Persistent imbalance, anti-apoptotic, and anti-inflammatory signature of circulating C-C chemokines and cytokines in patients with paroxysmal nocturnal hemoglobinuria.

Autor: Szlendak U; Department of Immunogenetics, Institute of Hematology and Transfusion Medicine, Warsaw, Poland., Krzymieniewska B; Laboratory of Immunophenotyping, Institute of Hematology and Transfusion Medicine, Warsaw, Poland., Mendek-Czajkowska E; Specialist Outpatient Clinic, Institute of Hematology and Transfusion Medicine, Warsaw, Poland., Rogatko-Koroś M; Department of Immunogenetics, Institute of Hematology and Transfusion Medicine, Warsaw, Poland., Witkowska A; Department of Immunogenetics, Institute of Hematology and Transfusion Medicine, Warsaw, Poland., Włodarska J; Day Treatment Department, Institute of Hematology and Transfusion Medicine, Warsaw, Poland., Drozd-Sokołowska J; Department of Hematology, Transplantology and Internal Medicine, University Clinical Center, Medical University of Warsaw, Warsaw, Poland., Spychalska J; Department of Hematological and Transfusion Immunology, Institute of Hematology and Transfusion Medicine, Warsaw, Poland., Budziszewska B; Department of Hematology, Institute of Hematology and Transfusion Medicine, Warsaw, Poland., Patkowska E; Department of Hematology, Institute of Hematology and Transfusion Medicine, Warsaw, Poland., Woźniak J; Laboratory of Immunophenotyping, Institute of Hematology and Transfusion Medicine, Warsaw, Poland., Krzywdzińska A; Laboratory of Immunophenotyping, Institute of Hematology and Transfusion Medicine, Warsaw, Poland., Jurek S; Department of Disorders of Hemostasis and Internal Medicine, Institute of Hematology and Transfusion Medicine, Warsaw, Poland., Juszczyński P; Department of Experimental Hematology, Institute of Hematology and Transfusion Medicine, Warsaw, Poland., Jaworska M; Department of Biochemistry and Biopharmaceuticals, National Medicines Institute, Warsaw, Poland., Rosłon M; Department of Biochemistry and Biopharmaceuticals, National Medicines Institute, Warsaw, Poland., Gruber-Bzura B; Department of Biochemistry and Biopharmaceuticals, National Medicines Institute, Warsaw, Poland., Wasilewski R; Department of Disorders of Hemostasis and Internal Medicine, Institute of Hematology and Transfusion Medicine, Warsaw, Poland., Baran B; Department of Hemostasis and Metabolic Diseases, Institute of Hematology and Transfusion Medicine, Warsaw, Poland., Windyga J; Department of Disorders of Hemostasis and Internal Medicine, Institute of Hematology and Transfusion Medicine, Warsaw, Poland., Nowak J; Department of Immunogenetics, Institute of Hematology and Transfusion Medicine, Warsaw, Poland. Electronic address: jnowak@ihit.waw.pl.
Jazyk: angličtina
Zdroj: Cytokine [Cytokine] 2022 Feb; Vol. 150, pp. 155780. Date of Electronic Publication: 2021 Dec 10.
DOI: 10.1016/j.cyto.2021.155780
Abstrakt: Objective: Paroxysmal nocturnal hemoglobinuria (PNH) is a clonal non-malignant disease in which hematopoietic cell apoptosis may play an important pathophysiological role. Previous studies of the content of phosphatidylinositol (3,4,5)-trisphosphate (PI(3,4,5)P3) indicated the possibility of remote transmission of anti-apoptotic signals between pathological and normal hematopoietic progenitors.
Methods: The study determined the plasma levels of beta chemokines and cytokines in N = 19 patients with PNH and 31 healthy controls. The research material was peripheral blood plasma (EDTA) stored at -80 °C until the test. Beta chemokine and cytokine concentrations were tested in duplicate with Bio-Plex Pro Human Cytokine Assay (Bio-Rad, Hercules, CA, USA) using a Luminex 200 flow cytometer and xPONENT software (Luminex Corporation, Austin, TX, USA). In peripheral blood CD34+ cells we tested the proportions of PI(3,4,5)P3+ and Annexin binding apoptotic phenotype using FC and phosflow.
Results: Compared to the control group, the PNH group showed a significant increase in the plasma concentration of some beta chemokines and cytokines, including MIP-1alpha/CCL3, eotaxin/CCL11, MCP1/CCL2, IL4 and G-CSF. In the group of PNH patients, a significant decrease in the concentration of some cytokines was also observed: RANTES/CCL5, MIP-1beta/CCL4, PDGF-BB and IL9. At the same time, the plasma concentrations of the chemokine IP-10/CXCL10 and the cytokines IFN-gamma, TNF, IL6 and IL10 showed no significant deviations from the values for the control group. Anti-apoptotic phenotype and phosphatidylinositol (3,4,5)-trisphosphate content in PNH clone of CD34+ cells were associated with the level of CCL3 and negatively associated with CCL5, CCL4, PDGF-BB and IL9.
Conclusions: This data suggest the existence of apoptotic and PI(3,4,5)P3 imbalance in PNH CD34+ cells driven by anti-apoptotic cytokine biosignature in PNH. Plasma cytokines and intracellular enzymes that regulate the phosphoinositide pathways may become a therapeutic target in PNH.
(Copyright © 2021 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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