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

Autor(es):Mostrar menos -

Felicio, Rafaela de Freitas Martins ; Maciel, Luciana Ribeiro Jarduli ; Mosella, Maritza Queiroz Salas ; Almeida, Felipe Campos ; de Lima, Keli Cristina ; de Azevedo, Julia Teixeira Cottas ; Gardinassi, Luiz Gustavo ; Ramos, Pablo Ivan Pereira ; de Santis, Gil Cunha ; Pinto, Ana Cristina Silva ; de Castro, Fabiola Attie ; Oliveira, Maria Carolina ; Malmegrim, Kelen Cristina Ribeiro

• Tipo de documento: Artigo Científico
• Fonte: Experimental Hematology; v. 137, p. 9-pg., 2024-08-16.

Resumo

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. (c) 2024 International Society for Experimental Hematology. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies. (AU)

• Processo FAPESP: 13/08135-2 - CTC - Centro de Terapia Celular
• Beneficiário: Dimas Tadeu Covas
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs
• Processo FAPESP: 16/22330-0 - Avaliação da reconstituição imunológica e função tímica em pacientes com doença falciforme submetidos ao transplante alogênico de células-tronco hematopoéticas
• Beneficiário: Kelen Cristina Ribeiro Malmegrim de Farias
• Modalidade de apoio: Auxílio à Pesquisa - Regular