AB0934 IL-6 AND ALLELIC POLYMORPHISM OF ITS GENE IN JUVENILE IDIOPATHIC ARTHRITIS
Authors: Agar Artsymovych, Olena Oshlianska
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> The development and maintenance of inflammation in juvenile idiopathic arthritis (JIA) is mediated by cytokine imbalance; interleukin 6(IL6) plays a leading role among pro-inflammatory cytokines. Its pathological synthesis has a negative impact on all organs and system. It is not excluded that its effector ability depends on genetic structures of IL6 gene. It has not been studied whether the allelic polymorphism of the IL6-174CG gene affects the effectiveness of targeted biological therapy. Objectives: to assess the IL6 dynamics level in serum of patients with ineffective JIA-treatment. <h3>Methods</h3> The level of IL6 in the serum of JIA patients 1-18y.o. was determined using ECLIA method, debut of the disease (54) and treatment failure (36: 6 oJIA, 14 pJIA, 10 enthJIA, 6 sJIA). In patients with JIA, allelic polymorphism of the IL6-174CG gene was studied by PCR-method using allele-specific primers. A correlation analysis of clinical and laboratory parameters was made. <h3>Results</h3> Among patients with ineffective treatment of JIA, the duration of the disease was 39.5±35.8 months, 62.9% were girls. 27 patients received GC (&lt;1mg/kg), 30-MTX(10-15mg/m2), 3-leflunomide, 1-AZA, 10-TZ, 16–ADA/ETA, 1-TFC, 5 were switched from antiTNF for antiIL6. The level of IL6 in the serum of JIA patients with treatment ineffectiveness was higher than at the beginning of disease (sJIA 52.40±73.84vs24.4±4.7(p &lt;0.05); pJIA 36.19±58.6vs2.3±0.25(p &lt;0.05); oJIA 8.69±5.27vs1±0.1; enthJIA 90.55±63.33vs .4±0.9pg/ml). There was no increase in IL6-level in patients with an unfavorable course of the RFpos-pJIA (8.4±7.35pg/ml) and with uveitis (5.59±4.94pg/ml) (norm.1.5–7pg/ml). In 57.1% of cases of RFneg-pJIA IL6 was elevated, in 3 children it was the highest (79.77-218.7pg/ml), they had anemia and osteoporosis. A high (51-484.6pg/ml) level was observed in 4 patients with enthJIA, in 1-inadequate therapy was performed, in 3 patients there was a fever, a lag in physical development, the highest CRP (up to 300 mg/ml). The correlation between the level of IL6 in the blood of children with JIA and the presence of lymphadenopathy in the debut of the disease (r=0.53), the child's age at the debut of the disease (r=0.63), examination (r=0.74), and the patient's weight (r=0.87), the duration from the onset of the disease to the initiation of biological therapy (r=0.44), the number of exacerbations in the first years of the disease (r=0.66-0.69), the formation of contractures and the limitation of movement in the joints (r=0.75), radiological progression in the 1st year from the debut (r=0.54), ESR (r=0.48), CRP (r=0.40), doctor's estimate of disease activity (r=0.79), ALT (r=0.69), AST (r=0.99), LDH (r=0.73) was found. There was no correlation with the number of affected joints (r=0.28), heart rate (r=0.48), metabolic abnormalities on the ECG (r=0.39). In children with an adverse course of JIA, IL6 correlated backward with TNF (r=-1), which was not observed in children at the onset of the disease (r=0.19). Analysis of the results of genetic examination showed that among children with treatment failure 50% had GC-allele of the IL-6-174GC gene, 27,3% had GG allele, and 23,7% had CC allele. <h3>Conclusion</h3> Treatment of JIA leads to changes in cytokine profile. The IL6-174CG gene is associated with a high level of IL6 in the blood. The longer the duration of the disease and the time before the start of treatment with biological DMARDs, the greater the likelihood of an increase of IL-6-level in serum. In cases of even short-term enzymemia in JIA, subclinical activity with IL-6 can be suggested. In case of presence of some signs (hyperthermia, osteoporosis, anemia) in patients with antiTNF, it is advisable to determine the level of IL-6 in blood serum. <h3>Disclosure of Interests</h3> None declared