Abnormal neutrophils present in peripheral blood of Chronic Atypical Neutrophilic Dermatosis with Lipodystrophy and Elevated Temperature (CANDLE) syndrome patients. (P4173)

Abstract

Abstract CANDLE syndrome (CS) is an autoinflammatory disease caused by autosomal recessive mutations in PSMB8. CANDLE involves dysregulation of the IFN signaling pathway and skin infiltrates of immature neutrophils and other cells. We investigated circulating neutrophils from patients with CS for changes in activation or homing markers and quantified the circulating low density granulocytes.. Compared with healthy donors (HD), or matched, paired unaffected parents (PP) carrying one copy of the mutated gene CS patients had increased proportions of immature CD10- neutrophils (7% in CS vs 2.6% in PP and vs 2.4% in HD). In addition, in CS, the reduced proportion of CD10+ mature neutrophils presented an activated phenotype based on expression of CD64 (8.6% vs 4.5% in PP vs 0.9% in HD). We illustrated changes in the maturation activation pattern of neutrophil by calculating the CD10+/CD10- ratio, and showed reduced ratio in CS patients, ratio=13.3 vs 40.1 in PP vs 44.4 in HD. We observed a reduction of CD62L and CD11b/CD18 expression on mature, and increased expression on the immature population. We observed higher circulating LDGs in PBMC fraction of CS (2%) compared to PP (1.1%) or HD (0.7%). The abnormal phenotype of circulating neutrophils, could explain the migration of immature neutrophils to inflammatory skin tissues; however, the overlap of this population with the increased circulating LDG population and their capacity to generate functional responses, remains still unclear.