Type 2 autoimmune hepatitis: Genetic susceptibility

Lapierre, Pascal; Álvarez, Fernando

doi:10.3389/fimmu.2022.1025343

Cited by 11 publications

(14 citation statements)

References 63 publications

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“…29 Anti-LC1 has mostly been reported in children and juveniles, and it is mainly associated with anti-LKM-1 reactivity. 9,12,30 However, our research focused on adult patients with liver disorders by excluding juveniles. Considering the scarcity of studies on anti-LC1 in the Asian population, our study investigated a Chinese population to reveal low prevalence of anti-LC1 in Chinese patients (2.42%, 214/8838), which was higher than the reported study (0.16%, 38/23 832), 10 and the difference in the results may be explained by population differences.…”

Section: Discussionmentioning

confidence: 99%

“…The disease-specificity of anti-LC1 in AIH is considered apparent, since it has not been observed in a large number of patients with other hepatic or extra-hepatic diseases. 11,12 Indeed, anti-LC1 can be detected in HCV infection. A previous study showed that 33% (6/18) of anti-LKM (pos) /HCV (pos) patients tested positive for anti-LC1 compared to 0.83% (1/120) of anti-LKM (neg) /HCV (pos) patients and 0% (0/120) of anti-LKM1 (neg) /HBV (pos) patients, suggesting that anti-LC1 screening may only have application potential for anti-LKM1 (pos) /HCV (pos) patients, given its low prevalence.…”

Section: Introductionmentioning

confidence: 99%

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Viral hepatitis is associated with increased risk of decompensated cirrhosis or liver failure in patients positive for liver cytosol antibody type 1

et al. 2023

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Liver cytosol antibody type 1 (anti‐LC1) is reported to be a marker of type 2 autoimmune hepatitis (AIH), a type of autoimmune liver disease (AILD). However, anti‐LC1 is not entirely disease‐specific, and its clinical value in other hepatic diseases has not been well elucidated. Our study aimed to explore the associations between the diagnoses and outcome of decompensated cirrhosis or liver failure (DC/LF) in patients positive for anti‐LC1. A total of 157 patients positive for anti‐LC1 were included in our final analysis. DC/LF was defined as the outcome of patients positive for anti‐LC1. The risk of DC/LF according to diagnosis was estimated using multivariable Cox proportional hazards models, while stratified Cox regression models were used in the subgroup analyses. The diagnoses of patients positive for anti‐LC1 were found to be comprised of various liver disorders. Versus other diagnoses, viral hepatitis was associated with a 2.25‐fold increased risk of DC/LF in these patients, independent of sex, age, disease course, treatment and drinking history. Additionally, the associations were more significant by subgroup analysis in male patients, younger patients, non‐newly diagnosed patients, patients without treatment and patients without drinking history. Anti‐LC1 is not a disease‐specific antibody, as it was found in multiple types of hepatic disease. Furthermore, viral hepatitis rather than AILD was associated with an increased risk of DC/LF in patients positive for anti‐LC1. These findings emphasize the important role of viral hepatitis in the progression of DC/LF in patients positive for anti‐LC1.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Viral hepatitis is associated with increased risk of decompensated cirrhosis or liver failure in patients positive for liver cytosol antibody type 1

et al. 2023

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“…Patients showing positivity for Anti-LKM/Anti-LC-1 antibody were excluded from our study. We had excluded two such patients from our study (positive for Anti-LKM antibody) as there is different genetic susceptibility for AIH-1 and AIH-2, thus we had enrolled adult Non-type 2 AIH cases ( 13 ).…”

Section: Methodsmentioning

confidence: 99%

HLA and Non-HLA gene polymorphisms in autoimmune hepatitis patients of North Indian adults

et al. 2023

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Autoimmune hepatitis (AIH) is a chronic and progressive disease of the liver. This is a multifactorial autoimmune disease with both environmental factors and genetic factors playing a role in its pathogenesis. Certain environmental agents like viruses, drugs, etc., can trigger the disease in a genetically susceptible individual. The present study was aimed to explore the distribution of human leukocyte antigen (HLA)-DRB1, Protein tyrosine phosphatase non-receptor type 22 (PTPN22) and Cytotoxic T-Lymphocyte-associated protein 4 (CTLA-4) polymorphisms in North Indian adult AIH patients and their associations with clinical and pathological characteristics associated with the disease. A total of 147 subjects with 47 cases and 100 healthy controls were enrolled. Diagnosis of AIH was made by Revised International Autoimmune Hepatitis Group scoring system. HLA-DRB1 Typing was done by Luminex-based reverse Sequence-Specific Oligonucleotide Probing (SSOP). Single nucleotide variant (SNV) genotyping for CTLA-4 and PTPN22 was done by simple probe-based SNP arrays. Results indicated SLA positive AIH patients are poor responders to therapy. A significant predispositional association of HLA-DRB1*03 was observed in AIH patients from the North Indian population (p= 0.0001, OR=4.83 (2.30-10.15). The frequency of the GG genotype of CTLA-4 CT 60 was significantly increased in AIH patients compared to controls. Multinomial analysis showed that CTLA-4 CT 60 is an independent predictor for cases.

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“…Numerous factors influence the onset and progression of AIH in children, with high-risk genetic elements playing a pivotal role. Genome-wide association studies (GWAS) have unequivocally linked specific HLA alleles, notably HLA-DRB1 03:01 and HLA-DRB1 07:01, with type 2 AIH [2, 6]. This genetic association underscores the crucial involvement of antigen-presenting cells (APCs) and activated CD4+ T helper cells in the pathogenesis of the disease.…”

Section: Introductionmentioning

confidence: 99%

“…It is a life-threatening inflammatory condition characterized by interface hepatitis and the gradual deterioration of liver tissue due to the immune system's attack, culminating in chronic fibrosis, liver failure, and potentially, mortality [1][2][3]. JAIH predominantly affects girls from infancy through late adolescence [4].…”

Section: Introductionmentioning

confidence: 99%

Advancing Tolerogenic Immunotherapy: A Multi-Epitope Vaccine Design Targeting the CYP2D6 Autoantigen in Autoimmune Hepatitis Through Immuno-Informatics

Kolla,

Kumar,

Nanjunadappa

et al. 2024

Preprint

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Juvenile autoimmune hepatitis (JAIH) is a rare autoimmune disorder affecting children, characterized by the immune system's misguided attack on liver cells, primarily targeting the CYP2D6 autoantigen. This repeated attack leads to hepatic inflammation, fibrosis, and eventual liver failure. Current therapeutic strategies predominantly rely on immunosuppressive agents or whole B cell depletion antibodies, which render patients susceptible to infections and cancers. Hence, there is an urgent need for antigen-specific therapies to mitigate the severity of autoimmune hepatitis. Tolerogenic antigens represent a promising avenue in immunotherapy, capable of dampening autoimmunity. Here, we present a novel computationally designed multi-epitope tolerogenic vaccine tailored to target CYP2D6, aimed at inducing tolerogenic dendritic cells (DCs) and halting autoimmune progression in JAIH patients. To validate our approach, we have developed a similar vaccine for testing in mouse models of JAIH. The selected tolerogenic epitopes exhibit antigenicity without allergenicity or toxicity, and specifically induce IL-10 production (restricted to CD4+ T cell epitopes). In our vaccine design, tolerogenic poly-epitopes are linked with Toll-like receptor (TLR)-4-agonist, the 50S ribosomal unit, and IL-10, effectively programming DCs towards a tolerogenic state. Molecular docking and dynamic simulations have confirmed strong binding affinities and stable complexes between the vaccine structures, TLR4 and IL-10 receptor alpha (IL-10RA), indicating their potential for in vivo DC interaction and programming. Consequently, this innovative vaccine approach demands further exploration through wet lab experiments to assess its tolerogenicity, safety, and efficacy, thereby laying the groundwork for potential application in clinical settings.

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Type 2 autoimmune hepatitis: Genetic susceptibility

Cited by 11 publications

References 63 publications

Viral hepatitis is associated with increased risk of decompensated cirrhosis or liver failure in patients positive for liver cytosol antibody type 1

Viral hepatitis is associated with increased risk of decompensated cirrhosis or liver failure in patients positive for liver cytosol antibody type 1

HLA and Non-HLA gene polymorphisms in autoimmune hepatitis patients of North Indian adults

Advancing Tolerogenic Immunotherapy: A Multi-Epitope Vaccine Design Targeting the CYP2D6 Autoantigen in Autoimmune Hepatitis Through Immuno-Informatics

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