LEVELS OF THE INTERLEUKINE 17 CYTOKINES FAMILY IN PATIENTS WITH RHEUMATOID ARTHRITIS

LEVELS OF THE INTERLEUKINE 17 CYTOKINES FAMILY IN PATIENTS WITH RHEUMATOID ARTHRITIS

Yerzhan Khochshanov

Master's degree student, Astana Medical University,

Kazakhstan, Astana

Rheumatoid arthritis (RA) is one of the frequent and severe chronic systemic immuno-inflammatory diseases affecting mainly joints [1], the prevalence of which, in different countries of the world, is 0.5-2% among the adult population [2]. By gender and age, RA occurs in women 2-3 times more often than in men, and the peak of disease onset is observed in individuals of working age [3]. Rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA) are the major serological markers of RA, that contributes to the severe RA form development [4]. In comparison with the RF, which may be present not only in RA, but also in other autoimmune and non-autoimmune diseases, ACPA are usually detected in about 2/3 of RA patients and in 1-3% of healthy individuals. Moreover, these antibodies are associated with a more severe and erosive phenotype of RA, with extra-articular manifestations [5].

It is known fact that immune response disorders underlie the pathogenesis of RA, while a crucial role in the occurrence and progression of the disease belongs to the lymphocytic and cytokine systems [6]. For instance, there is evidence indicating the variability of Th17 cells producing interleukin 17 (IL-17A, IL-17F), IL-6, IL-22, interferon γ (IFNy), tumor necrosis factor (TNFa) and etc. as an important process in the pathogenesis of RA, because Th17 can mutate under the influence of inflammatory, genetic and environmental factors [7].

CD161 is a marker of Th17 cells producing IL-17A, IL-17E/IL-25, IL-17F and etc. involved in the pathogenesis of RA. Determination of the percentage of CD4+CD161+ T cells in synovial fluid can be used as a prognostic marker of disease activity in RA [8], and their accumulation in synovial fluid and their high production of CD147 can contribute to local inflammation in RA [9]. Researchers from Poland analyzing the profile of cytokines associated with Th17 and Treg cells in RA patients, found that the concentration of IL-2, IL-17, IL-21 and IFNy in blood serum was significantly higher compared to  healthy individuals, and the levels of IL-22, IL-6, IL-10, IL-35 and TGF-β were equal in the study and control groups [10].

The IL-17 cytokine family includes IL-17A, IL-17B, IL-17C, IL-17D, IL-17E (or IL-25) and IL-17F, which are involved in protecting the body from various agents in various diseases, including autoimmune disorders, including RA [11]. In RA, IL-17A, IL-17B and IL-25 are involved in pathogenesis as proinflammatory cytokines, elevated levels of which were found in the synovial tissue of patients with RA [12]. Lavocat et al. assumed that IL-25 can act as an antagonist of IL-17A and inhibits its pro-inflammatory effects, they also found that synoviocytes produce IL-25 later from the onset of the disease compared to IL-17A, therefore IL-25 may act as a regulator of inflammation caused by IL-17A [13].

Our study included 35 female patients diagnosed with rheumatoid arthritis and a control group of 30 healthy individuals. All participants of the study measured the levels of the Interleukin 17 cytokines family (IL-17A, IL-17E (or IL-25) and IL-17F) in the blood serum. Determination of the cytokines level is carried out using a kit of Merck company’s MILLIPLEX MAP №1 Human Cytokine/Chemokine Magnetic Bead Panel for multiplex analysis by Luminex xMAP.

Figure 1 shows the content of levels of IL-17 cytokines family in the blood serum of patients with RA (CASE) and in healthy individuals of the control group (CONTROL).

Figure 1. The ratio of the levels of the IL-17 cytokines family in the blood serum of patients with RA (CASE) comparing to the control group (CONTROL)

There were statistically significant differences in the levels of all cytokines. IL-17A had Median (Me) 434,46 pg/mL (Q1-Q3: 225,43-771,58) in the study group, and Me=125,47 pg/mL (Q1-Q3: 28,13-234,57) in the control group. Asymp. Sig. was p=0,000015. IL-17E or IL-25 had p=0,001 (CASE: Me=5069,02 pg/mL (Q1-Q3: 3662,41-9361,50); CONTROL: Me=2884,82 pg/mL (Q1-Q3: 163,10-5313,57)). Median of IL-17F in patients with RA was 597,85 pg/mL (Q1-Q3: 383,0-1722,44), in control group – 246,63 pg/mL (Q1-Q3: 74,50-395,95), p value = 0,000006.

In conclusion, the levels of the IL-17 cytokines family are higher in patients with RA comparing to the healthy individuals of the control group. The immunological profile of RA patients is currently an urgent and insufficiently studied problem, including in Central Asia. Considering the immunopathogenetic data, morbidity, high disability and economic damage to RA, this problem, definitely, requires special attention.

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