title: Mannose binding lectin polymorphisms are associated with early age of disease onset and autoimmunity in common variable immunodeficiency.
abstract: Mannose binding lectin (MBL) is an important component of the innate immune response. Low producing MBL alleles are associated with an increased risk of infection, especially when adaptive immunity is already compromized. We investigated the role of MBL polymorphism in common variable immunodeficiency (CVID), a disease of unknown aetiology characterized by defective humoral immunity, recurrent infections and highly variable clinical phenotype. Six biallelic single nucleotide polymorphisms in the MBL promoter and coding region (- 550, - 221, + 4, codons 52, 54 and 57) were haplotyped using a novel PCR-SSP method in 163 CVID patients and 100 controls. Low producing coding alleles and promoter haplotypes were associated with early age of disease onset. The mean age of disease onset was 14.5 years in patients with low producing MBL coding alleles, compared with 25 years in patients with wild type coding regions (t-test P = 0.002). Mean age of onset in patients with the low producing LXPA haplotype was 6.8 years, compared with 29.3 years for the HYPA haplotype (P = 0.003). The MBL + 4 Q allele was associated with autoimmune disease (P = 0.003, OR 4.4). These results suggest that MBL deficiency compounds the antibody deficiency in CVID, and reinforces the ostensible role of MBL in innate immunity. MBL deficiency may also facilitate the development of autoimmune disease in CVID.
authors.affiliation: Current address: Level 8, Services and Teaching, Royal Adelaide Hospital, North Terrace, Adelaide, SA, 5000, Australia.
authors.forename: C G
authors.initials: CG
authors.lastname: Mullighan
authors.forename: S E
authors.initials: SE
authors.lastname: Marshall
authors.forename: K I
authors.initials: KI
authors.lastname: Welsh
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000483:Alleles; D015551:Autoimmunity; D002352:Carrier Proteins / Q000235:genetics*; D015331:Cohort Studies; D037222:Collectins; D017074:Common Variable Immunodeficiency / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006239:Haplotypes; D006801:Humans; D037102:Lectins / Q000235:genetics*; D008297:Male; D008351:Mannans / Q000378:metabolism*; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic
chemical_list: D002352:Carrier Proteins; D037222:Collectins; D037102:Lectins; D008351:Mannans