Zhuang Yun-Long, Li Xi-Xi, Xu Hui-Cong, Ye Hui, Sun Di, Liu Xiang-Zhong, Ren Gui-Jie
Blood Center of Shandong Province, Jinan, Shandong Province, China.
Iran J Immunol. 2018 Jun;15(2):112-121.
Entecavir (ETV) is commonly used to treat chronic hepatitis B (CHB) in China. However, certain percentages of e-Antigen (HBeAg) positive CHB patients do not respond to ETV therapy.
To investigate whether the killer immunoglobulin-like receptor (KIR) genes were associated with seroconversion in HBeAg positive CHB responder patients treated with ETV.
Polymerase chain reaction with sequence-specific primers (PCR-SSP) method was performed to genotype KIR genes in 200 healthy controls and 198 HBeAg-positive CHB patients which 59 were defined as the complete response group (CRG) to the treatment with ETV and 139 were defined as null or partial response group (NPRG).
The frequencies of KIR2DS2 and KIR2DS3 were significantly higher (P=0.030, OR=1.57,95%CI=2.36-1.05 and P=0.018, OR=1.773,95%CI=2.77-1.13, respectively), while, the frequencies of KIR2DL3, KIR2DS1 and KIR3DS1 were significantly lower (P=0.038, OR=0.525, 95%CI=0.96-0.29,and P=0.031, OR=0.640, 95%CI =0.95-0.43, and P=0.035, OR=0.641, 95%CI=0.96-0.43, respectively) in HBeAg-positive CHB patients than those in healthy controls. The frequency of KIR2DS3 gene was significantly higher in NPRG than that in CRG (P=0.018, OR=0.402, 95%CI=0.83-0.20). The frequencies of KIR2DL3 and KIR3DS1 genes were significantly higher in CRG than those in NPRG (P=0.019, OR=3.625, 95%CI=10.83-1.21 and P=0.041, OR=1.949, 95%CI=3.65-1.04, respectively).
Patients with KIR2DS3 might have negative responses to anti-HBV therapy with ETV and patients with KIR2DL3 and KIR3DS1 might have advantage in the therapy with ETV.
在中国,恩替卡韦(ETV)常用于治疗慢性乙型肝炎(CHB)。然而,一定比例的e抗原(HBeAg)阳性CHB患者对ETV治疗无反应。
探讨杀伤细胞免疫球蛋白样受体(KIR)基因是否与接受ETV治疗的HBeAg阳性CHB反应者的血清学转换有关。
采用序列特异性引物聚合酶链反应(PCR-SSP)方法对200例健康对照者和198例HBeAg阳性CHB患者的KIR基因进行基因分型,其中59例被定义为ETV治疗的完全反应组(CRG),139例被定义为无反应或部分反应组(NPRG)。
HBeAg阳性CHB患者中KIR2DS2和KIR2DS3的频率显著高于健康对照者(分别为P = 0.030,OR = 1.57,95%CI = 2.36 - 1.05;P = 0.018,OR = 1.773,95%CI = 2.77 - 1.13),而KIR2DL3、KIR2DS1和KIR3DS1的频率显著低于健康对照者(分别为P = 0.038,OR = 0.525,95%CI = 0.96 - 0.29;P = 0.031,OR = 0.640,95%CI = 0.95 - 0.43;P = 0.035,OR = 0.641,95%CI = 0.96 - 0.43)。NPRG中KIR2DS3基因的频率显著高于CRG(P = 0.018,OR = 0.402,95%CI = 0.83 - 0.20)。CRG中KIR2DL3和KIR3DS1基因的频率显著高于NPRG(分别为P = 0.019,OR = 3.625,95%CI = 10.83 - 1.21;P = 0.041,OR = 1.949,95%CI = 3.65 - 1.04)。
携带KIR2DS3的患者可能对ETV抗HBV治疗反应不佳,而携带KIR2DL3和KIR3DS1的患者在ETV治疗中可能具有优势。