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Proteus Infection May Be Linked to Rheumatoid Arthritis

Patients with rheumatoid arthritis (RA) have been have significantly elevated IgG and IgM antibodies to Proteus mirabilis and antibodies to both EQRRAA and ESSRAL peptides, according researchers in both Finland and Japan.

A total of 230 serum samples from patients with RA or systemic lupus erythematous (SLE) and from healthy controls were collected by T. Rashid and colleagues from Kings College in London, Helsinki University Hospital in Finland, the Shiga University of Medical Science, and Juntendo University, both in Japan. The subjects were then screened for total and class-specific antibodies against P. mirabilis, Escherichia coli and Serratia marcescens by indirect immunofluorescence assay. They were also tested to determine levels of isotypic antibodies against the shared epitope containing EQRRAA and ESSRAL peptides using enzyme-linked immunosorbent assay (ELISA).

Elevated levels of Proteus IgG antibodies were seen in Finnish patients with early (<12 months) and advanced RA compared to healthy controls (P < .001 early, P < .001 advanced). Similar elevations of the IgM Proteus antibody were seen in both Finnish RA groups when compared to controls. This pattern also followed for Proteus IgG and IgM antibodies in the Japanese cohorts against both healthy controls and patients with SLE. In both countries, no significant increases in antibody levels were seen against either E. coli or S. marcescens.

Significant elevations were mainly seen in the IgG class of antibodies to EQRRAA and ESRRAL peptides in both early and advanced RA patients in Finland. Again, the same basic pattern was seen in the Japanese patients when compared to healthy controls and those with SLE.

Finally, when total antibody levels against each of the tested microorganisms were compared with antibodies to EQRRAA and ESRRAL peptides among both Finnish and Japanese patients with RA, significant correlations were only observed between anti-Proteus and anti-QQRRAA (R= .79, P < .001) and anti-ESRRAL (R=.86, P < .001) peptide antibodies. In contrast, no significant correlation was found between E. coli or Serratia antibodies and the two peptides.

"Our findings of increased antibodies to Proteus but not E. coli or S. marcescens is a remarkable observation, as all these bacteria carry in their primary structure the homologous RA susceptibility sequence," said Dr. Rashid. "This characteristic provides strong evidence that RA patients have been infected by Proteus bacteria, probably in the upper respiratory tract, but not by E. coli or S. marcescens."



Clin Rheumatol 2004 Apr;12:134-41. "Antibacterial and antipeptide antibodies in Japanese and Finnish patients with rheumatoid arthritis"

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