POS0099 THE CELLULAR METABOLISM OF SLE NK CELLS IS PRIMARILY ALTERED AT THE LEVEL OF MITOCHONDRIAL RESPIRATION.

Background Systemic lupus erythematosus (SLE) is an inflammatory autoimmune disease, involving the development of autoreactive cells and autoantibodies. Natural Killer (NK) are innate immune that mediate interaction between adaptive system, however their role in SLE incompletely understood. NK decreased peripheral blood, exhibit reduced cytotoxicity, impaired cytokine production (1, 2). Furthermore, present phenotypic alterations: increased expression CD38 altered upregulation SLAMF7 after activation (3). To date, few studies evaluated molecular mechanisms underlying cell dysfunction SLE. Objectives We examined immunometabolic alterations cells. First, we characterized cellular metabolism by assessing glycolysis oxidative phosphorylation (OXPHOS) at basal level. Then, how can be manipulated to enhance function. In this perspective, ligation with daratumumab (DARA) elotuzumab (ELO) modulate OXPHOS. Methods cryopreserved PBMC from patients were isolated. Glycolysis OXPHOS studied using XF e 96 Seahorse. Expression metabolic receptors (CD71, GLUT-1, CD98), mitochondrial function (mitochondrial membrane potential, mass) calcium influx investigated FACS. Mitochondrial structure was electron confocal microscopy. Results compared healthy observed significantly (Figure 1A), whereas normal 1B). mass potential (by FACS 1C) microscopy) Electron microscope imaging showed profound ultrastructure 1D). No significant differences key metabolite transporters involved fueling CD98) controls. Second, DARA ELO influences Our data primarily enhances 1E), mainly increases glycolysis. Consistently, also CD71, GLUT-1 CD98. Next, effect on While stimulation adequately cells, engagement fails properly increase 1F), surface transporters, mass. Conclusion suggest metabolism, respiration. contrast, glucose similar Additionally, through different pathways: glycolysis, respectively. Therefore, priming unable engage dysfunctional These findings provide important insights alteration contribute a better understanding pathogenesis disease. References [1]Spada R, Rojas JM, Barber DF. Recent natural killer systemic erythematosus. J Leukoc Biol. 2015;98(4):479-87. [2]Park Y-W, Kee S-J, Cho Y-N, Lee E-H, H-Y, Kim E-M, et al. Impaired differentiation cytotoxicity Arthritis & Rheumatism. 2009;60(6):1753-63. [3]Humbel M, Bellanger F, Fluder N, Horisberger A, Suffiotti Fenwick C, Restoration Cell Cytotoxic Function With Elotuzumab Daratumumab Promotes Elimination Circulating Plasma Cells Patients Front Immunol. 2021;12:645478. Acknowledgements This study received funding Swiss National Science Foundation (Ambizione PZ00P3_173950 DC). Disclosure Interests None declared