Presence of Autoantibodies in Males and Females With Rheumatoid Arthritis: A Systematic Review and Metaanalysis

Objective. Rheumatoid arthritis (RA) is more common in females, and although the cause of RA is unknown, it is characterized by the production of autoantibodies. The aims of this study were to determine whether RA-associated autoantibodies are more often found in females than males and to identify factors that influence the relationship between sex and seropositivity. Methods. Databases were searched and studies of RA (N ≥ 100) were included if they reported proportion of seropositive patients with RA by sex. Metaanalyses and metaregression were conducted using the random-effects model. Covariates regressed were smoking, age, BMI, Health Assessment Questionnaire–Disability Index (HAQ-DI), and the Disease Activity Score in 28 joints (DAS28). Results. Eighty-four studies with a total of 141,381 subjects with rheumatoid factor (RF) seropositivity and 95,749 subjects with anticitrullinated protein antibody (ACPA) seropositivity met inclusion criteria. The mean age of participants ranged from 37 to 68 years and the proportion of female subjects ranged from 9% to 92%. Results indicated that females were less likely than males to be seropositive: odds ratio (OR) 0.84 [95% CI 0.77–0.91] for RF and OR 0.88 [95% CI 0.81–0.95] for ACPA. BMI, smoking, mean age, DAS28, and HAQ-DI did not affect the relationship between sex and seropositivity. Conclusion. Although studies report that females have higher RA disease activity than males and that seropositivity predicts worse outcomes, females were less likely to be seropositive than males.