Female hormonal factors and the development of anti-citrullinated protein antibodies in women at risk of rheumatoid arthritis

Abstract

In women at increased risk of RA, characteristic systemic autoimmunity was associated with menopause, suggesting that the acute decline in ovarian function might contribute to the development of autoimmunity associated with RA and potentially to the increased risk of RA in women.

Drs. Deane and Demoruelle reply

“…In the letter by Alpizar-Rodriguez and Finckh 1 , they describe their prior work in which they found, similar to our current report, an association between older age and anticitrullinated protein antibody (ACPA) positivity in first-degree relatives (FDR) of patients with rheumatoid arthritis (RA) 2,3 . In contrast to our findings, their data suggest that the strongest association between ACPA positivity and age is in women aged 45-55 years, and they did not find an association between ACPA positivity and age in men.…”

Prevotella copri in individuals at risk for rheumatoid arthritis

“…We identified participants in ‘pre-clinical RA’ stages based on the European League Against Rheumatism terminology for pre-clinical phases of RA 13. Operationally, we combined two pre-clinical RA stages for statistical power reasons: (1) ‘systemic autoimmunity associated with RA’ defined by anticitrullinated protein autoantibodies positivity and/or rheumatoid factor (RF) positivity,14 and/or (2) ‘symptoms and signs associated with possible RA’ as defined by the Connective Tissue Disease Screening Questionnaire with or without undifferentiated arthritis (see online supplementary text for details) 15–17. We included a control group, namely ‘FDR controls’, namely RA-FDRs without any autoantibodies or symptoms associated with possible RA.…”

Measuring ACPA in the general population or primary care: is it useful?

“…ACPAs are present in 0.8% of Caucasians without RA64 and in 1.7% of Asians without known autoimmune disease 65. Several factors are known to be associated with the presence of ACPA, such as older age, in particular for women where the perimenopausal period seems to be associated with an increased prevalence,66 tobacco smoking and undifferentiated joint complaints.…”

“…Examples of environmental risk factors increasing the likelihood of RA are, for example, obesity, tobacco smoking or other inhaled pollutants, certain nutritional habits; viral infections have also been suggested to increase the odds of developing the disease 69–72. Hormonal factors such as the rapid decline in ovarian function at menopause or after a total hysterectomy have been proposed as a condition warranting screening for autoimmunity 66. Other autoimmune comorbidities, such as autoimmune thyroiditis, have been demonstrated to increase the risk of RA and may justify regular screening for RA 73.…”