Abstract
There are limited studies on the association between systemic autoimmune rheumatic diseases (SARDs) and leptospirosis. Therefore, this study aims to identify the effects of leptospirosis on the risks of developing SARDs with a nationwide retrospective cohort study. Patients with leptospirosis who did not have a diagnosis of SARDs before the index date were enrolled from the Taiwan National Health Insurance Research Database between 2000 and 2010, as the leptospirosis cohort. For each patient with leptospirosis, one control without a history of leptospirosis and SARDs was randomly selected (non-leptospirosis cohort). Cox proportional hazards regression models were used to analyze the risk of SARDs according to sex, age, and comorbidities. Among the 23 million people in the cohort, 3,393 patients with leptospirosis (68.91% men, mean age 52.65 years) and 33,930 controls were followed for 18,778 and 232,999 person-years, respectively. The incidence of SARDs was higher in the leptospirosis cohort than in the non-leptospirosis cohort (1.38 vs 0.33 per 1000 person-years), with a hazard ratio (HR) of 4.42 (95% confidence interval [CI] = 2.82–6.92). The risk of developing SARDs was highest for leptospirosis patients aged ≥65 years (HR = 2.81% CI = 1.07–7.36) compared with patients aged ≤39 years. Patients with leptospirosis have a 4.42-fold higher risk of SARDs than that in the general population. Further research is warranted to investigate the mechanism underlying this association.
Highlights
Leptospirosis is a zoonotic disease caused by pathogenic spirochetes, genus Leptospira
Cytomegalovirus (CMV) infections were correlated with the induction and expansion of a proinflammatory CD4+/CD28− T cells in rheumatoid arthritis (RA) patients[11]; and Epstein-Barr virus (EBV) was regarded as an important trigger in the pathogenesis of systemic lupus erythematosus (SLE) as evidenced by the co-existence of anti-viral capsid antigen IgG and anti-dsDNA antibodies in the patients[12]
Leptospirosis had a higher risk of SLE and SS than non-leptospirosis cohort (Supplementary Table 1)
Summary
Leptospirosis is a zoonotic disease caused by pathogenic spirochetes, genus Leptospira. Autoimmune diseases are conditions that are triggered by the immune system initiating an attack on self-molecules due to the worsening of immunologic tolerance to auto-reactive immune cells[5]. Both environmental and genetic are significant contributors to the pathogenesis of autoimmune diseases[6]. The infection of Parvovirus B19 has been implicated www.nature.com/scientificreports in the pathogenesis of a variety of autoimmune disorders with the hallmark of inducing the production of autoantibodies in the host[10]. The relationship between leptospirosis and the development of SARDs is unclear; we conducted a longitudinal nationwide retrospective cohort study to investigate the occurrence of leptospirosis and the risk of developing SARDs subsequently in the same patients
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