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Polymorphisms of genes, associated with intracellular signaling pathways in juvenile idiopathic arthritis

Mukvich O.M., Telegeev G.D., Matskevich A.M., Gilfanova A.M.


SUMMARY. The study is aimed at determining changes in the nucleotide sequence in the genes, associated with the ac-tivation of intracellular signaling molecules and the risk of autoimmune dysregulation in patients with juvenile idiopathic arthritis (JIA). The next-generation sequencing (NGS) was performed on Illuminas HiSeq device (USA) in 36 children diagnosed with JIA. Nucleotide sequence changes were detected in the CASP10, CASP8, IL7R, IL10RA, IL12RB1, IL21R, MYD88, NFKB2, STAT5B, JAK3, IRAK4, UNC13D genes in 13 (36.11 %) patients, of which 7 (53.8 %) children had nucleotide sequence changes in the genes, associated with autoinflammatory syndromes (NOD2, NLRP12, MEFV, ADA2, PSTPIP1). Positive HLA-B27 was in 7 (53.8 %) patients with changes in autoimmunity genes, and only in 2 (8.6 %) children without changes in these genes, which demonstrates the asso-ciativity between HLA and the group of selected genes [OR = 12.25 (CI 1.99-75.19]. Thus, risk loci were identified in the CASP10, CASP8, IL7R, IL10RA, IL12RB1, IL21R, MYD88, NFKB2, STAT5B, JAK3, IRAK4, UNC13D genes in 36.11 % of patients with the JIA phenotype. These genes are associated with the activation of intracellular signaling molecules and initiation of autoimmune dysregulation. The patients with JIA, who had nucleotide sequence changes in autoimmunity genes, were significantly more likely to have mutations in autoinflammatory genes, which demonstrates the possibility of a mixed phenotype of autoimmune and autoinflammatory overlap in some individuals. The study confirms the importance of variable changes in the genes of the NF-kB, JAK/STAT intracellular signaling pathways in JIA, which may be informative for future therapeutic strategies when choosing targeted personalized therapeutic tactics.

Key words: children, juvenile idiopathic arthritis, genes, intracellular signaling pathways, autoimmunity, autoinflammation, next-generation sequencing

Tsitologiya i Genetika 2022, vol. 56, no. 3, pp. 24-34

  1. State Institution Institute of Pediatrics, Obstetrics and Gynecology of the NAMS of Ukraine, Kyiv
  2. Institute of Molecular Biology and Genetics of the NASU
  3. National Healthcare University of Ukraine of the Shupyk

E-mail: olena.mukvich, g.d.telegeev, matskevych90, anna_scherban

Mukvich O.M., Telegeev G.D., Matskevich A.M., Gilfanova A.M. Polymorphisms of genes, associated with intracellular signaling pathways in juvenile idiopathic arthritis, Tsitol Genet., 2022, vol. 56, no. 3, pp. 24-34.

In "Cytology and Genetics":
O. M. Mukvich, G. D. Telegeev, A. M. Matskevych & A. M. Gilfanova Polymorphisms of Genes Associated with Intracellular Signaling Pathways in Juvenile Idiopathic Arthritis, Cytol Genet., 2022, vol. 56, no. 3, pp. 226235
DOI: 10.3103/S0095452722030070


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