Defective formation of IgA memory B cells, Th1 and Th17 cells in symptomatic patients with selective IgA deficiency

ABSTRACT: Objective: Selective IgA deficiency (sIgAD) is the most common primary immunodeficiency in Western countries. Patients can suffer from recurrent infections and autoimmune diseases because of a largely unknown aetiology. To increase insights into the pathophysiology of the disease, we studied memory B and T cells and cytokine concentrations in peripheral blood. Methods: We analysed 30 sIgAD patients (12 children, 18 adults) through detailed phenotyping of peripheral B-cell, CD8+ T-cell and CD4+ T-cell subsets, sequence analysis of IGA and IGG transcripts, in vitro B-cell activation and blood cytokine measurements. Results: All patients had significantly decreased numbers of T-cell-dependent (TD; CD27+) and T-cell-independent (TI; CD27-) IgA memory B cells and increased CD21low B-cell numbers. IgM+IgD- memory B cells were decreased in children and normal in adult patients. IGA and IGG transcripts contained normal SHM levels. In sIgAD children, IGA transcripts more frequently used IGA2 than controls (58.5% vs. 25.1%), but not in adult patients. B-cell activation after in vitro stimulation was normal. However, adult sIgAD patients exhibited increased blood levels of TGF-β1, BAFF and APRIL, whereas they had decreased Th1 and Th17 cell numbers. Conclusion: Impaired IgA memory formation in sIgAD patients is not due to a B-cell activation defect. Instead, decreased Th1 and Th17 cell numbers and high blood levels of BAFF, APRIL and TGF-β1 might reflect disturbed regulation of IgA responses in vivo.These insights into B-cell extrinsic immune defects suggest the need for a broader immunological focus on genomics and functional analyses to unravel the pathogenesis of sIgAD.

• Autores: Moncada Vélez, Marcela; Franco Restrepo, José Luis; Franco Gallego, Alexander; Ahmadi, Fatemeh; Ash Dalm, Virgil; Lineth Rojas, Jessica; Orrego Arango, Julio César; Correa Vargas, Natalia; Hammarström, Lennart; Schreurs, Marco Wj; Dik, Willem A; van Hagen, P Martin; Boon, Louis; van Dongen, Jacques Jm; van der Burg, Mirjam; Pan Hammarström, Qiang; van Zelm, Menno C
• Tipo de recurso: Article of investigation
• Fecha de publicación: 2020
• Institución: Universidad de Antioquia
• Repositorio: Repositorio UdeA
• Idioma: eng
• OAI Identifier: oai:bibliotecadigital.udea.edu.co:10495/40528
• Acceso en línea: https://hdl.handle.net/10495/40528
• Palabra clave: Células B de Memoria; Memory B Cells; Células TH1; Th1 Cells; Células Th17; Th17 Cells; Inmunoglobulina A; Immunoglobulin A; Citocinas; Cytokines; Deficiencia de IgA; IgA Deficiency; https://id.nlm.nih.gov/mesh/D000091245; https://id.nlm.nih.gov/mesh/D018417; https://id.nlm.nih.gov/mesh/D058504; https://id.nlm.nih.gov/mesh/D007070; https://id.nlm.nih.gov/mesh/D016207; https://id.nlm.nih.gov/mesh/D017098
• Rights: openAccess
• License: http://creativecommons.org/licenses/by/2.5/co/