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Genetic polymorphism and decreased expression of HLA class II DP genes are associated with HBV reactivation in patients treated with immunomodulatory agents
Author(s) -
Matsuda Hidetaka,
Hiramatsu Katsushi,
Akazawa Yu,
Nosaka Takuto,
Saito Yasushi,
Ozaki Yoshihiko,
Hayama Ryoko,
Takahashi Kazuto,
Naito Tatsushi,
Ofuji Kazuya,
Ohtani Masahiro,
Nemoto Tomoyuki,
Hida Yukio,
Kimura Hideki,
Soya Yoshihiro,
Nakamoto Yasunari
Publication year - 2018
Publication title -
journal of medical virology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.782
H-Index - 121
eISSN - 1096-9071
pISSN - 0146-6615
DOI - 10.1002/jmv.25011
Subject(s) - genotype , single nucleotide polymorphism , human leukocyte antigen , odds ratio , hepatitis b virus , immunology , biology , allele , hepatitis b , gastroenterology , medicine , antigen , gene , virus , genetics
Hepatitis B virus (HBV) reactivation can be triggered by immunosuppressive chemotherapy. HLA class II molecules may play a role in HBV reactivation. Genetic polymorphism and mRNA expression of HLA class II were examined in patients with latent HBV infection treated with immunosuppressive therapies. Subjects with resolved HBV infection who had undergone treatment with immunosuppressive chemotherapies were retrospectively enrolled ( n = 42) and divided into reactivated ( n = 9) and non‐reactivated groups ( n = 33). Patients were genotyped for 17 single nucleotide polymorphisms (SNPs) within HLA class II DPA1 , and DPB1 , and mRNA expression levels of HLA class II genes were assessed. The frequency of the AA genotype of rs872956, a SNP in HLA‐DPB1 , was significantly higher in the reactivated group than in the non‐reactivated group (55.6% vs 12.1%, P < 0.05). The frequencies of the T allele and non‐AA genotypes (AT/TT) of rs3116996 (located in DPB1 ) were significantly higher in the reactivated group (T allele frequency: 16.7% vs 0.0% [ P < 0.01], non‐AA genotype frequency: 22.2% vs 0.0% [ P < 0.05]). Multivariate logistic regression identified the AA genotype of rs872956 as an independent protective factor against HBV reactivation (odds ratio [OR] = 18.1, 95% confidence interval [CI] = 2.6‐126.7, P < 0.01). mRNA expression of HLA‐DPB1 was lower in the HBV reactivated group than in the non‐reactivated group (median 276.1 ± 165.6/ β‐actin vs 371.4 ± 407.5/ β‐actin [ P < 0.05]). These results suggest the involvement of HLA class II molecules in HBV reactivation after treatment with immunomodulatory agents.