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Rheumatology Advance Access published online on August 9, 2005
Rheumatology, doi:10.1093/rheumatology/kei036
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© The Author 2005. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oupjournals.org
Received May 16, 2005
Accepted June 24, 2005

Original Papers

Elevated levels of IgM and IgA antibodies to Proteus mirabilis and IgM antibodies to Escherichia coli are associated with early rheumatoid factor (RF)-positive rheumatoid arthritis

M. M. Newkirk 1*, R. Goldbach-Mansky 2, B. W. Senior 3, J. Klippel 4, H. R. Schumacher Jr5, and H. S. El-Gabalawy 6

1 McGill University Health Centre, Montreal, Quebec, Canada; The first two authors contributed equally to this work
2 Arthritis and Rheumatism Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD; The first two authors contributed equally to this work; University of Pennsylvania and VA Medical Center, Philadelphia, PA
3 Department of Molecular and Cellular Pathology, University of Dundee, Dundee, UK
4 Arthritis Foundation, Atlanta, GA
5 University of Pennsylvania and VA Medical Center, Philadelphia, PA
6 Division of Rheumatology, University of Manitoba, Winnipeg, Manitoba, Canada

* To whom correspondence should be addressed.
M. M. Newkirk, E-mail: Marianna.newkirk{at}mcgill.ca


  Abstract

Objective. Antibodies to Proteus mirabilis were previously detected in patients with established rheumatoid arthritis (RA). We examined the prevalence of antibodies to P. mirabilis and their associations with RA in early synovitis patients.

Methods. Two hundred and forty-six patients with inflammatory arthritis for less than 1 yr were prospectively evaluated for 1 yr. Of these patients, 30% had rheumatoid factor (RF)-positive RA, 16% RF-negative RA, 17% a spondyloarthropathy and 37% undifferentiated arthritis. Serum antibodies to P. mirabilis, Escherichia coli and other potentially arthritogenic organisms (Chlamydia, Salmonella, Shigella, Campylobacter, Yersinia and parvovirus B19) and for antibodies specific for immunoglobulin (Ig) G damaged with advanced glycation end-products (anti-IgG-AGE) were measured.

Results. IgM and IgA anti-Proteus antibodies were significantly higher in patients with RF-positive RA compared with all other patient groups (P<0.0005 and P<0.005). Anti-P. mirabilis IgG, and IgG, IgA, and IgM antibodies to other potentially arthritogenic pathogens did not differ in the patient groups. IgM antibodies to E. coli were elevated in RF-positive RA patients. Anti-P. mirabilis IgM and IgA results were not explained by false-positive reactions, because after absorption of RF there was no decrease in antibodies to Proteus in 10 of 12 patients. Proteus and E. coli antibodies were highest in patients positive for both RF and anti-IgG-AGE antibodies (P<0.001). Patients with erosions tended to have higher IgA anti-Proteus titres, but no association with the shared HLA epitope or treatment was detected.

Conclusion. Anti-P. mirabilis IgM and IgA and anti-E. coli IgM antibody elevations are associated with early seropositive RA and the presence of anti-IgG-AGE antibodies. The role that P. mirabilis or E. coli plays in early RF-positive RA requires further investigation.

Keywords: Proteus antibodies; Early synovitis; Rheumatoid arthritis; Rheumatoid factor; Spondylarthritis.
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