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

Autoinflammation Candidate Genes in Juvenile Idiopathic Arthritis Mukvich Olena α & Matskevych Anna σ I. I ntroduction n modern rheumatology, juvenile idiopathic arthritis (JIA) is defined as a heterogeneous pathology of uncertain aetiology, which is based on the immune system dysfunction along with the formation of autoimmune reactions [Ringold S. and Angeles-Han S.T., 2019]. The existing criteria for the classification of JIA are based on the phenotypic, genetic and molecular heterogeneity of the disease, which requires further pathogenesis studying [Martini A. and Ravelli A, 2019]. Rheumatological tests are often negative in clinical symptomatology of JIA, and children without clinical symptomatology of arthritis may have false-positive specific antibodies, which contributes to the difficulty in diagnosis. Modern treatment technologies do not always make it possible to achieve the desired effect since the mechanisms of molecular remission and the ability to restore immunological tolerance remain unclear; sustained remission is achieved infrequently, requiring long-term pharmacological therapy without reliable predictive biomarkers for therapy response [Savic S, Wilson AG, et al, 2017]. Currently, there is increasing evidence that the concept of "juvenile idiopathic arthritis" involves a number of clinical and immunological syndromes with different development mechanisms, prognosis and therapeutic approaches [Savic S , Wilson , et al, 2017]. Recent studies indicate an important role of heredity in initiating autoimmune responses in JIA. The increase in the prevalence of familial risk to 40-50% among seropositive arthritis (especially in first degree relatives) is determined by the presence of a set of allelic genes in the HLA-DRB1 locus; the expression of these genes results in production of proteins on the membrane of immune cells containing "shared epitope" [Frisell T.,2016;Guseva V., 2019 ]. However, HLA genes determine only 17.0% to 56.0% of heredity, so the search for candidate genes is constantly expanding [Hollenbach J.A, 2010]. A genome-wide association studies in the GWAS study has identified 377 genes in 100 risk loci based on data from 29,880 patients with rheumatoid arthritis (RA); 98 of them were associated with a twofold increase in risk of its development, and 15 were identical to immunodeficiency syndromes, involved in the regulation of inflammatory processes, including caspase-8 and -10, autoimmune regulator (AIRE), IL-2 receptor α (CD25), protein tyrosine phosphatase receptor type C (CD45), protein 1, which activates VDJ recombination (RAG1), RAG2, CD40, serine-protein kinase ATM, non-receptor tyrosine-protein kinase TYK2 (TYK2), IFN γ -2 receptor, interferon regulatory factor 8, NFKB, TLR4 and others. [McAllister and Orozco G., 2011]. Mutations in the TNFRSF1A, NLRP3 , MEFV , NOD2 genes, etc, which determine the inflammatory processes due to abnormal activation of the innate immune system without the synthesis of highly active auto antibodies and antigen-specific T and B cells (synthesis of signaling proteins, interleukins, cytokines, TNF, NOD-like receptors ) associated with arthritis, are conventionally allocated to a separate group of systemic auto inflammatory diseases (SAIDs). However, there is I 1 Year 2022 85 © 2022 Global Journals Global Journal of Science Frontier Research Volume XXII Issue ersion I VII ( G ) Author α : Department of Pediatric Rheumatology and Auto inflammatory Diseases, Institute of Pediatrics, Obstetrics and Gynecology named after acad. O.M. Lukyanova of the NAMS of Ukraine: Kyiv, Ukraine. Author σ : Department of Pediatric Rheumatology and Auto inflammatory Diseases, Institute of Pediatrics, Obstetrics and Gynecology named after acad. O.M. Lukyanova of the NAMS of Ukraine: Kyiv, Ukraine, Platona Mayborody, 8 str., 04050, Kyiv, Ukraine. e-mail: matskevych90@gmail.com Abstract- Juvenile idiopathic arthritis (JIA) is a heterogeneous pathology with uncertain causative factors and prognosis, stemming from an immune system dysfunction with the development of autoimmune reactions. The most distinctive and potentially most severe of these is systemic JIA (sJIA), a disease characterized by sharp rises in temperature and rash. A thorough understanding of the complex of immune regulatory mechanisms along with genetic analysis reveals complex relationships between autoimmune reactions and auto inflammation. Sequencing of 15 auto inflammatory genes was performed in 62 patients with JIA: 26 – oligoarthritis, 20 – polyarthritis, 16 – systemic. Studies have shown that 16 (25.8%) patients with the clinical JIA phenotype had changes in nucleotide sequence in the genes encoding auto inflammatory immune response proteins. NOD2 changes were in 12 (19.3%) of them and 1 change in each of the 4 patients NLRP12 (heterozygote, c.1343G> C (p.Gly448Ala)), MEFV (pathogenic heterozygous, c.2082G> A (p.Met694Ile)), ADA2 (heterozygote, c.145C> T). Arg49Trp)), PSTPIP1 (heterozygote, c.806T> A (p.Ile269A)) in the group of studied children with JIA. The study will allow identifying individual genetic loci of JIA risk, expand understanding of the pathogenesis and spectrum of phenotypic manifestations of the disease, improve diagnosis and prediction of its course, as well as reveal new opportunities for monitoring patients with JIA and their personalized therapy. Keywords: children, arthritis, genes, autoinflammatory.