Abstract
Background/aim The aim of the study was to analyze the relationship of the immune response mediator genes’ polymorphic loci (TNFA rs1800629, LTA rs909253, IL1B rs16944, IL2-IL21 rs6822844, IL2RA rs2104286, IL6 rs1800795, IL10 rs1800872, MIF rs755622, CTLA4 rs3087243, NFKB1 rs28362491, PTPN22 rs2476601, PADI4 rs2240336) variants with the methotrexate efficacy in juvenile idiopathic arthritis (JIA).Materials and methods The study included 274 JIA patients from the Republic of Bashkortostan, Russia. Achieving the American College of Rheumatology Pediatric 30 (ACR Pedi 30) response was regarded as the presence of the response to methotrexate (otherwise, as the absence), while achieving clinical remission on medication (Wallace et al., 2011) - as the sufficient response (otherwise, as the insufficient). Genotyping was conducted by the real-time polymerase chain reaction.Results Associations with an altered risk of the nonresponse to methotrexate in JIA were observed for the alleles/genotypes of the loci IL10 rs1800872 (in girls) and NFKB1 rs28362491 (in girls); with an altered risk of the insufficient response to methotrexate in JIA – for the alleles/genotypes of the loci IL1B rs16944 (in boys), CTLA4 rs3087243 (in boys), NFKB1 rs28362491 (in girls) and the haplotype TNFA rs1800629*A - LTA rs909253*G (in girls).Conclusion As a result of the study, the relationship of the alleles/genotypes of the IL1B rs16944, IL10 rs1800872, CTLA4 rs3087243, NFKB1 rs28362491 polymorphic loci and the TNFA rs1800629*A - LTA rs909253*G haplotype with the methotrexate efficacy in JIA was established (taking into account the differences by sex).
Highlights
Juvenile idiopathic arthritis (JIA) is the most common childhood rheumatic disease, which begins before the age of 16 and is characterized by arthritis persisting at least 6 weeks [1,2,3]
Associations with an altered risk of the nonresponse to methotrexate in JIA were observed for the alleles/genotypes of the loci IL10 rs1800872 and NFKB1 rs28362491; with an altered risk of the insufficient response to methotrexate in JIA – for the alleles/genotypes of the loci IL1B rs16944, cytotoxic T-lymphocyte associated protein 4 (CTLA4) rs3087243, NFKB1 rs28362491 and the haplotype TNFA rs1800629*A - LTA rs909253*G
The study of the predisposition to the absence of the response to methotrexate in JIA When studying the IL10 rs1800872 polymorphic locus, no predictors of the absence of the response to methotrexate were found in the whole JIA group, as well as in boys with JIA (P > 0.1) (Table 1)
Summary
Juvenile idiopathic arthritis (JIA) is the most common childhood rheumatic disease, which begins before the age of 16 and is characterized by arthritis persisting at least 6 weeks [1,2,3]. The JIA diagnosis is entirely based on the clinical features, and the generally accepted disease classification is the International League of Associations for Rheumatology (ILAR) classification [1]. Steadily progressive disease, JIA can lead to short-term and long-term disability [2]. Early and effective therapy is crucial for preventing JIA complications and patients’ disability [3,4,5,6,7]. Methotrexate is the most widely used disease-modifying antirheumatic drug in the JIA treatment [4]. The antiinflammatory effects of methotrexate in JIA may be mediated by addition to folate antagonism mechanisms, such as adenosine release, inhibition of spermine/ spermidine production and/or alteration of cellular redox state [9]. It has been shown that methotrexate may directly or indirectly affect the expression and/or secretion of the various immune response mediators involved in
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