Dr. Utz has received consulting fees (less than $10,000) from Genentech.
Antigen microarray profiling of autoantibodies in rheumatoid arthritis
Article first published online: 2 SEP 2005
Copyright © 2005 by the American College of Rheumatology
Arthritis & Rheumatism
Volume 52, Issue 9, pages 2645–2655, September 2005
How to Cite
Hueber, W., Kidd, B. A., Tomooka, B. H., Lee, B. J., Bruce, B., Fries, J. F., Sønderstrup, G., Monach, P., Drijfhout, J. W., van Venrooij, W. J., Utz, P. J., Genovese, M. C. and Robinson, W. H. (2005), Antigen microarray profiling of autoantibodies in rheumatoid arthritis. Arthritis & Rheumatism, 52: 2645–2655. doi: 10.1002/art.21269
- Issue published online: 2 SEP 2005
- Article first published online: 2 SEP 2005
- Manuscript Accepted: 13 JUN 2005
- Manuscript Received: 31 MAR 2005
- Arthritis National Research Foundation Fellowship award
- FOCIS/Weiland Family Fellowship award
- NIH. Grant Number: AR-043584
- Abbot Scholar Award for Rheumatology Research
- Arthritis Foundation
- NIH (National Heart, Lung and Blood Institute [NHLBI])
- NIH (National Institute of Arthritis and Musculoskeletal and Skin Diseases)
- NIH. Grant Number: K08-AR-02133
- NHLBI Proteomics contract. Grant Number: N01-HV-28183
- Arthritis Foundation Chapter grants
- Investigator Award
- Veterans Affairs Health Care System funding
Because rheumatoid arthritis (RA) is a heterogeneous autoimmune disease in terms of disease manifestations, clinical outcomes, and therapeutic responses, we developed and applied a novel antigen microarray technology to identify distinct serum antibody profiles in patients with RA.
Synovial proteome microarrays, containing 225 peptides and proteins that represent candidate and control antigens, were developed. These arrays were used to profile autoantibodies in randomly selected sera from 2 different cohorts of patients: the Stanford Arthritis Center inception cohort, comprising 18 patients with established RA and 38 controls, and the Arthritis, Rheumatism, and Aging Medical Information System cohort, comprising 58 patients with a clinical diagnosis of RA of <6 months duration. Data were analyzed using the significance analysis of microarrays algorithm, the prediction analysis of microarrays algorithm, and Cluster software.
Antigen microarrays demonstrated that autoreactive B cell responses targeting citrullinated epitopes were present in a subset of patients with early RA with features predictive of the development of severe RA. In contrast, autoimmune targeting of the native epitopes contained on synovial arrays, including several human cartilage gp39 peptides and type II collagen, were associated with features predictive of less severe RA.
Proteomic analysis of autoantibody reactivities provides diagnostic information and allows stratification of patients with early RA into clinically relevant disease subsets.