Wu Teng, Wang Yunan, Xia Yunfei, Ji Juan, Tao Xinyu, Gu Zhifeng
Dalian Medical University, Dalian, China.
Department of Rheumatology, Affiliated Hospital of Nantong University, Nantong, China.
Clin Rheumatol. 2025 May 16. doi: 10.1007/s10067-025-07485-x.
Previous evidence suggests an association between rheumatoid arthritis (RA) and infectious diseases, but the causal relationship remains unclear. This study sought to explore causal associations between RA and five common infections: pneumonia, sepsis, urinary tract infections (UTI), skin and subcutaneous tissue infections (SSTI), and bacterial intestinal infections (BII).
To identify the causal links, we adopted a Mendelian randomization (MR) design utilizing the inverse variance weighted (IVW), weighted median (WM), and MR-Egger approaches. Univariable MR (UVMR) and multivariable MR (MVMR) analyses were performed using pooled genome-wide association studies (GWAS) data. Additionally, various sensitivity analyses were conducted to ensure the reliability of the results.
In the UVMR analysis, RA was potentially associated with elevated risks of pneumonia (OR = 1.034, 95% CI: 1.016-1.052, P < 0.001) and sepsis (OR = 1.079, 95% CI: 1.048-1.110, P = 3.507E-07). This association remained significant after adjusting for smoking, alcohol consumption, or type 2 diabetes mellitus (T2DM) in the MVMR analysis. However, no causal links were found between RA and UTI, SSTI, and BII. Sensitivity analyses showed no detectable heterogeneity or pleiotropy, strengthening the causal inference of results.
Our study provides strong evidence of the association between RA and increased risks of pneumonia and sepsis. Further research is required to validate these findings and elucidate the underlying mechanisms. Key Points • It remains unclear whether the increased susceptibility to infections in RA stems from a genetic predisposition or results from immunosuppressive treatments. • The MR method is employed to assess the relationship between RA and common infectious diseases. • Our MR study supports a potential causal relationship between RA and elevated risks of pneumonia and sepsis.
先前的证据表明类风湿性关节炎（RA）与传染病之间存在关联，但因果关系仍不明确。本研究旨在探讨RA与五种常见感染之间的因果关联：肺炎、败血症、尿路感染（UTI）、皮肤和皮下组织感染（SSTI）以及细菌性肠道感染（BII）。
为了确定因果关系，我们采用了孟德尔随机化（MR）设计，使用逆方差加权（IVW）、加权中位数（WM）和MR-Egger方法。使用汇总的全基因组关联研究（GWAS）数据进行单变量MR（UVMR）和多变量MR（MVMR）分析。此外，还进行了各种敏感性分析以确保结果的可靠性。
在UVMR分析中，RA可能与肺炎风险升高（OR = 1.034，95% CI：1.016 - 1.052，P < 0.001）和败血症风险升高（OR = 1.079，95% CI：1.048 - 1.110，P = 3.507E - 07）相关。在MVMR分析中，在调整吸烟、饮酒或2型糖尿病（T2DM）后，这种关联仍然显著。然而，未发现RA与UTI、SSTI和BII之间存在因果关系。敏感性分析显示没有可检测到的异质性或多效性，加强了结果的因果推断。
我们的研究提供了强有力的证据，证明RA与肺炎和败血症风险增加之间存在关联。需要进一步的研究来验证这些发现并阐明潜在机制。要点 • RA对感染易感性增加是源于遗传易感性还是免疫抑制治疗的结果仍不清楚。 • 采用MR方法评估RA与常见传染病之间的关系。 • 我们的MR研究支持RA与肺炎和败血症风险升高之间存在潜在因果关系。
