Dr. Mikuls has received consulting fees, speaking fees, and/or honoraria from Amgen, Genentech, and Bristol-Myers Squibb (less than $10,000 each). Patent applications (GB0701417.8 and PCT/GB08/000267) have been filed to protect Drs. Venables and Lundberg's and Mr. Kinloch's intellectual property as coinventors of the discovery of citrullinated α-enolase peptide 1 (CEP-1) and other sequences from citrullinated α-enolase and their use in the diagnosis and treatment of rheumatoid arthritis; the coinventors receive no royalties.
Rheumatoid Arthritis Basic Science Studies
Antibodies to citrullinated α-enolase peptide 1 are specific for rheumatoid arthritis and cross-react with bacterial enolase
Version of Record online: 29 SEP 2008
Copyright © 2008 by the American College of Rheumatology
Arthritis & Rheumatism
Volume 58, Issue 10, pages 3009–3019, October 2008
How to Cite
Lundberg, K., Kinloch, A., Fisher, B. A., Wegner, N., Wait, R., Charles, P., Mikuls, T. R. and Venables, P. J. (2008), Antibodies to citrullinated α-enolase peptide 1 are specific for rheumatoid arthritis and cross-react with bacterial enolase. Arthritis & Rheumatism, 58: 3009–3019. doi: 10.1002/art.23936
- Issue online: 29 SEP 2008
- Version of Record online: 29 SEP 2008
- Manuscript Accepted: 27 JUN 2008
- Manuscript Received: 17 OCT 2007
- Arthritis Research Campaign and the Medical Research Council UK
- NIH (from the National Institute of Arthritis and Musculoskeletal and Skin Diseases). Grant Number: AR-054539
To map the antibody response to human citrullinated α-enolase, a candidate autoantigen in rheumatoid arthritis (RA), and to examine cross-reactivity with bacterial enolase.
Serum samples obtained from patients with RA, disease control subjects, and healthy control subjects were tested by enzyme-linked immunosorbent assay (ELISA) for reactivity with citrullinated α-enolase peptides. Antibodies specific for the immunodominant epitope were raised in rabbits or were purified from RA sera. Cross-reactivity with other citrullinated epitopes was investigated by inhibition ELISAs, and cross-reactivity with bacterial enolase was investigated by immunoblotting.
An immunodominant peptide, citrullinated α-enolase peptide 1, was identified. Antibodies to this epitope were observed in 37–62% of sera obtained from patients with RA, 3% of sera obtained from disease control subjects, and 2% of sera obtained from healthy control subjects. Binding was inhibited with homologous peptide but not with the arginine-containing control peptide or with 4 citrullinated peptides from elsewhere on the molecule, indicating that antibody binding was dependent on both citrulline and flanking amino acids. The immunodominant peptide showed 82% homology with enolase from Porphyromonas gingivalis, and the levels of antibodies to citrullinated α-enolase peptide 1 correlated with the levels of antibodies to the bacterial peptide (r2 = 0.803, P < 0.0001). Affinity-purified antibodies to the human peptide cross-reacted with citrullinated recombinant P gingivalis enolase.
We have identified an immunodominant epitope in citrullinated α-enolase, to which antibodies are specific for RA. Our data on sequence similarity and cross-reactivity with bacterial enolase may indicate a role for bacterial infection, particularly with P gingivalis, in priming autoimmunity in a subset of patients with RA.