Chlamydia trachomatis – a “new/old” unconventional predictor of rheumatoid arthritis progression?

Introduction. The theory of mucosal development of rheumatoid arthritis (RA) is of considerable interest in relation to the search for unconventional predictors of RA progression, among which Chlamydia trachomatis (C. trachomatis) occupies a special place.
Objective: To study the effect of C. trachomatis on early and late outcomes of RA, as a potentially unfavorable predictor of the disease course.
Materials and methods. The study included 106 patients with a confirmed diagnosis of RA, lasting up to one year, without basic therapy. Patients were examined for the presence of C. trachomatis by PCR and ELISA and divided into two groups. The first (n = 69) included patients with C. trachomatis, the second (n = 37), patients without it. Clinical and laboratory parameters and markers of disease activity were assessed in the groups. The control group consisted of 34 healthy volunteers. The group of C. trachomatis+ patients was divided into two subgroups. The first consisted of patients (n = 30) with a course of antibacterial therapy (AB); the second, without AB therapy (n = 39). In both subgroups, the chances of development/non-development of short-term (12 months) and long-term (5; 10; 15 years) outcomes were assessed.
Results. Patients with RA with C. trachomatis were characterized by longer morning stiffness (49.1 [0.0; 102.0] vs. 14.9 [0.0; 27.2]; p = 0.043), CRP level (14.0 [0.5; 17.0] vs. 9.0 [5.0; 16.0]; p = 0.046). Eradication of C. trachomatis increased the chance of clinical and laboratory remission / low activity at 12 months of follow-up by 3.9 time (OR 3.9; 95% CI: 1.4–10.9; p = 0.009); and functional remission according to HAQ-DI by 4.3 times (OR 4.3; 95% CI: 1.4–13.5; p = 0.011) after 10 years; 8.1 times higher chance of not developing hand/foot deformities by the 5th year of observation (OR 8.1; 95% CI: 1.1–59.1; p = 0.039).
Conclusion. C. trachomatis can be considered an additional unconventional predictor of an unfavorable course of RA, the effect of which is apparently carried out indirectly through other arthritogenic factors.

For citation: Martusevich NA, Kostyuk SA, Pavlovskaya NА, Mitkovskaya NP. Chlamydia trachomatis – a “new/old” unconventional predictor of rheumatoid arthritis progression? Therapy (Moscow). 2026;12(5S):22–30.
https://doi.org/10.18565/therapy.2026.5-s5.22-30

INTRODUCTION

Rheumatoid arthritis (RA) is a chronic immune-mediated systemic inflammatory disease characterized by persistent inflammation and hyperplasia of the synovium, leading to joint erosion and damage, as well as a range of manifestations that contribute to the overall disease burden [1]. These changes are accompanied by impaired physical function, disability, and reduced quality of life, particularly because of symptoms such as pain, fatigue, and morning stiffness.

Despite major advances in understanding the mechanisms underlying the development and progression of RA and the development and implementation of novel advanced treatments, RA remains a major medical and social problem. The widespread implementation of the 2010 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification criteria, early diagnosis, and the treat-to-target strategy has substantially delayed the onset of disability, improved quality of life, and helped preserve physical function. Nevertheless, the treatment target is not always achieved even with the most current approaches, particularly in patients with difficult-to-treat RA [2].

Identifying predictors of an unfavorable RA course is an important area of research that may help optimize patient management and improve disease outcomes.

Traditional risk factors for an unfavorable RA course with rapid radiographic progression include female sex, high rheumatoid factor (RF) titers, anti-citrullinated protein antibody (ACPA) positivity, early development of joint erosions, high disease activity at onset, polyarticular involvement, carriage of HLA-Dw4 and HLA-Dw14 (HLA-DRB1*04), and lack of response to disease-modifying antirheumatic drugs within 6 months [3].

Against this background, arthritogenic microbial factors for which there is preliminary evidence of an etiologic role in RA may also warrant investigation as additional nontraditional predictors of an unfavorable disease course. In individuals at risk of RA and those with established disease, changes in the oral and gut microbiota correlate with immune activation. Specific bacterial taxa, including Segatella copri, Subdoligranulum didolesgii, Eggerthella lenta, and certain Streptococcus species, have been shown to contribute, among other effects, to RA progression through mechanisms involving molecular mimicry, antigen citrullination, trained immunity, and bacterial translocation [4].

In recent years, renewed interest in the mucosal hypothesis of RA pathogenesis has been accompanied by renewed attention to Chlamydia trachomatis (C. trachomatis) as a potential etiologic factor in RA. This interest is attributable to several factors: (a) during persistence, C. trachomatis can express heat shock protein 60 (HSP60), which shows a high degree of identity with the amino acid sequence of the corresponding human cell membrane protein, thereby promoting molecular mimicry and initiation of an immunopathologic process; (b) C. trachomatis DNA fragments have been detected in the synovial fluid of patients with RA; and (c) the infection is highly prevalent among patients with RA [5].

The first reports suggesting a possible role of C. trachomatis in the development of RA were published by Ford D.K. in 1988. He proposed that the incidental finding of lymphocyte reactivity to chlamydial antigens in the joints of patients with RA might be related to disease onset in some patients [6, 7]. In 2004, Jolly M. and Curran J.J. published the first case report describing isolation of C. trachomatis from the synovial fluid of a patient who was subsequently diagnosed with RA [8]. In Belarus, Soroka N.F. pioneered research on C. trachomatis as a possible etiologic factor in RA and described the clinical and laboratory features of C. trachomatis-associated RA [9]. A treatment approach for C. trachomatis-associated RA was also proposed. However, some of these studies were retrospective or observational, making their findings difficult to reproduce.

In 2025, the results of a prospective cohort study investigating the role of C. trachomatis in the development of RA were published [5]. The findings demonstrated an association between a history of chlamydial infection and the development of autoimmune abnormalities in first-degree relatives who subsequently developed RA.

We hypothesized that C. trachomatis, considered one of the possible etiologic factors in RA, may also serve as a predictor of an unfavorable disease course. Accordingly, this study aimed to investigate the effect of C. trachomatis on early and long-term RA outcomes and its potential role as an adverse prognostic factor in RA.

The following objectives were defined:

1. To investigate the clinical and immunologic characteristics of RA in patients with and without C. trachomatis infection;

2. To assess the odds of favorable and unfavorable RA outcomes in patients with and without C. trachomatis infection after 1, 5, and 15 years of follow-up;

3. To as...

N.A. Martusevich, S.A. Kostyuk, N. А. Paulouskaya, N.P. Mitkovskaya