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Polymorphisms of Genes Associated with Intracellular Signaling Pathways in Juvenile Idiopathic Arthritis


The aim of the study was to determine nucleotide sequence changes in the genes associated with the activation of intracellular signaling molecules and the risk of autoimmune dysregulation in patients with juvenile idiopathic arthritis (JIA). High-throughput panel-exome next-generation sequencing (NGS) was performed using the high-throughput Illumina HiSeq system (United States) in 36 children diagnosed with JIA. Nucleotide sequence changes were detected in the CASP10, CASP8, IL7R, IL10RA, IL12RB1, IL21R, MYD88, NFKB2, STAT5B, JAK3, IRAK4, and UNC13D genes in 13 (36.11%) patients, including seven (53.8%) children with nucleotide sequence changes associated with autoinflammatory syndromes (NOD2, NLRP12, MEFV, ADA2, and PSTPIP1). The seven HLA-B27-positive (53.8%) patients had changes in autoimmunity genes, whereas only two (8.6%) children had no changes in these genes, which showed associativity between HLA and the group of selected genes (OR = 12.25 (MukvichCI 1.99–75.19)). Thus, the risk loci were identified in 36.11% of patients with the JIA phenotype in the CASP10, CASP8, IL7R, IL10RA, IL12RB1, IL21R, MYD88, NFKB2, STAT5B, JAK3, IRAK4, and UNC13D genes associated with the activation of intracellular signaling molecules and the initiation of autoimmune dysregulation. The patients with JIA with nucleotide sequence changes in the autoimmunity genes developed mutations in the autoinflammatory genes significantly more frequently, which demonstrated a possibility for developing a combined overlapping autoimmune–autoinflammatory phenotype in definite individuals. The study confirms the significance of variative changes in the NFkB and JAK/STAT genes of intracellular signaling pathways for the onset of JIA, which may be informative for the development of future therapeutic strategies as well as for the personalization of therapeutic decisions.

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This study has not been supported by any particular grant from any financial establishments of the state, commercial, or noncommercial sectors.

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Correspondence to O. M. Mukvich, G. D. Telegeev, A. M. Matskevych or A. M. Gilfanova.

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Statement of compliance with standards of research involving humans as subjects. The studies were performed in compliance with good clinical practice (GCP) recommendations (1996), the Convention on Human Rights and Biomedicine (April 4, 1997), the World Medical Association Declaration of Helsinki (1964–2002), the Order of the Ministry of Health of Ukraine no. 281 of November 1, 2001, the Protocol of the study approved by the Local Ethics Committee for patients and parents participating in the study based on the Luk’yanova Institute of Pediatrics, Obstetrics and Gynecology, National Academy of Medical Sciences of Ukraine, and Protocol no. 7 of November 13, 2018. Each of the participants included in the study gave his or her informed voluntary consent. This article contains no investigations with the use of animals as the study objects. The statistical data treatment included only nonpersonified data on patients.

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Translated by N. Tarasyuk

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Mukvich, O.M., Telegeev, G.D., Matskevych, A.M. et al. Polymorphisms of Genes Associated with Intracellular Signaling Pathways in Juvenile Idiopathic Arthritis. Cytol. Genet. 56, 226–235 (2022).

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  • Keywords: children
  • juvenile idiopathic arthritis
  • genes
  • intracellular signaling pathways
  • autoimmunity
  • autoinflammation
  • panel exome sequencing