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Defects in memory B-cell and plasma cell subsets expressing different immunoglobulin-subclasses in patients with CVID and immunoglobulin subclass deficiencies

E. Blanco, M. Pérez-Andrés, S. Arriba-Méndez, C. Serrano, I. Criado, L. Del Pino-Molina, S. Silva, I. Madruga, M. Bakardjieva, C. Martins, A. Serra-Caetano, A. Romero, T. Contreras-Sanfeliciano, C. Bonroy, F. Sala, A. Martín, JM. Bastida, F....

. 2019 ; 144 (3) : 809-824. [pub] 20190228

Jazyk angličtina Země Spojené státy americké

Typ dokumentu časopisecké články, práce podpořená grantem

Perzistentní odkaz   https://www.medvik.cz/link/bmc20023702

BACKGROUND: Predominantly antibody deficiencies (PADs) are the most prevalent primary immunodeficiencies, but their B-cell defects and underlying genetic alterations remain largely unknown. OBJECTIVE: We investigated patients with PADs for the distribution of 41 blood B-cell and plasma cell (PC) subsets, including subsets defined by expression of distinct immunoglobulin heavy chain subclasses. METHODS: Blood samples from 139 patients with PADs, 61 patients with common variable immunodeficiency (CVID), 68 patients with selective IgA deficiency (IgAdef), 10 patients with IgG subclass deficiency with IgA deficiency, and 223 age-matched control subjects were studied by using flow cytometry with EuroFlow immunoglobulin isotype staining. Patients were classified according to their B-cell and PC immune profile, and the obtained patient clusters were correlated with clinical manifestations of PADs. RESULTS: Decreased counts of blood PCs, memory B cells (MBCs), or both expressing distinct IgA and IgG subclasses were identified in all patients with PADs. In patients with IgAdef, B-cell defects were mainly restricted to surface membrane (sm)IgA+ PCs and MBCs, with 2 clear subgroups showing strongly decreased numbers of smIgA+ PCs with mild versus severe smIgA+ MBC defects and higher frequencies of nonrespiratory tract infections, autoimmunity, and affected family members. Patients with IgG subclass deficiency with IgA deficiency and those with CVID showed defects in both smIgA+ and smIgG+ MBCs and PCs. Reduced numbers of switched PCs were systematically found in patients with CVID (absent in 98%), with 6 different defective MBC (and clinical) profiles: (1) profound decrease in MBC numbers; (2) defective CD27+ MBCs with almost normal IgG3+ MBCs; (3) absence of switched MBCs; and (4) presence of both unswitched and switched MBCs without and; (5) with IgG2+ MBCs; and (6) with IgA1+ MBCs. CONCLUSION: Distinct PAD defective B-cell patterns were identified that are associated with unique clinical profiles.

Bioinformatics service University of Salamanca Salamanca Spain

Biomedical Research Networking Centre Consortium of Oncology number CB 16 12 00233 Instituto de salud Carlos 3 Madrid Spain

Biomedical Research Networking Centre Consortium of Oncology number CB16 12 00400 Instituto de Salud Carlos 3 Madrid Spain

Centro de Salud Miguel Armijo Salamanca Spain

Clinical Immunology Department University Hospital La Paz and Physiopathology of Lymphocytes in Immunodeficiencies Group IdiPAZ Institute for Health Research Madrid Spain

CLIP Department of Haematology Oncology 2nd Faculty of Medicine Charles University Prague Czech Republic

Department of Clinical Immunology and Allergology St Anne's University Hospital and Faculty of Medicine Masaryk University Brno Czech Republic

Department of Immunohematology and Blood Transfusion Leiden University Medical Center Leiden The Netherlands

Department of Immunology Erasmus MC Rotterdam The Netherlands

Department of Laboratory Medicine University Hospital Ghent Ghent Belgium

Department of Medicine Cancer Research Centre Salamanca Spain

Department of Pediatrics Laboratory for Immunology Leiden University Medical Center Leiden The Netherlands

Department of Respiratory Diseases and Department of Pediatrics and Genetics University Hospital Ghent Ghent Belgium

Hospital D Estefânia CHLC Lisbon Portugal

Instituto de Medicina Molecular Faculdade de Medicina Universidade de Lisboa Lisbon Portugal

NOVA Medical School Faculdade de Ciências Médicas Universidade Nova de Lisboa Lisbon Portugal

Servicio de Alergia Hospital Universitario de Salamanca Institute for Biomedical Research of Salamanca Biomedical and Diagnosis Science Department University of Salamanca Salamanca Spain

Servicio de Bioquímica Clínica Hospital Universitario de Salamanca Salamanca Spain

Servicio de Hematología Hospital de Navarra Pamplona Spain

Servicio de Hematología Hospital Universitario de Salamanca Institute for Biomedical Research of Salamanca Salamanca Spain

Servicio de Inmunología Fundación Jiménez Díaz Madrid Spain

Servicio de Medicina Interna Hospital Universitario de Salamanca Institute for Biomedical Research of Salamanca Department of Medicine University of Salamanca Salamanca Spain

Servicio de Pediatría Hospital Universitario de Salamanca Salamanca Spain

Citace poskytuje Crossref.org

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