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+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.
Rensing-Ehl
A
A
Centre of Chronic Immunodeficiency, University Medical Centre, Freiburg, Germany.
Warnatz
K
K
Fuchs
S
S
Schlesier
M
M
Salzer
U
U
Draeger
R
R
Bondzio
I
I
Joos
Y
Y
Janda
A
A
Gomes
M
M
Abinun
M
M
Hambleton
S
S
Cant
A
A
Shackley
F
F
Flood
T
T
Waruiru
C
C
Beutel
K
K
Siepermann
K
K
Dueckers
G
G
Niehues
T
T
Wiesel
T
T
Schuster
V
V
Seidel
M G
MG
Minkov
M
M
Sirkiä
K
K
Kopp
M V
MV
Korhonen
M
M
Schwarz
K
K
Ehl
S
S
Speckmann
C
C
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
D015415:Biomarkers; D053222:Fas Ligand Protein; D007074:Immunoglobulin G; D019014:fas Receptor; D016753:Interleukin-10; D014805:Vitamin B 12