Clinical and immunological overlap between autoimmune lymphoproliferative syndrome and common variable immunodeficiency

Autoimmune lymphoproliferative syndrome (ALPS) is mainly caused by defects in the CD95 pathway Raised CD3+TCR alpha beta+CD4-CD8- double negative T cells and impaired T cell apoptosis are hallmarks of the disease In contrast, the B cell compartment has been less well studied We found an altered distribution of B cell subsets with raised transitional B cells and reduced marginal zone B cells, switched memory B cells and plasma blasts in most of 22 analyzed ALPS patients Moreover, 5 out of 66 ALPS patients presented with low IgG and susceptibility to infection revealing a significant overlap between ALPS and common variable immunodeficiency (CVID) In patients presenting with lymphoproliferation, cytopenia, hypogammaglobulinemia and impaired B cell differentiation, serum biomarkers were helpful in addition to apoptosis tests for the identification of ALPS patients Our observations may indicate a role for apoptosis defects in some diseases currently classified as CVID (C) 2010 Elsevier Inc All rights reserved