1. Frequency and perturbations of various peripheral blood cell populations before and after eculizumab treatment in paroxysmal nocturnal hemoglobinuria
- Author
-
Carmelo Gurnari, Hassan Awada, Bhumika J. Patel, Jaroslaw P. Maciejewski, Alexey Efanov, Valeria Visconte, Simona Pagliuca, Alan E. Lichtin, Mikkael A. Sekeres, Amy C Graham, and Jibran Durrani
- Subjects
0301 basic medicine ,Male ,Erythrocytes ,Reticulocytes ,PNH ,Clone (cell biology) ,Hemoglobinuria, Paroxysmal ,0302 clinical medicine ,hemic and lymphatic diseases ,Platelet ,Aged, 80 and over ,education.field_of_study ,Hematology ,Eculizumab ,Middle Aged ,Flow Cytometry ,medicine.anatomical_structure ,Molecular Medicine ,Female ,medicine.drug ,Adult ,Blood Platelets ,Platelets ,Population ,Complement ,Context (language use) ,Granulocyte ,Antibodies, Monoclonal, Humanized ,Article ,03 medical and health sciences ,Young Adult ,Erythroid Cells ,medicine ,Humans ,Peripheral blood cell ,education ,Molecular Biology ,Aged ,Blood Cells ,business.industry ,Cell Biology ,medicine.disease ,Settore MED/15 ,GPI-AP deficiency ,030104 developmental biology ,Complement Inactivating Agents ,Immunology ,Paroxysmal nocturnal hemoglobinuria ,business ,030215 immunology ,Granulocytes - Abstract
While red blood cells (RBCs) and granulocytes have been more studied, platelets and reticulocytes are not commonly used in paroxysmal nocturnal hemoglobinuria (PNH) flow-cytometry and less is known about susceptibility to complement-mediated destruction and effects of anti-complement therapy on these populations. We performed flow-cytometry of RBCs and granulocytes in 90 PNH patients and of platelets and reticulocytes in a subgroup (N = 36), to unveil perturbations of these populations during PNH disease course before and after anti-complement treatment. We found that platelets and reticulocytes were less sensitive to complement-mediated lysis than RBCs but not as resistant as granulocytes, as shown by mean sensitive fraction (difference in a given PNH population vs. PNH granulocyte clone size). In treated patients, reticulocytes, platelets, RBCs (with differences between type II and III) and granulocytes significantly increased post-treatment, confirming the role of PNH hematopoiesis within the context of anti-complement therapy. Moreover, we found that PNH platelet clone size reflects PNH granulocyte clone size. Finally, we established correlations between sensitive fraction of PNH cell-types and thrombosis. In sum, we applied a flow-cytometry panel for investigation of PNH peripheral blood populations' perturbations before and after eculizumab treatment to explore complement-sensitivity and kinetics of these cells during the disease course.
- Published
- 2021