An age-dependent association of mannose-binding lectin-2 genetic variants on HIV-1-related disease in children.
BACKGROUND
Mannose-binding lectin (MBL) is part of the lectin pathway of complement activation against various pathogens; however, its role in innate immune responses against HIV-1 infection in children is unknown.


OBJECTIVE
This study evaluated the effects of mannose-binding lectin-2 (MBL2) alleles on HIV-1 disease progression and central nervous system (CNS) impairment in children.


METHODS
A cohort of 1037 HIV-1-infected children enrolled in Pediatrics AIDS Clinical Trial Group protocols P152 and P300 before the availability of effective antiretroviral therapy was genotyped for MBL2 and evaluated for disease progression.


RESULTS
Children with the homozygous variant MBL2-O/O genotype were more likely to experience rapid disease progression and CNS impairment than those with the wild-type AA genotype. The effects were predominantly observed in children younger than 2 years. In unadjusted Cox proportional hazards models, children younger than 2 years with MBL2-O/O experienced more rapid disease progression (O/O vs AA: relative hazard [RH], 1.54; 95% CI, 1.07-2.22; P = .02; O/O vs A/O: RH, 2.28; 95% CI, 1.09-4.79; P = .029). Similarly, children with MBL2-O/O were more likely to experience rapid progression to CNS impairment (O/O vs A/A: RH, 2.78; 95% CI, 1.06-2.69, P = .027; O/O vs A/O: RH, 1.69; 95% CI, 1.07-7.21; P = .035). The effects remained significant after adjustment for CD4(+) lymphocyte count, plasma HIV-1 RNA, and other genotypes.


CONCLUSIONS
MBL2-O/O genotypes, which result in lower expression of MBL, are associated with more rapid HIV-1-related disease progression, including CNS impairment, predominantly in children younger than 2 years. These data suggest that MBL2 variants are associated with altered HIV-1 disease progression, particularly in young children.
Singh
Kumud K
KK
Department of Pediatrics, Division of Infectious Diseases, University of California, San Diego, La Jolla, Calif 92093-0672, USA. kusingh@ucsd.edu
Lieser
Alexis
A
Ruan
Ping K
PK
Fenton
Terry
T
Spector
Stephen A
SA
D000375:Aging; D000483:Alleles; D002493:Central Nervous System Diseases / Q000209:etiology / Q000235:genetics; D002675:Child, Preschool; D003071:Cognition; D018450:Disease Progression; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000235:genetics* / Q000503:physiopathology / Q000523:psychology / Q000821:virology; D015497:HIV-1; D006239:Haplotypes; D006801:Humans; D007223:Infant; D008297:Male; D037601:Mannose-Binding Lectin / Q000235:genetics*
C445619:MBL2 protein, human; D037601:Mannose-Binding Lectin