Mannan-binding lectin insufficiency in children with recurrent infections of the respiratory system

Abstract

SUMMARYBlood samples were collected over a 4-year period from 335 children (aged 1-16 years) suffering from recurrent respiratory infections and 78 controls. The patients were subdivided into four groups: I, children with no immune system defects detected ( n = 101); II, children with allergies ( n = 94); III, children with humoral response defects ( n = 93); and IV, children with disturbances of cellular immunity ( n = 66). Nineteen patients had both humoral and cellular abnormalities. All patients and controls were investigated to determine the exon 1 and promoter region variants of the mbl-2 gene. MBL serum concentrations were also determined in samples from 291 patients and 75 controls. The proportion of O (B, D or C) alleles was significantly higher in the patient group compared to controls, and this association was strongest for subgroup III. The promoter LX variant frequency was also commoner in the patients as a whole, and significantly so in subgroups II and IV. Genotypes markedly influenced MBL concentrations in all groups, and correlated with ability to activate the lectin pathway of complement activation. The strongest and most significant inverse correlations between serum MBL and respiratory disease were found in patient group III and in 17 patients with multiple humoral and/or cellular abnormalities. Among nine patients with unexpectedly low LP activity in view of their MBL concentrations, one person was found to be MASP-2 deficient. Our results indicate that mannan-binding lectin insufficiency, with or without a coexisting immune defect, is associated with the occurrence of recurrent respiratory infections in childhood, and this relationship is particularly strong and statistically significant in children with concomitant impairments of humoral immunity.

Deficiency of mannan-binding lectin associated serine protease-2 due to missense polymorphisms

“…In a study of patients with psoriasis and family members, 894 individuals were tested for p.D120G and a total of 62 heterozygotes and one homozygote were found, giving a gene frequency of 3.6% (the allele was not associated with psoriasis). 25 Homozygocity was reported in one individual in a group of 293 Polish children with respiratory infections 26 and in one child with CF. 27 We have encountered further three homozygous individuals, two admitted to the lung clinic at Aarhus University Hospital, and one colon cancer patient (not published).…”

Extremes of l-ficolin concentration in children with recurrent infections are associated with single nucleotide polymorphisms in the FCN2 gene

“…Subjects were selected from children with recurrent respiratory infections studied previously in relation to mannanbinding lectin and serum l-ficolin [17,20]. Blood was taken when no symptoms of infection were observed by physicians [17,20].…”

“…Blood was taken when no symptoms of infection were observed by physicians [17,20]. Approval of the local ethical commission was obtained, as was informed parental consent.…”

“…DNA samples prepared for our previous investigation [17,20] were used. In some cases, DNA was extracted de novo from blood samples, collected previously [20] and stored at -80°C.…”

“…In some cases, DNA was extracted de novo from blood samples, collected previously [20] and stored at -80°C.…”