Autoimmune Hepatitis Type Research Articles

Association of the killer immunoglobulin-like receptor genes KIR2DS1 and KIR2DS4 with pediatric autoimmune hepatitis type I in Egypt

BackgroundKiller cell immunoglobulin-like receptors (KIR) are considered to be the key receptors that control the development and function of human natural killer cells which play complex mechanisms in autoimmune diseases. We aimed in this study to assess possible associations between killer cell immunoglobulin-like receptors (KIR2DS1 and 2DS4) genes and susceptibility to autoimmune hepatitis type I in Egyptian children.ResultsIn the case-control study conducted on eighty children diagnosed as autoimmune hepatitis (AIH) type I and eighty apparently healthy age and sex-matched control, we found that KIR2DS1, -2DS4, KIR2DS4-full length allele, and homozygous KIR2DS4-full/full variant were significantly associated with AIH-I, while the KIR1D allele and homozygous KIR2DS4-del/del variant were significantly observed in controls (P < 0.05 each). Absence of KIR2DS4 gene was significant among ANA positive AIH-I patients, patients on steroid therapy alone, and patients showing complete disease remission (P < 0.05 each). Higher activity and fibrosis indices were found significantly in patients lacking one or both studied genes.ConclusionsChildren carrying KIR2DS1, -2DS4 genes, KIR2DS4-full length allele, and homozygous KIR2DS4-full/full variant could be more susceptible to develop autoimmune hepatitis type I.

Difficulties in differential diagnosis of inflammatory bowel diseases in patient with overlapping autoimmune hepatitis and primary sclerosing cholangitis

The article presents a clinical case of cross-syndrome of autoimmune hepatitis type 1 with primary sclerosing cholangitis. The main symptoms, laboratory and instrumental criteria of these diseases are discussed. Detection of specific antibodies is necessary for an accurate diagnosis. Interpretation of changes in the colon obtained by stepwise biopsy requires special attention. The described morphological picture does not allow to make an accurate diagnosis, it can be regarded as initial manifestations of Crohn's disease, microscopic or eosinophilic colitis, signs of worm-parasitic invasion. An example of a differential diagnostic search in such a situation is discussed.

Type 2 Autoimmune Hepatitis and Nonadherence to Medication Correlate With Premature Birth and Risk of Postpartum Flare.

Autoimmune hepatitis (AIH) is an immune‐mediated chronic liver disease that affects all ages, including women of childbearing age. Optimal management during pregnancy is poorly defined. We aimed to explore the clinical and biochemical course of AIH in the antenatal and postpartum periods, and assess factors associated with premature birth and postpartum flares. Pregnant women with AIH reviewed in the autoimmune liver disease clinic at the Queen Elizabeth Hospital Birmingham between 2009 and 2020 were identified retrospectively, and clinical, biochemical, and immunological data 1 year before conception to 1 year postpartum were collected. Analysis was performed to identify trends in blood markers over the antenatal period, with an interrupted time series approach used to assess postpartum trends. Data were available for n = 27 pregnancies (n = 20 women), with median gestation of 38 weeks (30% premature) and most having type 1 AIH (78%) and delivering via caesarean section (63%). Levels of alanine transaminase, aspartate transaminase, and immunoglobulin G all declined significantly during gestation, followed by significant step‐change increases after delivery. Postpartum flare developed in 58% of pregnancies. AIH type 2 was associated with a higher rate of premature births (67% vs. 19%, P = 0.044), and a trend toward a higher rate of postpartum flare (100% vs. 48%, P = 0.053). Although not significant, medication nonadherence was associated with almost double the risk of prematurity (40% vs. 24%, P = 0.415) and postpartum flare (80% vs. 44%, P = 0.109). Conclusion: Biochemical and immunological remission of AIH occurs during pregnancy, although subsequent postpartum flare is common. Type 2 AIH is associated with a higher risk of premature birth and postpartum flare, although further research is required to validate and explain this finding.

Signal transducer and activator of transcription gene polymorphism in type 1autoimmune hepatitis

Background: Autoimmune hepatitis (AIH) is one of the chronic inflammation types of the liver, characterized by hypergammaglobulinemia and autoantibodies formation. Signal transducer and activator of transcription 4 (STAT4) gene play an important role in dendritic cells, macrophages and activated peripheral blood monocytes. Many previous studies reported the association between STAT4 and some autoimmune diseases, and in a mouse model confirmed the association, STAT4 is an important factor in Th1-dependent liver injury. Aim: to assess the association of a signal transducer and activator of transcription STAT4 gene polymorphism and their interactions with type1 autoimmune hepatitis in children methods: This is across-sectional study, it was performed on 50 patients ages with autoimmune hepatitis from the Pediatric Hepatology Clinic of Benha University Hospitals. All children were subjected to full history taking, physical examination, anthropometric measurements, abdominal examination, serum transaminases, serum bilirubin and serum albumin, PT, PTT, INR, antinuclear antibodies (ANA), anti-smooth muscle antibody (ASMA), antimitochondrial antibody (AMA), anti-liver kidney microsomal antibody (Anti LKM), total IgG levels, hepatitis markers, liver biopsy and genotyping for STAT4 gene.Genotyping of STAT4 gene polymorphism. Conclusion: rs7574865 and rs7582694 in STAT4 gene minor alleles are associated with increased type 1 AIH risk.

Autoimmune hepatitis-is histology conclusive?

Liver biopsy is an essential and necessary element in the diagnosis and management of autoimmune hepatitis, and is of very special importance in the scoring system for diagnosis. Histopathology shows moderate to severe inflammatory infiltrates with abundant plasma cells in the enlarged portal tracts with interface hepatitis and moderate to severe necroinflammatory lesions in the lobules with lymphoplasmacytic reaction. Regeneration develops with rosette formation and regenerative nodules. One important issue is the differentiation between acute onset of autoimmune hepatitis and a flare up of chronic disease; this cannot be diagnosed in some cases clinically and therefore requires a biopsy to evaluate the stage of the disease. There are some variants of the disease with cholestatic features such as autoantibody negative autoimmune hepatitis and giant cell hepatitis as well as overlap syndromes with primary biliary cholangitis and primary sclerosing cholangitis. Clinically, three types of autoimmune hepatitis are differentiated according to autoantibody formation and the clinical picture, however, histopathologically there is no difference between these three types. Differential diagnosis of autoimmune hepatitis includes drug-induced liver injury with minocycline, alpha methyldopa, nitrofurantoin and checkpoint inhibitors such as infliximab. Wilson´s disease is also an important differential diagnosis especially in young adults. A liver biopsy is mandatory to confirm the diagnosis of autoimmune hepatitis but histopathology alone is not conclusive.

Autoimmune Hepatitis with Elevated Serum IgG4 Levels Have a High Prevalence of Cirrhosis at Diagnosis.

Background Some autoimmune hepatitis (AIH) patients have elevated serum IgG4 levels, and the clinical characteristics of such patients are currently incompletely characterized. Aim To analyze the clinical features and possible pathogenesis of AIH with elevated serum IgG4 levels. Methods According to their serum IgG4 value, patients were divided into elevated IgG4 (IgG4 > 1.35 g/l) and normal IgG4 (IgG4 ≤ 1.35 g/l) groups. Results Among the 152 patients included in this study, those in the elevated IgG4 group had the following characteristics: older onset age (56 ± 11.43 years vs. 49.49 ± 13.04 years, P=0.005), higher proportion of males (34.15% vs. 12.61%, P=0.002), higher prevalence of cirrhosis (56.10% vs. 36.04%, P=0.026), lower prevalence of extrahepatic autoimmune diseases (9.76% vs. 27.3%, P=0.023), and higher levels of IL-17 and IL-22 (P < 0.05). Logistic regression analysis results showed that elevated serum IgG4 levels and male sex were risk factors for AIH cirrhosis (male: odds ratio (OR) = 4.293, 95% confidence interval (CI): 1.592–11.575, P=0.004; and elevated serum IgG4: OR = 2.566, 95% CI: 1.065–6.187, P=0.036). No significant differences were found for the remission rate within 6 months between the two groups (69.70% vs. 76.14%, P=0.470). Conclusion The male proportion and cirrhosis prevalence were higher in AIH with elevated serum IgG4 levels at the time of diagnosis. Male sex and elevated serum IgG4 levels are independent risk factors for AIH cirrhosis, and TH17 cells are more likely involved in the pathogenesis of this type of AIH.

The association between juvenile autoimmune hepatitis and HLA-DRB1 alleles: Iraqi tertiary center experience.

Aim of the studyTo highlight the impact of the human leukocyte antigen (HLA) allele on susceptibility and prevention of autoimmune hepatitis (AIH) in Iraqi children.Material and methodsWe conducted a prospective study from children attending the Gastroenterology and Hepatology Clinic of Children’s Welfare Teaching Hospital over five years from the first of September 2015 to the thirty-first of August 2020. It included 19 patients with AIH; their age (at time of diagnosis) ranged between 3 and 16 years, with a female predominance of 78.9%. The diagnosis was made by clinical, serological, and histological features. In addition, 20 age- and sex-matched unrelated subjects of the same ethnic background were selected randomly from healthy individuals undergoing checkup as controls.Results19 patients diagnosed with AIH were included in this study, and 20 age- and sex-matched healthy controls, with a female predominance of 78.9%. The commonest autoantibodies found were smooth muscle antibody (SMA) in 13 (68.4%), antinuclear antibody (ANA) in 11 (57.9%). In AIH type 1, PCR showed higher frequencies among patients with HLA-DRB1*03, HLA-DRB1*04, HLA-DRB1*13 alleles in patients with AIH; moreover DRB1*11 and DRB1*15 were less frequent than in the control group. Frequency of HLA-DRB1*04 was 28% and HLA-DRB1*13 was 20% in AIH type 2 patients; HLA-DRB1*13 and HLA-DRB5 showed frequency of 25% for both and HLA-DRB4 frequency was 18.7%.ConclusionsHLA-DRB1*13, DRB1*04, and DRB1*03 are susceptibility alleles for the development of AIH type 1, while HLA-DRB1*13, HLA-DRB4 and DRB5 are susceptibility alleles for the development of AIH type 2 in Iraqi children.

Antineutrophil cytoplasmic antibody profiles differ according to type of primary sclerosing cholangitis and autoimmune hepatitis

OBJECTIVES:To determine the frequency of the antineutrophil cytoplasmic antibodies (ANCA), antiproteinase-3 and antimyeloperoxidase, in primary sclerosing cholangitis (PSC) with or without inflammatory bowel disease (IBD+ or IBD-) and in different types of autoimmune hepatitis (AIH). Additionally, to verify the agreement between ANCA patterns by indirect immunofluorescence and their antigenic specificities by ELISA.METHODS:For this study, 249 patients were enrolled (42 PSC/IBD+; 33 PSC/IBD-; 31 AIH type-1; 30 AIH type-2; 31 AIH type-3; 52 primary biliary cirrhosis; 30 healthy controls) whose serum samples were tested for ANCA autoantibodies.RESULTS:There were fewer female subjects in the PSC/IBD- group (p=0.034). Atypical perinuclear-ANCA was detected more frequently in PSC/IBD+ patients than in PSC/IBD- patients (p=0.005), and was significantly more frequent in type-1 (p<0.001) and type-3 AIH (p=0.012) than in type-2 AIH. Proteinase-3-ANCA was detected in 25 samples (only one with cytoplasmic-ANCA pattern), and more frequently in PSC/IBD+ than in PSC/IBD- patients (p=0.025). Myeloperoxidase-ANCA was identified in eight samples (none with the perinuclear-ANCA pattern). Among the 62 reactive samples for atypical perinuclear-ANCA, 13 had antigenic specific reactions for proteinase-3 and myeloperoxidase.CONCLUSIONS:PSC/IBD+ differed from PSC/IBD- in terms of sex and proteinase 3-ANCA and atypical perinuclear-ANCA reactivity, the latter of which was more frequently detected in type-1 and type-3 AIH than in type-2 AIH. There was no agreement between ANCA patterns and antigenic specificities in IBD and autoimmune liver diseases, which reinforces the need for proteinase-3 and myeloperoxidase antibody testing.

The role of diffusion tensor imaging of the liver in children with autoimmune hepatitis

PurposeTo evaluate the role of diffusion tensor imaging (DTI) of the liver in children with autoimmune hepatitis (AIH).Material and methodsA prospective study was done on 42 children with AIH (30 girls and 12 boys, with a mean age of 13 years) and 20 age- and sex-matched healthy control children. They underwent DTI of the liver and laboratory tests. Liver biopsy was done for the patients. The mean diffusivity (MD) and fractional anisotropy (FA) of the liver were calculated and correlated with the pathological results.ResultsThe mean MD and FA of the liver in children with AIH were 1.42 ± 0.06 × 10-3 mm2/s and 0.37 ± 0.11; and in the control children they were 1.55 ± 0.07 × 10-3 mm2/s and 0.25 ± 0.03, respectively. The MD and FA were significantly different in the children with AIH compared to the control children (p = 0.001). The cutoff MD and FA used to differentiate patients from controls were 1.50 × 10-3 mm2/s, 0.31 with AUC of 0.919 and 0.813, sensitivity of 97.6% and 66.7%, a specificity of 80% and 70%, an accuracy of 94.2% and 67.3%, PPV of 95.3 and 90.3, and NPV of 88.9 and 33.3, respectively. There was significantly lower MD and higher FA of the liver in children with AIH type I (n = 31) than type II (n = 11) (p = 0.001), and patients with (n = 9) and without (n = 33) overlap syndrome (p = 0.005).ConclusionsWe concluded that DTI parameters can help to diagnose AIH, detect its phenotyping, and give clues as to the presence of associated overlap syndrome.

Asymptomatic autoimmune hepatitis type 1 with normal IgG level and IgA deficiency – case report

Introduction. Autoimmune hepatitis (AIH) in children is a chronic inflammatory liver disease with a broad clinical spectrum, ranging from isolated elevated transaminases to acute liver failure. AIH is a rare condition, with an in­creased prevalence in the last years (2.4-9.9 per 100,000 chil­dren). Case report. We present the case of a young girl, 7 years old, who was admitted to our hospital for an in­crease of liver enzymes, discovered accidentally. She was asymptomatic, and no physical signs of chronic or acute liver disease were found at admission. The laboratory pa­ra­meters revealed increased transaminases without cho­les­tasis. The viral causes of hepatitis were excluded, along with alpha-1 antitrypsin deficiency and Wilson’s disease. She had a normal level of serum IgG and a low IgA level with positive antinuclear antibodies (1:80) and anti-smooth muscle antibodies (1:320), suggestive for the diagnosis of AIH type 1 and anti-liver kidney microsomal type 1 anti­bodies. The treatment with prednisone was started, and the evolution was favorable, with the normalization of la­bo­ra­tory parameters. Conclusions. This case highlights the importance of the early recognition of this pathology and the careful evaluation of any increased serum trans­ami­nases, even in asymptomatic children.

Development of Methods to Extract RNA From Archived Pediatric Needle Liver Biopsies to Produce Sequencing Data.

Genetic susceptibility has been proposed as etiopathogenic in several pediatric liver diseases including autoimmune hepatitis (AIH). High throughput sequencing (HTPS) has been applied to archived needle liver biopsies obtained from adults but rarely to pediatric biopsies. For conclusive diagnosis of AIH, most subjects have an initial formalin-fixed paraffin embedded (FFPE) needle liver biopsy that is eventually archived and may be stored for decades. Our goal was to develop methods to utilize tissue from archived needle liver biopsies for extraction of RNA sufficient to produce HTPS data. We extracted total RNA from 45 FFPE needle liver biopsy samples (24 AIH type 1 patients and 21 controls [ages 15_11 and 19_10]; biopsy storage time 0.5-20 years) and constructed cDNA libraries that were then sequenced on an Illumina HiSeq2000 platform. Forty (89%) of the libraries produced high-quality sequences for further analyses. The average number of sequences obtained per library from HTPS was 55,136,519 (range 14,914,291-184,027,499). There was a significant inverse relationship between the number of human reads obtained and the age of the specimen (P < 2_10_7). It was possible to classify more than 90% of the reads as known genes in samples that had been stored for less than 10 years. Archived needle liver biopsies can be used for sequence based interrogation of the etiologic origins of complex liver diseases of young subjects, such as AIH.

The Discovery of the Hepatitis D Virus: Three Princes of Serendip and the Recognition of Autoantibodies to Liver-Kidney Microsomes.

The Discovery of the Hepatitis D Virus: Three Princes of Serendip and the Recognition of Autoantibodies to Liver-Kidney Microsomes.

Presentation and Outcomes of Autoimmune Hepatitis Type 1 and Type 2 in Children: A Single-center Study.

Autoimmune hepatitis (AIH) is designated as type 1 or 2 (AIH-1/2) on the basis of serum autoantibody (Ab) profiles. In children, AIH may present as acute or chronic liver failure or cirrhotic AIH (ALF/CLF/CAIH) with or without overlap sclerosing cholangitis (SC). The aim of this study was to compare demographics, presentation, and outcomes between groups in children. A retrospective electronic chart review of children with AIH who met standard diagnostic criteria with histologic confirmation at Texas Children's Hospital was performed, with de novo AIH after liver transplant (LT) excluded. Patients were identified and divided into AIH-1, AIH-2, ALF, CAIH, AIH-SC, and LT and compared using chi-square analysis, Student t-test, and Mood median test. Among 91 children with AIH, 72 (79.1%) had AIH-1, 19 (20.9%) had AIH-2, 13 (14.3%) had ALF, 25 (27.5%) had CAIH, and 14 (15.4%) had AIH-SC. Both AIH-1/2 had female and Hispanic predominance (72.2/89.5%, 40.3/57.9%). AIH-2 presented at younger mean age in years than AIH-1 (6.8, 12.1, P < 0.05). Both AIH-1/2 had low rates of remission after 1 year of IS (25.4, 35.7%) and most recent (30.6, 54.5%) follow-up. Twenty-two (24.2) patients received LT: 16 had AIH-1 (72.7%), 6 had AIH-2 (27.3%), 9 (40.9%) had ALF, and 13 (59.1%) had CAIH. One-year patient and graft survivals were 100%. The epidemiology and clinical presentation of AIH-1 and -2 had a few subtle differences. AIH-1 was associated with more complications after LT. More data are needed to better characterize the 2 as separate disease entities.

THU127 - Developing antigen-specific immunotherapy for autoimmune hepatitis type 2 by identification of T cell epitopes

THU127 - Developing antigen-specific immunotherapy for autoimmune hepatitis type 2 by identification of T cell epitopes

Overlap of concurrent extrahepatic autoimmune diseases is associated with milder disease severity of newly diagnosed autoimmune hepatitis

BackgroundConcurrent extrahepatic autoimmune disorders (CEHAID) are frequently observed in autoimmune hepatitis (AIH). It is not clear whether there is any prognostic significance of CEHAID on AIH. The aim of this study was to examine the prognostic impact of CEHAID and the correlation with the disease severity of AIH. MethodsThis study included 65 hospitalized subjects who fulfilled the accepted criteria for AIH during an 8-year period (2009–2016). All records were manually screened for presence of associated autoimmune diseases. Disease severity of AIH was assessed by liver laboratory tests including the ratio of aspartate aminotransferase to alanine aminotransferase (AST/ALT) and liver histology. ResultsAmong the enrolled patients, 52 (80%) were female (median age 61 years, IQR 45–75). Fifty-six (86.2%) were classified as type-1 AIH. In 26 (40%) patients at least one additional extrahepatic autoimmune disease was diagnosed. Thirty-four subjects were referred to our hospital because of acute presentation of AIH (supposed by an acute elevation of hepatic enzymes) for subsequent liver biopsy resulting in initial diagnosis of AIH. This group was stratified into 3 subgroups: (A) AIH alone (n = 14); (B) overlap with primary biliary cirrhosis (PBC) / primary sclerosing cholangitis (PSC) (n = 11); and (C) with CEHAID (n = 9). AST/ALT ratio was the lowest in subgroup C (median 0.64, IQR 0.51–0.94; P = 0.023), compared to subgroup A (median 0.91, IQR 0.66–1.10) and subgroup B (median 1.10, IQR 0.89–1.36). Patients with AIH alone showed a trend to the highest grade of fibrosis (mean 2.3; 95% CI: 1.5–3.0) with no statistical significance compared to subjects with CEHAID (lowest grade of fibrosis; mean 1.5; 95% CI: 0.2–2.8; P = 0.380) whereas the ongoing inflammation was comparable. ConclusionsAST/ALT ratio and extent of fibrosis were lower in subjects with AIH and CEHAID, compared to subjects with only AIH. Therefore, the occurrence of CEHAID might be a predictor for lower disease severity of newly diagnosed acute onset AIH, possibly caused by an earlier diagnosis or different modes of damage.

Approach to the patient with acute severe autoimmune hepatitis.

SummaryAutoimmune hepatitis is associated with varied clinical presentations and natural history, as well as somewhat unpredictable treatment responses. Understanding how to stratify patients who require further escalation of therapy will help clinicians manage these patients. The presentation of acute severe autoimmune hepatitis (AS-AIH) is relatively uncommon, although its prevalence is potentially greater than currently perceived. Previous studies consist of small retrospective single-centre series and are not directly comparable due to the diversity of presentations, disease definitions and non-standardised treatment regimens. We define AS-AIH as those who present acutely with AIH and are icteric with an international normalised ratio ≥1.5 and no evidence of hepatic encephalopathy. Those with hepatic encephalopathy should be defined as having AS-AIH with acute liver failure. In this review, we provide a structured practical approach for diagnosing and managing this unique group of patients.

2020 international consensus on ANCA testing beyond systemic vasculitis.

This document follows up on a 2017 revised international consensus on anti-neutrophil cytoplasm antibodies (ANCA) testing in granulomatosis with polyangiitis and microscopic polyangiitis and focuses on the clinical and diagnostic value of ANCA detection in patients with connective tissue diseases, idiopathic interstitial pneumonia, autoimmune liver diseases, inflammatory bowel diseases, anti-glomerular basement membrane (GBM) disease, infections, malignancy, and during drug treatment. Current evidence suggests that in certain settings beyond systemic vasculitis, ANCA may have clinical, pathogenic and/or diagnostic relevance. Antigen-specific ANCA targeting proteinase-3 and myeloperoxidase should be tested by solid phase immunoassays in any patient with clinical features suggesting ANCA-associated vasculitis and in all patients with anti-GBM disease, idiopathic interstitial pneumonia, and infective endocarditis associated with nephritis, whereas in patients with other aforementioned disorders routine ANCA testing is not recommended. Among patients with autoimmune liver diseases or inflammatory bowel diseases, ANCA testing may be justified in patients with suspected autoimmune hepatitis type 1 who do not have conventional autoantibodies or in case of diagnostic uncertainty to discriminate ulcerative colitis from Crohn's disease. In these cases, ANCA should be tested by indirect immunofluorescence as the target antigens are not yet well characterized. Many questions concerning the optimal use of ANCA testing in patients without ANCA-associated vasculitis remain to be answered.

AB0511 INTERNATIONAL CONSENSUS ON ANCA TESTING AND INTERPRETATION BEYOND SYSTEMIC VASCULITIS

Background:ANCA can be detected in sera from patients with autoimmune, inflammatory, infectious or neoplastic diseases.Objectives:To issue a Consensus Statement on ANCA testing and interpretation beyond systemic vasculitis.Methods:This Statement was prepared by a group of experts, based on the results of a comprehensive search in PubMed.Results:In certain settings beyond systemic vasculitis, ANCA may have diagnostic, clinical, and/or prognostic relevance. Testing for PR3- and MPO-ANCA by specific immunoassays should be performed in any patient with clinical features suggesting ANCA-associated vasculitis and in patients with anti-GBM disease and idiopathic interstitial pneumonia. Routine ANCA testing is not recommended in patients with connective tissue diseases (CTD), autoimmune liver diseases, inflammatory bowel diseases, infections, and/or malignancy unless there is evidence for small vessel vasculitis. ANCA testing by specific immunoassays may be useful in patients with rheumatoid arthritis, systemic sclerosis or primary Sjögren’s syndrome who have kidney disease with a nephritic sediment or in patients with systemic lupus erythematosus if a kidney biopsy shows prominent necrotizing and crescentic lesions or proliferative lupus nephritis. ANCA testing may be justified in patients with suspected autoimmune hepatitis type 1, who do not have conventional disease-related autoantibodies, or in patients with inflammatory bowel diseases in case of diagnostic uncertainty to discriminate ulcerative colitis from Crohn’s disease. In these cases, ANCA should be tested by indirect immunofluorescence since target antigens are not well characterized. ANCA against bactericidal/permeability-increasing protein may be a biomarker for deteriorating lung function and a poor prognosis in patients with cystic fibrosis.Conclusion:ANCA testing is clinically relevant not only in patients with manifestations suggesting systemic vasculitis, but also in patients with certain other disorders, particularly in patients with anti-GBM disease or idiopathic interstitial pneumonia.Disclosure of Interests:Sergey Moiseev Grant/research support from: This work was supported by the 5-100 Project, Sechenov University, Moscow, Jan Willem Cohen Tervaert: None declared, Yoshihiro Arimura: None declared, Dimitrios Bogdanos: None declared, Csernok Elena: None declared, Jan Damoiseaux: None declared, Marc Ferrante: None declared, Luis Felipe Flores-Suárez: None declared, Marvin Fritzler: None declared, Pietro Invernizzi: None declared, David Jayne Grant/research support from: ChemoCentryx, GSK, Roche/Genentech, Sanofi-Genzyme, Consultant of: Astra-Zeneca, ChemoCentryx, GSK, InflaRx, Takeda, Insmed, Chugai, Boehringer-Ingelheim, J. Charles Jennette: None declared, Mark Little: None declared, Stephen P. McAdoo: None declared, Pavel Novikov Grant/research support from: This work was supported by the 5-100 Project, Sechenov University, Moscow, Charles D. Pusey: None declared, Antonella Radice: None declared, Alan D. Salama: None declared, Judith Savige: None declared, Mårten Segelmark: None declared, Yehuda Shoenfeld: None declared, Renato Alberto Sinico: None declared, Maria Jose Rego de Sousa: None declared, Ulrich Specks: None declared, Benjamin Terrier: None declared, Athanasios Tzioufas: None declared, Severine Vermeire: None declared, Ming-hui Zhao: None declared, Xavier Bossuyt: None declared

Comprehensive meta-analysis reveals an association of the HLA-DRB1*1602 allele with autoimmune diseases mediated predominantly by autoantibodies.

The human leukocytes antigen (HLA)-DRB1*16:02 allele has been suggested to be associated with many autoimmune diseases. However, a validation of the results of the different studies by a comprehensive analysis of the corresponding meta data is lacking. In this study, we performed a meta-analysis of the association between HLA-DRB1*16:02 allele with various autoimmune disorders. Our analysis shows that HLA-DRB1*16:02 allele was associated with systemic lupus erythematosus, anti-N-Methyl-d-Aspartate receptor (NMDAR) encephalitis, Graves' disease, myasthenia gravis, neuromyelitis optica and antibody-associated systemic vasculitis with microscopic polyangiitis (AASV-MPA). However, no such association was found for multiple sclerosis, autoimmune hepatitis type 1, rheumatoid arthritis, type 1 diabetes and Vogt-Koyanagi-Harada syndrome. Re-analysis of the studies after their categorization into autoantibody-dependent and T cell-dependent autoimmune diseases revealed that the HLA-DRB1*16:02 allele was strongly associated with disorder predominantly mediated by autoantibodies (OR=1.93; 95% CI=1.63-2.28, P=1.95×10-14) but not with those predominantly mediated by T cells (OR=1.08; 95% CI=0.87-1.34, P=.474). In addition, amino acid sequence alignment of common HLA-DRB1 subtypes demonstrated that HLA-DRB1*16:02 carries a unique motif of amino acid residues at position 67-74 which encodes the third hypervariable region. Taken together, the distinct pattern of disease association and the unique amino acid sequence of the third hypervariable region of the HLA-DRB1 provide some hints on how HLA-DRB1*16:02 is involved in the pathogenesis of autoimmune diseases.

Сlinical, immunological and morphological features in different types of autoimmune hepatitis

To studying the clinical, biochemical, immunological and morphological markers in patients with seronegative (SN) and seropositive (SP) AIH and the qualities of their response to the IST. This retrospective cohort study included 82 AIH patients over the course of the years 20142019. All patients were selected in accordance with the criteria of the simplified assessment system of the IAIHG. Clinical, laboratorial and morphological characteristics of the AIH were analyzed. Therapy response was evaluated by the level of the ALT and IgG in 612 months after the start of the IST. The study material underwent statistical analysis using methods of parametrical and nonparametrical analysis. Statistical analysis was performed in the Statistica 13.3 (developed by StatSoft Inc., USA). 67/82 (81.70%) of the patients studied were women, median age of 54 years old [38; 70]. Patients with the diagnosis of the possible AIH according to the IAIHG made 85.4% (70 people). Almost everyone 96% (79/82) had morphological features of the interface-hepatitis with the lymphocytic/plasmocytic infiltration; emperipolesis was discovered in 63% of patients (49/82), hepatocellular rosette in 23% (19/82). Patients with SN AIH comprised 36.5% (30/82), with SP 63.4% (52/82). Comparative analysis demonstrated that the clinical profile in patients with SN and SP AIH is the same, while the incidence of immuno-associated diseases is significantly higher in the group of seronegative AIH. The morphological profile in the two AIH groups is identical in both typical and atypical manifestations. The number of responders to IST was 63% (19/30) SN AIH vs 67% SP AIH (35/52), did not differ significantly (p=0.529).However, that the number of patients with liver cirrhosis in the SN AIH group was twice as big as the ones with SP: 37% vs 17% (p=0.089). A comparative analysis of clinical, laboratory, morphological and clinical manifestations in the SN and SP AIH groups did not detected statistically significant significant differences, which may indicate that SN and SP AIH are the faces of one disease. It is possible that AB cannot be identified within the known spectrum of antibodies, or antibodies have slow expression, or are suppressed by the immune system. In any case, suspicions of AIH, in the absence of antibodies, it is recommended that liver biopsy be performed for the timely diagnosis of AIH and IST. Сirrhosis was more often diagnosed in the group SN AIH, which may be due to a later diagnosis, and therefore to untimely IST. The found frequent association of SN AIH with other immune-associated diseases requires a carefully study of this problem. The variety of clinical manifestations of AIH requires further study, the identification of clinical phenotypes with certain feature. This can help in the future to timely identify potentially problematic patients and predict a response to IST.