In-depth blood immune profiling of Good syndrome patients.

Autor:	Torres-Valle A; Translational and Clinical Research Program, Centro de investigación del Cáncer (CIC), Instituto de Biología Molecular y Celular del Cáncer (IBMCC), Consejo Superior de Investigaciones Científicas (CSIC) and University of Salamanca (USAL), Salamanca, Spain.; Cytometry Service, NUCLEUS, Department of Medicine, University of Salamanca, Salamanca, Spain.; Instituto de Investigación Biomédica de Salamanca (IBSAL), Salamanca, Spain., Aragon L; Immunology Department, Donostia University Hospital, Osakidetza Basque Health Service, San Sebastián, Spain., Silva SL; Serviço de Imunoalergologia, Centro Hospitalar Universitário Lisboa Norte, Lisbon, Portugal.; Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal., Serrano C; Servicio de Inmunología, Fundación Jiménez Díaz, Madrid, Spain., Marcos M; Instituto de Investigación Biomédica de Salamanca (IBSAL), Salamanca, Spain.; Department of Internal Medicine, University Hospital of Salamanca, Salamanca, Spain.; Department of Medicine, University of Salamanca, Salamanca, Spain., Melero J; Servicio de inmunología y genética, Hospital Universitario de Badajoz, Badajoz, Spain., Bonroy C; Department of Laboratory Medicine, Ghent University Hospital, Ghent, Belgium.; Department of Diagnostic Sciences, Ghent University, Ghent, Belgium., Arenas-Caro PP; Immunology Department, Donostia University Hospital, Osakidetza Basque Health Service, San Sebastián, Spain., Casado DM; Immunology Department, Donostia University Hospital, Osakidetza Basque Health Service, San Sebastián, Spain., Olaizola PMR; Immunology Department, Donostia University Hospital, Osakidetza Basque Health Service, San Sebastián, Spain., Neirinck J; Department of Laboratory Medicine, Ghent University Hospital, Ghent, Belgium.; Department of Diagnostic Sciences, Ghent University, Ghent, Belgium., Hofmans M; Department of Laboratory Medicine, Ghent University Hospital, Ghent, Belgium.; Department of Diagnostic Sciences, Ghent University, Ghent, Belgium., de Arriba S; Pediatrics Department, University Hospital of Salamanca, Salamanca, Spain., Jara M; Instituto de Investigación Biomédica de Salamanca (IBSAL), Salamanca, Spain.; Biomedical Research Networking Centre Consortium of Oncology (CIBERONC), Instituto de Salud Carlos III, Madrid, Spain.; DNA Sequencing Service (NUCLEUS), University of Salamanca, Salamanca, Spain., Prieto C; Bioinformatics service (NUCLEUS), University of Salamanca, Salamanca, Spain., Sousa AE; Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal., Prada Á; Immunology Department, Donostia University Hospital, Osakidetza Basque Health Service, San Sebastián, Spain., van Dongen JJM; Translational and Clinical Research Program, Centro de investigación del Cáncer (CIC), Instituto de Biología Molecular y Celular del Cáncer (IBMCC), Consejo Superior de Investigaciones Científicas (CSIC) and University of Salamanca (USAL), Salamanca, Spain.; Cytometry Service, NUCLEUS, Department of Medicine, University of Salamanca, Salamanca, Spain.; Department of Immunology, Leiden University Medical Center, Leiden, Netherlands., Pérez-Andrés M; Translational and Clinical Research Program, Centro de investigación del Cáncer (CIC), Instituto de Biología Molecular y Celular del Cáncer (IBMCC), Consejo Superior de Investigaciones Científicas (CSIC) and University of Salamanca (USAL), Salamanca, Spain.; Cytometry Service, NUCLEUS, Department of Medicine, University of Salamanca, Salamanca, Spain.; Instituto de Investigación Biomédica de Salamanca (IBSAL), Salamanca, Spain.; Biomedical Research Networking Centre Consortium of Oncology (CIBERONC), Instituto de Salud Carlos III, Madrid, Spain., Orfao A; Translational and Clinical Research Program, Centro de investigación del Cáncer (CIC), Instituto de Biología Molecular y Celular del Cáncer (IBMCC), Consejo Superior de Investigaciones Científicas (CSIC) and University of Salamanca (USAL), Salamanca, Spain.; Cytometry Service, NUCLEUS, Department of Medicine, University of Salamanca, Salamanca, Spain.; Instituto de Investigación Biomédica de Salamanca (IBSAL), Salamanca, Spain.; Biomedical Research Networking Centre Consortium of Oncology (CIBERONC), Instituto de Salud Carlos III, Madrid, Spain.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2023 Nov 15; Vol. 14, pp. 1285088. Date of Electronic Publication: 2023 Nov 15 (Print Publication: 2023).
DOI:	10.3389/fimmu.2023.1285088
Abstrakt:	Introduction: Good syndrome (GS) is a rare adult-onset immunodeficiency first described in 1954. It is characterized by the coexistence of a thymoma and hypogammaglobulinemia, associated with an increased susceptibility to infections and autoimmunity. The classification and management of GS has been long hampered by the lack of data about the underlying immune alterations, a controversy existing on whether it is a unique diagnostic entity vs . a subtype of Common Variable Immune Deficiency (CVID). Methods: Here, we used high-sensitive flow cytometry to investigate the distribution of up to 70 different immune cell populations in blood of GS patients (n=9) compared to age-matched CVID patients (n=55) and healthy donors (n=61). Results: All 9 GS patients displayed reduced B-cell counts -down to undetectable levels (<0.1 cells/μL) in 8/9 cases-, together with decreased numbers of total CD4 + T-cells, NK-cells, neutrophils, and basophils vs. age-matched healthy donors. In contrast, they showed expanded TCRγδ + T-cells (p ≤ 0.05). Except for a deeper B-cell defect, the pattern of immune cell alteration in blood was similar in GS and (age-matched) CVID patients. In depth analysis of CD4 + T-cells revealed significantly decreased blood counts of naïve, central memory (CM) and transitional memory (TM) TCD4 + cells and their functional compartments of T follicular helper (TFH), regulatory T cells (Tregs), T helper (Th)2, Th17, Th22, Th1/Th17 and Th1/Th2 cells. In addition, GS patients also showed decreased NK-cell, neutrophil, basophil, classical monocyte and of both CD1c + and CD141 + myeloid dendritic cell counts in blood, in parallel to an expansion of total and terminal effector TCRγδ + T-cells. Interestingly, those GS patients who developed hypogammaglobulinemia several years after the thymoma presented with an immunological and clinical phenotype which more closely resembled a combined immune humoral and cellular defect, with poorer response to immunoglobulin replacement therapy, as compared to those in whom the thymoma and hypogammaglobulinemia were simultaneously detected. Discussion: Our findings provide a more accurate definition of the immune cell defects of GS patients and contribute to a better discrimination among GS patients between those with a pure B-cell defect vs . those suffering from a combined immunodeficiency with important consequences on the diagnosis and management of the disease. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision. (Copyright © 2023 Torres-Valle, Aragon, Silva, Serrano, Marcos, Melero, Bonroy, Arenas-Caro, Casado, Olaizola, Neirinck, Hofmans, de Arriba, Jara, Prieto, Sousa, Prada, van Dongen, Pérez-Andrés and Orfao.)
Databáze:	MEDLINE
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