慢性乙型肝炎干扰素治疗与KIR基因多态性及干扰素抗体的相关性研究

Study on the Correlation between KIR Gene Polymorphism and Interferon Antibody in Patients with Chronic Hepatitis B

目的:为观察KIR基因对干扰素疗效的作用及其与干扰素抗体产生的相关性,将慢性乙型肝炎干扰素治疗的患者进行KIR基因多态性、血清干扰素抗体进行综合分析。方法:随机选取应用干扰素治疗的慢乙肝患者60例,检测KIR基因分型、相关生化免疫指标及HBV-DNA载量以及干扰素抗体。根据研究对象对干扰素的治疗情况,将其分为治疗有效组和治疗无效组,将两组患者的KIR分型结果进行统计学处理;另外根据是否产生干扰素抗体,将研究对象分为抗体生成组和非抗体生成组,并分别对KIR分型的结果及其疗效进行统计学处理,分析两组KIR分型的差异性及对干扰素治疗效果的影响。结果:(1)在60例研究对象中共检出17种KIR基因的24个等位基因,其中假基因3DP、框架基因2DL4、3DL2、3DL3在两组研究对象中出现的频率为100%,KIR2DL2*001-005、2DS2*001-005、3DP1*001/002/004、2DL5等位基因在干扰素治疗有效组表达频率明显高于治疗无效组,KIR2DS4*003-007等位基因在治疗有效组频率明显低于治疗无效组,差异均有统计学意义(P<0.05),其他等位基因分布比较,差异无统计学意义(P>0.05)。(2)60例研究对象治疗后血清抗-干扰素抗体阳性者有8例(13.33%),其中包括治疗有效组6例(20.00%),治疗无效组2例(6.67%),差异无统计学意义(P=0.254)。(3)2DL5B*002/004/007、3DL1*001-009/015-020及3DP1*003与干扰素抗体的产生均有相关性(P<0.05)。结论:(1)可能同慢乙肝患者干扰素应答有关的KIR基因有:KIR2DL2*001-005、2DS2*001-005、3DP1*001/002/004、2DL5,可能同干扰素治疗无效有关的KIR基因为KIR2DS4*003-007。(2)抗干扰素抗体对干扰素疗效影响较小,且阳性率较低。(3)KIR基因型中可能与抗-干扰素抗体产生有关的包括:2DL5B*002/004/007、3DL1*001-009/015-020及3DP1*003。

Objective： In order to observe the effect of KIR gene on the therapeutic effect of interferon and its correlation with the production of interferon antibody, to analyze the KIR gene polymorphism and serum interferon antibody.Method： 60 cases of chronic HBV infection were randomly selected, and the KIR genotype was detected, the interferon antibody, the HBV-DNA carrier rate and the related immunological indexes and biochemical tests were performed.According to the response to interferon therapy, the test objects were divided into effective treatment group and ineffective treatment group, two groups of KIR typing results were analyzed ; the other according to interferon antibody production or not, the test objects were divided into antibody group and non antibody group, and the type of KIR effect and the results of the two groups were statistically differences, analysis of the impact of the antibody on the efficacy of two groups and KIR typing results.Result： （ 1 ） In 60 subjects were detected in the 17 KIR genes and 24 alleles, including false gene 3DP, gene 2DIA, 3DL2 framework and 3DL3 in two groups of subjects in the frequency was 100%, the KIR2DL2＊001-005, 2DS2＊001-005, 3DPI＊001/002/004, 2DL5 allele in treatment effective group were significantly higher than those in ineffective treatment group, the frequency of KIR2DS4＊003-007 allele in the effective treatment group was significantly lower than that in ineffective treatment group, the differences were statistically significant （P〈0.05）, there was no significant difference in the distribution of other alleles （ P〉0.05 ） . （ 2 ） 60 patients with after treatment, there were 8 cases （ 13.33% ） with positive anti interferon antibody, including the treatment of effective group of 6 cases （ 20.00% ）, 2 cases in ineffective treatment group, the difference was not statistically significant （ P=0.254 ） . （3） 2DL5B＊002/004/007, 3DLI＊001-009/015-020 and 3DPl＊003 were correlated with the production of interferon antibody （P〈0.05） .Conclusion： （ 1 ） KIR genes may associated with the response to interferon in patients with chronic hepatitis B： KIR2DL2＊001-005, 2DS2＊001-005, 3DPI＊001/002/004, 2DL5, KIR may be associated with interferon therapy ineffective： KIR2DS4＊003-007. （ 2 ） Anti interferon antibody has little effect on interferon, and the positive rate is low. （ 3 ） KIR genotype may be related to anti interferon antibody production： 2DL5B＊002/004/007, 3DL1＊001-009/015-020 and 3DP1＊003.