Arthritis & Rheumatism, Volume 60,
October 2009 Abstract Supplement

The 2009 ACR/ARHP Annual Scientific Meeting
Philadelphia October 16-21, 2009.


Association of Rheumatoid Arthritis (RA)-Related Autoimmunity and Joint Findings in Unaffected at-Risk Populations

Kolfenbach1,  J. R., Deane1,  K. D., Derber1,  L. A., O'Donnell1,  C., Weisman2,  M.H., Buckner3,  J.H., Mikuls4,  T. R.

U Colo Denver, Aurora, CO
Cedars-Sinai Medical Center, Los Angeles, CA
Benaroya Rsch Ini., Seattle, WA
U Nebraska, Omaha, NE
Feinstein Insititute Med Rsch, Manhasset, NY
U Chicago, Oak Park, IL
U Colo Denver

Purpose:

The presence of RA-related autoantibodies prior to diagnosis suggests that there is a pre-clinical period in RA. Prospective analysis of pre-diagnosis RA may allow for a more complete understanding of early disease pathogenesis. We have established prospective cohorts with subjects at potentially higher risk for RA based on genetic risk factors, with intent to examine RA-related autoimmunity in these populations. The purpose of our current analysis was to identify RA-related autoantibodies within these populations and to examine potential associations with clinical endpoints such as joint disease and systemic inflammation.

Methods:

We have created a prospective cohort of first-degree relatives (FDRs) of probands with RA as part of the SERA study (Studies of the Etiology of RA). FDRs without RA by ACR criteria are evaluated during a clinical research visit where joint examination and laboratory data are independently obtained. Identical analysis is performed on a second at-risk DR4-enriched population containing parents of children with high risk HLA alleles and/or Type I diabetes (DAISY parents, Diabetes and AutoImmunity Study of the Young). Prevalence of high-risk genetic markers was compared between these cohorts and the general population using control data from the North American Rheumatoid Arthritis Consortium (NARAC). Association analysis was performed by chi-square and Fisher's exact testing.

Results:

Data from 1058 FDRs and 627 DAISY parents was analyzed. Prevalence of the shared epitope (SE) (>=1 allele) was higher in the FDR and DAISY cohorts than the general population (55%, 51.6%, and 43% respectively; p < 0.01). Prevalence of the PTPN22 polymorphism (>=1 allele) was higher in FDRs than the general population (20% vs. 15.9%; p <0.05). One or more autoantibodies were detected in 15.9% of FDRs and 14.2% of DAISY parents. RF-IgM positivity in FDRs was associated with >= 1 tender joint on exam (OR 2.50, 95% CI 1.27–4.89) and elevated CRP (OR 5.31, 95% CI 1.45–19.52). In DAISY parents, RF-IgM was associated with >= 1 swollen joint (OR 4.22, 95% CI 1.80–9.93).

Conclusion:

Autoantibodies in these at-risk populations are associated with joint swelling and tenderness as well as elevated CRP. Follow-up of subjects with very early signs of clinical disease will be valuable to further understanding the factors associated with transition to a phenotype that meets full ACR or other classification criteria. In addition, these findings support the utility of further prospective analysis of at-risk populations in the study of RA development prior to clinical diagnosis.

To cite this abstract, please use the following information:
Kolfenbach, J. R., Deane, K. D., Derber, L. A., O'Donnell, C., Weisman, M.H., Buckner, J.H., et al; Association of Rheumatoid Arthritis (RA)-Related Autoimmunity and Joint Findings in Unaffected at-Risk Populations [abstract]. Arthritis Rheum 2009;60 Suppl 10 :371
DOI: 10.1002/art.25454

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