Selective deficits in blood dendritic cell subsets in common variable immunodeficiency and X-linked agammaglobulinaemia but not specific polysaccharide antibody deficiency

• Published in: Clinical immunology (Orlando, Fla.) Fla.), 2008-04, Vol.127 (1), p.34-42
• Main Authors: Yong, Patrick F.K, Workman, Sarita, Wahid, Faisal, Exley, Andrew, Webster, A. David B, Ibrahim, Mohammad A.A
• Format: Article
• Language: English
• Subjects: Adult; Agammaglobulinemia - immunology; Aged; Allergy and Immunology; Biological and medical sciences; Cell Count; Common variable immunodeficiency; Common Variable Immunodeficiency - immunology; Dendritic cells; Dendritic Cells - cytology; Female; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Genetic Diseases, X-Linked - immunology; Humans; Immunologic Deficiency Syndromes - immunology; Male; Middle Aged; Polysaccharides - immunology; Primary immunodeficiency; Specific polysaccharide antibody deficiency; X-linked agammaglobulinaemia
• ISSN: 1521-6616; 1521-7035
• DOI: 10.1016/j.clim.2007.12.007

Abstract Myeloid and plasmacytoid dendritic cells (MDCs, PDCs) play critical roles in B cell development and antibody production. Primary antibody deficiencies in humans might therefore reflect a deficit in MDCs and/or PDCs. We tested this hypothesis by measuring dendritic cell (DC) subset numbers in patients with common variable immunodeficiency (CVID), X-linked agammaglobulinaemia (XLA) and specific polysaccharide antibody deficiency (SPAD). In CVID both MDC and PDC numbers were markedly reduced. There was a graded reduction in all DC subsets across the Freiburg CVID groups (memory B cell classification) and the greatest deficit was seen in group Ia cases with the most severe disease. In contrast, MDC numbers alone were reduced in XLA whilst in SPAD the DC numbers were normal. In CVID, the number of MDCs correlated strongly with switched memory B cell percentage and total B cell count. Low numbers of DCs correlated with a greater incidence of autoimmunity, splenomegaly and granulomatous disease, and a higher incidence of clinical complications. Measurement of MDC and PDC numbers provides both prognostic information for clinical management and classification of CVID cases for future pathogenetic research. Our findings are consistent with the hypothesis that deficits in DC subsets are a critical feature in CVID.