Frequency and perturbations of various peripheral blood cell populations before and after eculizumab treatment in paroxysmal nocturnal hemoglobinuria

Autor: 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, Jibran Durrani
Jazyk: angličtina
Rok vydání: 2021
Předmět:
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
Zdroj: Blood Cells Mol Dis
Popis: 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.
Databáze: OpenAIRE
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