Patients with Chlamydia-associated arthritis have ocular (trachoma), not genital, serovars of C. trachomatis in synovial tissue

Abstract

Some individuals with a genital Chlamydia trachomatis infection develop inflammatory arthritis, but it is unknown whether particular chlamydial serovar(s) engender the disease more often than others. We defined serovar in synovial tissues from arthritis patients infected with this organism. DNA from synovial biopsies of 36 patients with PCR-confirmed synovial C. trachomatis was analyzed. Diagnoses included reactive arthritis, undifferentiated oligoarthritis, rheumatoid arthritis, and osteoarthritis. The chlamydial omp1 and trpA genes were amplified, cloned, and 10 or more clones from each sample were sequenced. The cytotoxin locus also was analyzed. omp1 sequences showed 2 patients having only C. trachomatis A serovar, 1 with only B, and 33 having only C, all ocular serovars. Analyses of trpA and the cytotoxin locus uniformly displayed standard ocular serovar characteristics for each patient. Identification of ocular chlamydial serovars in the synovia of arthritis patients is unexpected. These observations suggest that urogenital chlamydial infections, while consisting primarily of organisms of genital serovars, include some of ocular serovar(s). They further suggest that during such infections unknown selection pressures favor establishment of the latter in the synovium to the exclusion of genital serovar chlamydiae.

Figure 1

Predicted omp1 (major outer membrane protein) amino acid sequence deduced from DNA sequences from synovial tissues of 4 representative arthritis patients (#11, 13, 15, 18) compared to the prototype C serovar sequence (C). Nonconserved amino acids are indicated by bold underlined capital letters. Patient samples are from Tampa (patient 18) and from Philadelphia (patients 11, 15, 13).

Figure 2

Representative DNA sequences from the trpA gene of C. trachomatis from selected patient samples. These included patients #5 and #32, both of whom had C serovar as judged from omp1 sequence, #7, who had A serovar from the omp1 sequence, and #36, who had B serovar as judged from the omp1 sequence. PCR amplification, cloning, and sequence determination were done as described in Patients and Methods. Below the patient trpA sequences the congruent sequence from serovars A, B, and C, and from the Group I genital serovars G, F, I, H, and J, are included for comparison [22].

Figure 3

The DNA sequence of one trpA clone from patient 2 displaying recombined elements containing in part the ocular type sequence (underlined) and in part the Group II genital type sequence (italics). PCR amplification, cloning, and sequence determination were done as described in Patients and Methods.

Figure 4

Representative PCR amplifications to assess the deletion in the plasticity zone on the C. trachomatis chromosome, in the region of the cytotoxin locus. PCR amplification, and display on standard 1% agarose gels, were as described in Patients and Methods. Lanes are: 1, 1 kbp size stds; 2, positive control (A serovar DNA as template); 3, positive control (K serovar DNA as template); 4, negative control (water as template); 5, 7, 8, DNA from patients 1, 11, 29; 6, DNA from an irrelevant (PCR-negative) patient. Ocular serovars produce a PCR product of about 1850 bp, while Group I genital serovars product a PCR product of about 900 bp. See [22].