title: Normal ICOS, ICOSL and AID alleles in Danish patients with common variable immunodeficiency.
abstract: Common variable immunodeficiency, CVID, is a primary antibody deficiency characterized by decreased levels of serum immunoglobulin G (IgG), decreased IgA and/or IgM and recurrent infections. It is assumed to be heterogeneous group of disorders caused by different genetic defects. Some patients have decreased levels of class switched memory B cells and/or decreased levels of somatic hypermutation which points to defects in the germinal centre (GC) reactions as cause of the disease in these patients. The inducible costimulator, ICOS, and its' ligand, ICOSL, are both involved in and necessary for the GC reaction and so is activation-induced cytidine deaminase, AID. Therefore, we sequenced the ICOS, ICOSL and AID genes in a cohort of 34 Danish CVID patients. We found 13 new single nucleotide polymorphisms (SNP) in the intron regions of the ICOSL gene as well as one SNP in exon 3. However, none of these polymorphisms were associated with CVID. We did not find a previously reported CVID-causing ICOS gene deletion or any other unique mutations in the ICOS or AID genes.
authors.affiliation: Department of Clinical Immunology, Odense University Hospital, Copenhagen, Denmark.
authors.forename: L
authors.initials: L
authors.lastname: Ohm-Laursen
authors.forename: L
authors.initials: L
authors.lastname: Schjebel
authors.forename: K
authors.initials: K
authors.lastname: Jacobsen
authors.forename: H
authors.initials: H
authors.lastname: Permin
authors.forename: A
authors.initials: A
authors.lastname: Svejgaard
authors.forename: T
authors.initials: T
authors.lastname: Barington
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte / Q000235:genetics*; D002648:Child; D015331:Cohort Studies; D017074:Common Variable Immunodeficiency / Q000235:genetics*; D003564:Cytidine Deaminase; D043525:Cytosine Deaminase / Q000235:genetics*; D003718:Denmark; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D060945:Inducible T-Cell Co-Stimulator Ligand; D060889:Inducible T-Cell Co-Stimulator Protein; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011506:Proteins / Q000235:genetics*; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
chemical_list: D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; C556692:ICOS protein, human; C498514:ICOSLG protein, human; D060945:Inducible T-Cell Co-Stimulator Ligand; D060889:Inducible T-Cell Co-Stimulator Protein; D011506:Proteins; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D043525:Cytosine Deaminase; D003564:Cytidine Deaminase