AB0052 GENE POLYMORPHISM TNFAIP3 RS6920220 IS ASSOCIATED WITH A SPECIFIC CYTOKINE PATTERN IN PATIENTS WITH EARLY RHEUMATOID ARTHRITIS
Authors: Irina Guseva, Anastasia Avdeeva, Maria Cherkasova, Elena Samarkina, Evgeny Nasonov
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Genetic factors are known to substantially influence the production of cytokines. <h3>Objectives:</h3> This prospective study was aimed to explore whether the polymorphisms of immune response genes were associated with cytokines/chemokine production in patients with early rheumatoid arthritis (eRA) and whether a biological therapy affected this association. <h3>Methods:</h3> 44 eRA patients (36 females; median age 55.0 [46; 60,0]; median disease duration 7,0 [4,0; 11,0] months; DAS28 5.9 [4,8; 6,4]) were included. 89% were positive for IgM rheumatoid, 92% - anti-CCP positive. "Gene candidate" approach was used to search for the following gene polymorphisms (SNPs): P<i>TPN22</i> (+1858 C/T, rs2476601), <i>CTLA4</i> (+49A/G, rs231775), <i>TNFAIP3</i> (rs675520, rs6920220, rs10499194), <i>IL6</i> (-174G/C, rs1800795), <i>IL6R</i> (+358A/C, rs8192284), <i>TNFA</i> (-308A/G, rs1800629), <i>MCP1/CCL</i><i>2</i> (+2581A/G, rs1024611),<i> IL10</i> (-592A/C, rs1800872, -1082 A/G, rs1800896). Serum levels of 27 cytokine/chemokines were measured using the xMAP multiplexing technology at baseline, at 12 and 24 weeks after initiation of therapy. All patients were treated with methotrexate and/or biological therapy in accordance with the treat-to-target strategy (REMARCA study). <h3>Results:</h3> Among all studied SNPs only polymorphism rs6920220 of gene <i>TNFAIP3</i> was associated with a certain cytokine/chemokine production across all time-points: baseline, 12 and 24 weeks. At baseline, the carriers of GG genotype (27 pts) showed significantly higher serum levels of the following mediators, compared to the patients with GA/AA genotypes (17 pts): <b>IL8</b> (42.8± 23.0 pg/ml vs 25.5±8.4 pg/ml, p&lt;0.0001), <b>IL-17</b> (20.4±15.8 pg/ml vs 11.5±12.1 pg/ml, p=0.017), <b>MIP-1a</b> (19.1±40.5 pg/ml vs 9.8±2.7 pg/ml, p=0.036), <b>MIP-1b (</b>155.4±45.0 pg/ml vs 117.6±47.2 pg/ml, p=0.013), <b>PDGF-BB (</b>6967.5±3275.7 pg/ml vs 4600.6±1826.0 pg/ml, p=0.018). At week 12<sup>th</sup>, <b>IL-8</b> serum levels were the only ones to remain associated with polymorphism rs6920220 (p=0.015). At week 24<sup>th</sup>, the carriers of GG genotype had higher serum levels of several cytokines/chemokines, compared to the patients with GA/AA genotypes<b>: IL-8</b> (47.9±26.2 pg/ml vs 33.7±19.3 pg/ml, p=0.05), <b>IP-10 (</b>2451.7±1825.2 pg/ml vs 1404.9±941.1 pg/ml, p=0,037), <b>MIP-1b</b> (150.7±68.2 pg/ml vs 89.7±33.8 pg/ml, p=0.004), <b>PDGF-BB</b> (6150.9±2667.6 pg/ml vs 3915.4±1343.5 pg/ml, p=0.046). There was no statistically significant difference in production of IL-8, IP-10, MIP-1b, and PDGF-BB prior to and after 24 weeks of therapy. <h3>Conclusion:</h3> The results suggest that polymorphism rs6920220 of gene <i>TNFAIP3</i> is linked to a particular cytokine/chemokine pattern. Biological therapy used according to the treat-to-target strategy for 24 weeks does not lead to the reduced production of IL-8, IP-10, MIP-1b, and PDGF-BB in the carriers of GG genotype. <h3>Disclosure of Interests:</h3> None declared