细胞毒性T淋巴细胞相关蛋白4(CTLA-4)减弱细胞毒性T淋巴细胞(CTL)活化。这项研究是为了检查CTLA-4基因型/单倍型之间的关系,乙型肝炎表面抗原(HBsAg),和乙型肝炎核心相关抗原(HBcrAg)水平,以及它们对慢性HBV感染临床过程的潜在影响。
■我们招募了145名基因型B或C慢性HBV感染的初治患者,最初是乙型肝炎e抗原(HBeAg)阳性,并从平均年龄7.08岁开始随访研究队列中总共4,787人年。我们还招募了另外69名基因型B或C慢性HBV感染的初治成人作为验证队列。我们评估了两个队列中的CTLA-4基因单核苷酸多态性rs4553808(-A1661G)/rs5742909(-C318T),以及研究队列中的血清HBsAg和HBcrAg水平。
■CTLA-4启动子单倍型与研究队列中10岁和15岁的HBsAg和HBcrAg水平相关。CTLA-4AA/CC单倍型患者显示早期自发性HBeAg血清转换(风险比=1.58;p=0.02),和更快速的年度下降血清HBsAg水平比其他患者(0.09vs.0.03log10IU/ml/年,p=0.02)。CTLA-4AA/CC单倍型也预测HBeAg血清转换的验证队列(P=0.01)。
■具有CTLA-4AA/CC单倍型的慢性HBV感染患者在儿童和早期自发性HBeAg血清转换中具有较低的血清HBsAg和HBcrAg水平。
■细胞毒性T淋巴细胞相关蛋白4(CTLA-4)在慢性HBV感染儿童中的作用之前尚未研究。在一个非常长期的队列中,从童年到成年,我们发现CTLA-4单倍型与儿童时期HBV生物标志物水平相关,并且与慢性HBV感染的临床病程相关.CTLA-4通路可作为抗HBV感染治疗剂开发的未来目标。
UNASSIGNED: Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) attenuates cytotoxic T lymphocyte (CTL) activation. This study was performed to examine the relationships between CTLA-4 genotypes/haplotypes, hepatitis B surface antigen (HBsAg), and hepatitis B core-related antigen (HBcrAg) levels, and their potential impact on the clinical course of chronic HBV infection.
UNASSIGNED: We recruited 145 treatment-naïve patients with genotype B or C chronic HBV infection who were initially hepatitis B e-antigen (HBeAg)-positive and had been followed from a mean age of 7.08 years for a total of 4,787 person-years in the study cohort. We also recruited another 69 treatment-naïve adults with genotype B or C chronic HBV infection as a validation cohort. We assessed the CTLA-4 gene single nucleotide polymorphisms rs4553808 (-A1661G)/rs5742909 (-C318T) in both cohorts, and the serum HBsAg and HBcrAg levels in the study cohort.
UNASSIGNED: CTLA-4 promoter haplotypes were associated with HBsAg and HBcrAg levels at 10 and 15 years of age in the study cohort. Patients with the CTLA-4 AA/CC haplotype showed earlier spontaneous HBeAg seroconversion (hazard ratio = 1.58; p = 0.02), and a more rapid annual decline in the serum HBsAg level than other patients (0.09 vs. 0.03 log10 IU/ml/year, p = 0.02). The CTLA-4 AA/CC haplotype was also predictive of HBeAg seroconversion in the validation cohort (p = 0.01).
UNASSIGNED: Chronic HBV-infected patients with a CTLA-4 AA/CC haplotype had lower serum HBsAg and HBcrAg levels in childhood and earlier spontaneous HBeAg seroconversion.
UNASSIGNED: The role of cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) in chronic HBV-infected children has not been studied previously. In a very long-term cohort followed from childhood to adulthood, we showed that CTLA-4 haplotypes are associated with HBV biomarker levels in childhood and are correlated with the clinical course of chronic HBV infection. CTLA-4 pathway may serve as a future target for the development of therapeutic agents against HBV infection.