Epstein-Barr virus serologic abnormalities and risk of rheumatoid arthritis among women

Abstract

Background: Epstein-Barr virus (EBV) infection and the immune response may be involved in the pathogenesis of rheumatoid arthritis (RA). Past studies have suggested an association between EBV and RA. Methods: We studied the association between EBV serologies and RA risk in a nested case-control study in the Nurses' Health Study (NHS) cohorts. We confirmed incident RA cases from 1990 to 2002 by questionnaire and medical record review. Each incident case with blood collected prior to RA symptoms was matched with a healthy participant by time of day and date of blood collection, birth year, menopausal status and postmenopausal hormone use. Immunofluorescence assays measured serologic EBV responses: viral capsid antigen, early-antigen-diffuse and early antigen-complex (restricted and diffuse), Epstein Barr nuclear antigen (EBNA)-1, EBNA-2 and cytomegalovirus (CMV), as control. All were reported as titers, except CMV, which was reported as positive or negative. Antinuclear antibody positive samples were excluded. Elevated EBV antibody titers were defined as the upper 20% (or nearest titer) among controls. Conditional logistic regression analyses modeled RA risk associated with elevated EBV titers or the presence/absence of CMV, further adjusted for pack-years smoking and alcohol intake. Results: Eighty-seven incident RA cases were identified. Mean time to RA after blood draw was 6.2 ( ± 3.5) years in NHS and 1.9 ( ± 0.6) years in NHS II. Antibody titers against EBV were not significantly different between pre-RA cases and controls. Conclusions: In this prospective study of women, we observed no association between EBV serologies and RA risk.

Keywords::

• Rheumatoid arthritis
• epstein Barr virus
• virus
• risk factors
• epidemiology

Acknowledgements

The authors thank Frank Speizer, Susan Hankinson, and Walter Willett as well as Kim Bertrand and Karen Corsano for their assistance. We would also like to thank Frederick C. S. Wang, MD and William Marshall, MD, for their EBV knowledge and expertise.

Declaration of interest: Funded by NIH grants AR42630, CA87969, CA50385, R01 AR49880, K24 AR0524-01, UL1 RR025758, and R01 AR59073. The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.