Being Male Found to Significantly Influence the Development of RA

A team of researchers, lead by Lindsey A. Criswell, M.D., M.PH, from the University of California examined families with a history of RA among both their female and male members to investigate how the disease affects the sexes differently. The results were presented in the October 2006 issue of Arthritis & Rheumatism.

Currently two million adults in the United States suffer from RA, the female to male ratio of which is three to one. Among women, disease occurrence increases from the age of puberty and peaks around menopause; while RA is rare in men under age 45. These trends have prompted numerous studies into the role of hormones in the development of RA. However, sex differences in specific risk factors, disease expression, and response to treatment have remained largely unexplored until recently.

The study focused on 1,004 affected members of 467 Caucasian families within which two or more siblings met the American College of Rheumatology (ACR) criteria for RA. All families were recruited from the North American Rheumatoid Arthritis Consortium, a resource for gene mapping studies. Each RA patient was interviewed to collect relevant personal details, including age at onset of RA symptoms, age at RA diagnosis, medication history, and smoking history. Each patient was examined for joint tenderness, completed a Health Assessment Questionnaire (HAQ), and underwent radiographs of the hands and wrists to evaluate bone erosions. Each patient was also genotyped for markers in the HLA region and tested for two hallmarks of the disease: rheumatoid factor (RF) and antibodies to cyclic citrullinated peptides (CCP).

Comparisons of demographic and clinical features between men and women with RA revealed several differences. Although male patients had significantly later onset of RA, they showed harsher signs of the disease, were more likely to test positive for RF factor and anti-CCP antibodies, and had higher concentrations of auto-antibodies than female patients. Men were also found to be significantly more likely to have a history of smoking. Female patients had significantly higher HAQ scores, which translates into poorer function, and were more likely to have other autoimmune diseases, particularly autoimmune thyroid disease, than male patients.

The most notable finding involved women who shared RA with a brother. Among them, the presence and production of anti-CCP antibodies was significantly higher than among female patients without an affected male sibling. These findings suggest that the sisters of men with RA are approximately twice as likely to be anti-CCP autoantibody positive and to have higher anti-CCP titers as the general population of women with RA. The researchers also concluded that increased production of anti-CCP antibodies appears to be a feature of families with affected males rather than an inherent characteristic of male RA patients.

The team insisted that additional studies of families with affected males will be helpful in identifying additional genetic or other risk factors.

Article References
Sex Difference in Rheumatoid Arthritis, site accessed on 10/10/2006.