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Abstract Systemic lupus erythematosus (SLE) is characterized by disruptions in cell death pathways and impaired clearance of apoptotic cells, resulting in immune dysregulation and tissue damage. This review explores the complex interplay of regulated cell death (RCD) mechanisms, including apoptosis, necroptosis, pyroptosis, NETosis, autophagy, and ferroptosis, in the pathogenesis of SLE. These pathways release autoantigens and danger signals, triggering autoimmune reactions and inflammation. Six various RCDs have mutual associates to support immune dysregulation and are associated with SLE. Apoptosis intrinsically induces immune tolerance by packaging dying cells into immunologically inert fragments. Deficiencies in apoptotic clearance will result in impaired tolerance. Necroptosis, pyroptosis, NETosis, and ferroptosis lead to cell membrane destruction, production of intracellular immunostimulatory components, and triggering a strong inflammatory immune reaction. Abnormal autophagic activity affects the development, differentiation, function, and metabolism of many immune cell subpopulations. Investigating the interconnections between cell death pathways and SLE sheds light on the disease's underlying mechanisms and provides opportunities for novel therapeutic interventions. The convergence of precision medicine and innovative strategies targeting these intricate pathways holds promise for expanding the landscape of SLE treatment.

Abstract Introduction Agents that can be used for the treatment of neuropsychiatric lupus (NPSLE) are lacking in the therapeutic armamentarium. Belimumab is a monoclonal antibody targeting the B‐cell activating factor (BAFF) and is approved by the US Food and Drug Administration as an additional treatment for systemic lupus erythematosus patients with persistent disease activity and lupus nephritis (LN); however, severe active central nervous system manifestations were excluded. Case Report We report on a treatment‐naïve LN patient with refractory NPSLE complicated with progressive posterior reversible encephalopathy syndrome (PRES) who was successfully treated via the combination of mycophenolate and belimumab, resulting in reversal of persistent headache and neuroradiologic manifestations. Conclusion Research on this topic could be relevant for identifying a possible correlation between BAFF and psychiatric NPSLE manifestations.