Juvenile idiopathic arthritis (JIA) is the most common paediatric rheumatological disorder and is classified by subtype according to International League of Associations for Rheumatology criteria. Depending on the number of joints affected, presence of extra-articular manifestations, systemic symptoms, serology and genetic factors, JIA is divided into oligoarticular, polyarticular, systemic, psoriatic, enthesitis-related and undifferentiated arthritis. This review provides an overview of advances in understanding of JIA pathogenesis focusing on aetiology, histopathology, immunological changes associated with disease activity, and best treatment options. Greater understanding of JIA as a collective of complex inflammatory diseases is discussed within the context of therapeutic interventions, including traditional non-biologic and up-to-date biologic disease-modifying anti-rheumatic drugs. Whilst the advent of advanced therapeutics has improved clinical outcomes, a considerable number of patients remain unresponsive to treatment, emphasising the need for further understanding of disease progression and remission to support stratification of patients to treatment pathways.

Mesenchymal stem cells (MSCs) modulate immune responses and maintain self-tolerance. Their trophic activities and regenerative properties make them potential immunosuppressants for treating autoimmune and autoinflammatory diseases. MSCs are drawn to sites of injury and inflammation where they can both reduce inflammation and contribute to tissue regeneration. An increased understanding of the role of MSCs in the development and progression of autoimmune disorders has revealed that MSCs are passive targets in the inflammatory process, becoming impaired by it and exhibiting loss of immunomodulatory activity. MSCs have been considered as potential novel cell therapies for severe autoimmune and autoinflammatory diseases, which at present have only disease modifying rather than curative treatment options. MSCs are emerging as potential therapies for severe autoimmune and autoinflammatory diseases. Clinical application of MSCs in rare cases of severe disease in which other existing treatment modalities have failed, have demonstrated potential use in treating multiple diseases, including rheumatoid arthritis, systemic lupus erythematosus, myocardial infarction, liver cirrhosis, spinal cord injury, multiple sclerosis, and COVID-19 pneumonia. This review explores the biological mechanisms behind the role of MSCs in autoimmune and autoinflammatory diseases. It also covers their immunomodulatory capabilities, potential therapeutic applications, and the challenges and risks associated with MSC therapy.

Osteoarthritis is a chronic degenerative disease characterized by the destructive changes in the articular cartilage, synovitis, subchondral bone sclerosis and osteophyte formation. Today it is the most common joint disease and one of the main causes of disability of elderly people. This review provides an overview of advances in understanding of osteoarthritis etiology, pathogenesis, histopathology, as well as the results of up-to-date research of the molecular mechanisms underlying this heterogeneous age-related disease at the clinical and fundamental levels. The article is devoted to a comprehensive review of the osteoarthritis problem, compiled considering the classical understanding of morphological changes, clinical picture, diagnostic methods, and current therapy protocols, supplemented by the modern trends of world research with the prospect of further development and implementation of the latest therapeutic methods, such as nerve growth factor-inhibitors, fibroblast growth factor-18 and stem cells treatments.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease of unknown aetiology, with the broad range of antibodies affecting various organs and tissues, leading to rapid disability and even to lethal outcome. Our objective was to make an analysis of the results of relevant global studies about genetic mutations, spectrum of antibodies and cytokines involved in the pathogenesis of SLE. The search was conducted in PubMed and Google Scholar platforms using keywords “systemic lupus erythematosus”, “genetic mutations”, “autoantibodies”, “cytokine production”, “sequencing”, “NGS" and "exome". Several genes were found to be involved in the pathogenesis of SLE, the majority of which were associated with B- and T-cell abnormal activation. The results of different studies revealed an association of active SLE with the increase in specific circulating autoantibodies. Based on the results of the current review, a preliminary list of autoantibodies, genes and cytokines associated with the development of SLE was prepared. Future directions will include the assessment of association of genes, antibodies and cytokines in SLE patients from the local Kazakh population, and the development of genetic-immunologic panel for the early diagnosis of this disease.

Background: Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease characterized by the production of various antibodies and immune complex-mediated injury. Limited information exists about Kazakh patients, a heterogeneous group with different clinical manifestations and potentially unique genetic basis. Objective: To describe the clinical features, associated autoantibody and cytokine profile, and the frequency of rare variants in a limited panel of genes. Method: This study enrolled 43 Kazakh individuals: 25 with SLE and 18 healthy controls. Disease activity was assessed using the SLEDAI-2K score. Laboratory tests included C3 and C4 complement components, interleukin (IL)-6, IL-5, IL-10, IL-18, IFN and antiphospholipid IgG/IgM identified by ELISA. The antinuclear factor (ANF) on HEp-2 cells was detected using indirect immunofluorescence. Specific autoantibodies were identified by immunoblotting. A custom AmpliSeq panel of 120 genes was used on the Ion Proton Sequencer. Results: SLE patients (SLEDAI-2K = 11,48 ± 8,7) demonstrated skin lesions (88%), joint involvement (84%), lupus nephritis (56%), and hematological disorders (40% patients). Cardiac and vascular injury was each observed in 36% of patients, while involvement of nervous system, mucous membranes, and thyroid gland each occurred in 8% of cases. Immunological tests revealed positive ANF in the majority of patients (92%) with anti-dsDNA, nucleosomes, Smith, SS-A/Ro52, SS-A/Ro60, U1-snRNP, and Rib-P0 antibodies. IL-6, IL-18, IFN levels were markedly elevated in patients with SLE relative to controls ( p = .02), reflecting enhanced systemic inflammatory activity. Elevated IL-10 was found as well in patients with SLE relative to controls ( p = .02). According to the results of gene panel sequencing, the most significant variants were found in genes SAMD9L, REL, IRAK1, PTPRC, TLR7, TNFAIP3, IL6ST, BLK, CCR5, TFPI, CLEC16 A, IL2RB, ITGA2B, ABCC2, KIF5A, NCF2, and CD5, none of which showed statistically important enrichment in the disease cohort. Conclusion: Analysis of data obtained from Kazakh patients with SLE revealed diverse autoimmune profiles, including various antibodies, pro- and anti-inflammatory cytokines, as well as several variants in REL, IRAK1, PTRPC, IL6ST genes. The findings presented may contribute to the development of personalized diagnostic tools for predicting disease trajectories and guiding treatment decisions.