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. Long-Term Survivor Study.
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 the 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.
Chen
Y
Y
Department of Pediatrics, Columbia University, New York, NY 10032, USA.
Winchester
R
R
Korber
B
B
Gagliano
J
J
Bryson
Y
Y
Hutto
C
C
Martin
N
N
McSherry
G
G
Petru
A
A
Wara
D
D
Ammann
A
A
D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000401:mortality / Q000635:transmission*; D000483:Alleles; D002648:Child; D003430:Cross-Sectional Studies; D015234:HLA-A Antigens / Q000235:genetics*; D006684:HLA-DR Antigens / Q000235:genetics*; D059810:HLA-DR Serological Subtypes; D059811:HLA-DRB1 Chains; D006801:Humans; D018445:Infectious Disease Transmission, Vertical
D015234:HLA-A Antigens; D006684:HLA-DR Antigens; D059810:HLA-DR Serological Subtypes; C097337:HLA-DR13 antigen; D059811:HLA-DRB1 Chains