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3«шиитеимм-лэишаи» ЖШ / MEDICAL sciences
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MEDICAL SCIENCES
УДК 616.72-002.77
Kotenko Oleksandra Martynov Yurii Basenko Mariia Bogutska Olha DOI: 10.24412/2520-6990-2023-29188-7-8 LITERATURE REVIEW: CURRENT PROBLEMS AND FUTURE PROSPECTS IN THE STUDY OF
JUVENILE IDIOPATHIC ARTHRITIS
Abstract
Juvenile idiopathic arthritis (JIA) is a rare disease with distinct signs of varying severity, which often leads to disability in children. In the practice of pediatric rheumatology, JIA is one of the most common diseases. In recent years, progress in understanding the immunopathogenesis of the disease has led to improved therapies with significant improvements in patient outcomes. Despite these advances, there remain subgroups of JIA patients with refractory disease and severe disease-related complications, including various types of hypersensitivity reactions to biologic drugs, lack of diagnostic andprognostic biomarkers, and lower physical activity compared to healthy peers. This review highlights existing options for diagnosis, treatment of JIA, physical activity and/or exercise as a non-drug alternative to reduce inflammation, and explores potentialfuture diagnostic and therapeutic tools.
Key words: juvenile idiopathic arthritis, biomarkers, biological treatments, hypersensitivity reactions, physical activity, inflammation.
Introduction
Juvenile idiopathic arthritis (JIA) is a diverse group of pediatric rheumatic disorders affecting children under 16 years for at least six weeks. It comprises seven categories according to the 2001 ILAR consensus conference, each with varying characteristics, including synovial inflammation, structural changes, and functional impairments. A new preliminary classification by PRINTO has been approved [1].
Etiology
Chronic arthritis in JIA involves an autoimmun e attack on the synovial membrane, driven by overproduced proinflammatory cytokines (e.g., TNF-a, IL-1, IL-6). Autoreactive CD4+ T cells, particularly Th1 and Th17 cells, contribute to inflammation, along with S100 family proteins. Reduced anti-inflammatory IL-10 and impaired regulatory T cells disrupt immune tolerance. Genetic factors play a significant role, evidenced by familial aggregation and concordance rates in monozygotic twins [2,3].
Pathophys iology
Immune mechanisms in JIA subtypes differ. In oligoarthritis, polyarthritis, and psoriatic arthritis, IL-17 triggers joint damage via proinflammatory cytokines. ERA involves IL-23-driven inflammation, leading to bone formation via IL-22. Systemic arthritis results from constant innate immunity activation with proinflammatory cytokines like IL-1 beta, IL-6, and IL-18. Recent research highlights the role of the adaptive immune system, with distinct T cell subgroups identified during various disease stages. Regulatory T cells producing IL-17 rise during early inflammation, and achieving early remission with IL-1 blockade limits CD4 effector T cell expansion with IL-17, supporting the "window of opportunity" theory [4,5].
Diagnosis of JIA
Early diagnosis and prognosis are challenging due to the lack of validated biomarkers. Common initial lab tests include CBC, ESR, CRP, ANA, RF, anti-CCP antibodies, and HLA-B27. While these tests are widely used, a positive RF or anti-CCP has limited diagnostic value but may indicate a worse disease course. Fibrinogen, AST, and triglycerides are recommended in potential macrophage activation syndrome cases. Identifying new non-invasive diagnostic biomarkers is crucial [1].
MicroRNAs (miRNAs) as Potential Biomarkers
MiRNAs, short non-coding RNAs, have gained attention in JIA research due to their role in inflammatory responses and immune function. Dysregulated miRNAs show diagnostic and prognostic potential in rheumatic diseases. Challenges in miRNA research include isolation and quantification techniques, as well as a lack of consensus in methodologies and data normalization [6,7,8,9].
Use of MiRNAs in Predicting Treatment Response
Recent studies in rheumatoid arthritis indicate miRNAs as indicators of anti-inflammatory treatment efficacy, particularly in predicting responses to metho-trexate and cytokine inhibitors. In a study involving DMARD patients, specific miRNAs were examined before methotrexate treatment, with responders showing lower baseline miRNA levels than non-responders. A double-blind study with early rheumatoid arthritis patients revealed that those with specific miRNA profiles responded better to adalimumab with methotrexat e [10,11]. These findings have potential implications for
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MEDICAL SCIENCES / «<g®[L[L®@U[]UM~J0U®MaL» ®29Ш©)), 2023
predicting therapy responses in autoimmune and inflammatory conditions like JIA, offering improved targeted interventions [10,11].
Treatment of JIA
JIA treatment involves medications, physiotherapy, surgery, and psychosocial support based on disease subtype and severity. NSAIDs provide initial symptom relief, but their use has decreased with more aggressive treatments like methotrexate and biologics
[5].
Biological Treatment of JIA
Biologics, which target cytokines, receptors, signaling molecules, or cells, have seen increased use. They come in various forms and include TNF inhibitors, B-cell inhibitors, interleukin inhibitors, and selective costimulation modulators. However, biologics can cause hypersensitivity reactions, including infusion-related reactions (IRRs) and cytokine release reactions (CRRs) [12,13]. Predictable reactions can be prevented with slower administration and premedication [15].
Physical Activity in JIA Patients
Physical activity offers holistic benefits to JIA patients, addressing physiological, behavioral, and functional aspects. It helps manage inflammation, improve sleep, and alleviate symptoms. Tailored activities based on individual symptoms, lifestyle, and fitness levels are essential. However, the optimal methods and timing for physical activity in treatment schedules require further investigation [6].
References
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