Platelet integrin signaling: wherefore art thou?

Such differences in white blood cell (WBC) count could clearly impact on disease course. Ahuja and colleagues previously reported that DARC-null individuals show increased susceptibility to HIV infection, but slower HIV disease progression once infected. 2 In this issue of Blood, Kulkarni et al examine associations among WBC count, DARC genotype, and survival in a large natural history cohort of HIV-infected Americans of both European (EA) and African (AA) descent. Leukopenia, defined as an average WBC count during disease of less than 4 ϫ 10 9 cells per liter, was associated with faster HIV disease progression rates, but notably leukopenic AAs had a slower disease course than leukopenic EAs. As in un-infected AAs, the DARC-null state was associated with low WBC count in HIV ϩ AAs. Significantly , among leukopenic subjects, there was a survival advantage for DARC-null AAs compared with DARC-positive AAs or EAs. By contrast, rates of disease progression in nonleukopenic AAs did not differ by DARC genotype. Although the mechanism(s) underpinning the survival advantage in DARC-null leukopenics remains unclear, several thought-provoking possibilities are aired in the article's discussion. It should be noted, however, that several recent studies failed to find associations , in other cohorts, between DARC genotype and an individual's susceptibility to HIV infection or disease progression. 7-10 Possible explanations for these discrepancies have been discussed previously by Ahuja and colleagues. 11 One of these explanations is highlighted in this new report by Kulkarni et al. It suggests that it is the strong interaction between DARC genotype and WBC counts that influences HIV disease course. Further studies are required to determine, for example, whether similar interactions influence HIV susceptibility, and how DARC genotype and WBC counts are mechanistically linked. Nonetheless, the novel functions emerging for DARC in homeostasis and disease mean that we are steadily making progress toward the heart of DARCness, and it is clearly going to be an exciting and illuminating journey. Conflict-of-interest disclosure: The author declares no competing financial interests. ■ REFERENCES 1. Kulkarni H, Marconi VC, He W, et al. The Duffy-null state is associated with a survival advantage in leukopenic HIV-infected persons of African ancestry.tor for chemokines mediates trans-infection of HIV-1 from red blood cells to target cells and affects HIV-AIDS susceptibility .phil count in people of African descent is due to a regulatory variant in the Duffy antigen receptor for chemokines gene. antigen receptor for chemokines: no influence on HIV …