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Background:The pathological process of juvenile idiopathic arthritis (JIA) largely depends on pro-inflammatory cytokines, the polymorphism of the alleles of some genes of which we have the opportunity to study. No studies have been conducted on the dependence of certain features of the pathological process of JIA on the polymorphism of the IL-6(G-174C) and TNF(G308A) genes.Objectives:To reveal the dependence of JIA phenotypes and its course on genetic polymorphism of alleles IL-6 and TNF.Methods:Polymorphism of the IL-6 and TNF genes was studied by PCR-method using allele-specific primers 44 patients 1-17 y.o. (24f, 20m) with JIA. The level of IL-6 and TNFα in the serum was determined using ECLIA and CLIA methods.Results:There were 73% cases with an unfavorable course of the disease (UCD) of the patients with the CC allele of the IL-6 gene, for most patients average activity was JADAS27 13.5±1.6. oJIA (50%) & uveitis (30%) were the most frequent among subgroups. The level of serum IL6 was 74.1±69.5 pg/ml, TNFα 27.4±17.3 pg/ml (ratio IL6/TNFα=4.3±2.1). Among patients with GC IL6 70% female, 79% with UCD. More often pJIA (36%, including all RF+) and eJIA (35%) were noted with the largest frequency of inclusion of the hip joints (33%), spine (35%), detection of secondary osteoporosis (43%). The metabolic changes were registered on the ECG in 82% cases. The serum IL-6 level was 11.35±2.95 pg/ml, TNF 241.75 pg/ml (IL-6/TNFα=0.047, p<0.05 vs CC allele). Children with GG IL-6 (wild allele) with a more favorable course of the JIA (31%, less than in the CC and GC groups (p<0.05), only 8% had the highest disease activity), the largest number of patients with sJIA (25%) was registered in this group. The detection of HLA B27 was significantly lower (p<0.05) than in other alleles, while 60% cases were ANA+ (more than in the group GC, p<0.05). The highest level of serum IL6 (35.3±18.9 pg/ml) & the highest average number of mutations in folate metabolism genes (4±0.51) were revealed in this group. The wild allele GG prevailed (n=32) among the TNF gene alleles, sex ratio 1:1, UCD in 70%. The number of active joints, ESR, CRP, ANA-positivity (50%), HLA B27+ (53%) were unsignificantly higher than in GA TNF allele, while serum IL6 level (22.8±9.8 pg/ml) & TNFα (12.3±4.1 pg/ml) were lower. In patients with the GA TNF gene allele, an UCD (73%), eJIA (36%) were noted slightly more often. By such parameters as the patient’s gender, the presence of uveitis, damage to the hip joints, the type of synovitis, metabolic changes on the ECG, indicators were observed comparable with the wild allele group. IL6 level was 48.3±39.2 pg/ml, TNFα 636.5±420.1 pg/ml, IL6/TNFα=0.07±0.06 (vs 1.9±0.5 in GG group, p<0.05). The genotype of two wild alleles TNF GG with IL6 GG expectedly showed the smallest proportion of the UCD (33%, p <0.05), the most frequency of ANA-positivity (71%), with no uveitis and RF+pJIA in this group. All cases of RF+pJIA had TNF GA and IL6 GC. oJIA prevailed (57%) in the TNF GG&IL6 CC group, there was not a single case of sJIA, and the AJ number was the smallest (2.86±0,5). The largest group was TNF GG & IL6 GC (n=14). 91% of cases had UCD, AJ=6.6±2.4, damage to the hip joints in 40%, ESR 23.7±6.7 mm/h, CRP 14.5±5.4 mg/l, metabolic changes on the ECG in 100%, but ANA+ only at 13%. In general, there was no correlation between the cytokine content in the blood serum during of active disease in the examined children with features of allelic polymorphism of these genes.Conclusion:Depending on the allele polymorphism of the IL-6 and TNF genes, certain phenotypes of the JIA course may be distinguished. Thus, revealing the polymorphism of these alleles in patients at the onset of the disease, we can predict to some extent its course and take this into account when choosing treatment tactics.Disclosure of Interests:None declared

BackgroundThe 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.MethodsThe 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.ResultsAmong 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 (<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 <0.05); pJIA 36.19±58.6vs2.3±0.25(p <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 th...

BackgroundAppointment of modern methods of treatment led to a modification of the course of juvenile idiopathic arthritis (JIA). In Ukraine, the basic preparations were prescribed at JIA since 1984, then the biological registered only in 2011ObjectivesTo evaluate the effect of treatment changes on activity indicators, functional disorders and physical development of patients with JIA.Methods: retrospective analysis of medical records of 67 patients in 2018 and compared with the data of the clinical registry of the department in 1997-2010 (231 children). The diagnosis of JIA is based on the PRINTO criteria, the evaluation of the activity was performed for JADAS27, the JADI functional disturbances, the linear growth delay was estimated for SD, the BMI calculation using the Kettl formula was performed.ResultsThe analysis showed that the structure of sub-variants of JIA during the 20 yrs. did not significantly change (10.6% sJIA, 31.9% oJIA, 8.5% RF+pJIA, 29.8% RF-pJIA, 12.8% of the eA). Compared to the historical control group, there was a decrease in the total no. of affected joints, which increased with age (from 4.92±0.7 in 1-6 yrs. to 7.7±1.8 in adolescents now compared with 5.33±0.8 & 14,3±1,02 in the past). The max. no. of injured joints was at RF+pJIA (17.0±2.9), and 38.3% of the limbs were deformed. In recent years, JIA did not show visceral lesions (12.8% in past). JADAS27 was generally low, the max. for sJIA 7,1±5,0, eA 6,7±0,79, and RF-pJIA 6,5±1,04. The greater activity of the disease was observed on average in children aged 10-14 y, 5,8±0,9 (3,3±0,9 at 6-10 & 5.0±1.3 in 1-6 y). The race was the best in oJIA: an acceptable state of symptoms was 27%, a lack of activity of 27%, while with pJIA in 40% - high activity of the disease. Indicator JADAS27 did not significantly depend on serological features: ANA+ 3.9+0.6 (r=-0.06), RF+ 4.5±1.0 (r=-0.2), HLA B27 7.2±0.8 (r=0.05), sero-neg. 4.9±0.6 (r=-0.6). In cases of relapse or persistence of active inflammation in patients with ≥5 y, JADAS27 was lower when DMARDS was administered before 3 mo. from the debut of the disease (1.8±1.2 vs. 3.5±0.7). In patients with high disease activity, the combination of DMARDS and sCS was worse in the first 6 mo. from the debut (JADAS 6.6±1.2- 5.5±1.7) than DMARDS + ADA (4.0± 2.3 - 0,0) and DMARDS + TOCY (5,2±1,2 - 3,6±1,3). The max. JADI were in RF-pJIA (2,0±1,3), in general, JADI increased with age (<6y 0.55±0.3; >10y 1.7±0.9). JADI didn`t depend on the onset age (r=-0.12), disease duration (r=0.16), ANA detection (1.8±1.1; r=0.18), the RF (1.2±0.5; r=0.07); HLA B27 0.5±0.3 (r=-0.1); seronegative (1.02±0.4; r=0.07). In patients last years of FI II-III cen. marked with a higher frequency of 35.9%. A smaller proportion of patients with growth retardation was observed than in previous yrs. (10.4 vs 49%). The delay in linear growth with JIA is -1.37±0.06SD now, the degree of growth retardation depends on the duration of the disease (up to 3y -1.2±0.1, 8-13y 1.6±0.07) and the variant of the course (the max. growth retardation rate ...