Insomnia increases the risk for specific autoimmune diseases: A large-scale retrospective cohort study

Sarah Stenger ^1,2* Artem Vorobyev ³ Katja Bieber ² Tanja Lange ⁴ Ralf J Ludwig* ^2,3 Jennifer Elisabeth Hundt* ²

• ¹ University of Lübeck, Lübeck, Germany
• ² Lübeck Institute of Experimental Dermatology, University of Lübeck, Lübeck, Schleswig-Holstein, Germany
• ³ Department of Dermatology, Allergology and Venereology, University Hospital Schleswig-Holstein, Lübeck, Schleswig-Holstein, Germany
• ⁴ Department of Rheumatology and Clinical Immunology, University of Schleswig-Holstein, Lübeck, Lübeck, Germany

The global rise of autoimmune diseases presents a significant medical challenge, with inadequate treatment options, high morbidity risks, and escalating healthcare costs. While the underlying mechanisms of autoimmune disease development are not fully understood, both genetic predispositions and lifestyle factors, particularly sleep, play critical roles. Insomnia and circadian rhythm sleep disorders not only impair sleep but also disrupt multiorgan interactions by dysregulating sympathetic nervous system activity, altering immune responses, and influencing neuroendocrine function. These disruptions can contribute to immune system dysregulation, increasing the risk of autoimmune disease development. To assess the impact of impaired sleep on the risk of developing autoimmune diseases, a global population-based retrospective cohort study was conducted using electronic health records from the TriNetX US Global Collaborative Network, including 351,366 subjects in each propensity score matched group. Twenty autoimmune diseases were examined, and propensity score matching was employed to reduce bias. Three sensitivity analyses were conducted to test the robustness of the results. The study identified significantly increased risks for several autoimmune diseases associated with impaired sleep, likely mediated by dysregulated neuroimmune and autonomic interactions. Specifically, cutaneous lupus erythematosus (hazard ratio (HR) = 2.119; confidence interval (CI) 1.674-2.682; p < 0.0001), rheumatoid arthritis (HR = 1.404; CI 1.313-1.501; p < 0.0001), Sjögren syndrome (HR = 1.84; CI 1.64-2.066; p < 0.0001), and autoimmune thyroiditis (HR = 1.348; CI 1.246-1.458; p < 0.0001) showed significantly increased risks. No diseases demonstrated reduced risks, and 4 out of 20 tested diseases did not show significant HR increases in any analysis. This study highlights the integral role of sleep in maintaining immune homeostasis through multi-organ interactions involving the autonomic nervous system, immune signalling pathways, and endocrine regulation. Disruptions in these systems due to chronic sleep impairment may predispose individuals to autoimmune diseases by altering inflammatory responses and immune tolerance. These findings underscore the necessity of recognizing and treating sleep disorders not only for general well-being but also as a potential strategy to mitigate the long-term risk of autoimmune disease development.