Frontiers in immunology · 2026
Low serum complement C3 levels are associated with all-cause mortality in Chinese centenarians: a prospective cohort study.
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Zhang WeiGuang, Duan Yuting, Li Zhe, Liu Miaomiao, Wang Qiushi, Wang Yang, Zhang Zehao, Qu Zeyu, Zhu Qiao, Zhao Yali, Liu Miao, He Yao, Luo Qing, Zhang Jie, Chen Yizhi
Аннотация
BACKGROUND: The complement system plays an important role in innate immunity and age-related inflammation, but its prognostic value in centenarians remains unclear. This study aimed to examine the associations between serum complement C3 and C4 levels and all-cause mortality among centenarians.
METHODS: We studied centenarians in Hainan Island, China. We used multivariable-adjusted restricted cubic splines, Cox proportional hazards models, and Kaplan-Meier survival analysis to assess the relationships between serum C3 and C4 levels and all-cause mortality.
RESULTS: A total of 906 centenarians were included in the final analysis. During a median follow-up of 30.1 months, 838 (92.5%) participants died. There was a significant inverse linear relationship between serum C3 levels and all-cause mortality (P = 0.031). Compared with the highest C3 quartile (Q4), individuals in the lowest quartile (Q1) had an increased risk of all-cause mortality (hazard ratio = 1.337; 95% confidence interval: 1.092-1.635; P = 0.005), whereas C4 levels showed no significant relationship with mortality (P > 0.05). When we used Q1 (0.86 g/L) as a cut-off, centenarians with C3 levels below this threshold also showed a higher mortality risk than those above this threshold (hazard ratio = 1.250; 95% confidence interval: 1.063-1.470; P = 0.007). A Kaplan-Meier analysis further indicated a shorter survival time in the lowest C3 quartile (Q1 vs. Q4: 26 vs. 34 months, P = 0.002). In contrast, C4 levels were not significantly associated with survival.
CONCLUSION: Serum complement C3 levels, but not C4 levels, might be associated with the risk of all-cause mortality in centenarians. However, because all centenarians were recruited from Hainan Island, external validation in other regions and ethnic populations is warranted.
METHODS: We studied centenarians in Hainan Island, China. We used multivariable-adjusted restricted cubic splines, Cox proportional hazards models, and Kaplan-Meier survival analysis to assess the relationships between serum C3 and C4 levels and all-cause mortality.
RESULTS: A total of 906 centenarians were included in the final analysis. During a median follow-up of 30.1 months, 838 (92.5%) participants died. There was a significant inverse linear relationship between serum C3 levels and all-cause mortality (P = 0.031). Compared with the highest C3 quartile (Q4), individuals in the lowest quartile (Q1) had an increased risk of all-cause mortality (hazard ratio = 1.337; 95% confidence interval: 1.092-1.635; P = 0.005), whereas C4 levels showed no significant relationship with mortality (P > 0.05). When we used Q1 (0.86 g/L) as a cut-off, centenarians with C3 levels below this threshold also showed a higher mortality risk than those above this threshold (hazard ratio = 1.250; 95% confidence interval: 1.063-1.470; P = 0.007). A Kaplan-Meier analysis further indicated a shorter survival time in the lowest C3 quartile (Q1 vs. Q4: 26 vs. 34 months, P = 0.002). In contrast, C4 levels were not significantly associated with survival.
CONCLUSION: Serum complement C3 levels, but not C4 levels, might be associated with the risk of all-cause mortality in centenarians. However, because all centenarians were recruited from Hainan Island, external validation in other regions and ethnic populations is warranted.