Osseous Langerhans Histiocytosis and indomethacin efficacy based on homing gene expression

OLEXEN CINTHIA M; ERRASTI ANDREA E*; LAVA MARIA CATALINA; ROSSO, DIEGO A.*; RISNIK DENISE MARIEL; CARRERA SILVA EUGENIO A*

Mar del Plata

Congreso; Reunión Conjunta SAIC-SAI-SAFIS 2022; 2022

Langerhans cell Histiocytosis (LCH) is a rare inflammatory and my- eloid proliferative disorder, leading to the accumulation of CD1a+/ CD207+ cells into different tissues causing a wide range of lesions and compromise. Indomethacin, a non-selective COX inhibitor, has proven to be effective and well accepted for patients with bone af- fection, but its specific mechanism has not yet been established. We hypothesize that Indomethacin affects the homing of pathogenic Langerhans cells (LC) or their precursors to the bone. We retro- spectively (2018-2022), evaluate the outcome of patients with bone LCH under indomethacin treatment analyzing bone healing, clinical improvement, presence of circulating CD1a+/CD207+ cells, and the expression of homing and migration molecules in sorted circulating mononuclear myeloid cells. The effect of indomethacin and ibupro- fen on the expression of homing genes was evaluated in vitro in a inflammatory LC-like model (IL-4 plus GM-CSF plus TGF􏰀 plus TNF􏰁 plus dexamethasone) by qPCR and flow cytometry. We have found 21 patients with bone compromise and indomethacin treat- ment, and curiously the clinical improvement still showed circulating CD1a+/CD207+ cells suggesting a potential restraining mechanism to the bone. AXL, a tyrosine kinase receptor involved in cancer cell migration, is increased in patients with LCH (N=13, P=0.01) and par- ticularly higher in bone compromise (N=6, P