmune pathogenetic mechanisms can lead to liver injury in susceptible individuals irrespective of the primary defect. Characterization of the autoantigen-autoantibody repertoire continues to be an attractive and important tool to get access to the correct diagnosis and to gain insight into the as yet unresolved mystery of how hepatic tolerance is given up and AIH ensues.

Controversies in the management of the antiphospholipid syndrome: can we ever stop warfarin?

Ana Fonseca — 2008-11-11T00:00:00Z

Patients with antiphospholipid syndrome are at increased risk for recurrent arterial and venous thrombosis and therefore benefit from long term warfarin therapy. The optimal duration of warfarin therapy after a first venous thromboembolic event is however a matter of some controversy and many questions remain unanswered. After reviewing and analysing the available evidence, we discuss some common scenarios in everyday clinical practice where treatment decisions are difficult.

Virus-mediated autoimmunity in Multiple Sclerosis

Nikolaos Grigoriadis — 2006-02-19T00:00:00Z

Epidemiological data suggest the notion that in Multiple Sclerosis (MS) is an acquired autoimmune disease and the cause may be an environmental factor(s), probably infectious, in genetically susceptible individuals. Several cases of viral induced demyelinatimg encephalomyelitis in human beings and in experimental models as well as the presence of IgG oligoclonal bands in the cerebrospinal fluid indicate that the infectious factor may be viral. However, the absence of a specific virus identification in MS central nervous system may hardly support this notion. On the other hand, the partial response of patients with MS to immunosuppressive and immunomodulatory therapy support the evidence of an autoimmune etiology for MS. However, the autoimmune hypothesis shares the same criticism with the infectious one in that no autoantigen(s) specific to and causative for MS has ever been identified. Nevertheless, the absence of identifiable infectious agent, especially viral does not rule out its presence at a certain time – point and the concomitant long term triggering of an autoimmune cascade of events thereafter. Several concepts have emerged in an attempt to explain the autoimmune mechanisms and ongoing neurodegeneration in MS on the basis of the infectious – viral hypothesis.

Cytochrome-P450 enzymes and autoimmunity: expansion of the relationship and introduction of free radicals as the link

M.r. Namazi — 2009-06-25T00:00:00Z

The Cytochrome-P-450 enzymes (CYP) are among the most important xenobiotic-metabolizing enzymes, which produce reactive oxygen species (ROS) as the result of metabolizing xenobiotics.ROS are believed to play important roles in the pathophysiology of autoimmune diseases. ROS can alter the structure of cellular antigens to produce a "neo-antigen" which could mount an autoimmune response against the original antigen through molecular mimicry. ROS are involved in apoptosis, activation of antigen presenting cells and initiation or amplification of diverse immunologic reactions.Taking all these facts together, it could be speculated that CYP may be involved in the initiation and/or amplification of autoimmune phenomena.

Prevalence of antibodies to Ro-52 in a serologically defined population of patients with systemic sclerosis

Jennifer Parker — 2009-03-06T00:00:00Z

Background: Antibodies against Ro-52 have been described in patients with a broad spectrum of autoimmune disease, most commonly in association with anti-Ro-60 in systemic lupus erythematosus and Sjogrens syndrome. However, in inflammatory myositis anti-Ro-52 is frequently present without anti-Ro-60 and is closely linked to the presence of aminoacyl-tRNA synthetase (aats) antibodies. To date there have been no comprehensive reports on the frequency of anti-Ro-52 in systemic sclerosis (SSc), a disease characterised by hallmark autoantibodies that occur in non-overlapping subsets. Clinically, each antibody-defined group has a distinct pattern of organ involvement, some featuring myositis.ObjectivesTo determine the frequency of anti-Ro-52 in serologically defined groups of SSc patients and to investigate a possible link with myositis-associated autoantibodies. Methods: Serum samples from 1010 patients with SSc and 55 and 32 patients with anti-aats and anti-Ku respectively were tested for the presence of anti-Ro-52 using a commercial ELISA. Results: The prevalence of anti-Ro-52 was 15–38% in nine of the eleven sub-groups. There were no significant differences in mean anti-Ro-52 levels in these groups with the exception of that defined by the presence of anti-U1-RNP. In the remaining groups defined by anti-Ro-60 and anti-aats, anti-Ro-52 was present in 92% and 100% respectively. In sera from non-SSc patients with anti-aats, anti-Ro-52 was detected in 64%. Conclusion: Anti-Ro-52 is present throughout the SSc population. It is neither more prevalent in the myositis-associated antibody groups nor does it segregate with any other major SSc-specific autoantibodies. The co-existence of anti-Ro-52 with both anti-Ro-60 and anti-aats is confirmed.

Antiphospholipid (Hughes) syndrome: beyond pregnancy morbidity and thrombosis

Maria Mialdea — 2009-05-19T00:00:00Z

The antiphospholipid syndrome is an autoimmune disease characterised by recurrent arterial or venous thrombosis, pregnancy morbidity and the persistence of positive antiphospholipid antibodies. Many other clinical manifestations may occur including heart valve disease, livedo reticularis, thrombocytopenia and neurological manifestations such as migraine and seizures. We review a number of other manfestations including stenotic lesions, coronary artery disease and accelerated atherosclerosis, skeletal disorders and the concept of seronegative antiphospholipid syndrome.

Are classification criteria for vasculitis useful in clinical practice? Observations and lessons from Colombia

Paul Mendez Patarroyo — 2009-02-27T00:00:00Z

IntroductionIdiopathic systemic vasculitis represents a group of clinical entities having non-specific etiology with the common characteristic of acute or chronic inflammatory compromise of the small and large vessels walls, associated with fibrinoid necrosis.ObjectivesTo describe the most common inflammatory vascular diseases in a long historical cohort of patients from San Juan de Dios Hospital located in Bogota, Colombia using two different systems and a clinical histopathological correlation format, and to make a comparison between them. Methods: We reviewed all previously ascertained cases of vasculitis confirmed by biopsy processed between 1953 and 1990, and systematically collected data on all new cases of vasculitis from 1991 to 1997 at the Hospital San Juan de Dios (Bogota – Colombia). The cases were classified in accordance with the Chapel Hill Consensus criteria, and the system proposed by J.T. Lie. Results: Of 165,556 biopsy tissue specimens obtained during this period from our hospital, 0.18% had vasculitis, perivasculitis or vasculopathy. These included 304 histopathological biopsies from 292 patients. Cutaneous leukocytoclastic vasculitis (64 histological specimens) was the most frequently encountered type of "primary" vasculitis followed by thromboangiitis obliterans (38 specimens), and polyarteritis nodosa (24 specimens). Vasculitis associated with connective tissue diseases (33 specimens) and infection (20 specimens) were the main forms of secondary vasculitis, a category that was omitted from the Chapel Hill consensus report. We found that 65.8% of our histopathological diagnoses could not be classified according to the Chapel Hill classification, and 35.2% could not be classified according to the classification of Lie. Only 8.9% of cases remained unclassified by our system after clinical and histological correlation. Conclusion: Current vasculitis classification schemes are designed for classification, rather that diagnosis of disease and do not adequately address some common forms of inflammatory vascular diseases, including those of infectious etiology and unusual etiology seen in clinical practice. Based on our clinical experience, we suggest a classification outline which practitioners can use which emphasizes correlation of the clinical picture to the histopathology findings for diagnosis and therapy, which may promote better clinical practice and standardization for clinical trials.