Liver transplantation in autoimmune liver diseases

Liver transplantation is indicated for terminal phases of autoimmune hepatitis, primary biliary cirrhosis and primary sclerosing cholangitis. Indications for transplantation in autoimmune liver diseases are similar to those used in other acute or chronic liver diseases. Therapeutic advances have reduced the need for transplantation for autoimmune hepatitis and primary biliary cirrhosis but not for primary sclerosing cholangitis. Overall, outcomes of transplantation for autoimmune liver diseases are excellent. However, recurrence of autoimmune liver diseases in the allograft has variable impacts on graft and patient survivals. Treatment of recurrent diseases requires changes in immunosuppression or addition of ursodeoxycholic acid. Among autoimmune liver diseases, only autoimmune hepatitis occurs de novo in recipients transplanted for other diseases. Patients transplanted for autoimmune hepatitis or primary sclerosing cholangitis are at risk for reactivation or de novo onset of ulcerative colitis. Better understanding of the pathogenesis of recurrent autoimmune liver diseases is needed to devise effective means of prevention and treatment.     

Sj?gren's syndrome in relation to other autoimmune diseases.

Autoimmune diseases can be divided into primary autoimmune diseases, in which the immune system is over-reactive, leading to an oligoclonal B cell stimulation, and secondary autoimmune diseases, in which the immune system is completely normal but some autoantigens are slightly altered, and are thus considered to be foreign. Sj?gren's syndrome probably has characteristics of both types of autoimmune disease. The primary autoimmune diseases can be divided into organ-specific autoimmune diseases like thyroiditis, gastritis and adrenalitis, and generalised autoimmune diseases, such as systemic lupus erythematosus (SLE) and rheumatoid arthritis. Sj?gren's syndrome has characteristics of both types of primary autoimmune disease, and therefore occupies a central position among the other autoimmune diseases. The focal position of the disease in the present issue of The Netherlands Journal of Medicine is because of the symposium organized for the occasion of the fifth anniversary of the "Dutch Association of Patients with Sj?gren's Syndrome", of which this issue is the report.     

Polyautoimmunity in rheumatological conditions

Co‐occurrence of autoimmune diseases (ADs) within an individual is postulated to be a frequent phenomenon in rheumatic diseases. Similar clinical signs and symptoms, pathophysiological mechanisms, genetic factors within autoimmune diseases and aggregation of diverse ADs within families sustain the theory of shared pathogenesis of several ADs (autoimmune tautology). Polyautoimmunity (PA) is defined as the presence of more than one autoimmune disease in a single patient. When three or more autoimmune diseases coexist, this condition is called multiple autoimmune syndrome (MAS). This analysis summarizes an estimated prevalence of PA in the most common rheumatic diseases, the presumable risk factors for PA and influence of concomitant diseases on the course of disease.     

Autoimmunity, infertility and assisted reproductive technologies

Despite strongly held opinions, a trustworthy scientific basis for most statements about autoimmunity, autoimmune diseases and assisted reproductive technologies (ART) does not exist. It is not likely that autoimmunity causes infertility, nor that patients with autoimmune diseases are unusually infertile. When carefully monitored in selected patients, ART does not appear to harm patients who have pre-existing autoimmune diseases, but the ovarian hyperstimulation syndrome and multiple gestation pregnancies impart independent risks. Stable autoimmune diseases without major organ damage probably do not affect the outcomes of ART pregnancies. Children born of ART pregnancies are apparently normal at birth, whether or not the genetic or birth mother has autoimmune disease, but long-term follow-up is not available. Male fertility is probably not altered by autoimmune disease. Fiscal, ethical and moral issues related to ART in patients with autoimmune diseases are beyond the scope of this discussion but remain important.     

血吸虫感染调节自身免疫性疾病和过敏性疾病的研究进展

血吸虫感染可下调Th1细胞介导的自身免疫性疾病和Th2细胞介导的过敏性疾病。新近研究发现,致病性CD4+T细胞亚群、Th17细胞也参与多种自身免疫等病理性疾病的发病,血吸虫感染也可下调自身免疫性疾病中的Th17细胞反应。本文综述了血吸虫感染下调自身免疫或过敏性疾病中Th1、Th2、Th17细胞的反应及其作用机制的研究进展。     

Autoimmune disease aggregation in families with primary Sjögren's syndrome

OBJECTIVE: Diverse autoimmune diseases may coexist in the same individual and in families, implying a common etiology. We examined the aggregation of autoimmune diseases among first-degree relatives (FDR) of patients with primary Sj?gren's syndrome (pSS). METHODS: This was a population-based case-control family study in which 101 families of women classified as having pSS according to the revised American-European criteria and 124 families of matched controls without autoimmune disease were enrolled to investigate the presence of autoimmune diseases. We performed a genetic analysis that included familial correlation and recurrent risk ratios. RESULTS: In family cases, 38% had at least one FDR with an autoimmune disease, versus 22% in control families [odds ratio (OR) 2.2, 95% confidence interval (CI) 1.2-3.9, p = 0.01]. An autoimmune disease was registered for 7.3% of 876 patients' FDR as compared with 3.85% of 857 controls' FDR (OR 1.97, 95% CI 1.28-3.03, p = 0.002). The most frequent autoimmune diseases registered among the pSS patients' FDR were autoimmune thyroid disease (AITD), systemic lupus erythematosus, and rheumatoid arthritis, which disclosed aggregation. The proband phenotype (i.e., pSS) was correlated with AITD, systemic sclerosis, and all autoimmune diseases when considered together as a trait. Maternal transmission of the autoimmunity trait was observed in cases but not in controls. CONCLUSION: Our results indicate that autoimmune diseases cluster within families of patients with pSS. This familial aggregation of autoimmune diseases adds further evidence that clinically different autoimmune phenotypes might share common susceptibility gene variants, which acting in epistatic pleitropy may represent risk factors for autoimmunity.     

The environment and antiphospholipid syndrome

The etiology of autoimmune diseases is multifactorial. The degree to which genetic and environmental factors influence susceptibility to autoimmune diseases is poorly defined. It is believed that versatile clinical presentations of autoimmune diseases stem from various combinations of the genetic and environmental factors. One of the newly diagnosed autoimmune diseases is the antiphospholipid syndrome (APS). APS is characterized by vascular thrombosis, and/or pregnancy morbidity associated with anticardiolipin (aCL), anti-beta2-glycoprotein-I (anti-beta2GPI) and lupus anticoagulant (LAC).     

The management of autoimmunity in patients with cholestatic liver diseases

Cholestatic liver diseases are rare diseases that often lead to cirrhosis and its consequent complications. In addition to liver-related morbidity, patients with cholestatic liver diseases often suffer from autoimmune diseases that affect several organs and tissues. The robust and efficient data collection and collaboration between hepatologists and rheumatologists have led to significant advancements in understanding the relationship between the cholestatic liver diseases and associated autoimmune diseases. In this paper, we discuss the cholestatic liver diseases (primary biliary cirrhosis, primary sclerosing cholangitis and immunoglobulin G4 associated cholangitis) and associated autoimmune diseases.     

雌激素与自身免疫性疾病

自身免疫性疾病的发病存在明显的性别差异，女性的发病率常高于男性，文章就雌激素在自身免疫性疾病发生机制中的作用，特别是近年来雌激素对免疫细胞信号，细胞分化，下丘脑－垂体－肾上腺（HPA）轴的激活，自身免疫性疾病的发生和缓解等方面的研究作一介绍，进一步探讨雌激素调节异常对自身免疫性疾病发生的影响。     

Low prevalence of hepatitis B virus infection in patients with autoimmune diseases in a Chinese patient population

Hepatitis B is a very common communicable disease in China but the prevalence of hepatitis B virus (HBV) infection in patients with autoimmune diseases is unknown. We retrospectively investigated the prevalence of autoimmune diseases in patients with HBV infection. The medical records of 4060 patients with autoimmune or nonautoimmune diseases were reviewed. A positive test result for hepatitis B surface antigen (HBsAg) was used to indicate the presence of HBV infection. Autoimmune diseases included autoimmune hepatitis, primary biliary cirrhosis, systemic lupus erythematosus and ulcerative colitis. Nonautoimmune conditions included inguinal hernia, appendicitis and pregnant or postpartum women. The proportion of autoimmune disease patients who were HBsAg positive (2.24%) was significantly lower than that of nonautoimmune disease patients who were HBsAg positive (4.58%; P = 0.0014). Regarding hepatic autoimmune diseases, the positivity rates for HBsAg in autoimmune hepatitis patients (0.83%) and primary biliary cirrhosis patients (1.02%) were both significantly lower than in nonautoimmune patients (4.58%; P = 0.006 and 0.004, respectively). Patients with hepatic autoimmune disease were significantly less likely to be HBsAg positive (0.93%) than patients with non‐hepatic autoimmune disease (3.99%; P = 0.002). Patients with autoimmune diseases, especially those with hepatic autoimmune disease, may more efficiently clear HBV than patients with nonautoimmune diseases.     

Familial clustering of autoimmune diseases in patients with dilated cardiomyopathy

In this study, we examined the hypothesis that dilated cardiomyopathy (DCM) shares genetic risk factors with other diseases of presumed autoimmune etiology, and, therefore, the same multiple genes in combination with environmental factors lead to numerous different autoimmune diseases. In accordance with this hypothesis, we showed an increased prevalence of autoimmune diseases in first-degree relatives of patients with DCM. Also, T-cell activation, as reflected in high levels of the soluble interleukin-2 receptor, appears to identify patients with DCM with a clustering of autoimmune diseases.     

Endomyocardial substrate of ventricular arrhythmias in patients with autoimmune rheumatic diseases

Introduction

Delayed enhancement-magnetic resonance imaging (DE-MRI) has demonstrated that nonischemic cardiomyopathy is mainly characterized by intramural or epicardial fibrosis whereas global endomyocardial fibrosis suggests cardiac involvement in autoimmune rheumatic diseases or amyloidosis. Conduction disorders and sudden cardiac death are important manifestations of autoimmune rheumatic diseases with cardiac involvement but the substrates of ventricular arrhythmias in autoimmune rheumatic diseases have not been fully elucidated.

Methods and Results

20 patients with autoimmune rheumatic diseases presenting with ventricular tachycardia (VT) (n = 11) or frequent ventricular extrasystoles (n = 9) underwent DE-MRI and/or endocardial electroanatomical mapping of the left ventricle (LV). Ten patients with autoimmune rheumatic diseases underwent VT ablation. Global endomyocardial fibrosis without myocardial thickening and unrelated to coronary territories was detected by DE-MRI or electroanatomical voltage mapping in 9 of 20 patients with autoimmune rheumatic diseases. In the other patients with autoimmune rheumatic diseases, limited regions of predominantly epicardial (n = 4) and intramyocardial (n = 5) fibrosis or only minimal fibrosis (n = 2) were found using DE-MRI. Endocardial low-amplitude diastolic potentials and pre-systolic Purkinje or fascicular potentials, mostly within fibrotic areas, were identified as the targets of successful VT ablation in 7 of 10 patients with autoimmune rheumatic diseases.

Conclusion

Global endomyocardial fibrosis can be a tool to diagnose severe cardiac involvement in autoimmune rheumatic diseases and may serve as the substrate of ventricular arrhythmias in a substantial part of patients.     

Use of proteomics in analysis of autoimmune diseases

Autoimmune diseases are common by diseases characterized by disorders of immune responses and autoimmune impairment involving multiple tissues, organs and systems. The autoantigens (Ags)/autoantibodies (Abs) are not only hallmarks but also involved in pathogenesis of autoimmune diseases. In recent years, proteomics technologies have been used and demonstrated effective in searching new Ags/Abs as well as disease biomarkers in autoimmune diseases.     

Celiac disease and autoimmune diseases or systemic disease. Six cases and a review of the literature

BACKGROUND: Celiac disease is an autoimmune disorder which may be associated with another autoimmune or systemic disease. OBJECTIVE: To determine the links between autoimmune diseases and celiac disease. PATIENTS AND METHODS: Among 31 patients with a celiac disease, we selected those who had another autoimmune or systemic disease. RESULTS: We report 6 patients with such disease association: 3 with autoimmune thyroiditis including one also with Grave's disease, 2 with systemic lupus erythematosus including one also with insulin-dependent diabetes mellitus, and 1 with temporal arteritis. CONCLUSION: The link between celiac disease and autoimmune thyroiditis or insulin-dependent diabetes mellitus seems to be real but many discrepancies are observed for the other autoimmune diseases. After a literature review, we suggest a summary of effective associations between celiac disease and autoimmune or systemic diseases.     

Spectrum and frequency of autoimmune derangements in lymphoproliferative disorders: analysis of 637 cases and comparison with myeloproliferative diseases

The records of 637 patients with lymphoproliferative disorders and 346 patients with myeloproliferative disorders were retrospectively analysed for the presence of additional autoimmune derangements. The frequency of autoimmune perturbations in lymphoproliferative diseases (51 cases; 8.0%) was significantly higher than in myeloproliferative diseases (six cases; 1.7%; P less than 0.0001). Rheumatic disorders, autoallergic haematological manifestations and other organ-specific autoimmune derangements were responsible for about one third each of the observed disturbances. Autoimmune diseases which preceded the onset of malignancy, occurred in lymphoproliferative and myeloproliferative disorders with a comparable frequency without significant differences between individual subgroups of lymphoproliferative diseases. In contrast, autoimmune complications developing in the course of the neoplastic disease were significantly more frequent in lymphoproliferative (4.9%) than in myeloproliferative disorders (0.3%; P less than 0.0005). Here marked differences were observed between individual lymphoma entities, the rate of concomitant autoimmune derangements ranging from zero to over 15%. With the exception of centroblastic-centrocytic lymphoma which in no case was associated with secondary autoimmune complications, the proportion of patients with autoimmune perturbations increased with improving prognosis of the lymphoproliferative diseases. Possible pathogenetic mechanisms involved in the manifestation of autoimmune complications in malignant lymphomas are discussed.     

Acute myeloid leukemia developing in patients with autoimmune diseases

Therapy-related acute myeloid leukemia is an unfortunate complication of cancer treatment, particularly for patients with highly curable primary malignancies and favorable life expectancy. The risk of developing therapy-related acute myeloid leukemia also applies to patients with non-malignant conditions, such as autoimmune diseases treated with cytotoxic and/or immunosuppressive agents. There is considerable evidence to suggest that there is an increased occurrence of hematologic malignancies in patients with autoimmune diseases compared to the general population, with a further increase in risk after exposure to cytotoxic therapies. Unfortunately, studies have failed to reveal a clear correlation between leukemia development and exposure to individual agents used for the treatment of autoimmune diseases. Given the dismal outcome of secondary acute myeloid leukemia and the wide range of available agents for treatment of autoimmune diseases, an increased awareness of this risk and further investigation into the pathogenetic mechanisms of acute leukemia in autoimmune disease patients are warranted. This article will review the data available on the development of acute myeloid leukemia in patients with autoimmune diseases. Possible leukemogeneic mechanisms in these patients, as well as evidence supporting the association of their primary immunosuppressive status and their exposure to specific therapies, will also be reviewed. This review also supports the idea that it may be misleading to label leukemias that develop in patients with autoimmune diseases who are exposed to cytotoxic agents as 'therapy-related leukemias'. A better understanding of the molecular defects in autoimmune disease patients who develop acute leukemia will lead to a better understanding of the association between these two diseases entities.     

Autoimmune diseases in a Danish cohort of 4,866 carriers of constitutional structural chromosomal rearrangements

OBJECTIVE: Constitutional structural chromosomal rearrangements (CSCRs) have facilitated the identification of genes associated with early-onset monogenic disorders and, more recently, genes associated with common and late-onset disorders. In an attempt to find genetic clues to their etiologies, we studied the risk of autoimmune diseases in a Danish cohort of CSCR carriers. METHODS: We followed up 4,866 CSCR carriers over 71,230 person-years (1980 through 2004) for autoimmune diseases recorded in the Danish Hospital Discharge Register. Standardized incidence ratios (SIRs) and 95% confidence intervals (95% CIs) served as measures of the relative risk. To identify possible candidate loci for autoimmune diseases, the reported chromosomal breakpoints and deletions in CSCR carriers who developed autoimmune diseases were compared with previously suggested loci for these diseases. RESULTS: The overall risk of any autoimmune disease among CSCR carriers was inconspicuous (SIR 1.2 [95% CI 0.95-1.5]; n = 74 cases observed versus 61.3 expected), but carriers of rearrangements involving chromosomes 2, 19, and 21 were at significantly increased risk. For the specific autoimmune diseases studied, cohort members were at significantly increased risk of Dupuytren's contracture, pernicious anemia, and juvenile rheumatoid arthritis (JRA). Sixteen carriers who developed an autoimmune disease had a chromosomal breakpoint or deletion coinciding with a previously suggested locus, including deletions 18p11, 18q22, and 22q11 associated with JRA. CONCLUSION: CSCR carriers do not have a generalized predisposition to autoimmune diseases. However, we confirmed a number of reported susceptibility loci for JRA, and we suggest new susceptibility loci on chromosomes 5 and 11 for Dupuytren's contracture, and 19p13 as a possible shared susceptibility locus for a range of autoimmune diseases.     

Treatment of autoimmune diseases by inhibition of T-cell costimulation

Advances in our understanding of the mechanisms involved in immune activation and immune tolerance have laid the foundation for the development of new strategies for treating autoimmune diseases. In particular, the dissection of the two-signal process of T-cell activation has identified distinct targets that may provide a means of blocking pathological autoimmune responses without causing sustained blockade of protective immune responses. These strategies have shown great promise in animal models for autoimmune diseases, and they are currently the focus of clinical investigation in several autoimmune diseases of humans.     

Generalized Vitiligo Associated Autoimmune Diseases in Japanese Patients Their Families

BackgroundGeneralized vitiligo is an acquired disorder in which depigmented macules result from the autoimmune loss of melanocytes from the involved regions of skin. Generalized vitiligo is frequently associated with other autoimmune diseases, particularly autoimmune thyroid diseases (Hashimoto's thyroiditis and Graves' disease), rheumatoid arthritis, adult-onset type 1 diabetes mellitus, psoriasis, pernicious anemia, systemic lupus erythematosus, and Addison's disease.MethodsOne hundred and thirty-three Japanese patients with generalized vitiligo were enrolled in this study to investigate the occurrence of autoimmune diseases in Japanese patients with generalized vitiligo and their families.ResultsTwenty-seven of the patients with generalized vitiligo (20.3%) had autoimmune diseases, particularly autoimmune thyroid disease (sixteen patients, 12%) and alopecia areata (seven patients, 5.3%). Thirty-five patients (26.3%) had a family history of generalized vitiligo and/or other autoimmune diseases. Familial generalized vitiligo was present in fifteen (11.3%), including four families with members affected by autoimmune disorders. Twenty (15.0%) had one or more family members with only autoimmune disorders.ConclusionsAmong Japanese vitiligo patients, there is a subgroup with strong evidence of genetically determined susceptibility to not only vitiligo, but also to autoimmune thyroid disease and other autoimmune disorders.     

抗核抗体的研究进展

自身抗体是指抗自身细胞内、细胞表面和细胞外抗原的免疫球蛋白,是自身免疫和自身免疫性疾病重要特征之一。抗核抗体是指抗细胞内所有抗原成分的自身抗体的总称,某些自身免疫性疾病伴有特征性的自身抗体谱,而疾病标记性抗体或特异性抗体可诊断和鉴别诊断疾病特性。自身抗体可判断疾病的活动性及预后,观察治疗反应,指导临床治疗。进一步的抗核抗体谱研究,可阐明抗核抗体与自身免疫性疾病的相关性。该文对抗核抗体谱及其靶抗原与疾病的相关性进行了综述。