Transcriptome profiling reveals distinct alterations in the B-cell signature and dysregulation of peripheral B-cell subsets in sickle cell anemia patients.

Autor: Felício RFM; Center for Cell-based Therapy, Regional Blood Center of Ribeirão Preto, Ribeirão Preto. Medical School, University of São Paulo, Ribeirão Preto, Brazil; Graduation Program in Bioscience and Biotechnology, Department of Clinical Analysis, Toxicology and Food Science, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil., Jarduli-Maciel LR; Graduation Program in Bioscience and Biotechnology, Department of Clinical Analysis, Toxicology and Food Science, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil., Mosella MQS; Graduation Program in Genetics, Department of Genetics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil., Almeida FC; Graduation Program in Bioscience and Biotechnology, Department of Clinical Analysis, Toxicology and Food Science, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil., de Lima KC; Graduation Program in Bioscience and Biotechnology, Department of Clinical Analysis, Toxicology and Food Science, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil., de Azevedo JTC; Center for Cell-based Therapy, Regional Blood Center of Ribeirão Preto, Ribeirão Preto. Medical School, University of São Paulo, Ribeirão Preto, Brazil., Gardinassi LG; Department of Biosciences and Technology, Institute of Tropical Pathology and Public Health, Federal University of Goiás, Goiânia, Brazil., Ramos PIP; Center of Data and Knowledge Integration for Health Instituto Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, Brazil., de Santis GC; Center for Cell-based Therapy, Regional Blood Center of Ribeirão Preto, Ribeirão Preto. Medical School, University of São Paulo, Ribeirão Preto, Brazil., Silva-Pinto AC; Center for Cell-based Therapy, Regional Blood Center of Ribeirão Preto, Ribeirão Preto. Medical School, University of São Paulo, Ribeirão Preto, Brazil., de Castro FA; Department of Clinical, Toxicological and Bromatological Analysis, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil., Oliveira MC; Center for Cell-based Therapy, Regional Blood Center of Ribeirão Preto, Ribeirão Preto. Medical School, University of São Paulo, Ribeirão Preto, Brazil; Department of Internal Medicine, Division of Clinical Immunology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil., Malmegrim KCR; Center for Cell-based Therapy, Regional Blood Center of Ribeirão Preto, Ribeirão Preto. Medical School, University of São Paulo, Ribeirão Preto, Brazil; Department of Clinical, Toxicological and Bromatological Analysis, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil. Electronic address: kelenfarias@fcfrp.usp.br.
Jazyk: angličtina
Zdroj: Experimental hematology [Exp Hematol] 2024 Sep; Vol. 137, pp. 104254. Date of Electronic Publication: 2024 Jun 12.
DOI: 10.1016/j.exphem.2024.104254
Abstrakt: Sickle cell anemia (SCA) is characterized by immune system activation and heightened susceptibility to infections. We hypothesized that SCA patients exhibit transcriptional alterations in B-cell-related genes, impacting their peripheral B-cell compartment and leading to dysregulated humoral immunity and increased infection susceptibility. Our objective was to conduct an in silico analysis of whole blood transcriptomes from SCA patients and healthy controls obtained from public repositories. We aimed to identify alterations in the adaptive immune system and validate these findings in our own SCA patient cohort. Bioinformatic analyses unveiled significant transcriptional alterations in B-cell signatures, developmental pathways, and signaling pathways. These results were validated in peripheral blood mononuclear cells from our SCA patient cohort and controls using real-time polymerase chain reaction and flow cytometry. Ninety genes exhibited differential expression, with 70 upregulated and 20 downregulated. Dysregulation in the B-cell compartment of SCA patients was evident, characterized by increased frequencies of immature and naive B-cells, and decreased percentages of memory B-cell subsets compared with healthy controls. Our findings highlight previously unexplored transcriptional and quantitative alterations in peripheral B-cells among SCA patients. Understanding these changes sheds light on the mechanisms contributing to the heightened infection risk in this population. Future studies should delve deeper into these molecular changes to develop targeted interventions and therapeutic strategies aimed at mitigating infection susceptibility in individuals with SCA.
Competing Interests: Conflicts of Interest Disclosure The authors have nothing to disclose.
(Copyright © 2024 International Society for Experimental Hematology. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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