The first report described as an important study: The association of mannose-binding lectin gene 2 polymorphisms in children with down syndrome (original) (raw)
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Journal of Infectious …, 2008
Background. Mannose-binding lectin (MBL) is an important component of innate immunity, and its deficiency is associated with susceptibility to recurrent infections. Methods. This exploratory study investigated the association of serum MBL concentrations and MBL2 gene polymorphisms with respiratory tract infections in young men. We genotyped 6 single-nucleotide polymorphisms (SNPs) in the promoter region (alleles H/L, X/Y, and P/Q) and exon 1 (variant alleles B, C, and D and wild-type allele A) of the MBL2 gene by real-time polymerase chain reaction and measured serum MBL concentrations in 111 Finnish military recruits with asthma and 362 without. Results. An MBL level below the median concentration was a significant risk factor for infections (asthma statusadjusted odds ratio [OR], 2.5 [95% confidence interval {CI}, 1.4-4.5]). Among the 6 SNPs, there was a significant association between the promoter Y/Y genotype and infections (OR, 2.3 [95% CI, 1.2-4.4]) and a borderline significant association between exon 1 variant alleles and infections (OR, 1.7 [95% CI, 0.9-3.1]), after adjustment for asthma status. Conclusion. These preliminary results suggest, for the first time, an association between MBL level and respiratory tract infections in young men and a possible association between infections and MBL2 polymorphisms.
Human Immunology, 2010
Down syndrome (DS) is the most frequent cause of intellectual disability worldwide. DS individuals present abnormalities in the immune system that include high susceptibility to recurrent infections (RI) as well as to autoimmune diseases. Respiratory tract infections remain one of the major causes of death in DS individuals. Mannan-binding lectin (MBL) functions as an opsonina and initiates the lectin complement pathway. MBL deficiency was shown to increase the susceptibility to different infectious diseases, notably by extracellular pathogens. In the present study, MBL circulating levels were evaluated in 150 children with DS from Brazil, to clarify whether MBL deficiency is associated with the presence of RI in these patients. According to the clinical history 30.7% (46/150) of the DS children experienced RI, and MBL deficiency was seen in 34.8% (16/46) of them compared with 13.5% (14/104) of the DS children without RI (p ϭ 0.005, odds ratio ϭ 3.43, 95% confidence interval ϭ 1.5-7.85). Moreover, MBL deficiency was significantly associated with the occurrence of pneumonia when compared with DS without RI (37.5%, 12/32 vs. 13.5% 14/104, p ϭ 0.005, odds ratio ϭ 3.68, 95% confidence interval ϭ 1.5-6.95). These findings demonstrated that MBL deficiency increases the susceptibility to RI in DS patients and that, in the future, they could potentially benefit from MBL therapy. ᭧
Innate Immunity, 2009
Objective: Mannose-binding lectin (MBL) has been shown to inhibit infection of host cells by Chlamydia pneumoniae in vitro. We studied if MBL levels and MBL2 polymorphisms associate with the presence of C. pneumoniae antibodies in vivo. Materials and Methods: Single nucleotide polymorphisms (SNPs) of the MBL2 gene (promoter alleles H/L, X/Y and P/Q; and exon 1 variant alleles B, C and D and wild-type allele A) were genotyped and serum MBL concentrations and C. pneumoniae IgG, IgA and IgM antibodies were analysed in 889 Finnish military recruits. Results: An MBL level below the median concentration and the MBL2 P/P genotype were significant risk factors of IgG or IgA seroconversions or the presence of IgM antibodies during military service (adjusted odds ratio (OR) 1.5; 95% confidence interval (CI) 1.1-2.1 and OR 1.5; 95% CI 1.0-2.2, respectively). In addition, the promoter Y/Y (OR 1.6; 95% CI 1.1-2.3) and exon 1 variant allele genotypes (OR 1.4; 95% CI 1.0-2.0) were possibly associated with elevated antibodies. Conclusions: These results suggest, for the first time, that low serum MBL levels and MBL2 polymorphisms may associate with elevated C. pneumoniae antibodies and seroconversions and thus support the previous findings in vitro.
Clinical & Experimental Immunology, 2008
Mannose-binding lectin (MBL), activating protein of the lectin pathway of the complement system, is an important component of the non-specific immune response. MBL2 gene polymorphisms, both in the coding and promoter regions, lead to low or deficient serum MBL levels. Low serum MBL levels were shown to be associated with serious infectious complications, mainly in patients in whom other non-specific immune system barriers were disturbed (granulocytopenia, cystic fibrosis). We have analysed two promoter (-550 and -221) and three exon (codons 52, 54 and 57) MBL2 polymorphisms in a total of 94 patients with common variable immunodeficiency (CVID) from two immunodeficiency centres. Low-producing genotypes were associated with the presence of bronchiectasis (P = 0·009), lung fibrosis (P = 0·037) and also with respiratory insufficiency (P = 0·029). We could not demonstrate any association of MBL deficiency with age at onset of clinical symptoms, age at diagnosis, the number of pneumonias before diagnosis or serum immunoglobulin (Ig)G, IgA and IgM levels before initiation of Ig treatment. No association with emphysema development was observed, such as with lung function test abnormalities. No effect of MBL2 genotypes on the presence of diarrhoea, granuloma formation, lymphadenopathy, splenomegaly, frequency of respiratory tract infection or the number of antibiotic courses of the patients was observed. Our study suggests that low MBL-producing genotypes predispose to bronchiectasis formation, and also fibrosis and respiratory insufficiency development, but have no effect on other complications in CVID patients.