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

J 2019

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

BLANCO, Elena, Martin PEREZ-ANDRES, Sonia ARRIBA-MENDEZ, Cristina SERRANO, Ignacio CRIADO et. al.

Basic information

Original name

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

Authors

BLANCO, Elena (724 Spain), Martin PEREZ-ANDRES (724 Spain), Sonia ARRIBA-MENDEZ (724 Spain), Cristina SERRANO (724 Spain), Ignacio CRIADO (724 Spain), Lucia DEL PINO-MOLINA (724 Spain), Susana SILVA (620 Portugal), Ignacio MADRUGA (724 Spain), Marina BAKARDJIEVA (203 Czech Republic), Catarina MARTINS (620 Portugal), Ana SERRA-CAETANO (620 Portugal), Alfonso ROMERO (724 Spain), Teresa CONTRERAS-SANFELICIANO (724 Spain), Carolien BONROY (56 Belgium), Francisco SALA (724 Spain), Alejandro MARTIN (724 Spain), Jose Maria BASTIDA (724 Spain), Felix LORENTE (724 Spain), Carlos PRIETO (724 Spain), Ignacio DAVILA (724 Spain), Miguel MARCOS (724 Spain), Tomas KALINA (203 Czech Republic), Marcela VLKOVÁ (203 Czech Republic, belonging to the institution), Zita CHOVANCOVÁ (203 Czech Republic, belonging to the institution), Ana Isabel CORDEIRO (620 Portugal), Jan PHILIPPE (56 Belgium), Filomeen HAERYNCK (56 Belgium), Eduardo LOPEZ-GRANADOS (724 Spain), Ana E. SOUSA (620 Portugal), Mirjam VAN DER BURG (528 Netherlands), Jacques J. M. VAN DONGEN (528 Netherlands) and Alberto ORFAO (724 Spain, guarantor)

Edition

Journal of allergy and clinical immunology, New York, Mosby-Elsevier, 2019, 0091-6749

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30102 Immunology

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 10.228

RIV identification code

RIV/00216224:14110/19:00112958

Organization unit

Faculty of Medicine

DOI

http://dx.doi.org/10.1016/j.jaci.2019.02.017

UT WoS

000485222300025

Keywords in English

Immunodeficiency; primary antibody deficiency; selective IgA deficiency; common variable immunodeficiency; immunophenotyping; immunoglobulins; immunoglobulin subclasses; memory B cells; plasma cells; flow cytometry; diagnosis; classification

Abstract

V originále

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 (MB Cs), 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.

Citovat

BLANCO, Elena, Martin PEREZ-ANDRES, Sonia ARRIBA-MENDEZ, Cristina SERRANO, Ignacio CRIADO, Lucia DEL PINO-MOLINA, Susana SILVA, Ignacio MADRUGA, Marina BAKARDJIEVA, Catarina MARTINS, Ana SERRA-CAETANO, Alfonso ROMERO, Teresa CONTRERAS-SANFELICIANO, Carolien BONROY, Francisco SALA, Alejandro MARTIN, Jose Maria BASTIDA, Felix LORENTE, Carlos PRIETO, Ignacio DAVILA, Miguel MARCOS, Tomas KALINA, Marcela VLKOVÁ, Zita CHOVANCOVÁ, Ana Isabel CORDEIRO, Jan PHILIPPE, Filomeen HAERYNCK, Eduardo LOPEZ-GRANADOS, Ana E. SOUSA, Mirjam VAN DER BURG, Jacques J. M. VAN DONGEN and Alberto ORFAO. Defects in memory B-cell and plasma cell subsets expressing different immunoglobulin-subclasses in patients with CVID and immunoglobulin subclass deficiencies. Journal of allergy and clinical immunology. New York: Mosby-Elsevier, 2019, vol. 144, No 3, p. 809-824. ISSN 0091-6749. Available from: https://dx.doi.org/10.1016/j.jaci.2019.02.017.

@article{1623036,
   author = {Blanco, Elena and PerezandAndres, Martin and ArribaandMendez, Sonia and Serrano, Cristina and Criado, Ignacio and Del PinoandMolina, Lucia and Silva, Susana and Madruga, Ignacio and Bakardjieva, Marina and Martins, Catarina and SerraandCaetano, Ana and Romero, Alfonso and ContrerasandSanfeliciano, Teresa and Bonroy, Carolien and Sala, Francisco and Martin, Alejandro and Bastida, Jose Maria and Lorente, Felix and Prieto, Carlos and Davila, Ignacio and Marcos, Miguel and Kalina, Tomas and Vlková, Marcela and Chovancová, Zita and Cordeiro, Ana Isabel and Philippe, Jan and Haerynck, Filomeen and LopezandGranados, Eduardo and Sousa, Ana E. and van der Burg, Mirjam and van Dongen, Jacques J. M. and Orfao, Alberto},
   article_location = {New York},
   article_number = {3},
   doi = {http://dx.doi.org/10.1016/j.jaci.2019.02.017},
   keywords = {Immunodeficiency; primary antibody deficiency; selective IgA deficiency; common variable immunodeficiency; immunophenotyping; immunoglobulins; immunoglobulin subclasses; memory B cells; plasma cells; flow cytometry; diagnosis; classification},
   language = {eng},
   issn = {0091-6749},
   journal = {Journal of allergy and clinical immunology},
   title = {Defects in memory B-cell and plasma cell subsets expressing different immunoglobulin-subclasses in patients with CVID and immunoglobulin subclass deficiencies},
   url = {http://dx.doi.org/10.1016/j.jaci.2019.02.017},
   volume = {144},
   year = {2019}
}

TY  - JOUR
ID  - 1623036
AU  - Blanco, Elena - Perez-Andres, Martin - Arriba-Mendez, Sonia - Serrano, Cristina - Criado, Ignacio - Del Pino-Molina, Lucia - Silva, Susana - Madruga, Ignacio - Bakardjieva, Marina - Martins, Catarina - Serra-Caetano, Ana - Romero, Alfonso - Contreras-Sanfeliciano, Teresa - Bonroy, Carolien - Sala, Francisco - Martin, Alejandro - Bastida, Jose Maria - Lorente, Felix - Prieto, Carlos - Davila, Ignacio - Marcos, Miguel - Kalina, Tomas - Vlková, Marcela - Chovancová, Zita - Cordeiro, Ana Isabel - Philippe, Jan - Haerynck, Filomeen - Lopez-Granados, Eduardo - Sousa, Ana E. - van der Burg, Mirjam - van Dongen, Jacques J. M. - Orfao, Alberto
PY  - 2019
TI  - Defects in memory B-cell and plasma cell subsets expressing different immunoglobulin-subclasses in patients with CVID and immunoglobulin subclass deficiencies
JF  - Journal of allergy and clinical immunology
VL  - 144
IS  - 3
SP  - 809-824
EP  - 809-824
PB  - Mosby-Elsevier
SN  - 00916749
KW  - Immunodeficiency
KW  - primary antibody deficiency
KW  - selective IgA deficiency
KW  - common variable immunodeficiency
KW  - immunophenotyping
KW  - immunoglobulins
KW  - immunoglobulin subclasses
KW  - memory B cells
KW  - plasma cells
KW  - flow cytometry
KW  - diagnosis
KW  - classification
UR  - http://dx.doi.org/10.1016/j.jaci.2019.02.017
L2  - http://dx.doi.org/10.1016/j.jaci.2019.02.017
N2  - 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 (MB Cs), 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.
ER  -

BLANCO, Elena, Martin PEREZ-ANDRES, Sonia ARRIBA-MENDEZ, Cristina SERRANO, Ignacio CRIADO, Lucia DEL PINO-MOLINA, Susana SILVA, Ignacio MADRUGA, Marina BAKARDJIEVA, Catarina MARTINS, Ana SERRA-CAETANO, Alfonso ROMERO, Teresa CONTRERAS-SANFELICIANO, Carolien BONROY, Francisco SALA, Alejandro MARTIN, Jose Maria BASTIDA, Felix LORENTE, Carlos PRIETO, Ignacio DAVILA, Miguel MARCOS, Tomas KALINA, Marcela VLKOVÁ, Zita CHOVANCOVÁ, Ana Isabel CORDEIRO, Jan PHILIPPE, Filomeen HAERYNCK, Eduardo LOPEZ-GRANADOS, Ana E. SOUSA, Mirjam VAN DER BURG, Jacques J. M. VAN DONGEN and Alberto ORFAO. Defects in memory B-cell and plasma cell subsets expressing different immunoglobulin-subclasses in patients with CVID and immunoglobulin subclass deficiencies. \textit{Journal of allergy and clinical immunology}. New York: Mosby-Elsevier, 2019, vol.~144, No~3, p.~809-824. ISSN~0091-6749. Available from: https://dx.doi.org/10.1016/j.jaci.2019.02.017.

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