SAN FRANCISCO — The identification of 14 target antigens and autoantibody markers for rheumatoid arthritis could help improve early diagnosis, especially in patients who are negative for conventional markers of the disease.
Eleven novel antigen-antibody systems that are specific to rheumatoid arthritis and three that are associated with the disease were identified by applying an autoantibody-profiling procedure based on cDNA phage display to clones of synovial tissue from 92 patients with rheumatoid arthritis (RA), 30 rheumatic controls, and 38 healthy controls, Klaartje Somers reported at the annual meeting of the Federation of Clinical Immunology Societies.
Combining the 11 RA-specific antigen clones into a panel produced 100% specificity and 37% sensitivity for diagnosis. Using all 14 antigen clones in a panel decreased the specificity to 85% but increased sensitivity to 53%. By deleting one of the RA-associated antigen clones and using the other 13 markers, specificity improved to 90% and the sensitivity remained at 53%, said Ms. Somers of Hasselt (Belgium) University, Diepenbeek.
Individually, 9 of 14 clones produced antibody reactivity significant enough to discriminate between RA patients and controls, according to results of ROC (receiver operating characteristics) analyses.
“Very interesting” findings emerged when the panel of 14 target antigens was applied to cloned synovial fluid from 31 patients with RA who were negative for one or two conventional markers of the disease—rheumatoid factor and/or anti-cyclic citrullinated peptide antibodies (ACPA), she said. Among these patients, 17 (55%) produced antibodies against the panel of 14 antigens.
Combining the panel's results with testing for rheumatoid factor and ACPA increased the sensitivity for diagnosis of RA, she added. In general, approximately a third of patients with established RA and a higher proportion with early RA will be negative for rheumatoid factor and/or ACPA. In the current study, a positive test for rheumatoid factor and/or ACPA carried a 54% sensitivity in detecting RA.
The sensitivity for diagnosis increased to 71% with testing for the two conventional markers plus applying the 11-clone panel of novel RA-specific antigens, and increased further (to 79%) with testing for the two conventional markers plus the 14-clone panel of new markers, Ms. Somers and her associates reported.
Three of the clones showed exclusive immunoreactivity in RA patients who were negative for rheumatoid factor and ACPA, who may represent a subset of all patients with RA, she said.
Antibodies to the new target antigens could be detected in early-phase RA and were significantly associated with higher levels of C-reactive protein (indicative of greater inflammation) both at the first sampling and in follow-up samples.
Preliminary immunohistochemical testing for individual novel antigens on some of the initial synovial tissue samples produced increased staining in patients with RA but not in controls, indicating increased expression of these antigens in patients with RA. “That could be an explanation for the autoantibody production that we have identified,” Ms. Somers said.
Ms. Somers reports no conflicts of interest related to this study.
http://www.rheumatologynews.com/article/S1541-9800(09)70183-8/fulltext.
“Very interesting” findings emerged when the panel of 14 target antigens was applied to cloned synovial fluid from 31 patients with RA who were negative for one or two conventional markers of the disease—rheumatoid factor and/or anti-cyclic citrullinated peptide antibodies (ACPA), she said. Among these patients, 17 (55%) produced antibodies against the panel of 14 antigens.
http://www.rheumatologynews.com/article/S1541-9800(09)70183-8/fulltext