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Detection of Latent Tuberculosis Infection in Patients with Rheumatological Diseases Who Receive Immunosuppressive
Anna Starshinova1,2,3, Adilia Sabirova2,3, Alexey Maslyanskiy1,4
1Almazov National Research Medical Center, 197341 St. Petersburg, Russia.
Abstract:
Background/Objectives: Latent tuberculosis infection (LTBI) is a persistent immune response to Mycobacterium tuberculosis antigens in the absence of clinically active tuberculosis. It is now established that progression from LTBI to active tuberculosis is directly associated with immune dysregulation, which frequently occurs in immune-mediated diseases requiring treatment with immunosuppressive agents. The aim of this study was to identify LTBI in patients with rheumatological diseases receiving immunosuppressive therapy using contemporary immunodiagnostic methods. Materials and Methods: A retrospective, prospective, group-control study was conducted, analyzing the results of immunodiagnostics in patients with rheumatological diseases on immunosuppressive therapy and without established contact with tuberculosis patients (n = 44; main group). The control group consisted of healthy individuals (n = 51) with no history of tuberculosis contact, clinical or radiological manifestations of the disease, or signs of chronic pathology exacerbation. Both groups were predominantly female (72.7% in the main group and 62.8% in the control group). The mean age in the patient group was 49.1 years (95% CI [44.77; 53.43]). Rheumatoid arthritis was diagnosed in 29.6% (13) of patients (95% CI [16.06; 43.03]). Articular syndrome was observed in at least 72.7% (32) of patients (95% CI [59.57; 85.89]). In 54.6% (24) of cases (95% CI [39.83; 69.26]), patients received biologic immunosuppressive therapy as basic treatment. In 15.9% (7) of cases (95% CI [5.10; 26.72]), patients received conventional synthetic disease-modifying antirheumatic drugs (DMARDs). Of these, 71.43% (5) (95% CI [35.24; 92.44]) underwent comprehensive examination to exclude active tuberculosis prior to biologic therapy initiation. For immunodiagnostics, all subjects underwent an interferon-gamma release assay (IGRA) and/or testing with a recombinant tuberculosis antigen (ATR) sample, with dynamic assessment of test results. All patients with positive immunodiagnostic results underwent multidetector computed tomography of the chest organs. The level of LTBI in the comparison groups was defined as the percentage of positive immunological test results at a significance level of p < 0.05. Statistical data processing was performed using Microsoft Excel 2019. Results: In the main group, positive immunodiagnostic results were recorded in 20.5% (9) of cases (95% CI [8.54; 32.37]), which is significantly higher than in the control group of healthy individuals (5.8% (3), 95% CI [1.41; 16.54]). This reflects statistically significant differences in immunological test results between groups receiving and not receiving immunosuppressive therapy (χ2 = 4.545, p = 0.034). Dynamic evaluation of the ATR sample revealed positive results in 21.7% (5) of cases (95% CI [4.88; 38.60]), with four out of five patients demonstrating positive conversion. In the third assessment, positivity was observed in 33.33% (5) of cases (95% CI [9.48; 57.19]), which was higher than in the first (χ2 = 1.025, p = 0.312) and second assessments (χ2 = 0.629, p = 0.428), although these differences were not statistically significant. Notably, in two out of five patients, the ATR test result changed from negative to positive. Conclusions: In patients with rheumatological diseases receiving immunosuppressive therapy, LTBI was detected in 20.5%, which is significantly higher than in healthy individuals (5.8%, p = 0.034). Furthermore, there was an increase in the proportion of positive tests over time (up to 21.7% and 33.3% on immunotherapy), suggesting an increasing risk of progression to active tuberculosis infection.
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