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2020

ANUÁRIO DO HOSPITAL
DONA ESTEFÂNIA

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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

Elena Blanco, PhD,a,b* Martın Perez-Andres, PhD,a,b* Sonia Arriba-Mendez, MD, PhD,c Cristina Serrano, MD,d Ignacio Criado, PhD,a,b Lucıa Del Pino-Molina, PhD,e Susana Silva, MD, PhD,f Ignacio Madruga, MD,g Marina Bakardjieva, MSc,h Catarina Martins, PhD,i Ana Serra-Caetano, MSc,f Alfonso Romero, MD,j, Teresa Contreras-Sanfeliciano, MD,k Carolien Bonroy, PhD,l Francisco Sala, MD,m Alejandro Martın, MD, PhD,n,o JoseMarıa Bastida, MD, PhD,n,o Felix Lorente, MD, PhD,c Carlos Prieto, PhD,p Ignacio Davila, MD, PhD,q, Miguel Marcos, MD, PhD,g Tomas Kalina, MD, PhD,h Marcela Vlkova, PhD,r Zita Chovancova, MD, PhD,r, Ana Isabel Cordeiro, MD,s Jan Philippe, MD, PhD,l Filomeen Haerynck, MD, PhD,t Eduardo Lopez-Granados, MD, PhD,e Ana E. Sousa, PhD,f Mirjam van der Burg, PhD,u,v Jacques J. M. van Dongen, MD, PhD,w" and Alberto Orfao, MD, PhD,a,b" on behalf of the EuroFlow PID group

On behalf of the EuroFlow PID group Salamanca, Madrid, and Pamplona, Spain; Lisbon, Portugal; Prague and Brno, Czech Republic; Ghent, Belgium; and Rotterdam and Leiden, The Netherlands

- Publicação Journal Allergy clinical immunology, volume 144, number 3, september 2019

Introdução: Predominantly antibody deficiencies (PADs) are the most prevalent primary immunodeficiencies, but their B-cell defects and underlying genetic alterations remain largely unknown.
Objectivo: 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.
Metodos: 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.
Resultados: 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)IgA1 PCs and MBCs, with 2 clear subgroups showing strongly decreased numbers of smIgA1 PCs with mild versus severe smIgA1 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 smIgA1 and smIgG1 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 CD271 MBCs with almost normal IgG31 MBCs; (3) absence of switched MBCs; and (4) presence of both unswitched and switched MBCs without and; (5) with IgG21 MBCs; and (6) with IgA11 MBCs.
Conclusão: Distinct PAD defective B-cell patterns were identified that are associated with unique clinical profiles. (J Allergy Clin Immunol 2019;144:809-24.)

Palavras Chave: common variable immunodeficiency, diagnosis, flow cytometry, immunodeficiency, immuno- phenotyping