Defects in memory B-cell and plasma cell subsets expressing different immunoglobulin-subclasses in patients with CVID and immunoglobulin subclass deficiencies
Language English Country United States Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
30826363
DOI
10.1016/j.jaci.2019.02.017
PII: S0091-6749(19)30280-5
Knihovny.cz E-resources
- Keywords
- Immunodeficiency, classification, common variable immunodeficiency, diagnosis, flow cytometry, immunoglobulin subclasses, immunoglobulins, immunophenotyping, memory B cells, plasma cells, primary antibody deficiency, selective IgA deficiency,
- MeSH
- Child MeSH
- Adult MeSH
- Immunoglobulins deficiency immunology MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Plasma Cells immunology MeSH
- Cell Count MeSH
- B-Lymphocyte Subsets immunology MeSH
- Child, Preschool MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Immunologic Deficiency Syndromes immunology MeSH
- Check Tag
- Child MeSH
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Male MeSH
- Child, Preschool MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Immunoglobulins MeSH
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
Centro de Salud Miguel Armijo Salamanca Spain
Department of Laboratory Medicine 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 Bioquímica Clínica Hospital Universitario de Salamanca Salamanca Spain
Servicio de Hematología Hospital de Navarra Pamplona Spain
Servicio de Inmunología Fundación Jiménez Díaz Madrid Spain
Servicio de Pediatría Hospital Universitario de Salamanca Salamanca Spain
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