Background: Mannose-binding lectin (MBL; encoded by MBL-2) is a circulating pattern-recognition molecule that recognizes microbial carbohydrate motifs, leading to complement activation and cell lysis. Mutations in the MBL-2 promoter and of the MBL-2 gene exon 1 result in reduced protein levels and increased susceptibility to infection. We have investigated the effect of MBL-2 polymorphisms on susceptibility and progression of HIV-1 infection in children.
Patients and methods: One-hundred and twenty-eight children, aged 2-16 years were recruited. MBL-2 genotypes were determined by PCR and heteroduplex analyses. Serum MBL levels were measured by ELISA. Comparison of genotypes (A=wild type, O=variant alleles) and protein levels between groups was performed using chi-squared, Mann-Whitney U or Kruskal-Wallis tests.
Results: Children were classified according to the Centers for Disease Control and Prevention clinical classification: A, B or C (mildly symptomatic [n=39], moderately symptomatic [n=58] or severely symptomatic AIDS [n=31]) or immune category 1 (n=77), 2 (n=46) or 3 (n=5). Analysis of MBL-2 genotypes with respect to clinical classification yielded minimal differences. However, patients in immunological categories 2 and 3 (<25% CD4+ T cells) were more likely to have MBL-2 variant alleles (P=0.01). We further explored MBL status with respect to disease progression. Only 1/10 long-term non-progressors (LTNPs) had an MBL-2 mutation (A/D) with a corresponding protein level of 611 ng/ml.
Conclusions: MBL deficiency was more frequent in patients with severe disease as assessed by CD4+ T-cell status. MBL-2 variants may be less frequent in children classified as LTNPs. MBL analysis could be useful in identifying children with slow disease progression and, consequently, may not require immediate antiretroviral treatement.