Classical Autoimmune Diseases Research Articles

A DNA-Methylated Sight on Autoimmune Inflammation Network across RA, pSS, and SLE.

Methylation variabilities of inflammatory cytokines play important roles in the development of systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and primary Sjögren's syndrome (pSS). With heightened focus on personalized and precise medicine, it is necessary to compare and contrast the difference and similarity of cytokine methylation status between the 3 most classic autoimmune diseases (AIDs). In this study, we integrated 5 Cytokine-Chips from genome-wide DNA methylation datasets of the 3 kind of AIDs, delta-beta value was calculated for intergroup difference, and comprehensive bioinformatics analyses of cytokine genes with aberrant methylations were performed. 125 shared differential methylation variabilities (DMVs) were identified. There were 102 shared DMVs with similar methylation status; 3 hypomethylated differential methylation regions (DMRs) across the AIDs were found, and all 3 DMRs were hypomethylated. DMRs (AZU1, LTBR, and RTEL1) were likely to serve as activator in the inflammatory process. Particularly, AZU1 and LTBR with hypomethylated TSS and first exon located in the promoter regions were able to trigger inflammation signaling cascades and play critical roles in autoimmune tautology. Moreover, functional epigenetic module (FEM) algorithm showed that different inflammatory networks are involved in different AIDs; 5 hotspots were identified as biologically plausible pathways in inducing or perpetuating of inflammation which are epigenetically deregulated in AIDs. We concluded methylation variabilities among the same cytokines can greatly impact the perpetuation of inflammatory process or signal pathway of AIDs. Differentiating the cytokine methylation status will serve as valuable resource for researchers alike to gain better understanding of the epigenetic mechanisms of the three AIDs. Even more importantly, better understanding of cytokine methylation variability existing between the three classic AIDs will aid in identification of potential epigenetic biomarkers and therapeutic targets. This trial is registered with ChiCTR-INR-16010290, a clinical trial for the treatment of rheumatoid arthritis with Warming yang and Smoothening Meridians.

Hepatotoxicity of immune checkpoint inhibitors: a histology study of seven cases in comparison with autoimmune hepatitis and idiosyncratic drug-induced liver injury

AbstractThe adverse effects of immune checkpoint inhibitors in various organs may be attributed to immune-mediated processes triggered by disrupted self-tolerance; however, it remains unclear whether they are similar or dissimilar to classic organ-specific autoimmune diseases. The present study aimed to compare clinicopathologic features between checkpoint inhibitor-induced liver injury and acutely presenting autoimmune hepatitis or idiosyncratic drug-induced liver injury. Seven patients treated with nivolumab (n = 5) or ipilimumab (n = 2) presented with liver dysfunction a median of 41 days (range 21–120) after the initiation of immunotherapy. All patients had elevated liver enzymes, whereas hyper-bilirubinemia was less common. None of the patients had antinuclear antibodies or IgG elevations. Stopping the immunotherapy and additional immunosuppression with corticosteroids normalized or decreased liver enzymes in all patients treated. Histologically, all biopsies showed predominantly lobular hepatitis with milder portal inflammation. Centrilobular confluent necrosis and plasmacytosis were observed in a single case, and were markedly less common and milder than those in autoimmune hepatitis (p = 0.017 and p < 0.001, respectively). Bile duct injury, micro-abscesses, and extramedullary hematopoiesis were also found in one case each. Immunostaining revealed the presence of large numbers of CD3+ and CD8+ lymphocytes, whereas CD20+ B cells and CD4+ T cells were fewer in checkpoint inhibitor-induced liver injury than in autoimmune hepatitis or drug-induced liver injury. In conclusion, liver injury caused by cancer immunotherapy shares some features with injury of autoimmune hepatitis; however, there are obvious differences between the two conditions. Checkpoint inhibitor-induced liver injury may represent an immune-mediated, less zone-selective hepatocyte necrosis not requiring the strong activation of helper T cells and immunoglobulin production.

Polymyalgia rheumatica: an autoinflammatory disorder?

Polymyalgia rheumatica (PMR) is an elderly onset syndrome characterised by aching and stiffness in the shoulders and the pelvic girdle associated to increased levels of acute phase reactants and rapid...

Should Giant Cell Hepatitis With Autoimmune Haemolythic Anaemia Be Considered a Paediatric Autoimmune Liver Disease?

Reply: We thank Dr Nastasio et al for their informative letter on giant cell hepatitis with Coombs positive haemolytic anaemia (GCH-AHA) (1). When we were commissioned by the ESPGHAN Hepatology Committee to write the Position Statement on Paediatric Autoimmune Liver Disease (2), we did consider the possibility of including GCH-AHA (3) and neonatal haemochromatosis (4), rare conditions with a possible autoimmune component to their pathogeneses. We decided not to include them for the following reasons. The major aim of the Position Statement was to formulate a diagnostic and management protocol for juvenile autoimmune liver disease on the basis of what available in the literature on conditions recapitulating classical autoimmune hepatitis, that is, sharing in common serological (positivity for anti-nuclear, anti-smooth muscle, anti-liver kidney microsomal type 1, anti-liver cytosol type 1, and/or anti soluble liver antigen) and histological (interface hepatitis, rosette formation, multilobular collapse) features. These conditions, which include autoimmune hepatitis, autoimmune sclerosing cholangitis (overlap between autoimmune hepatitis and sclerosing cholangitis) and autoimmune hepatitis after liver transplant, are not as rare as hitherto believed in the course of childhood, and, though sharing several laboratory and clinical features, differ in terms of diagnostic criteria, management, and outcome, prompting the need for a Position Statement. GCH-AHA, which most likely has an autoimmune component to its pathogenesis, is a rare disease affecting almost exclusively infants and is associated to a number of immune mediated disorders, as noted in Dr Nastasio's letter (5), raising the question as to whether the underlying problem in these children is immune dysregulation (6). The typical histological features of GCH-AHA are diffuse giant cell transformation of hepatocytes and inflammation, different from those of classical autoimmune hepatitis, rarely posing problems in regards to differential diagnosis between the 2 conditions. GCH-AHA does respond, at least partially, to immunosuppression and relapses frequently when treatment is withdrawn (5). B-cell–mediated immunity appears to be involved in both liver and systemic damage, as anti-B cell monoclonal antibodies (rituximab) are to date the most effective treatment for this condition (7), though not in all patients (8). In conclusion, we do agree that GCH-AHA has a strong immune/autoimmune component to its pathogenesis, but it differs from the more common and classical autoimmune liver diseases of childhood and adolescence. Multi-centre collaboration for a better characterisation of this serious disorder is warranted to understand its pathogenesis and devise more effective treatment.

Autoimmune phenomena and disease in cancer patients treated with immune checkpoint inhibitors.

The discovery and approved treatment with immune checkpoint inhibitors (ICIs) for a variety of cancers has changed dramatically the morbidity and mortality rates for these patients. Despite the obvious benefits, their use is associated with unique immune-related adverse effects (irAEs), including autoimmune conditions such as: inflammatory arthritis, myositis, vasculitis and Sicca syndrome. The appearance of ICIs-induced autoimmune irAE requires from oncologists and rheumatologists a different approach to the identification and treatment of these conditions, which may differ from the classic and traditional approach to rheumatologic diseases. It should be taken into consideration that ICIs therapy in patients with preexisting autoimmunity could be possible, but with a cost of causing disease exacerbation. In this extensive review, we present the autoimmune irAEs, mostly as phenomena, but also as classic autoimmune diseases as well as therapeutic options for the side effects.

On chronic fatigue syndrome and nosological categories.

Chronic fatigue syndrome (CFS) is a heterogeneous disease which presents with pronounced disabling fatigue, sleep disturbances, and cognitive impairment that negatively affects patients' functional capability. CFS remains a poorly defined entity and its etiology is still in question. CFS is neither a novel diagnosis nor a new medical condition. From as early as the eighteenth century, a constellation of perplexing symptoms was observed that resembled symptoms of CFS. Commencing with "febricula" and ending with CFS, many names for the disease were proposed including neurocirculatory asthenia, atypical poliomyelitis, Royal Free disease, effort syndrome, Akureyri disease, Tapanui disease, chronic Epstein-Barr virus syndrome, and myalgic encephalitis. To date, it remains unclear whether CFS has an autoimmune component or is a condition that precedes a full-blown autoimmune disease. Research suggests that CFS may overlap with other diseases including postural orthostatic tachycardia syndrome (POTS), autoimmune syndrome induced by adjuvants (ASIA), and Sjögren's syndrome. Additionally, it has been postulated that the earliest manifestations of some autoimmune diseases can present with vague non-specific symptoms similar to CFS. Sometimes only when exposed to a secondary stimulus (e.g., antigen) which could accelerate the natural course of the disease would an individual develop the classic autoimmune disease. Due to the similarity of symptoms, it has been postulated that CFS could simply be an early manifestation of an autoimmune disease. This paper will provide a historical background review of this disease and a discussion of CFS as an entity overlapping with multiple other conditions.

Autoimmunity in uveitis.

Recent insights into the pathogenesis of immune-mediated diseases proposed a new classification, which includes autoimmune and auto-inflammatory diseases. The prevalence of specific autoimmune and auto-inflammatory diseases in uveitis and/or scleritis is not yet known. In this study, we examine the presence of systemic immune-mediated diseases in patients with uveitis and/or scleritis and put a special emphasis on autoimmune disorders by reporting on their clinical manifestations and visual prognosis. In this retrospective study, we reviewed data of 1327 patients presenting with uveitis and/or scleritis between January 2010 and July 2016 at the Erasmus Medical Center, Rotterdam, the Netherlands. All patients with noninfectious uveitis and/or scleritis were classified according to novel criteria for immune-mediated diseases. Various clinical data, including visual acuity (VA), of patients with uveitis of autoimmune origin were registered during 5-year follow-up. The origin of uveitis was in 5% (62/1327) autoimmune, in 15% (197/1327) auto-inflammatory and in 14% (180/1327) mixed autoimmune/auto-inflammatory. Patients with classical autoimmune connective tissue disease (N=17) suffered mostly from rheumatoid arthritis and granulomatosis with polyangiitis and exhibited predominantly scleritis (53%). After 5years of follow-up, none of the eyes of these patients developed legal blindness (VA of <0.1). The VA in patients with uveitis associated with autoimmune neuro-ophthalmological diseases (multiple sclerosis and neuromyelitis optica; N=27) remained stable over time. Uveitis and scleritis of autoimmune origin were observed in 5% of the total series. The term autoimmune uveitis should not be used as a synonym for intraocular inflammation of noninfectious origin.

Activation of the classical complement pathway and auto-immune diseases

Activation of the classical complement pathway and auto-immune diseases

Association between Silicone Breast Implants and Autoimmune Diseases

BACKGROUND AND AIM: Silicone breast implants have, for a long time, been considered as biologically inert and harmless. However the relationship between silicone breast implants and the risk of autoimmune diseases has generated intense medical interest. The aim of our review is to summarize the data linking silicone breast implants and autoimmune diseases, including the most recent association with autoimmune/inflammatory syndrome induced by adjuvants (ASIA).METHODS: The clinical research included articles from the last 16 years using the MeSH terms “breast implants” and “autoimmune diseases” and also the following terms: “autoimmune/inflammatory syndrome induced by adjuvants” and “Shoenfeld’s syndrome”. The Oxford 2011 Levels of Evidence was used to assign a level-of-evidence.Eligible articles included those who described a population of adult women (&gt;17 years), which have breast implants versus women without implants. The clinical outcome measured was the development of an autoimmune disease.RESULTS: Of the 268 obtained articles, five matched eligibility criteria (one meta-analysis, two systematic reviews and two cohort studies). Results show that although studies could not confirm an association between silicone breast implants and classical autoimmune diseases, a few studies demonstrated an association between implantsand undefined symptoms such as fatigue, arthralgia, myalgia and cognitive symptoms, which resembled a newly introduced syndrome, known as ASIA.CONCLUSIONS: Evidence remains inconclusive about any association between silicone breast implants and classical autoimmune diseases. ASIA seems to be linked to previous exposition to an adjuvant such as silicone. However, we will need better evidence from large studies with accurate methodology to determine whether any true association exists between ASIA syndrome and silicone breast implants.

Impact of Microbes on the Pathogenesis of Primary Biliary Cirrhosis (PBC) and Primary Sclerosing Cholangitis (PSC).

Primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) represent the major clinical entities of chronic cholestatic liver diseases. Both disorders are characterized by portal inflammation and slowly progress to obliterative fibrosis and eventually liver cirrhosis. Although immune-pathogenic mechanisms have been implicated in the pathogenesis of PBC and PSC, neither disorder is considered to be a classical autoimmune disease, as PSC and PBC patients do not respond to immune-suppressants. Furthermore, the decreased bile flow resulting from the immune-mediated tissue assault and the subsequent accumulation of toxic bile products in PBC and PSC not only perpetuates biliary epithelial damage, but also alters the composition of the intestinal and biliary microbiota and its mutual interactions with the host. Consistent with the close association of PSC and inflammatory bowel disease (IBD), the polyclonal hyper IgM response in PBC and (auto-)antibodies which cross-react to microbial antigens in both diseases, an expansion of individual microbes leads to shifts in the composition of the intestinal or biliary microbiota and a subsequent altered integrity of epithelial layers, promoting microbial translocation. These changes have been implicated in the pathogenesis of both devastating disorders. Thus, we will discuss here these recent findings in the context of novel and alternative therapeutic options.

Genetic selection pressure in TLR9 gene may enforce risk for SLE in Indian Tamils

Objectives Lupus is a classical systemic autoimmune disease with genetics as one of the well known causative factors for the disease pathogenesis. Toll-like receptors are the major pattern recognition receptors associated with innate immunity and also act as an interface with the adaptive immunity. Genetic polymorphisms in genes encoding TLRs were implicated in the development of infections, malignancies and autoimmune diseases. TLR9 is a member of TLR family, and recognizes the CpG DNA motifs of pathogens. Though the incidence rate of lupus in Asians was reported to be low (30 - 50/100,000 population), poor disease prognosis due to higher incidence of renal complications and aggressive disease worsens the scenario. The ability of TLR9 to detect and elicit an immune response against double-stranded DNA makes TLR9 a relevant factor to be tested for its association with the clinical and serological phenotypes of lupus. However, lack of relevant genetic data on normative frequencies of the TLR9 (rs187084) polymorphism may serve as a constraint to derive the sample size to conduct case control association studies. Hence this study was conducted to establish the normative frequency of TLR9 (rs187084) polymorphism in Indian Tamils. Materials and methods The TLR9 (rs187084) polymorphism was screened in South Indian Tamils ( n = 208) by PCR-RFLP. Results and discussion We observed a higher occurrence of the mutant allele (65%) in South Indian Tamils. No gender disparity with respect to the mutant allele frequency was observed. The higher incidence of mutant allele in both genders suggests that this population had undergone a genetic selection pressure as an evolutionary genetic measure to withstand the prevailing endemic infections like TB and malaria. Though the enhanced expression of TLR9 was protective against infections, it may also influence the development of autoimmune diseases. Conclusion The higher incidence of theTLR9 (rs187084) over-expression mutation in Indian Tamils is suggestive of a genetic adaptation or selection pressure to withstand the prevailing endemic infectious and parasitic diseases. However, this genetic adaptation poses a greater risk to develop autoimmune diseases like SLE etc through complex gene environment interactions. The normative frequency of the TLR9 (rs187084) polymorphism established in our population could now be used to define the sample size for future case control studies.

Anti-LG3 Antibodies Aggravate Renal Ischemia-Reperfusion Injury and Long-Term Renal Allograft Dysfunction.

Pretransplant autoantibodies to LG3 and angiotensin II type 1 receptors (AT1R) are associated with acute rejection in kidney transplant recipients, whereas antivimentin autoantibodies participate in heart transplant rejection. Ischemia-reperfusion injury (IRI) can modify self-antigenic targets. We hypothesized that ischemia-reperfusion creates permissive conditions for autoantibodies to interact with their antigenic targets and leads to enhanced renal damage and dysfunction. In 172 kidney transplant recipients, we found that pretransplant anti-LG3 antibodies were associated with an increased risk of delayed graft function (DGF). Pretransplant anti-LG3 antibodies are inversely associated with graft function at 1 year after transplantation in patients who experienced DGF, independent of rejection. Pretransplant anti-AT1R and antivimentin were not associated with DGF or its functional outcome. In a model of renal IRI in mice, passive transfer of anti-LG3 IgG led to enhanced dysfunction and microvascular injury compared with passive transfer with control IgG. Passive transfer of anti-LG3 antibodies also favored intrarenal microvascular complement activation, microvascular rarefaction and fibrosis after IRI. Our results suggest that anti-LG3 antibodies are novel aggravating factors for renal IRI. These results provide novel insights into the pathways that modulate the severity of renal injury at the time of transplantation and their impact on long-term outcomes.

Autoimmune liver disease: evaluating overlapping and cross-over presentations-a case-based discussion.

The three classic autoimmune liver diseases are recognised based on identifying varying clinical, laboratory, histological and radiological features that collectively classify patients. In the absence of defined aetiological factors, it is recognised that disease spectrum is broad, and, in this context, it is not infrequent for disease boundaries to be blurred, leading to overlapping features that may be present at the time of diagnosis or may appear later in the course of disease. Given the absence of accepted diagnostic criteria for overlap/cross-over syndromes, alongside weak data for intervention, it is recommended that a multidisciplinary, patient-specific approach be used to establish individual treatment pathways.

International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways.

Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery data sets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4,261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined<5 × 10−8) and used pathway analysis to identify JAK-STAT/IL12/IL27 signalling and cytokine–cytokine pathways, for which relevant therapies exist.

Autoimmunity versus autoinflammation--friend or foe?

"Autoimmunity" is a designation dependent on the conventional immunological issue of self/non-self discrimination. Identification of novel target autoantigens is still an important issue ongoing in classical tissue-specific autoimmune bullous diseases and autoimmune connective tissue diseases. In contrast, synchronized with the paradigm shift of the fundamental aspect of immunity to danger sensing/signaling, distinct collagen-like diseases have been defined by the genetic mutations causing dysregulated innate immunity/inflammation and have been designated as “autoinflammatory”diseases. Due to the clinical and etiological similarities,the concept of autoinflammatory diseases has expanded to include non-hereditary collagen-like diseases, tissue-specific chronic idiopathic inflammatory diseases and metabolic diseases. On the other hand, various genetic causes of autoimmune diseases have been identified and the border of these two pathophysiologies is becoming obscure. Instead, a variable mixture of both autoimmunity and autoinflammation can cause each inflammatory phenotype with a variable level of antigen specificity

Pathogen Infection as a Possible Cause for Autoimmune Hepatitis

Autoimmune disorders afflicting the liver comprise the bona fide autoimmune diseases, primary biliary cirrhosis, primary sclerosing cholangitis, and autoimmune hepatitis as well as drug-induced autoimmune-like diseases, such as halothane hepatitis. Whereas drug-induced forms of acute or chronic hepatitis often have a clear triggering factor, the etiology of classical autoimmune liver diseases is only poorly understood. Besides a genetic component present in disease susceptible individuals, environmental triggering factors are likely to play a role in the initiation and/or propagation of the disease. In this article, we will review on current evidence obtained from epidemiological associations, case studies, and findings in animal models for pathogens, to be involved in the etiology of autoimmune liver disease with a special focus on autoimmune hepatitis.

Role of innate immunity in the pathogenesis of type 1 and type 2 diabetes.

The importance of innate immunity in host defense is becoming clear after discovery of innate immune receptors such as Toll-like receptor or Nod-like receptor. Innate immune system plays an important role in diverse pathological situations such as autoimmune diseases. Role of innate immunity in the pathogenesis of metabolic disorders such as type 2 diabetes, metabolic syndrome or atherosclerosis that has not been previously considered as inflammatory disorders, is also being appreciated. Here, the role of innate immunity in the development of type 1 diabetes, a classical organ-specific autoimmune disease, and type 2 diabetes will be discussed, focusing on the role of specific innate immune receptors involved in these disease processes.Graphical

P03-027 - A brief Case report on specific undiagnosed condition, whose provisional diagnosis on the basis of provisional lab investigation proved as one of the component of autoinflammatory disorder

The autoinflammatory syndromes are a newly recognized group of immune disorders that lack the high titers of self-reactive antibodies and T cells characteristic of classic autoimmune disease. , patients with these illnesses experience unprovoked inflammatory disease in the absence of underlying infection.(Curr Top Microbiol Immunol. 2006;305:127-60). In the category of autoinflamation this disease is a a lesion particularly known as CRMO or chronic recurrent mutifocal osteomylitis a rare condition in which bones have an lesion, inflammation and pain but without a focus of infection .the result of its inheritance pattern is still being debated and the distinguishing feature from the autoimmune pattern is still not clear. It is classified as an auto inflammatory disease due to its recurrent out breaks and lack of any known pathogen.this disease tends to range from 4 to 14 years of age and 10 years as median. As by current statistics it occur 1:1000000 and primarly in girls with a 5:1 ratio. CRMO may similar to a painful bone lesion such as arthritis , RF , bacterial osteomylitis ,ewings sarcoma, lymphoma, eosinophilic granuloma or LAH. When all the prevoious illness are ruled out and a bone biopsy turns negative for any known cancer CRMO is usually diagnosed. As such the common medication given for reducing the inflammation are such as NSAIDS and steroids, antibiotics are not prescribed as there is no evident focus of infection. Congenital dyserthropoitic anaemia and CRMO , uncommon childhood diseases an association with sweet syndrome may be interelated .( journal of paediatrics 115 (5, part 1):730-4. Dol10.1016/S0022-3476(89)80650. A retrospective review of autoinflamatory diseases in Saudi children at rheumatology clinic showed that of the 34 children with a mean age 118 months , consanguinity was present in 40 %. And in which FMF 50%, CRMO 23.5%, EOS 8.8%, MWS 6 %.(Ann Saudi med . 2012 ;32(1);43-8(ISSN;0975-4466). CRMO is sometimes associated with palmoplantar pustulosis and frequent relapses may be present with remission lasting for 4-16 weeks. The most distal case if the affected series . classical Xray diagnosis reveled skeletal changes consistent with appearance of acute or chronic heamoatogenic osteomylits.morphologically CRMO begins as an acute inflammatory process either predominance of PMN leucocytes, with occasionally form absesses and osteoclastic bone resorption. At a later stage it may present as lymphocytes and inflamatoty infiltrate and occasional granulomatous foci and signs of new bone formation.

Do post-translational beta cell protein modifications trigger type 1 diabetes?

Type 1 diabetes is considered an autoimmune disease characterised by specific T cell-mediated destruction of the insulin-producing beta cells. Yet, except for insulin, no beta cell-specific antigens have been discovered. This may imply that the autoantigens in type 1 diabetes exist in modified forms capable of specifically triggering beta cell destruction. In other immune-mediated diseases, autoantigens targeted by the immune system have undergone post-translational modification (PTM), thereby creating tissue-specific neo-epitopes. In a similar manner, PTM of beta cell proteins might create beta cell-specific neo-epitopes. We suggest that the current paradigm of type 1 diabetes as a classical autoimmune disease should be reconsidered since the immune response may not be directed against native beta cell proteins. A modified model for the pathogenetic events taking place in islets leading to the T cell attack against beta cells is presented. In this model, PTM plays a prominent role in triggering beta cell destruction. We discuss literature of relevance and perform genetic and human islet gene expression analyses. Both direct and circumstantial support for the involvement of PTM in type 1 diabetes exists in the published literature. Furthermore, we report that cytokines change the expression levels of several genes encoding proteins involved in PTM processes in human islets, and that there are type 1 diabetes-associated polymorphisms in a number of these. In conclusion, data from the literature and presented experimental data support the notion that PTM of beta cell proteins may be involved in triggering beta cell destruction in type 1 diabetes. If the beta cell antigens recognised by the immune system foremost come from modified proteins rather than native ones, the concept of type 1 diabetes as a classical autoimmune disease is open for debate.

Liver transplantation and autoimmune liver diseases

Liver transplantation (LT) is an effective treatment for patients with end-stage autoimmune liver diseases such as primary biliary cirrhosis, primary sclerosing cholangitis, and autoimmune hepatitis. Indications for LT for these diseases do not differ substantially from those used for other acute or chronic liver diseases. Despite the good outcomes reported, the recurrence of autoimmune liver disease is relatively common in the allograft. In addition, it has become apparent that autoimmunity and autoimmune liver disease can arise de novo after transplantation for nonautoimmune liver disorders. An awareness of the existence of recurrent autoimmune liver diseases and de novo autoimmune hepatitis after LT has important clinical implications because their management differs from the standard antirejection treatment and is similar to the management of classic autoimmune liver diseases in the native liver.