Defects in memory B-cell and plasma cell subsets expressing different immunoglobulin-subclasses in patients with CVID and immunoglobulin subclass deficiencies
| Autor(a) principal: | |
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| Data de Publicação: | 2019 |
| Outros Autores: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
| Texto Completo: | http://hdl.handle.net/10362/147794 |
Resumo: | Funding: E.B. was supported by a grant from the Junta de Castilla y Leon (Fondo Social Europeo, ORDEN EDU/346/2013, Valladolid, Spain). This work was supported by the CB16/ 12/00400 and CB/16/12/00233 grants (CIBERONC, Instituto de Salud Carlos III, Ministerio de Economıa y Competitividad, Madrid, Spain, and FONDOS FEDER), the FIS PI12/00905-FEDER grant (Fondo de Investigacion Sanitaria of Instituto de Salud Carlos III, Madrid, Spain) and a grant from Fundacion Mutua Madrile~na (Madrid, Spain). The coordination and innovation processes of this study were supported by the EuroFlow Consortium. |
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Defects in memory B-cell and plasma cell subsets expressing different immunoglobulin-subclasses in patients with CVID and immunoglobulin subclass deficienciesclassificationcommon variable immunodeficiencydiagnosisflow cytometryImmunodeficiencyimmunoglobulin subclassesimmunoglobulinsimmunophenotypingmemory B cellsplasma cellsprimary antibody deficiencyselective IgA deficiencyImmunology and AllergyImmunologyFunding: E.B. was supported by a grant from the Junta de Castilla y Leon (Fondo Social Europeo, ORDEN EDU/346/2013, Valladolid, Spain). This work was supported by the CB16/ 12/00400 and CB/16/12/00233 grants (CIBERONC, Instituto de Salud Carlos III, Ministerio de Economıa y Competitividad, Madrid, Spain, and FONDOS FEDER), the FIS PI12/00905-FEDER grant (Fondo de Investigacion Sanitaria of Instituto de Salud Carlos III, Madrid, Spain) and a grant from Fundacion Mutua Madrile~na (Madrid, Spain). The coordination and innovation processes of this study were supported by the EuroFlow Consortium.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 IgG 3 + MBCs; (3) absence of switched MBCs; and (4) presence of both unswitched and switched MBCs without and; (5) with IgG 2 + MBCs; and (6) with IgA 1 + MBCs. Conclusion: Distinct PAD defective B-cell patterns were identified that are associated with unique clinical profiles.NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)RUNBlanco, ElenaPérez-Andrés, MartínArriba-Méndez, SoniaSerrano, CristinaCriado, IgnacioDel Pino-Molina, LucíaSilva, SusanaMadruga, IgnacioBakardjieva, MarinaMartins, CatarinaSerra-Caetano, AnaRomero, AlfonsoContreras-Sanfeliciano, TeresaBonroy, CarolienSala, FranciscoMartín, AlejandroBastida, José MaríaLorente, FélixPrieto, CarlosDávila, IgnacioMarcos, MiguelKalina, TomasVlkova, MarcelaChovancova, ZitaCordeiro, Ana IsabelPhilippé, JanHaerynck, FilomeenLópez-Granados, EduardoSousa, Ana E.van der Burg, Mirjamvan Dongen, Jacques J.M.Orfao, Alberto2023-01-18T22:12:22Z2019-092019-09-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10362/147794eng0091-6749PURE: 12746797https://doi.org/10.1016/j.jaci.2019.02.017info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-03-11T05:29:01Zoai:run.unl.pt:10362/147794Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:53:04.629532Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
| dc.title.none.fl_str_mv |
Defects in memory B-cell and plasma cell subsets expressing different immunoglobulin-subclasses in patients with CVID and immunoglobulin subclass deficiencies |
| title |
Defects in memory B-cell and plasma cell subsets expressing different immunoglobulin-subclasses in patients with CVID and immunoglobulin subclass deficiencies |
| spellingShingle |
Defects in memory B-cell and plasma cell subsets expressing different immunoglobulin-subclasses in patients with CVID and immunoglobulin subclass deficiencies Blanco, Elena classification common variable immunodeficiency diagnosis flow cytometry Immunodeficiency immunoglobulin subclasses immunoglobulins immunophenotyping memory B cells plasma cells primary antibody deficiency selective IgA deficiency Immunology and Allergy Immunology |
| title_short |
Defects in memory B-cell and plasma cell subsets expressing different immunoglobulin-subclasses in patients with CVID and immunoglobulin subclass deficiencies |
| title_full |
Defects in memory B-cell and plasma cell subsets expressing different immunoglobulin-subclasses in patients with CVID and immunoglobulin subclass deficiencies |
| title_fullStr |
Defects in memory B-cell and plasma cell subsets expressing different immunoglobulin-subclasses in patients with CVID and immunoglobulin subclass deficiencies |
| title_full_unstemmed |
Defects in memory B-cell and plasma cell subsets expressing different immunoglobulin-subclasses in patients with CVID and immunoglobulin subclass deficiencies |
| title_sort |
Defects in memory B-cell and plasma cell subsets expressing different immunoglobulin-subclasses in patients with CVID and immunoglobulin subclass deficiencies |
| author |
Blanco, Elena |
| author_facet |
Blanco, Elena Pérez-Andrés, Martín Arriba-Méndez, Sonia Serrano, Cristina Criado, Ignacio Del Pino-Molina, Lucía Silva, Susana Madruga, Ignacio Bakardjieva, Marina Martins, Catarina Serra-Caetano, Ana Romero, Alfonso Contreras-Sanfeliciano, Teresa Bonroy, Carolien Sala, Francisco Martín, Alejandro Bastida, José María Lorente, Félix Prieto, Carlos Dávila, Ignacio Marcos, Miguel Kalina, Tomas Vlkova, Marcela Chovancova, Zita Cordeiro, Ana Isabel Philippé, Jan Haerynck, Filomeen López-Granados, Eduardo Sousa, Ana E. van der Burg, Mirjam van Dongen, Jacques J.M. Orfao, Alberto |
| author_role |
author |
| author2 |
Pérez-Andrés, Martín Arriba-Méndez, Sonia Serrano, Cristina Criado, Ignacio Del Pino-Molina, Lucía Silva, Susana Madruga, Ignacio Bakardjieva, Marina Martins, Catarina Serra-Caetano, Ana Romero, Alfonso Contreras-Sanfeliciano, Teresa Bonroy, Carolien Sala, Francisco Martín, Alejandro Bastida, José María Lorente, Félix Prieto, Carlos Dávila, Ignacio Marcos, Miguel Kalina, Tomas Vlkova, Marcela Chovancova, Zita Cordeiro, Ana Isabel Philippé, Jan Haerynck, Filomeen López-Granados, Eduardo Sousa, Ana E. van der Burg, Mirjam van Dongen, Jacques J.M. Orfao, Alberto |
| author2_role |
author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM) RUN |
| dc.contributor.author.fl_str_mv |
Blanco, Elena Pérez-Andrés, Martín Arriba-Méndez, Sonia Serrano, Cristina Criado, Ignacio Del Pino-Molina, Lucía Silva, Susana Madruga, Ignacio Bakardjieva, Marina Martins, Catarina Serra-Caetano, Ana Romero, Alfonso Contreras-Sanfeliciano, Teresa Bonroy, Carolien Sala, Francisco Martín, Alejandro Bastida, José María Lorente, Félix Prieto, Carlos Dávila, Ignacio Marcos, Miguel Kalina, Tomas Vlkova, Marcela Chovancova, Zita Cordeiro, Ana Isabel Philippé, Jan Haerynck, Filomeen López-Granados, Eduardo Sousa, Ana E. van der Burg, Mirjam van Dongen, Jacques J.M. Orfao, Alberto |
| dc.subject.por.fl_str_mv |
classification common variable immunodeficiency diagnosis flow cytometry Immunodeficiency immunoglobulin subclasses immunoglobulins immunophenotyping memory B cells plasma cells primary antibody deficiency selective IgA deficiency Immunology and Allergy Immunology |
| topic |
classification common variable immunodeficiency diagnosis flow cytometry Immunodeficiency immunoglobulin subclasses immunoglobulins immunophenotyping memory B cells plasma cells primary antibody deficiency selective IgA deficiency Immunology and Allergy Immunology |
| description |
Funding: E.B. was supported by a grant from the Junta de Castilla y Leon (Fondo Social Europeo, ORDEN EDU/346/2013, Valladolid, Spain). This work was supported by the CB16/ 12/00400 and CB/16/12/00233 grants (CIBERONC, Instituto de Salud Carlos III, Ministerio de Economıa y Competitividad, Madrid, Spain, and FONDOS FEDER), the FIS PI12/00905-FEDER grant (Fondo de Investigacion Sanitaria of Instituto de Salud Carlos III, Madrid, Spain) and a grant from Fundacion Mutua Madrile~na (Madrid, Spain). The coordination and innovation processes of this study were supported by the EuroFlow Consortium. |
| publishDate |
2019 |
| dc.date.none.fl_str_mv |
2019-09 2019-09-01T00:00:00Z 2023-01-18T22:12:22Z |
| dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
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article |
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publishedVersion |
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http://hdl.handle.net/10362/147794 |
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http://hdl.handle.net/10362/147794 |
| dc.language.iso.fl_str_mv |
eng |
| language |
eng |
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0091-6749 PURE: 12746797 https://doi.org/10.1016/j.jaci.2019.02.017 |
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info:eu-repo/semantics/openAccess |
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openAccess |
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