title: Rare mutations in TNFRSF13B increase the risk of asthma symptoms in Swedish children.
abstract: TACI (transmembrane activator and calcium modulator and cyclophilin ligand interactor) mutations seem to be associated with autoimmunity and common variable immunodeficiency in humans. Because of its role in immune responses, we investigated the association between TACI mutations and infection proneness/asthma symptoms in children. A total of 2372 children were genotyped for TACI mutations (I87N, C104R, S144X, A181E, R202H and ins204A). Serum IgA, IgG and specific IgE levels were determined in children with mutations. Data on parentally reported allergic diseases and infections were collected. In all, 55 individuals with TACI mutations were identified. Children with TACI mutations had a 2-fold increased risk of wheeze at 2 and 4 years of age and a 2.5-fold increased risk of asthma was seen at 4 years of age. None of the children with mutations suffered from IgA deficiency (<0.07 g l(-1)). No significant differences in serum IgG levels or specific IgE were found. Common variants in asthma susceptibility genes may account for up to 40% of cases of childhood-onset asthma, indicating a high contribution, compared with other common disorders. The role of rare variants/mutations in the pathogenesis of asthma is less clear. We conclude that mutations in TACI are the contributing factors for asthma symptoms in Swedish children, although the mechanisms still remain elusive.
authors.affiliation: Division of Clinical Immunology, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
authors.forename: M
authors.initials: M
authors.lastname: Janzi
authors.forename: E
authors.initials: E
authors.lastname: Melén
authors.forename: I
authors.initials: I
authors.lastname: Kull
authors.forename: M
authors.initials: M
authors.lastname: Wickman
authors.forename: L
authors.initials: L
authors.lastname: Hammarström
mesh_terms: D001249:Asthma / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D009154:Mutation; D011379:Prognosis; D013548:Sweden / Q000453:epidemiology; D053303:Transmembrane Activator and CAML Interactor Protein / Q000235:genetics* / Q000276:immunology
chemical_list: D007070:Immunoglobulin A; D007074:Immunoglobulin G; C108467:TNFRSF13B protein, human; D053303:Transmembrane Activator and CAML Interactor Protein