TY - JOUR
T1 - Selective deficits in blood dendritic cell subsets in common variable immunodeficiency and X-linked agammaglobulinaemia but not specific polysaccharide antibody deficiency
AU - Yong, Patrick F.K.
AU - Workman, Sarita
AU - Wahid, Faisal
AU - Exley, Andrew
AU - Webster, A. David B.
AU - Ibrahim, Mohammad A.A.
N1 - Funding Information:
This work was supported by King's College Hospital Charitable Trust and Papworth Hospital NHS Foundation Trust charitable funds.
Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2008/4
Y1 - 2008/4
N2 - 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.
AB - 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.
KW - Common variable immunodeficiency
KW - Dendritic cells
KW - Primary immunodeficiency
KW - Specific polysaccharide antibody deficiency
KW - X-linked agammaglobulinaemia
UR - http://www.scopus.com/inward/record.url?scp=40849115956&partnerID=8YFLogxK
U2 - 10.1016/j.clim.2007.12.007
DO - 10.1016/j.clim.2007.12.007
M3 - Article
C2 - 18295543
AN - SCOPUS:40849115956
SN - 1521-6616
VL - 127
SP - 34
EP - 42
JO - CLINICAL IMMUNOLOGY
JF - CLINICAL IMMUNOLOGY
IS - 1
ER -