Mannose-binding lectin in susceptibility and progression of HIV-1 infection in children.
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.


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.
Dzwonek
Agnieszka
A
Infectious Diseases Et Microbiology Unit, Institute of Child Health, University College London, UK.
Novelli
Vas
V
Bajaj-Elliott
Mona
M
Turner
Malcolm
M
Clapson
Margaret
M
Klein
Nigel
N
D000293:Adolescent; D018791:CD4 Lymphocyte Count; D002648:Child; D002675:Child, Preschool; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D015658:HIV Infections / Q000235:genetics* / Q000276:immunology / Q000503:physiopathology*; D020276:HIV Long-Term Survivors; D015497:HIV-1 / Q000472:pathogenicity; D020180:Heteroduplex Analysis; D006801:Humans; D008297:Male; D037601:Mannose-Binding Lectin / Q000097:blood* / Q000235:genetics*; D016133:Polymerase Chain Reaction
D037601:Mannose-Binding Lectin