Association of autoimmune diseases with the occurrence and 28-day mortality of sepsis: an observational and Mendelian randomization study

Abstract

Abstract Background Observational studies have indicated a potential association between autoimmune diseases and the occurrence of sepsis, with an increased risk of mortality among affected patients. However, whether a causal relationship exists between the two remains unknown. Methods We accessed genomic data from both the MRC Integrative Epidemiology Unit (MRC-IEU) and the FinnGen consortium, encompassing genome-wide association studies for 10 autoimmune disorders. Genome-wide association study data for sepsis and its 28-day mortality were obtained from MRC-IEU. We employed univariable, multivariable, and reverse Mendelian randomization (MR) analyses to explore potential associations between autoimmune disorders and the occurrence of sepsis. Additionally, a two-step mediation MR analysis was performed to investigate indirect factors possibly influencing the relationship between the two. For 28-day mortality in sepsis, we first analyzed the relationship between autoimmune diseases and 28-day mortality in sepsis by MIMIC-IV database, and further verified the relationship by MR analysis. Results In univariable MR analysis, there appeared to be causal relationships between genetically predicted type 1 diabetes (OR = 1.036, 95% CI = 1.023–1.048, p = 9.130E-09), rheumatoid arthritis (OR = 1.077, 95% CI = 1.058–1.097, p = 1.00E-15) and sepsis, while a potential causal link was observed between celiac disease and sepsis (OR = 1.013, 95% CI = 1.002–1.024, p = 0.026). In a subsequent multivariable MR analysis, only rheumatoid arthritis was found to be independently associated with the risk of sepsis. Other autoimmune diseases were not found to have a causal association with sepsis. Furthermore, for all autoimmune diseases no causal link was established between autoimmune disorders and 28-day mortality from sepsis, aligning with the results obtained from the retrospective analysis of the MIMIC database. In reverse MR analysis, sepsis was suggested to potentially trigger the onset of psoriasis (OR = 1.084, 95% CI = 1.040–1.131, p = 1.488E-04), but this result requires further validation. Conclusion Apart from rheumatoid arthritis, there is no causal relationship between other autoimmune diseases and sepsis. At the genetic level, we did not find a causal relationship between autoimmune diseases and 28-day sepsis mortality, which is consistent with the results from the observational study from MIMIC-IV. Additionally, sepsis may increase the risk of developing psoriasis.