Altered DNA methylation pattern characterizes the peripheral immune cells of patients with autoimmune hepatitis - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Liver International Année : 2022

Altered DNA methylation pattern characterizes the peripheral immune cells of patients with autoimmune hepatitis

Résumé

Background and aims: Little is known about the impact of DNA methylation modifications on autoimmune hepatitis (AIH) pathogenesis and therapeutic response. We investigated the potential alterations of DNA methylation in AIH peripheral lymphocytes at diagnosis and remission. Methods: Ten AIH patients at diagnosis (time-point 1; AIH-tp1), 8/10 following biochemical response (time-point 2; AIH-tp2), 9 primary biliary cholangitis (PBC) and 10 healthy controls (HC) were investigated. Peripheral CD19(+) and CD4(+) cells were isolated. Global DNA methylation (5m C)/hydroxymethylation (5hm C) was studied by ELISAs. mRNA of DNA methylation (DNMT1/3A/3B) and their counteracting hydroxymethylation enzymes (TET1/2/3) was determined by quantitative RT-PCR. Epigenome wide association study (EWAS) was performed in CD4(+) cells (Illumina HumanMethylation 850 K array) in AIH and HC. Total 5m C/5hm C was also assessed by immunohistochemistry (IHC) on paraffin-embedded liver sections. Results: Reduced TET1 and increased DNMT3A mRNA levels characterized CD19(+) and CD4(+)-lymphocytes from AIH-tp1 compared to HC and PBC, respectively, without affecting global DNA 5m C/5hm C. In AIH-tp1, CD4(+) DNMT3A expression was negatively correlated with serum IgG (P = .03). In remission, DNMT3A decreased in both CD19(+) and CD4(+) cells compared to AIH-tp1 (P = .02, P = .03 respectively). EWAS in CD4(+) cells from AIH patients confirmed important modifications in genes implicated in immune responses (HLA-DP, TNF, lnRNAs and CD86). IHC showed increased 5hm C staining of periportal infiltrating lymphocytes in AIH-tp1 compared to HC and PBC. Conclusion: Altered TET1 and DNMT3A expressions, characterize peripheral lymphocytes in AIH. DNMT3A was associated with disease activity and decreased following remission. Gene DNA methylation modifications affect immunological pathways that may play an important role in AIH pathogenesis

Dates et versions

hal-04019884 , version 1 (08-03-2023)

Identifiants

Citer

Kalliopi Zachou, Pinelopi Arvaniti, Aggeliki Lyberopoulou, Eirini Sevdali, Matthaios Speletas, et al.. Altered DNA methylation pattern characterizes the peripheral immune cells of patients with autoimmune hepatitis. Liver International, 2022, 42 (6), pp.1355-1368. ⟨10.1111/liv.15176⟩. ⟨hal-04019884⟩
49 Consultations
0 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More