RAPID DETECTION OF PATHOLOGICAL CD1A+CD207+ MYELOID CIRCULATING CELLS IN BLOOD AND THEIR IMPLICATION IN LANGERHANS CELL HISTIOCYTOSIS

NOWAK W; CARRERA SILVA EA; OLEXEN CINTHIA M; FORTUNATI DANIELA; ROSSO, DIEGO A.; ERRASTI ANDREA E

Buenos Aires

Congreso; Reunión Annual Conjunta SAIC-SAI-SAFIS 2020; 2020

Langerhans Cell Histiocytosis (LCH) is an inflammatory neoplasm characterized by an abnormal accumulation of CD207+CD1a+ myeloid cells in almost any tissue. Disease etiology is under debate, and it is not clear if LCH results from malignant transformation or unbalanced immune response. Previously, we found CD207+CD1a+ circulating cells in patients with active LCH with an important prognostic potential. We aimed to validate a rapid detection method of blood circulating CD1a+CD207+ cells to define a cellular disease activity in pediatric LCH patients and correlate with organ location and gene expression. CD207 and CD1a levels were measured in 7 blood myeloid compartments by flow cytometry. 188 pediatric LCH blood samples and 22 controls were analyzed. Survival and migration genes were evaluated in sorted circulating myeloid cells by RT-qPCR. We foundCD207+ and/or CD1a+ circulating cells in all active LCH patients, while controls and non-active LCH patients were negative. We established a cellular activity score adding the percentage of CD207+/CD1a+ cells in each of the 7 myeloid compartments, which was validated by ROC curve analysis (AUC:0.81, Sen.:0.79, Spe.:0.77, Y.Index:29.5). LCH patients with a score higher than 29were categorized as cellular active disease. Multivariate analysis showed specific CD207+/CD1a+ cell populations correlate with organ localization. Bone LCH was defined by CD1a+ in CD11bHCD14L/CD11cCD1c+. Skin LCH showed CD1a+CD207+ cells in CD11bHCD11cH/CD11b+CD11cL populations. Multisystem patients presented CD207+ cells in CD11bHCD14H/CD11bHCD14L/CD11cCD1c+. We also observed a differential gene expression of IL7R, SNAIL, NCAD and MMP1/9 dependent on organ compromise. Summarizing, we propose a rapid method to detect pathological CD207+CD1a+ cells in LCH patient?s peripheral blood and define a cellular activity score as an instrument to follow-up the activity disease, even before clinical manifestations, and potentially predict organ compromise.