IL-17A, IL-17F, and IL-23 in Patients with Rheumatoid Arthritis.

Abstract

The aim of the study was to determine the clinical and diagnostic value of IL-17A, IL-17F, and IL-23 in RA patients in the advanced stage of the disease. MATERIALS AND METHODS: . We examined 154 patients with a reliable diagnosis of RA according to ACR/EULAR criteria (2010), predominantly (73.4%) female, middle-aged (56.0 (50.0; 64.0) years), disease duration of 9.4 (3.0; 13.0) years, radiologic stages II (34.4%) and III (37.0%), and moderate to high activity (DAS28-ESR 5.40 (4.65; 6.00). Of these, 83.8% patients were seropositive for IgM rheumatoid factor (IgM RF), and 68.8% had antibodies to cyclic citrullinated peptide (ACCP). As many as 144 (93.5%) patients were taking DMARDs (methotrexate, leflunamide, and sulfasalazine), as well as nonsteroidal antiinflammatory drugs (NSAIDs) and glucocorticoids (GCs) up to 10 mg/day in terms of prednisolone. The serum levels of IL-17A, IL-17F, and IL-23 were investigated using multiplex xMAR technology. The upper limit of the norm (M+3σ) in 20 sera of healthy donors was 1.78 pg/mL for IL-17A, 9.5 pg/mL for IL-17F, and 91.55 pg/mL for IL-23. RESULTS. : IL-17A (1.16 (0.50; 2.39) pg/mL) and IL-17F (5.02 (1.00; 138.80) pg/mL) concentrations in RA patients were not significantly different from controls (0.78 (0.00; 1.65) pg/mL and 4.02 (1.46; 7.31) pg/mL, p > 0.05). In contrast, IL-23 levels were significantly higher in patients than in donors (21.36 (2.50; 4626.22) pg/mL and 14.63 (0.00; 91.55) pg/mL, p < 0.05). High values of IL-17F (71 patients, 46.1%) and IL-23 (66 patients, 42.9%) were significantly more frequently detected than IL-17A (46 patients, 29.9%: p = 0.003 and p = 0.02, respectively). Overproduction of IL-17A and IL-17F was simultaneously observed in 37 (24.0%) patients, and 32 (20.8%) patients had an increase in IL-17A, IL-17F, and IL-23. Correlations between IL-17A and IL-17F concentrations (r = 0.44, p < 0.05), IL-17A and IL-23 (r = 0.40, p < 0.05), IL-17F and IL-23 (r = 0.94, p < 0.05) were found. No statistically significant differences were found between the concentration of IL-17A, IL-17F, and IL-23 and the frequency of their elevation in RA patients positive or negative for IgM RF, as well as for ACCP. When IL-17A level was elevated, CDAI and SDAI indices and IgM RF concentration were significantly higher than in the comparison group (p < 0.05). In patients with IL-17F overproduction, predominance of ESR and CRP values was revealed in comparison with the normal values of this index (p < 0.05). At the same time, IL-17A concentration correlated with SDAI (r = 0.17, p < 0.05), IgM RF values (r = 0.19, p < 0.05), and ACCP (r = 0.19, p < 0.05). When IL-23 values were high, the HR was significantly lower (28, p < 0.05), and the groups did not differ in other indices of disease activity, IgM RF and ACCP. No differences in clinical and laboratory indices of RA activity were found between patients with simultaneous elevation of one, two, or three cytokines and groups of patients with their normal concentrations. In RA patients in the advanced stage of the disease, IL-17F overproduction prevails over the frequency of IL-17A elevation. The concentration of IL-23 in serum is significantly higher in patients with RA compared to the control group, and its high values are found in 42.7% of patients. The combined overproduction of IL-17A and IL-17F; IL-17A, IL-17F, and IL-23 does not increase the proinflammatory potential of each individual cytokine.