CURRENT ISSUES OF VITAMIN D IN JUVENILE IDIOPATHIC ARTHRITIS
Authors: Antipkin Yuriy , Omelchenko Liudmyla , Mukvich Olena 
Published: December 2022

Background. Children with juvenile idiopathic arthritis (JIA) represent a special cohort of patients with chronic somatic pathology, characterized by severe damage to the musculoskeletal system and other vital organs and systems, which is associated with immune and metabolic changes in the body. Data regarding the provision of vitamin D (VD) in patients with JIA and the significance of its deficiency in the initiation, activation of the autoimmune process, the prognosis of the course of the disease, the risk of developing complications and the effectiveness of protocol therapy are contradictory.
Objective. To investigate the body's supply of vitamin D in patients with juvenile idiopathic arthritis with the determination of the trigger factors of its deficiency, the assessment of the immune status and changes in the nucleotide sequence in the genes of innate immunity.
Materials and methods. Research was conducted during 2016-2021 at the Institute in 119 patients with JIA aged 6 to 12 years. The concentration of 25OHD was determined in blood serum using commercial Vitamin D3 kits (Screeningkit, Switzerland). Immunological studies were performed by flow cytofluorimetry and enzyme immunoassay. For panel sequencing of 407 genes regulating immune functions, high-throughput panel exome sequencing was used on Illumina's HiSeq machine (made in the USA) at the Invitae laboratory (USA). The obtained digital data were processed by methods of statistical analysis using the Microsoft Excel computer package.
Results. A high frequency of low supply of vitamin D in patients with JIA was revealed: vitamin D insufficiency was diagnosed in 96 (80.6 %), and its deficiency - in 38 (31.9 %) children. The lowest levels of 25ОНD concentration in blood serum (less than 15 ng/ml) are observed in patients with stage II–III disease activity, especially at the beginning of the pathological process. Vitamin D deficiency (DVD) was associated with the activity and severity of the clinical course, frequent exacerbation of the joint syndrome, the expressiveness of changes in the humoral and cellular immunity of patients. The main risk factors for reducing the body's supply of WD in patients with JIA have been determined, which must be taken into account during their observation and treatment.
High activity of JIA in patients with VD deficiency in the body was associated with a significant increase in the number of CD3+ T-cells, CD3+CD4+ helper-inducer T-cells, activated HLA-DR+/CD3+ T-cells, ESR, C-reactive protein concentration (CRP), tumor necrosis factor (TNF), circulating immune complexes (CIC), immunoglobulins, which allows considering DWD as a likely predictor of severe and prognostically unfavorable course of rheumatic disease.
Nucleotide sequence changes in the NOD2 gene were detected in 18.1 % of patients with JIA: c.2104C>T (p.Arg702Trp), c.3019dupC (p.Leu1007Profs*2). The of variable changes in patients with JIA is statistically significantly different from the population [VSh = 11.39; 95 % CI (2.39-54.22)]. DVD was detected in all children with mutations in the NOD2 gene – (17.2 ± 3.29) ng/ml, and in children without changes in the nucleotide sequence - in 23 (85.1 %) children [SS = 0.097; DI (0.03-0.31)], the concentration of VD is significantly higher - [(26.68 ± 2.34) ng/ml, p = 0.026].
Conclusions. The conducted studies confirm the presence of a decrease in the body's supply of vitamin D in patients with JIA, which is associated with a high activity of the pathological process and pronounced immunological changes in the body, which allows us to consider its deficiency as a likely predictor of a severe and prognostically unfavorable course of the disease. It has been proven that the concentration of vitamin D in JIA is higher in patients without changes in the nucleotide sequence in the NOD2 gene, which must be taken into account when predicting and evaluating the body's response to the treatment of juvenile arthritis.
Key words: juvenile idiopathic arthritis, vitamin D, immunological status, genetic sequencing, children.