Global Journal of Science Frontier Research, G: Bio-Tech & Genetics, Volume 22 Issue 2

increasing evidence that innate immunity plays a significant role in the pathogenesis of autoimmune diseases, including JIA [Angelotti F., 2017]. We have also noticed that some patients with juvenile arthritis have symptoms as patients with systemic auto inflammatory disorders have (fever, severe joint swelling, erythematous rash, increased ESR, C-reactive protein). These patients do not respond or do not respond adequately to protocol therapy, have frequent aggravations and an intermediate prognosis. Identification of such patients from a heterogeneous group of children with arthritis for personalized therapy is an urgent task of modern Rheumatology. Objective: to determine the features of the clinical progression of JIA on the background of changes in the nucleotide sequence of innate immunity genes . II. M aterials and M ethods Studies were conducted in 62 children diagnosed with JIA from 1 to 17 years (27 boys, 35 girls), who were observed in the Department of Connective Tissue Diseases of the Institute. The average duration of the disease was (4.3±3.3) years. The diagnosis of JIA has been established according to the criteria of the International League of Associations for Rheumatology, ILAR [Ringold S., 2020]. Genetic changes have been verified and decoded in the ExAC genetic database(A MedGen ID is a unique identifier referring to an article in MedGen, NCBI's centralized database of information about genetic disorders and phenotypes. Search by MedGen ID at http://www.ncbi.nlm.nih.gov/medgen. An OMIM number is a unique identifier referring to a comprehensive entry in Online Mendelian Inheritance of Man (OMIM). Search by OMIM number at http://omim.org/ ) Parents of patients under 12 years and patients over 12 years have received informed consent for the examination and have provided written consent. The study was performed in compliance with the provisions of the GCP (1996), the Convention on Human Rights and Biomedicine (04.04.1997), the World Medical Association Declaration of Helsinki (1964-2002), the Order of the Ministry of Health of Ukraine № 281 dated 01.11.2001. Patients were stratified by clinical subtypes of JIA: 26 (41.9 %) patients with oligoarthritis, 20 (32.2 %) with polyarthritis, 16 (25.8 %) with systemic arthritis. 19 (30.6%) children were positive for HLA-B27-antigen (JIA enthesitis-related, HLA-B27-positive – JIA-B27), and 4 (6.4%) children were with anterior uveitis (JIA-uveitis). At the onset of the disease, 35 (56.4 %) children had increased acute phase indicators (stage II activity). All children were negative for rheumatoid factor (RF) and did not have antibodies to citrullinated vimentin ( А - ССР ), 35 (56.4%) children were positive for antinuclear factor (ANF+) (table 1). 4 (6.4%) patients were diagnosed with selective IgA immunodeficiency. Table 1: General characteristics of patients with JIA Indicator Indicator values Number of patients, abs.number 62 Age, years Me 9 (1-17) Duration of illness, years (4,3±3,3) Gender (boys/girls), abs.number 27/35 JIA subtype, abs.number (%): Oligoarthritis JIA Polyarthritis JIA Systemic JIA 26 (41,9) 20 (32,2 ) 16 (25,8) ANA ( + ), abs. n. (%) 35 (56,4 ) ANA ( - ), abs. n. (%) 27 (43,5 ) HLA-B27 ( + ), abs.n. (%) 19 (30,6 ) HLA-B27 ( - ), abs. n. (%) 43 (69,3) АССР (-),abs. n (%) 62 (100) RF (-),abs. n (%) 62(100) Selective IgA deficiency, abs. n (%) 4 (6,4) ANA-antinuclear antibodies, IgA-immunoglobulin A; HLA-B27- Human leukocyte antigen B27; ACCP- anti-citrullinated protein antibody; RF - rheumatoid factor For the genetic sequencing, a sample of the condensed epithelium of the oral cavity was taken into a Saliva Collection Kit Oragene TM test tube (DNA Genotek Inc.3000-500 Palladium Drive Ottawa, ON, Canada K2V 1C2). A high-performance panel exomic new generation sequencing (NGS), based on the decoding of fragments of the DNA molecule, has been performed on the Illumina's HiSeq device (manufactured in the USA) in the Invitae laboratory (USA), each change in the nucleotide sequence is sequenced by Sanger. The target enrichment was applied to coding gene sequences of auto inflammatory syndromes: NOD2, NLRC4, NLRP12, NLRP3, PLCG2, MEFV, ADA2, ELANE, LPIN2, MVK, NLRC4, PSMB8, PSTPIP1, TNFRSF1A, TRNT1. III. R esults The results have shown that 16 (25.8 %) patients with the clinical JIA phenotype had changes in the nucleotide sequence in the genes encoding auto inflammatory immune response proteins, of which 12 (19.3%) children had changes in the NOD2 [c.2104C>T (p.Arg702Trp)] This sequence change replaces arginine with tryptophan at codon 702 of the NOD2 protein (p.Arg702Trp). The arginine residue is moderately conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is present in population databases (rs2066844, ExAC 3%), including multiple homozygous individuals. Numerous population-based case-control studies have shown that this variant confers an elevated risk of Crohn's disease [Peter I, Mitchell AA,2011; Hradsky O, 2008; Naderi N., 2011; Lakatos PL., 2005; Tukel T., © 2022 Global Journals 1 Year 2022 86 Global Journal of Science Frontier Research Volume XXII Issue ersion I VII ( G ) Autoinflammation Candidate Genes in Juvenile Idiopathic Arthritis