Pathogenesis of Systemic Lupus Erythematosus

Tissue Damage and Clinical Manifestations

Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disease characterized by widespread inflammation and tissue damage in multiple organs. The disease primarily affects the skin, joints, kidneys, and the nervous system, with a highly variable clinical presentation.

Etiology and Pathogenesis

The exact cause of SLE remains unknown, but genetic predisposition, environmental triggers, and hormonal factors play significant roles. The pathogenesis involves:

• Autoantibody Production: The hallmark of SLE is the production of autoantibodies, particularly antinuclear antibodies (ANA), leading to immune complex formation.
• Complement Activation: Immune complexes activate the complement system, triggering inflammatory responses and tissue damage.
• Apoptotic Dysregulation: Impaired clearance of apoptotic cells results in immune activation and persistent autoimmunity.
• Genetic Susceptibility: Mutations in genes such as HLA-DR, IRF5, and STAT4 contribute to disease pathogenesis.

Clinical Manifestations

SLE manifests in diverse symptoms depending on the organ systems involved:

• Cutaneous: Malar rash, discoid lupus, photosensitivity.
• Musculoskeletal: Polyarthritis, myalgia.
• Renal: Lupus nephritis, proteinuria.
• Neurological: Seizures, cognitive dysfunction.
• Hematological: Anemia, thrombocytopenia.

Diagnosis and Prognosis

Diagnosis of SLE is based on clinical criteria and laboratory findings, including ANA positivity, anti-dsDNA antibodies, and complement levels. Prognosis varies depending on the severity and organ involvement, with renal and neurological complications often leading to increased morbidity.