A patent application that includes Drs. Deane, Robinson, and Holers has been filed for the use of biomarkers to predict clinically actionable events in rheumatoid arthritis, and royalties have been received for this patent. In addition, licensing agreements regarding the use of biomarkers have been established.
Relatives Without Rheumatoid Arthritis Show Reactivity to Anti–Citrullinated Protein/Peptide Antibodies That Are Associated With Arthritis-Related Traits: Studies of the Etiology of Rheumatoid Arthritis†
Article first published online: 26 JUL 2013
Copyright © 2013 by the American College of Rheumatology
Arthritis & Rheumatism
Volume 65, Issue 8, pages 1995–2004, August 2013
How to Cite
Young, K. A., Deane, K. D., Derber, L. A., Hughes-Austin, J. M., Wagner, C. A., Sokolove, J., Weisman, M. H., Buckner, J. H., Mikuls, T. R., O'Dell, J. R., Keating, R. M., Gregersen, P. K., Robinson, W. H., Holers, V. M. and Norris, J. M. (2013), Relatives Without Rheumatoid Arthritis Show Reactivity to Anti–Citrullinated Protein/Peptide Antibodies That Are Associated With Arthritis-Related Traits: Studies of the Etiology of Rheumatoid Arthritis. Arthritis & Rheumatism, 65: 1995–2004. doi: 10.1002/art.38022
- Issue published online: 26 JUL 2013
- Article first published online: 26 JUL 2013
- Accepted manuscript online: 10 JUN 2013 08:56AM EST
- Manuscript Accepted: 9 MAY 2013
- Manuscript Received: 27 JUL 2012
- NIH (National Institute for Arthritis and Musculoskeletal and Skin Diseases). Grant Numbers: R01-AR-051394, T32-AR-007534-25
- National Institute of Allergy and Infectious Diseases Autoimmunity Prevention Center. Grant Number: U19-AI-050864
- Rheumatology Research Foundation. Grant Number: Within Our Reach grant II-T-11-14
- Walter S. and Lucienne Driskill Foundation
To examine reactivity to anti–citrullinated protein/peptide antibodies (ACPAs) and determine associations between ACPAs and other rheumatoid arthritis (RA)–related autoantibodies and clinically assessed swollen or tender joints in unaffected first-degree relatives of RA patients.
Serum samples were obtained from first-degree relatives without RA according to the 1987 American College of Rheumatology (ACR) and the 2010 ACR/European League Against Rheumatism classification criteria. A bead-based assay was used to measure 16 separate ACPAs in sera from 111 antibody-positive first-degree relatives who were positive on at least 1 visit for any of 5 RA-related autoantibodies (rheumatoid factor [RF], anti–cyclic citrullinated peptide 2 [anti–CCP-2], and RF isotypes), and sera from 99 antibody-negative first-degree relatives who were never autoantibody positive. Cutoffs for positivity for each ACPA were determined using receiver operating characteristic curves derived from data on 200 RA patients and 98 blood donor controls, in which positivity for ≥9 ACPAs had 92% specificity and 62% sensitivity for RA. In first-degree relatives, ACPA reactivity was assessed, and associations between ACPAs (number positive, and positivity for ≥9 ACPAs) and RA-related characteristics were examined.
Fifty-seven percent of anti–CCP-2–positive first-degree relatives and 8% of anti–CCP-2– negative first-degree relatives were positive for ≥9 ACPAs. After adjusting for age, sex, ethnicity, and pack-years of smoking, an increasing number of ACPAs was directly associated with the presence of ≥1 tender joint on examination (odds ratio [OR] 1.18, 95% confidence interval [95% CI] 1.04–1.34), with the greatest risk of having ≥1 tender joint seen in first-degree relatives positive for ≥9 ACPAs (OR 5.00, 95% CI 1.37–18.18).
RA-free first-degree relatives (even those negative for RF and anti–CCP-2) demonstrate reactivity to multiple ACPAs, and the presence of an increasing number of ACPAs may be associated with signs of joint inflammation. Prospective evaluation of the relationship between these findings and the progression of classifiable RA is warranted.