Susceptibility to type 1 autoimmune hepatitis is associated with shared amino acid sequences at positions 70–74 of the HLA-DRB1 molecule

Lim, Young-Suk; Oh, Heung‐Bum; Choi, Sung‐Eun; Kwon, Ok‐Seon; Heo, Yong‐Seok; Lee, Han Chu; Suh, Dong Jin

doi:10.1016/j.jhep.2007.08.019

Cited by 46 publications

(48 citation statements)

References 21 publications

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“…DRB1*0404 and DRB1*0405 are the alleles associated with the occurrence of type 1 autoimmune hepatitis in Japan [61][62][63][64][65], mainland China [66], and Mexico [67] ( Table 1). DRB1*0405 and DQB1*0401 are the susceptibility alleles in South Korea [68]; DRB1*1301 influences disease occurrence in the children of Argentina [42,69] Dig Dis Sci and Brazil [40,70]; and DRB1*1301 and DRB1*0301 are the susceptibility alleles in Venezuela [71]. A meta-analysis of 694 cases of autoimmune hepatitis and 1769 normal subjects reported from South America has implicated DQB1*02, DQB1*0603, DRB1*0405, and DRB1*1301 as the principal susceptibility alleles in this region [72].…”

Section: Insights Into the Genetic Predispositions For Autoimmune Hepmentioning

confidence: 99%

“…The amino acid sequence in the critical Dig Dis Sci DRb67-72 location, especially the presence of a negatively charged glutamic acid (E) at position DRb71, alters the electrostatic and steric properties of the antigen-binding groove and can affect the selection of foreign or selfantigens that trigger the disease. In Korea, the susceptibility alleles for type 1 autoimmune hepatitis are DRB1*0405 and DQB1*0401, and the critical amino acid motif associated with autoimmune hepatitis is Q (glutamine), R (arginine), R (arginine), A (alanine), and A (alanine) at positions DRb70-74 [68].…”

Section: Insights Into the Exogenous Antigenic Trigger Of Autoimmune mentioning

confidence: 99%

“…Sequence QRRAA at positions DRb70-74 [68] Unique susceptibility sequence [68] Critical sequences can determine antigen selection [29,111,114] Susceptibility may relate to single amino acid in critical location [29] Different antigens with similar configurations can be displayed by same class II MHC molecules [110] Susceptibility associated with different class II MHC molecules and different antigens [114] Characterization of exogenous triggering antigens…”

Section: Insights Into the Principal Target Autoantigen Of Autoimmunementioning

confidence: 99%

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Transitioning from Idiopathic to Explainable Autoimmune Hepatitis

Czaja

2015

Dig Dis Sci

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Autoimmune hepatitis lacks an identifiable cause, and its diagnosis requires the exclusion of etiologically defined diseases that resemble it. Insights into its pathogenesis are moving autoimmune hepatitis from an idiopathic to explainable disease, and the goal of this review is to describe the insights that are hastening this transition. Two types of autoimmune hepatitis are justified by serological markers, but they also have distinctive genetic associations (DRB1 and DQB1 genes) and autoantigens. DRB1 alleles are the principal susceptibility factors in white adults, and a six amino acid sequence encoded in the antigen-binding groove of class II molecules of the major histocompatibility complex can influence the selection of autoantigens. Polymorphisms, including variants of SH2B3 and CARD10 genes, may affect immune reactivity and disease severity. The cytochrome mono-oxygenase, CYP2D6, is the autoantigen associated with type 2 autoimmune hepatitis, and it shares homologies with multiple viruses that might promote self-intolerance by molecular mimicry. Chemokines, especially CXCL9 and CXCL10, orchestrate the migration of effector cells to sites of injury and are associated with disease severity. Cells of the innate and adaptive immune responses promote tissue damage, and possible deficiencies in the number and function of regulatory T cells may facilitate the injurious process. Receptor-mediated apoptosis is the principal mechanism of hepatocyte loss, and cell-mediated and antibody-dependent mechanisms of cytotoxicity also contribute. Insights that explain autoimmune hepatitis will allow triggering exogenous antigens to be characterized, risk management to be improved, prognostic indices to be refined, and site-specific therapeutic interventions to emerge.

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Section: Insights Into the Genetic Predispositions For Autoimmune Hepmentioning

confidence: 99%

Section: Insights Into the Exogenous Antigenic Trigger Of Autoimmune mentioning

confidence: 99%

Section: Insights Into the Principal Target Autoantigen Of Autoimmunementioning

confidence: 99%

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Transitioning from Idiopathic to Explainable Autoimmune Hepatitis

Czaja

2015

Dig Dis Sci

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“…Molecular analysis of HLA DR by the use of PCR-based DNA typing techniques have shown that susceptibility to type 1 AIH is associated specifically with the DRB1*03:01 and DRB1*04:01 alleles in Caucasians [10], DRB1*04:05 in Japanese [11] , Koreans [12] and Argentine adults [13], DRB1*04:04 in Mexicans [14], and DRB1*13:01 in Argentine children [15] and Brazilians [15] in the HLA class II DRB1 locus, which encodes the polymorphic β chain of the HLA-DR antigen (Table 1). We earlier performed HLA-genotyping of Japanese AIH patients and showed that the predisposition to type 1 AIH was associated with DRB1*04:05, as well as with DQB1*04:01 (Table 2), which is in strong linkage disequilibrium with DRB1*04:05 [16].…”

Section: Hla Susceptibility Genesmentioning

confidence: 99%

Genetic background of autoimmune hepatitis in Japan

2010

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“…Similarly, HLA-DR4 (DRB1 * 0405) was also suggested to be a disease susceptibility gene in Chinese patients [35] . In Korea, HLA-DR3 and HLA-DR4 are suggested to be involved in the susceptibility to AIH, but HLA-DR4 was more frequently observed than HLA-DR3 [35,39] . In Taiwan, HLA-DQ5 (50%), HLA-CW7 (50%), HLA-A11 (55%), and HLA-DR4 (36%) were frequent in AIH patients [23] .…”

Section: Geneticsmentioning

confidence: 99%

Similarities and Differences in Autoimmune Hepatitis Epidemiology between East and West: Autoimmune Hepatitis in East Asia, Southeast Asia, and South Asia

Enomoto

Nishiguchi²

2016

Inflamm Intest Dis

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Background: Autoimmune hepatitis (AIH)is a relatively rare disease that can develop regardless of age or ethnicity. However, its clinical features differ between eastern and western populations due to several heterogeneous genetic and environmental factors. We herein report the clinical characteristics of AIH patients in East Asia, Southeast Asia, and South Asia. Summary and Key Messages: The prevalence of AIH in eastern countries is considered to be lower than in western countries. Although a few young patients with type 2 AIH have been observed in South Asia, most patients in Asia are middle-aged women with type 1 AIH who respond well to steroid-based immunosuppressive therapy. Human leukocyte antigen DR4 is suggested to be an influential factor in the genetic background of AIH patients in Asia, particularly in East Asia. Notably, AIH may be induced by some societal- or culture-associated medicines, including herbal medicines. The IAIHG (International Autoimmune Hepatitis Group) scoring systems are generally accepted as the standard diagnostic methods for AIH in Asian countries. The results of repeated nationwide surveys in Japan suggest that the clinical features of AIH patients in East Asia are changing, with IgG levels and rates of anti-nuclear antibody positivity decreasing.

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Susceptibility to type 1 autoimmune hepatitis is associated with shared amino acid sequences at positions 70–74 of the HLA-DRB1 molecule

Cited by 46 publications

References 21 publications

Transitioning from Idiopathic to Explainable Autoimmune Hepatitis

Transitioning from Idiopathic to Explainable Autoimmune Hepatitis

Genetic background of autoimmune hepatitis in Japan

Similarities and Differences in Autoimmune Hepatitis Epidemiology between East and West: Autoimmune Hepatitis in East Asia, Southeast Asia, and South Asia

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