Genetic Associations between Autoimmune Diseases and the Risks of Sepsis and 28-day Mortality in critical care : A Two-Sample Mendelian Randomization Study

Abstract

Abstract Background Sepsis is a prominent reason for admission in the Intensive Care Unit (ICU), where certain autoimmune diseases exhibit dysregulation of cytokines similar in sepsis. Existing research suggests that individuals with autoimmune disorders are more susceptible to developing sepsis and experiencing higher mortality rates. This highlights the need for more precise strategies. However, current observational studies provide conflicting conclusions regarding the relationship between autoimmune conditions and sepsis. Therefore, we utilize the Mendelian randomization(MR) to further investigate this association. Methods We conducted a two-sample MR study in European population to assess causal relationships between autoimmune diseases and sepsis, we employed the inverse variance-weighted (IVW) method and used Cochran's Q test for heterogeneity. We performed MR Egger intercept and MR pleiotropy residual sum and outlier (MR-PRESSO) global test to test for potential imbalanced pleiotropy. Results Genetically predicted Crohn's disease (β = 0.067, se = 0.034, p = 0.046, OR = 1.069, 95% CI = 1.001–1.141) and idiopathic thrombocytopenic purpura (β = 0.069, se = 0.031, p = 0.023, OR = 1.071, 95% CI = 1.009–1.136) were positively associated with an increased risk of sepsis in critical care. Conversely, rheumatoid arthritis (β=-0.104, se = 0.047, p = 0.025, OR = 0.901, 95% CI = 0.823–0.987), ulcerative colitis (β=-0.208, se = 0.084, p = 0.013, OR = 0.812, 95% CI = 0.690–0.957), and narcolepsy (β=-0.202, se = 0.092, p = 0.028, OR = 0.818, 95% CI = 0.684–0.978) were associated with a reduced risk of sepsis in critical care. Moreover, Crohn's disease (β = 0.234, se = 0.067, p = 0.001, OR = 1.263, 95% CI = 1.108–1.440) and idiopathic thrombocytopenic purpura (β = 0.158, se = 0.061, p = 0.009, OR = 1.171, 95% CI = 1.041–1.317) were also linked to an increased risk of 28-day mortality of sepsis in critical care. In contrast, multiple sclerosis (β=-0.261, se = 0.112, p = 0.020, OR = 0.771, 95% CI = 0.619—0.960) and narcolepsy (β=-0.536, se = 0.184, p = 0.003, OR = 0.585, 95% CI = 0.408—0.838) were linked to a decreased risk of 28-day mortality of sepsis in critical care. Conclusion This MR study identified causal associations between certain autoimmune diseases and risks of sepsis in critical care, and 28-day mortality in the European population. These findings provide us with a more refined approach to preventing the incidence of sepsis among individuals afflicted with autoimmune diseases. Additionally, exploring the underlying mechanisms of autoimmune diseases may potentially yield innovative approaches to diagnosing and treating sepsis.