SYSTEMIC LUPUS ERYTHEMATOSUS: AUTOIMMUNE MECHANISMS AND ORGAN DAMAGE
Keywords:
Systemic lupus erythematosus, autoimmunity, autoantibodies, lupus nephritis, type I interferon, complement, organ damage, belimumab, anifrolumab.Abstract
Systemic lupus erythematosus (SLE) is a chronic, multisystem autoimmune disease characterized by loss of self-tolerance, production of pathogenic autoantibodies, and immune complex-mediated inflammation that can affect the skin, joints, kidneys, blood cells, nervous system, and serosal surfaces. This narrative review synthesizes current evidence on the immunopathogenesis and organ-specific manifestations of SLE, drawing on the 2019 EULAR/American College of Rheumatology (ACR) classification criteria, the 2023 EULAR management recommendations, and recent trial data on biologic and targeted therapies. Disease pathogenesis reflects a self-amplifying cycle in which genetic susceptibility and environmental triggers impair clearance of apoptotic debris, promote loss of tolerance in autoreactive B and T lymphocytes, and drive immune complex deposition, complement activation, and a dominant type I interferon signature that sustains tissue inflammation and progressive organ damage. Lupus nephritis and neuropsychiatric involvement remain the principal drivers of morbidity and require prompt, biopsy- or presentation-guided treatment. Management has shifted toward early, individualized combination therapy — hydroxychloroquine as a foundation for nearly all patients, glucocorticoid minimization, and earlier introduction of immunosuppressive or biologic agents such as belimumab, anifrolumab, and voclosporin — aimed at achieving sustained remission or low disease activity while limiting cumulative organ damage. A mechanism-based understanding of SLE, combined with structured classification and severity assessment, is central to improving long-term outcomes, including within the healthcare system of Uzbekistan.
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