[1548] Differential Expression of Activation-Related Antigens on Masts Cells and Eosinophils in Patients with Systemic Mastocytosis and Hypereosinophilic Syndrome

Olga Simakova, Todd Wilson, Melinda Wang, Nicolas Olivares, Amy Klion, Dean D Metcalfe, Irina Maric. NIH, CC, Bethesda, MD; NIH, NIAID, Bethesda, MD

Background: Systemic mastocytosis (SM) is a rare myeloproliferative disorder characterized by accumulation of neoplastic mast cells in one or more organs. Most patients with SM show a variable degree of eosinophilia in bone marrow samples, and in 20-30% of cases eosinophilia is present in the peripheral blood. Patients with hypereosinophilic syndrome (HES), in addition to hypereosinophilia, usually also show a variable increase in mast cell burden. Differences in activation of mast cells and eosinophils in these two disorders have not been described. We thus analyzed expression of activation-related antigens in these two patient populations using flow cytometry.
Design: A total of 71 study participants were evaluated at the NIH Clinical Center as a part of clinical research protocols studying mastocytosis and hypereosinophilia. Patients were diagnosed with SM (48) or HES (23) using the WHO diagnostic criteria. Normal volunteers (9) were analyzed in parallel. Immunophenotyic analysis of activation markers was performed using directly conjugated antibodies against CD11c, CD35, CD59, CD63, and CD69. Multicolor acquisition and analysis were performed using BD FACS Canto and Diva software. Results were expressed as GM ratio.
Results: Results of the analysis of mast cells are shown in the table below. All complement – related markers that were tested (CD11c, CD35, CD59) were markedly increased on mast cells in subjects with SM. In contrast, mast cells from HES patients showed no change in expression of CD11c and CD35, and a significant decrease in the expression of CD59. Similarly, CD63 (lysosomal membrane antigen involved in regulation of cell activation) and CD69 (early-activation antigen) were markedly up-regulated on mast cells in SM, but not on mast cells in HES. Analysis of the early eosinophil activation using CD69 revealed the opposite pattern: CD69 was significantly more up-regulated on bone marrow eosinophils in HES patients than in mastocytosis patients (1.5 vs 1.1 GM ratio; p<0.05).

Dx (# of patients)Mast Cell #CD11cCD35CD59CD63CD69
SM (48)2818.9*10.4*57.6*57.4*4.8*
HES (23)382.71.77.9*3.01.3
NV (9)
* p <0.05

Conclusions: These results suggest that mast cells and eosinophils in SM and HES show differential expression of activation-related antigens. Mast cells are significantly more activated in SM than in HES, while eosinophils are more activated in HES than SM.
Category: Hematopathology

Wednesday, March 21, 2012 9:30 AM

Poster Session V # 226, Wednesday Morning


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