ORIGINAL ARTICLE S. Chandrashekara Æ M.N. Ramesh Æ A. Shobha Y. Saravanan Æ H.S. Vadiraja Æ B.V. Navaneeth M.R. Sandhya Belwadi Proteus mirabilis and rheumatoid arthritis: no association with the disease Received: 12 September 2002 / Accepted: 7 March 2003 Ó Clinical Rheumatology 2003 Abstract Proteus mirabilis (PM) is implicated in differ- ent studies in the pathogenesis of rheumatoid arthritis (RA) because of the structural homogeneity of its haemolysin B precursor with EQRRAA sequences in DRB 1 haplotype. The aim of the study was to compare the levels of antibodies specific to PM in the sera of patients with RA and healthy controls in our popula- tion. Serum samples from 78 consecutive RA patients and 75 healthy controls were analysed for the presence of IgG isotype and total immunoglobulins (IgG+ IgA+IgM) against PM using enzyme-linked immuno- sorbent assay (ELISA) with two kinds of antigen prep- aration, whole bacteria and SDS-lysed bacterial extract. There was no significant increase in the concentrations of anti-Proteus antibodies (APA) in patients with RA compared to healthy controls in our population, when SDS-lysed bacterial extract or whole bacteria were used as antigen. The APA levels did not correlate with serum CRP levels. Infection with P. mirabilis is found to have no pathological or aggravating role in RA. Keywords Anti-Proteus antibodies Æ Proteus mirabilis Æ Rheumatoid arthritis Abbreviations APA anti-Proteus antibodies Æ CRP C-reactive protein Æ HLA human leukocyte antigen Æ HRP horseradish peroxidase Æ OD optical density Æ OPD o-phenylene diamine Æ PBS phosphate- buffered saline Æ PM Proteus mirabilis Æ RF rheumatoid factor Æ SDS sodium dodecyl sulphate Introduction The aetiology of rheumatoid arthritis (RA) is not clear, both environmental and genetic factors having been implicated in its development. Infection is one of the leading environmental factors blamed for the develop- ment of the disease [1]. Both bacterial and viral infections have been implicated; prominent among these is Proteus mirabilis (PM) infection [1] because one of its hexamer sequences (surface membrane haemolysin B precursor sequence) is similar to the amino acid sequence in the DRB1 haplotype EQRRAA [1]. In their study, Tiwana et al. demonstrated strong reactivity in the sera of RA patients against a 16 amino acid synthetic peptide sequence derived from PM [2]. Similarly different studies have observed elevated levels of antibodies against PM in active RA compared to healthy controls, as well as in inactive RA, using different antigen preparations [3,4]. In a study employing culture technique to demonstrate PM, the probable presence of asymptomatic but non-signifi- cant levels of PM infection was observed more frequently in active RA than in controls [5]. In a developing country like India enterobacterial infection rates are high. Therefore, studies in this subcontinent could ascertain the rate of PM infection in RA. This prompted us to compare serum antibody titres against PM in the com- munity with those of RA patients. In order to avoid differences arising as a result of the use of different antigen preparations, we used two types: whole, and SDS-lysed bacterial extract. To avoid the influence of nosocomial infection, patients admitted to hospital in the previous 2 months were excluded from the study. Patients and methods Serum samples Serum samples were obtained from 78 consecutive RA patients with a mean age of 44 years (range 19–79) and C-reactive protein (CRP) >10 mg/l attending the Department of Clinical Immunology Clin Rheumatol (2003) 22: 218–220 DOI 10.1007/s10067-003-0713-6 S. Chandrashekara (&) Æ M.N. Ramesh Æ A. Shobha Y. Saravanan Æ H.S. Vadiraja Æ B.V. Navaneeth M.R. Sandhya Belwadi Department of Clinical Immunology, M.S. Ramaiah Medical College, MSRIT Nagar, Mathikere, Bangalore 560054, India e-mail: chandrashekara_s@yahoo.com Tel.: +91-080-3444737 Fax: +91-080-3601924