SUN-646 Immune Landscape and Clinical Characteristics of Patients with Acquired Partial and Generalized Lipodystrophy Syndromes

Abstract Disclosure: O. Besci: None. C.D. Uwandu: None. U. Cavdar: None. B. Akinci: None. D. Gilio: None. M.C. Foss de Freitas: None. K. Walkovich: None. E.A. Oral: Regeneron Pharmaceuticals, Rhythm Pharmaceuticals, Novo Nordisk, Amryt Pharmaceuticals, Ionis Pharmaceuticals Inc., Morphic Medical, Rejuvenate Bio, Fractyl Laboratories. Introduction: Acquired lipodystrophy syndromes (ALS) are characterized by loss of adipose tissue and associated metabolic abnormalities, manifesting in either partial (APL) or generalized forms (AGL). Increasing evidence of ALS links to autoimmunity, infections, malignancies, and associated treatments highlights the need for an understanding of the associated immune-mediated mechanisms. Objective: We sought to provide immune-related insights on ALS by correlating coexisting disorders with their underlying immune mechanisms and identifying patterns of phenotypic presentations via comprehensive case review and literature analysis. Methods: We retrospectively reviewed all cases from the University of Michigan (n = 30) and published cases (n = 462). We systematically searched PubMed for ALS studies published in English with full-text availability from 2004 to the present (last accessed: December, 2024) and reviewed references from comprehensive studies (1919-2004) to identify phenotypical descriptions matching the published diagnostic criteria for AGL and APL1,2. Barraquer-Simons syndrome and phenotypes resembling Dunnigan syndrome, with lipoatrophy in the extremities and fat retention in the face, neck, and abdomen, were classified as APL. Cases were categorized based on immune mechanisms and presenting phenotypes. Results: In our analysis of 492 patients with ALS, 32% (n=159) had AGL and 68% (n=333) had APL. ALS with autoimmune disorders was significantly more common in AGL compared to APL (39% vs 26%, p=0.004), as was ALS with regulatory T cell defects (7% vs. 1%, p<0.001), colitis (7% vs. 2%, p=0.01) and panniculitis (26% vs. 1%, p<0.001). ALS associated with malignancy, involving immune checkpoint inhibitors (7% vs. 1%, p<0.001), lymphoma (6% vs. <1%, p<0.001), and paraneoplastic syndromes (2% vs. <1%, p=0.04) predominantly exhibited the AGL phenotype, whereas prior exposure to HSCT/TBI was significantly associated with the APL phenotype (5% vs. <1%, p=0.01). While C3 deficiency was significantly more common in APL compared to AGL (39% vs 4%, p<0.001), C4 deficiency was more frequently observed in AGL than in APL (5% vs 1%, p=0.02). Conclusion: Our study highlights the diverse clinical manifestations of patients with APL and AGL, emphasizing ALS with autoimmune disorders, regulatory T-cell defects, lymphoma, panniculitis and colitis are predominantly linked to the AGL, while complement deficiencies and prior HSCT/TBI exposure are more frequently associated with APL. References: 1. Misra A, Garg A. Clinical features and metabolic derangements in acquired generalized lipodystrophy: case reports and review of the literature. Medicine (Baltimore). 2003. 2. Misra A, Peethambaram A, Garg A. Clinical features and metabolic and autoimmune derangements in acquired partial lipodystrophy: report of 35 cases and review of the literature. Medicine (Baltimore). 2004. Presentation: Sunday, July 13, 2025