1. Patients who developed rheumatoid arthritis (RA) were less likely to have had a gastrointestinal (GI) or genitourinary (GU) infection within the previous two years.
2. Recent gastroenteritis was linked with a lowere RA risk in patients with both the presence and absence of anti-citrullinated protein antibodies (ACPA).
Evidence Rating Level: 3 (Average)
Study Rundown: A connection between recent infections and the risk of rheumatoid arthritis (RA) has long been hypothesized. In addition, the connection between the microbiome and autoimmunity has been an important area of investigation, especially for RA. This Swedish case-control study, a subset of the Epidemiological Investigation of Rheumatoid Arthritis (EIRA) study, documented incidence of RA over a 10 year period and collected data about infections within in two years preceding diagnosis. After adjusting for socioeconomic status and smoking, the study found that patients with a recent history of gastroenteritis and urinary tract infection had a lower risk of developing RA than those that did not. While prostatitis also showed a borderline significant reduction in risk, there was no association found with sinusitis, tonsillitis, and pneumonia. When separating the patients into anti-citrullinated protein antibody (ACPA)+, a frequently used biomarker for RA, and ACPA- groups, a decreased risk of RA in patients with previous gastroenteritis history was still found in both groups. However, ACPA+ RA risk was also reduced in patients with urinary tract infections, genital infections, or sinusitis, while there was a borderline significant increase risk of ACPA- RA associated with sinusitis.
The results of this study are intriguing in that they generate evidence to hypothesize that a mechanistic link between the microbiome and RA may exist. Still, the data presented in this study is not without its potential for bias, especially since history of recent infection was self-reported and the exact nature of the reported infections could not be discerned. In addition, an analysis of risk by sex would have been informative, though female patients made up 72% of participants and may have made detecting differences from males more difficult. Overall, the findings warrant a more rigorous study to further parse the relationship between host microbiome, infection, and autoimmunity.
Relevant Reading: Microbial infection and rheumatoid arthritis
In-Depth [case-control study]: 6401 participants, 72% female and 83% of sampled participants from the EIRA study, were included in this Swedish study from 1996-2009. Patients with RA were given a questionnaire about infection within the previous two years as were control patients that were age, sex, and residence area matched, selected by incidence density sampling randomly. For the entire sample, recent gastroenteritis (OR = 0.71 CI95% 0.63-0.80), urinary tract infection (OR = 0.78 CI95% 0.68-0.90), and prostatitis (OR = 0.80 CI95% 0.64-1.00) were associated with lower risk of RA. No association was found for sinusitis, tonsillitis, and pneumonia. Further, ACPA+ patients had a decreased risk of RA with a previous history of gastroenteritis, urinary tract infection, genital infection, and sinusitis, while ACPA- patients only had reduced risk with gastroenteritis and an increased risk of RA with sinusitis. No significant differences in RA risk were detectable by very recent infections versus infection from 1-2 years ago, smoking, sex, socioeconomic status, and epitope status.
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