Although the etiology of RA is uncertain, it is defined by the generation of autoantibodies. For a study, researchers sought to determine if females had more RA-related autoantibodies than males and to find variables that impact the association between sex and seropositivity.

Databases were searched, and RA studies (N≥100) were considered if the proportion of seropositive individuals with RA by sex was reported. The random-effects model was used in meta-analyses and metaregression. Smoking, age, BMI, the Health Assessment Questionnaire-Disability Index (HAQ-DI), and the Disease Activity Score in 28 (DAS28) joints were regressed covariates. 

About 84 studies were included, with a total of 141,381 patients with RF seropositivity and 95,749 subjects with anticitrullinated protein antibody (ACPA) seropositivity. The participants’ average age varied from 37 to 68 years, while the proportion of female patients ranged from 9 to 92%. Females were less likely than men to be seropositive, with odds ratios (OR) of 0.84 [95% CI 0.77-0.91] for RF and 0.88 [95% CI 0.81-0.95] for ACPA. BMI, smoking, mean age, DAS28, and HAQ-DI had no effect on the sex-seropositivity association.

Despite the fact that studies show that girls had more RA disease activity than males and that seropositivity predicts poorer outcomes, females were less likely to be seropositive than males.