Autoimmune mechanisms, including cellular and humoral immune, are likely to participate in the pathogenesis of at least a subgroup of idiopathic dilated cardiomyopathy (IDC), in which cellular immune-mediation plays...Autoimmune mechanisms, including cellular and humoral immune, are likely to participate in the pathogenesis of at least a subgroup of idiopathic dilated cardiomyopathy (IDC), in which cellular immune-mediation plays a more important role. Cytotoxic T lymphocyte associated antigen-4 (CTLA-4) is the major negative regulatory factor of cellular immunity. This study was conducted to investigate the association of CTIA-4 gene exon 1 A49→G polymorphism with susceptibility to IDC in Han Chinese and its influences on serum soluble CTIA-4 (sCrLA-4) and Th1/Th2 cytokine bias. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) techniques were used to analyze the dimorphism of CTL4-4 exon 1 in the unrelated Han ethnic population in Heilongjiang Province ( including 48 IDC patients and 50 normal controls). Serum sCTLA-4, IFN-γ and IL-4 were evaluated by ELISA, with the ratio of IFN-γ/IL-4 as indicator for Th1/Th2 bias. Compared with controls, the frequencies of GG genotype (0.6042 and 0.3600, P = 0.012) and the G allele (0.7396 and 0.5600, P = 0.008) were significantly increased in IDC patients. Increased serum sCTIA-4 was found in the 1DC group compared with the controls [ ( 1.87 ± 1.06) μg/L vs. (0.54 ± 0.19) 〉g/L, P 〈 0.05 ~. 1FN-7 was much lower in IDC patients than that of the controls [ ( 16.38 ± 6.25) ng/L vs. (29.81 ± 10.66) ng/L (P 〈 0.05)~., whereas no statistical difference of IL-4 was found between the two groups I (12.85 ± 1.86) ng/L vs. (12.11 ± 2.76) ng/L], so the ratio of IFN-γ/IL-4 declined significantly ( 1.63 ± 0.50 vs. 3.01 ± 0.89, P 〈 0.05). Linear regression analysis manifested a significant interrelationship between the GG genotype, G allele frequencies and serum sCTLA-4, IFN-γ/IL-4 in the IDC group ( r = 0.57, P = 0. 021 and r = 0.32, P = 0. 036). CTLA-4 gene A49→G substitution was associated with an increased IDC risk, which implicated that the CTLA-4 gene exon 1 may have a considerable 展开更多
免疫检查点是一类免疫抑制性分子,通过调节免疫反应的强度和广度,从而避免正常组织的损伤和破坏。近年来研究发现肿瘤细胞可通过激活免疫检查点活性,从而逃避免疫系统的监视。免疫检查点抑制剂则通过拮抗免疫检查点蛋白,促进T细胞活化,...免疫检查点是一类免疫抑制性分子,通过调节免疫反应的强度和广度,从而避免正常组织的损伤和破坏。近年来研究发现肿瘤细胞可通过激活免疫检查点活性,从而逃避免疫系统的监视。免疫检查点抑制剂则通过拮抗免疫检查点蛋白,促进T细胞活化,进而产生抗肿瘤免疫效应。免疫检查点抑制剂在多种实体瘤的治疗方面已显示出良好的疗效。在淋巴瘤的治疗领域,虽然尚处于起步阶段,检查点抑制剂亦显示出良好的疗效及安全性。本文主要总结免疫检查点蛋白细胞毒性T淋巴细胞相关抗原-4(cytotoxic T lymphocyte associated antigen-4,CTLA-4)、程序性死亡受体-1(programmed death-1,PD-1)及其程序性死亡受体配体-1(programmed death ligand 1,PD-L1)的生物学活性,并介绍相应抗体药物在淋巴瘤研究中的进展。展开更多
文摘Autoimmune mechanisms, including cellular and humoral immune, are likely to participate in the pathogenesis of at least a subgroup of idiopathic dilated cardiomyopathy (IDC), in which cellular immune-mediation plays a more important role. Cytotoxic T lymphocyte associated antigen-4 (CTLA-4) is the major negative regulatory factor of cellular immunity. This study was conducted to investigate the association of CTIA-4 gene exon 1 A49→G polymorphism with susceptibility to IDC in Han Chinese and its influences on serum soluble CTIA-4 (sCrLA-4) and Th1/Th2 cytokine bias. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) techniques were used to analyze the dimorphism of CTL4-4 exon 1 in the unrelated Han ethnic population in Heilongjiang Province ( including 48 IDC patients and 50 normal controls). Serum sCTLA-4, IFN-γ and IL-4 were evaluated by ELISA, with the ratio of IFN-γ/IL-4 as indicator for Th1/Th2 bias. Compared with controls, the frequencies of GG genotype (0.6042 and 0.3600, P = 0.012) and the G allele (0.7396 and 0.5600, P = 0.008) were significantly increased in IDC patients. Increased serum sCTIA-4 was found in the 1DC group compared with the controls [ ( 1.87 ± 1.06) μg/L vs. (0.54 ± 0.19) 〉g/L, P 〈 0.05 ~. 1FN-7 was much lower in IDC patients than that of the controls [ ( 16.38 ± 6.25) ng/L vs. (29.81 ± 10.66) ng/L (P 〈 0.05)~., whereas no statistical difference of IL-4 was found between the two groups I (12.85 ± 1.86) ng/L vs. (12.11 ± 2.76) ng/L], so the ratio of IFN-γ/IL-4 declined significantly ( 1.63 ± 0.50 vs. 3.01 ± 0.89, P 〈 0.05). Linear regression analysis manifested a significant interrelationship between the GG genotype, G allele frequencies and serum sCTLA-4, IFN-γ/IL-4 in the IDC group ( r = 0.57, P = 0. 021 and r = 0.32, P = 0. 036). CTLA-4 gene A49→G substitution was associated with an increased IDC risk, which implicated that the CTLA-4 gene exon 1 may have a considerable
文摘免疫检查点是一类免疫抑制性分子,通过调节免疫反应的强度和广度,从而避免正常组织的损伤和破坏。近年来研究发现肿瘤细胞可通过激活免疫检查点活性,从而逃避免疫系统的监视。免疫检查点抑制剂则通过拮抗免疫检查点蛋白,促进T细胞活化,进而产生抗肿瘤免疫效应。免疫检查点抑制剂在多种实体瘤的治疗方面已显示出良好的疗效。在淋巴瘤的治疗领域,虽然尚处于起步阶段,检查点抑制剂亦显示出良好的疗效及安全性。本文主要总结免疫检查点蛋白细胞毒性T淋巴细胞相关抗原-4(cytotoxic T lymphocyte associated antigen-4,CTLA-4)、程序性死亡受体-1(programmed death-1,PD-1)及其程序性死亡受体配体-1(programmed death ligand 1,PD-L1)的生物学活性,并介绍相应抗体药物在淋巴瘤研究中的进展。