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The possibility that some bacterial-specific factor(s) may play a role in triggering Chlamydia trachomatis reactive arthritis was investigated.Since the variable domains of the major outer membrane protein (MOMP) contain the serovar-determining epitopes of C trachomatis, the ability of serum IgG to recognize peptides mimicking these epitopes was determined in 2 groups of infected patients, one with and the other without reactive arthritis. Because asymptomatic C trachomatis infections are frequent, and nonspecific reactions due to inflammation could be observed, this study was also performed with samples from healthy blood donors and from patients with inflammatory arthritis unrelated to C trachomatis infection.A predominant reactivity against peptides duplicating the J serovar-specific epitopes was only observed in the group of patients with reactive arthritis. For positive samples, differences between the two groups of C trachomatis-infected patients were clearly observed. The mean numbers of positive responses obtained for each of the 7 peptides of the MOMP domain I or each of the 8 peptides of the MOMP domain IV were significantly higher for samples from patients with reactive arthritis (4.7 and 6) than for those from patients with only C trachomatis urogenital infection (1.3 and 2.9).Patients with reactive arthritis had a pattern of reactivities that was compatible with infection by several serotypes of bacteria. Repeated exposures to C trachomatis might therefore be involved in the development of the disease.