Influence of HLA alleles on the rate of progression of vertically transmitted HIV infection in children: Association of several HLA-DR13 alleles with long-term survivorship and the potential association of HLA-A*2301 with rapid progression to AIDS

被引:40
作者
Chen, Y
Winchester, R
Korber, B
Gagliano, J
Bryson, Y
Hutto, C
Martin, N
McSherry, G
Petru, A
Wara, D
Ammann, A
机构
[1] COLUMBIA UNIV, NEW YORK, NY USA
[2] SANTA FE INST, SANTA FE, NM 87501 USA
[3] UNIV CALIF LOS ANGELES, SCH MED, LOS ANGELES, CA USA
[4] UNIV MIAMI, MIAMI, FL 33152 USA
[5] PEDIAT AIDS FDN, SANTA MONICA, CA USA
[6] UNIV MED & DENT NEW JERSEY, NEW JERSEY MED SCH, NEWARK, NJ 07103 USA
[7] CHILDRENS HOSP, OAKLAND, CA 94609 USA
[8] UNIV CALIF SAN FRANCISCO, SCH MED, SAN FRANCISCO, CA 94143 USA
关键词
D O I
10.1016/S0198-8859(97)00092-X
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The influence of host immunogenetics on the outcome of vertically transmitted HIV infection in children was examined in a multicenter cross sectional study of long term survivors and rapid progressors. Sequence-based typing was performed for the DRB1, DQB1 and HLA-A loci. 36.7% of 30 children surviving more than 8 years had one or more of the HLA-DR13 alleles, versus none of 14 rapidly progressing children who died within 2 years of age, p = 0.009, Haldane RR = 17.1, The alleles variably associated with this beneficial response to HIV were: DRB1*1301, DRB1*1302, DRB1*1303 and DRB1*1310, suggesting that che DR13 effect acted as a dominant trait. An additional 6 children were typed only by the SSOP method resulting in 44.4% of 36 long term surviving children with a DR13 allele and none of 14 rapid progressors, p = 0.002, Haldane RR = 23.3. No single DQB1 allele accounted for the HLA-DR13 allele association. In contrast, the presence of HLA A*2301 was associated with rapid progression to AIDS, 4% of long term survivors vs. 57.1% of 7 rapid progressors, p = 0.0006, RR = 0.031. Although the sample size is small, the marked differences in allele frequency along with differences between the peptide binding pockets of the HLA-A9 group of alleles including HLA A*2301 and the remainder of the HLA-A alleles suggest a structural basis for the dominant disadvantageous immune response to HIV conferred by A*2301, (C) American Society for Histocompatibility and Immunogenetics, 1997. Published by Elsevier Science Inc.
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页码:154 / 162
页数:9
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