COMPARISON OF THE DIAGNOSTIC INFORMATIVE VALUE OF DETERMINATION OF MRNA OF SOME HOMEOSTATIC AND PROINFLAMMATORY CYTOKINES IN THE SYNOVIAL MEMBRANE OF PATIENTS WITH RHEUMATOID ARTHRITIS

The problem of the early diagnosis of rheumatoid arthritis (RA) remains relevant, which is associated with the limited potential of available biomarkers and the heterogeneity of the disease. Chemokines and cytokines produced by the synovial membrane of the patients play a leading role in the pathogenesis of the disease, suggesting that they may be used as promising biomarkers.

Objective: to comparatively investigate the relative mRNA expression of the homeostatic chemokines: stromal cellderived factor 1 (SDF-1/CXCL12), B-cell-attracting chemokine-1 (BCA-1/CXCL13), their receptors CXCR4 and CXCR5, the proinflammatory chemokines: macrophage chemotactic protein-1 (MCP-1/CCL2), T cell expressed and secreted chemokine on activation (CCL5/RANTES), interleukin-8 (IL-8) (IL-8/CXCL8), IL-17, and vascular endothelial growth factor (VEGF) in the synovial membrane biopsy specimens from patients with RA or osteoarthritis (OA) and from healthy individuals and to estimate the diagnostic informative value of these biomarkers.

Subjects and methods. The expression of mRNA was estimated using a real-time polymerase chain reaction assay. The RA group included 28 patients, their median age was 47 [35; 54] years; disease duration – 8 [4; 12] years; DAS28 – 4.9 [3.9; 5.5]; 16 and 14 patients were seropositive for rheumatoid factor and anti-cyclic citrulinated peptide antibodies, respectively. The OA group comprised 22 patients whose median age was 70.5 [61; 74] years. Fifteen clinically healthy individuals with a median age of 45 [28; 64] years were also examined.

Results and discussion. The RA group was noted to have significantly higher RANTES, IL-8, IL-17, VEGF, BCA-1, and CXCR5 mRNA levels than the OA group and healthy individuals. In the patients with OA, the level of the homeostatic chemokines BCA-1 and SDF-1, which had B-cell chemoattractant activities, was higher than that in the control group, which may suggest that they are implicated in the pathogenesis of the disease. The determination of RANTES mRNA expression was most informative in diagnosing RA: the area under the curve (AUC), 0.91 [95% confidence interval (CI), 0.84–0.99]; diagnostic sensitivity, 72.97% (95% CI, 55.88–86.21), diagnostic specificity, 96.15% (95% CI, 80.36–99.90); positive likelihood ratio (LR+), 18.95; negative likelihood ratio (LR-), 0.28 at a diagnostic threshold of 0.0350, so was CBC1 mRNA. The AUC for BCA-1 was 0.78 (95% CI, 0.66–0.89); diagnostic sensitivity, 56.25% (95% CI, 37.66–73.64), diagnostic specificity, 92.59% (95% CI, 75.71–99.09); LR+, 7.59; LR-, 0.47 at a diagnostic threshold of 0.0184.

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