| Summary: | 碩士 === 中山醫學大學 === 醫學研究所 === 98 === Background：Imbalance of immune tolerance had been found to associate with the occurrence of autoimmune diseases. The CD4+ and CD8+ T cells had also been revealed more predominant expression in ankylosing spondylitis (AS) patients than healthy controls, and such expression may relate to the imbalance in the negative signal of activated T cells. Especially, cytotoxic T lymphocyte antigen-4 (CTLA-4) might play a role in the inhibition of activated T cells in the initial period of autoimmune tolerance. Programmed cell death-1(PD-1) binds its ligands, programmed cell death-1 ligand 1(PD-L1) and programmed cell death-1 ligand 2 (PD-L2), and induced negative signals that might maintain the balance of immune tolerance during late and sequential periods. However, molecular roles of autoimmune tolerance-related genes in AS development are unclear. Therefore, we designed a hospital-based case-control study to evaluate the association between CTLA-4, PD-1, PD-L1, and PD-L2 genetic polymorphisms and AS occurrences and clinical manifestations.
Methods and Materials：A total of 325 AS patients and 325 age and gender-matched controls were recruited in our study. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was applied to identify the CTLA-4 A+49G, PD-1 G-536A, PD-L1 A8923C, and PD-L2 C47103T genotypes. The disease activity and functional status of AS patients were evaluated by Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), and Bath Ankylosing Spondylitis Global (BAS-G).
Results：Our results showed that those who carried PD-1 G-536A G allele had a 1.42 fold (95% confidence interval; 95% C.I. = 1.14-1.76) significant risk of AS than those with A allele. Those who carried PD-L2 T allele also had a significantly lower risk of AS development than those with C allele (relative risk; RR = 0.01; 95% C.I. = 0.001-0.070). In addition, those who simultaneously carried PD-1 GG or GA, PD-L1 CC, and PD-L2 CC genotypes had a significant combined effect in AS occurrence (RR = 7.17; 95% C.I. = 1.38-37.31). Compared to the carriers with CTLA-4 GG and PD-1 AA combined genotypes, the carriers with CTLA-4 AA or AG and PD-1 GG or GA genotypes had a 2.30 fold (95% C.I. = 1.27-4.16) risk for disease development.
Conclusion：These results show that CTLA-4, PD-1, PD-L1, and PD-L2 genes may associate with the imbalance of autoimmune tolerance in AS patients.
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