ICOS deficiency in patients with common variable immunodeficiency.
Common variable immunodeficiency (CVID) is the most frequent clinically significant primary antibody deficiency in man, predisposing to recurrent bacterial infections. Recently, we showed that the homozygous loss of the inducible costimulator (ICOS) on activated T cells may result in an adult onset form of CVID with autosomal recessive inheritance (AR-CVID). We screened 181 sporadic CVID patients and 13 CVID patients from nine families with AR-CVID for mutations in ICOS by genomic DNA sequencing. In the AR-CVID families, the genomic integrity of the ligand for ICOS (ICOS-L) was also evaluated. In two of the nine AR-CVID families, we identified five individuals with ICOS deficiency, carrying the identical large genomic deletion of ICOS as previously described. In the remaining seven AR-CVID families, we subsequently sequenced the coding region of the ICOS ligand but found no mutations. The incidence of ICOS deficiency among patients with CVID is less than 5%. Worldwide, there are now a total of nine patients diagnosed with ICOS deficiency most likely due to a common founder. ICOS-L deficiency could not be identified in families with AR-CVID.
Salzer
Ulrich
U
Division of Rheumatology and Clinical Immunology, University of Freiburg, 79106 Freiburg, Germany.
Maul-Pavicic
Andrea
A
Cunningham-Rundles
Charlotte
C
Urschel
Simon
S
Belohradsky
Bernd H
BH
Litzman
Jiri
J
Holm
Are
A
Franco
José Luis
JL
Plebani
Alessandro
A
Hammarstrom
Lennart
L
Skrabl
Andrea
A
Schwinger
Wolfgang
W
Grimbacher
Bodo
B
D000293:Adolescent; D000328:Adult; D000945:Antigens, Differentiation, T-Lymphocyte / Q000737:chemistry / Q000235:genetics* / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D017074:Common Variable Immunodeficiency / Q000235:genetics* / Q000276:immunology*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007136:Immunoglobulins / Q000276:immunology; D060889:Inducible T-Cell Co-Stimulator Protein; D008297:Male; D010375:Pedigree; D013601:T-Lymphocytes / Q000276:immunology
D000945:Antigens, Differentiation, T-Lymphocyte; C556692:ICOS protein, human; D007136:Immunoglobulins; D060889:Inducible T-Cell Co-Stimulator Protein