New class I and II HLA alleles strongly associated with opposite patterns of progression to AIDS.
The genetics of resistance to infection by HIV-1 cohort consists of 200 slow and 75 rapid progressors to AIDS corresponding to the extremes of HIV disease outcome of 20,000 Caucasians of European descent. A comprehensive analysis of HLA class I and class II genes in this highly informative cohort has identified HLA alleles associated with fast or slow progression, including several not described previously. A quantitative analysis shows an overall HLA influence independent of and equal in magnitude (for the protective effect) to the effect of the CCR5-Delta32 mutation. Among HLA class I genes, A29 (p = 0.001) and B22 (p < 0.0001) are significantly associated with rapid progression, whereas B14 (p = 0.001) and C8 (p = 0.004) are significantly associated with nonprogression. The class I alleles B27, B57, C14 (protective), and C16, as well as B35 (susceptible), are also influential, but their effects are less robust. Influence of class II alleles was only observed for DR11. These results confirm the influence of the immune system on disease progression and may have implications on peptide-based vaccine development.
Hendel
H
H
Laboratoire de Physiologie Cellulaire, Université Pierre et Marie Curie, Paris, France.
Caillat-Zucman
S
S
Lebuanec
H
H
Carrington
M
M
O'Brien
S
S
Andrieu
J M
JM
Schächter
F
F
Zagury
D
D
Rappaport
J
J
Winkler
C
C
Nelson
G W
GW
Zagury
J F
JF
D000163:Acquired Immunodeficiency Syndrome / Q000209:etiology / Q000235:genetics* / Q000276:immunology*; D000483:Alleles; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000235:genetics; D018450:Disease Progression; D020022:Genetic Predisposition to Disease / Q000276:immunology; D006680:HLA Antigens / Q000235:genetics*; D006681:HLA-D Antigens / Q000235:genetics*; D006684:HLA-DR Antigens / Q000235:genetics; D059810:HLA-DR Serological Subtypes; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D015810:Linkage Disequilibrium / Q000276:immunology; D054390:Receptors, CCR2; D019713:Receptors, CCR5 / Q000235:genetics; D019707:Receptors, Chemokine / Q000235:genetics
C515334:CCR2 protein, human; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D006680:HLA Antigens; D006681:HLA-D Antigens; D006684:HLA-DR Antigens; D059810:HLA-DR Serological Subtypes; C080766:HLA-DR11 antigen; D015395:Histocompatibility Antigens Class I; D054390:Receptors, CCR2; D019713:Receptors, CCR5; D019707:Receptors, Chemokine