title: B-cell maturation defects in common variable immunodeficiency and association with clinical features.
abstract: OBJECTIVE
  Patients with common variable immunodeficiency (CVID) often have defects in post-antigenic B-cell differentiation with fewer memory B cells and impaired isotype switching. We aimed to classify CVID patients according to these defects and determine whether this predicted clinical manifestations.
  
  
  METHODS
  We analysed the memory marker CD27, maturation marker CD21, and IgD on peripheral blood B cells from 31 CVID patients and 23 controls using a whole-blood lysis technique, allocated patients according to two classifications ('Freiburg' and 'Paris') and correlated results with clinical manifestations.
  
  
  RESULTS
  CVID patients had fewer memory (CD27(+)) B cells and isotype-switched (IgD(-)) memory B cells in absolute number and proportion. Many CVID patients had increased immature (CD21(-)) B cells. Lymphoproliferation and autoimmune cytopenias were found almost exclusively in these patients, including Freiburg group Ia (decreased switched memory and increased immature B cells), but also those with normal switched memory and increased immature B cells. The Paris classification was less useful in predicting clinical manifestations.
  
  
  CONCLUSIONS
  CVID is associated with defects in memory B-cell differentiation. Subclassification helps identify patients with clinical manifestations, particularly lymphoproliferation and autoimmune cytopenias in those with impaired B-cell maturation and isotype switching. Routine B-cell phenotyping may assist clinicians in predicting these clinical features.
authors.affiliation: Institute of Clinical Pathology and Medical Research, Westmead Hospital, Westmead, Sydney, New South Wales, Australia.
authors.forename: Lucinda J
authors.initials: LJ
authors.lastname: Berglund
authors.forename: Sue W J
authors.initials: SW
authors.lastname: Wong
authors.forename: David A
authors.initials: DA
authors.lastname: Fulcher
mesh_terms: D000328:Adult; D000368:Aged; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology*; D017074:Common Variable Immunodeficiency / Q000145:classification* / Q000276:immunology*; D005260:Female; D006801:Humans; D017578:Immunoglobulin Class Switching; D007072:Immunoglobulin D; D007156:Immunologic Memory; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D017464:Receptors, Complement 3d / Q000378:metabolism; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000378:metabolism
chemical_list: D007072:Immunoglobulin D; D017464:Receptors, Complement 3d; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7