Risk factors for primary Sjögren’s Syndrome: a systematic review and meta-analysis

Objectives The aim of this study was to analyze the risk factors for primary Sjögren’s Syndrome (pSS) by conducting a meta-analysis of observational studies. Methods Four electronic databases were searched from inception to August 2022. The search strategy included medical subject headings (MeSH) and text words. Outcomes were calculated and reported as the odds ratio (OR) and 95% confidence interval (CI). Results Twelve studies consisting of nine case–control and three cohort studies were analyzed. Significant positive relationships between infection, a family history of autoimmune disease in first-degree relatives, negative stressful life events, CGGGG insertion/deletion polymorphisms in the IRF5 gene and the onset of pSS were found, with pooled ORs and 95% CIs of 2.73 (1.93, 3.86), 5.93 (3.34, 10.52), 1.69 (1.27, 2.24) and 2.69 (1.97, 3.66), respectively. In contrast, the results showed that a history of smoking was not associated with the onset of pSS, with a pooled OR and 95% CI of 1.39 (0.76, 2.53). However, a statistically significant negative association between current smoking and pSS was detected, with a pooled OR and 95% CI of 0.4 (0.29, 0.83). Conclusions Our research indicated that infection, a family history of autoimmune disease in first-degree relatives, negative stressful life events and CGGGG insertion/deletion polymorphisms in the IRF5 gene might be risk factors for pSS. In contrast, our study demonstrated that a history of smoking was not associated with the onset of pSS, whereas current smoking was negatively associated with pSS onset. Systematic review registration We registered this review on INPLASY ( https://inplasy.com/ ) under registration number INPLASY202230005.