PMID- 29075265 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20191120 IS - 1664-3224 (Print) IS - 1664-3224 (Electronic) IS - 1664-3224 (Linking) VI - 8 DP - 2017 TI - KIR3DS1/HLA-B Bw4-80Ile Genotype Is Correlated with the IFN-alpha Therapy Response in hepatitis B e antigen-Positive Chronic Hepatitis B. PG - 1285 LID - 10.3389/fimmu.2017.01285 [doi] LID - 1285 AB - To date, several on-treatment-level virological and serological indices that may predict the response to interferon alpha (IFN-alpha) have been reported. However, no effective predictors, such as drug-response genes, that can be detected before administration of anti-hepatitis B virus (HBV) therapy with IFN-alpha, have been found. In the diverse range of chronic viral infection, genes that affect human immunity play important roles in understanding host and viral co-evolution. Killer-cell immunoglobulin-like receptors (KIRs), which are highly polymorphic at the allele and haplotype levels, participate in the antiviral function of natural killer (NK) cells via fine-tuning inhibition and activation of NK-cell responses that occur when the NK cells interact with human leukocyte antigen (HLA) class I molecules on target cells. For each individual, the pairing of KIR and HLA ligand is genetically determined. To investigate whether a particular KIR and HLA repertoire influences the risk of HBV infection and response to IFN-alpha treatment for chronic hepatitis B (CHB), we genotyped the KIRs and HLA ligands of 119 hepatitis B e antigen (HBeAg)-positive CHB patients. These patients included 43 patients who achieved sustained response (SR) induced by IFN-alpha treatment for 48 weeks, 76 patients who achieved no response (NR), and 96 healthy subjects as controls. SR was defined as HBeAg loss with HBV DNA < 2,000 IU/ml and alanine aminotransferase normalization at 24 weeks posttreatment (week 72). In this study, we showed that activating KIR genes were less prevalent in Han Chinese, especially in Han Chinese with CHB, than in Caucasians. Furthermore, the KIR3DS1 gene, in combination with HLA-B Bw4-80Ile, strongly influenced the therapeutic outcomes for CHB patients who were treated with IFN-alpha. The frequency of the combination of genes encoding KIR3DS1 and HLA-B Bw4-80Ile was higher in patients who had a sustained treatment response than in patients who had NR [35.3 versus 1.3%; odds ratio (OR) = 19.85; P = 0.0008]. Activating KIR3DS1 and HLA-B Bw4-80Ile synergistically predicted SR to IFN-alpha for HBeAg-positive CHB patients. Genotyping for the KIR3DS1 gene and the HLA-B Bw4-80Ile allele might help physicians choose the optimal candidates for anti-HBV treatment with IFN-alpha. FAU - Li, Wenting AU - Li W AD - The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences and Medical Center, Institute of Immunology, University of Science and Technology of China, Hefei, China. FAU - Shen, Xiaokun AU - Shen X AD - The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences and Medical Center, Institute of Immunology, University of Science and Technology of China, Hefei, China. FAU - Fu, Binqing AU - Fu B AD - The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences and Medical Center, Institute of Immunology, University of Science and Technology of China, Hefei, China. AD - Hefei National Laboratory for Physical Sciences at Microscale, University of Science and Technology of China, Hefei, China. FAU - Guo, Chuang AU - Guo C AD - The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences and Medical Center, Institute of Immunology, University of Science and Technology of China, Hefei, China. FAU - Liu, Yanyan AU - Liu Y AD - Department of Infectious Diseases, the First Affiliated Hospital of Anhui Medical University, Hefei, China. FAU - Ye, Ying AU - Ye Y AD - Department of Infectious Diseases, the First Affiliated Hospital of Anhui Medical University, Hefei, China. FAU - Sun, Rui AU - Sun R AD - The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences and Medical Center, Institute of Immunology, University of Science and Technology of China, Hefei, China. AD - Hefei National Laboratory for Physical Sciences at Microscale, University of Science and Technology of China, Hefei, China. FAU - Li, Jiabin AU - Li J AD - Department of Infectious Diseases, the First Affiliated Hospital of Anhui Medical University, Hefei, China. FAU - Tian, Zhigang AU - Tian Z AD - The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences and Medical Center, Institute of Immunology, University of Science and Technology of China, Hefei, China. AD - Hefei National Laboratory for Physical Sciences at Microscale, University of Science and Technology of China, Hefei, China. FAU - Wei, Haiming AU - Wei H AD - The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences and Medical Center, Institute of Immunology, University of Science and Technology of China, Hefei, China. AD - Hefei National Laboratory for Physical Sciences at Microscale, University of Science and Technology of China, Hefei, China. LA - eng PT - Journal Article DEP - 20171011 PL - Switzerland TA - Front Immunol JT - Frontiers in immunology JID - 101560960 PMC - PMC5641573 OTO - NOTNLM OT - genotype OT - hepatitis B virus OT - interferon alpha OT - killer-cell immunoglobulin-like receptors/human leukocyte antigen OT - sustained response OT - therapy EDAT- 2017/10/28 06:00 MHDA- 2017/10/28 06:01 PMCR- 2017/01/01 CRDT- 2017/10/28 06:00 PHST- 2017/06/13 00:00 [received] PHST- 2017/09/25 00:00 [accepted] PHST- 2017/10/28 06:00 [entrez] PHST- 2017/10/28 06:00 [pubmed] PHST- 2017/10/28 06:01 [medline] PHST- 2017/01/01 00:00 [pmc-release] AID - 10.3389/fimmu.2017.01285 [doi] PST - epublish SO - Front Immunol. 2017 Oct 11;8:1285. doi: 10.3389/fimmu.2017.01285. eCollection 2017.