title: Clinical and immunological overlap between autoimmune lymphoproliferative syndrome and common variable immunodeficiency.
abstract: Autoimmune lymphoproliferative syndrome (ALPS) is mainly caused by defects in the CD95 pathway. Raised CD3+TCRαβ+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.
authors.affiliation: Centre of Chronic Immunodeficiency, University Medical Centre, Freiburg, Germany.
authors.forename: A
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authors.lastname: Rensing-Ehl
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authors.lastname: Warnatz
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authors.lastname: Fuchs
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authors.lastname: Schlesier
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authors.lastname: Bondzio
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authors.lastname: Gomes
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authors.lastname: Abinun
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authors.lastname: Hambleton
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authors.lastname: Shackley
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authors.lastname: Waruiru
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authors.lastname: Beutel
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authors.lastname: Siepermann
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authors.lastname: Dueckers
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authors.lastname: Niehues
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authors.lastname: Wiesel
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authors.lastname: Schuster
authors.forename: M G
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authors.lastname: Seidel
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authors.lastname: Minkov
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authors.initials: K
authors.lastname: Sirkiä
authors.forename: M V
authors.initials: MV
authors.lastname: Kopp
authors.forename: M
authors.initials: M
authors.lastname: Korhonen
authors.forename: K
authors.initials: K
authors.lastname: Schwarz
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authors.lastname: Ehl
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authors.initials: C
authors.lastname: Speckmann
mesh_terms: D000293:Adolescent; D000328:Adult; D000361:Agammaglobulinemia / Q000276:immunology; D017209:Apoptosis; D056735:Autoimmune Lymphoproliferative Syndrome / Q000175:diagnosis* / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D015415:Biomarkers / Q000097:blood; D002648:Child; D002675:Child, Preschool; D017074:Common Variable Immunodeficiency / Q000175:diagnosis* / Q000276:immunology*; D003937:Diagnosis, Differential; D053222:Fas Ligand Protein / Q000097:blood* / Q000276:immunology; D005434:Flow Cytometry; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D016753:Interleukin-10 / Q000097:blood* / Q000276:immunology; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology; D010641:Phenotype; D013601:T-Lymphocytes / Q000276:immunology; D014805:Vitamin B 12 / Q000097:blood* / Q000276:immunology; D019014:fas Receptor / Q000097:blood / Q000276:immunology
chemical_list: D015415:Biomarkers; D053222:Fas Ligand Protein; D007074:Immunoglobulin G; D019014:fas Receptor; D016753:Interleukin-10; D014805:Vitamin B 12