title: 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.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: McGill University Health Centre, 1650 Cedar Ave., Montreal, QC, Canada H3G 1A4. Marianna.newkirk@mcgill.ca
authors.forename: M M
authors.initials: MM
authors.lastname: Newkirk
authors.forename: R
authors.initials: R
authors.lastname: Goldbach-Mansky
authors.forename: B W
authors.initials: BW
authors.lastname: Senior
authors.forename: J
authors.initials: J
authors.lastname: Klippel
authors.forename: H R
authors.initials: HR
authors.lastname: Schumacher
authors.forename: H S
authors.initials: HS
authors.lastname: El-Gabalawy
mesh_terms: D000328:Adult; D000888:Antibodies, Anti-Idiotypic / Q000097:blood; D000907:Antibodies, Bacterial / Q000097:blood*; D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000382:microbiology; D015415:Biomarkers / Q000097:blood; D004926:Escherichia coli / Q000276:immunology*; D005260:Female; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011513:Proteus mirabilis / Q000276:immunology*; D012217:Rheumatoid Factor / Q000097:blood*; D025241:Spondylarthritis / Q000276:immunology / Q000382:microbiology; D013585:Synovitis / Q000276:immunology / Q000382:microbiology
chemical_list: D000888:Antibodies, Anti-Idiotypic; D000907:Antibodies, Bacterial; D015415:Biomarkers; D007070:Immunoglobulin A; D007075:Immunoglobulin M; C048844:anti-IgG; D012217:Rheumatoid Factor