Clinical Investigation
Chlamydia trachomatis Is Present and Metabolically Active During the Remitting Phase in Synovial Tissues From Patients With Chronic Chlamydia-induced Reactive Arthritis

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Abstract

Background

Patients with chronic Chlamydia-induced reactive arthritis (ReA) often show a remitting-relapsing disease phenotype. Some information regarding bacterial and host responses to one another during active disease is available but no information for quiescence. This article presents the first molecular genetic insight into the behavior of bacterium and host during remitting ReA.

Methods

Synovial biopsies were procured from the knees of 4 patients with quiescent ReA by the Parker-Pearson technique. Nucleic acids prepared from them were analyzed by real-time polymerase chain reaction (PCR) and reverse transcription–PCR, and results were compared with data averaged from the knee synovial tissue samples of 10 patients with active ReA.

Results

Real-time PCR indicated that bacterial load in remitting samples was approximately 20% of that in active disease samples. Transcripts from the p60-encoding gene were equal to or higher than those seen in active disease. Messenger RNAs (mRNAs) from the paralog p60-encoding genes were equal to or lower than those of active disease. Host mRNAs encoding interleukin-10, tumor necrosis factor-α and interferon-γ were 4-fold lower than those in active disease samples, whereas monocyte chemotactic protein 1 and regulated upon activation, normal t-cell expressed, and secreted mRNA levels were equal to or higher.

Conclusions

Bacterial load in synovial tissue of patients with remitting disease is lower than that of active disease, but mRNAs encoding proinflammatory proteins are equal to or higher than those of active disease. Transcription in the host is attenuated for cytokines and chemokines. These initial results demonstrate that organism is present and metabolically active in synovium during the remitting phase of chronic Chlamydia-induced ReA and that the genetic events characterizing quiescence are complex.

Section snippets

Patient Samples

Not surprisingly, it is difficult to obtain samples from patients in the remitting/quiescent phase of chronic Chlamydia-induced ReA. However, one of the authors (J.D.C.) was able to obtain synovial biopsies from 4 consenting patients, under an approved protocol; these were patients 1, 2, 3 and 7 in a continuing study. With one exception, all were single samples from individuals with quiescent disease; the exception was 2 samples from one patient, the first (sample 7A) was obtained during

Bacterial Load and Levels of Selected Chlamydial Transcripts During Quiescent ReA

We first assessed whether chlamydiae were present in synovial tissue in patients with remitting disease, and if so, what the bacterial load was in the samples compared with values for load averaged from congruent freezer library samples from 10 patients with well-characterized, active Chlamydia-induced arthritis (Table 3). Standard PCR analyses indeed showed that the organism was present in each remitting sample (data not shown), and as shown in Figure 1A, the relative level of C trachomatis

DISCUSSION

Chlamydia trachomatis, the causative agent in Chlamydia-induced arthritis, exists in synovial tissues in the persistent infection form rather than the form characteristic of active infection2., 3., 4., 7. for review. In this state, chlamydiae display an unusual transcript profile compared with that seen during normal active infection,4., 11., 14., 15. and we hypothesized that if the organism is indeed present in synovial tissue during the remitting disease phase, then the significantly lower

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The authors declare no conflicts of interest.

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