382 Association of Mannose-binding Lectin B Allele with Slower Progression to AIDS in Perinatally HIV-1 Infected Children but Not with HIV-1 Vertical Transmission A. Mangano*, D. Mecikovsky, S. Lusso, R. Bologna, L. Sen Hosp Natl de Pediatrķa "Prof Dr Juan P Garrahan," Buenos Aires, Argentina
Background: When the specific immune system is damaged, innate immunity might take a leading role in combating infections. Mannose binding lectin (MBL) is one of the most important components of innate immunity. Thus, the participation of MBL as a host factor in HIV-1 infection should to be evaluated mainly in children when at infection the specific immune system is immature. Three (3) different mutations in the exon 1 of MBL gene can lower MBL levels impairing opsonisation and phagocitosis. The wild-type allele is called A and the variants B (Gly54Asp), C (Gly57Glut), and D (Arg52Cys).
Objectives: 1)To establish the frequency of MBL variants in Argentine population; and 2) to analyze whether the MBL alleles are associated with HIV-1 susceptibility and disease progression in a pediatric cohort perinatally exposed to HIV-1.
Methods: We investigated the presence of MBL genetic variants in 169 blood donors (control population) and 248 perinatally HIV-1 exposed children (61 infected and 187 exposed uninfected-EU-) who attended at the Hospital de Pediatrķa "JP Garrahan" (Bs. As., Argentina). The study included children born to HIV-1 seropositive mothers that did not receive antiretroviral treatment during pregnancy. MBL genotyping was assessed by PCR-RFLP assays. Survival analyses were performed to determine the association between MBL genotypes and time to AIDS.
Results: Of the MBL variants only the B allele was identified in Argentinean population with a frequency of 0.2041(32% A/B heterozygotes; 4% B/B homozygotes). The distribution of the B allele did not differ significantly between HIV-1 infected (0.2377) and EU (0.2059) and was similar to the control population. Of the 61 infected children with a clinical follow-up at our hospital, 44 developed AIDS. Kaplan-Meier analysis of time to AIDS showed that children carriers of MBL B allele (n = 26) progressed to AIDS significantly slower than MBL wild-type (n = 35) (p = 0.03, log rank test). The benefit was manifested by a median AIDS-free survival time of 64 mos in MBL A/B heterozygotes compared to 18 mos in MBL wild type homozygotes.
Conclusions: MBL B allele was more frequent in the Argentinean population (considered Hispanic-Caucasian) compared to other Caucasian populations (20% vs 5%-10%). The MBL B allele does not seem to affect HIV-1 mother-to-child transmission whereas showed a significant protection against progression to pediatric AIDS.
