AEGiS-14IAC: Plasma soluble CCR5 -- a protective role in HIV infection?

14th International AIDS Conference


Barcelona, Spain - July 7-12, 2002

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Plasma soluble CCR5 -- a protective role in HIV infection?

Int Conf AIDS 2002 Jul 7-12; 14:(abstract no. A10069)

Tsimanis A, Kalinkovich A, Barak K, Bentwich Z
R.Ben-Ari Institute of Clinical Immunology and AIDS Center, Kaplan Medical Center, Hebrew University Hadassah Medical School, Rehovot, Israel

BACKGROUND: CCR5 has a central role in determining susceptibility to HIV infection. The possibility that a soluble form of CCR5 (sCCR5) may be present in normal plasma and influence susceptibility or resistance to infection by HIV was therefore explored.

METHODS: Levels of sCCR5 in plasma were assessed using a dual antibody sandwich ELISA system. Plasma samples obtained from HIV non-infected, HIV infected, and HIV discordant couples, of Ethiopian and non-Ethiopian origin, were studied. Further characterization of the sCCR5 was performed using ultracentifugation, immunoprecipitation and Western blotting.

RESULTS: sCCR5 was found in a higher proportion of plasma samples obtained from normal Israeli non-Ethiopians than in Ethiopians, 23/89 (25.8%) vs 6/70 (8.6%) (p<0.02). In HIV infected individuals, proportion of positive plasma samples decreased in the non-Ethiopians (7/83 (8.4%) and was the same in Ethiopians (4/71 (6.6%). In discordant couples, sCCR5 was found in 3/57 (5.3%) among Ethiopians in contrast to none (0/8) of the samples obtained from the non-Ethiopian donors. Plasma levels of MIP-1[beta] were significantly higher in samples positive for sCCR5 than in negative samples (p<0.05). Estimated MW of the sCCR5 is ~20KD, smaller than membrane-bound CCR5 (~40KD).

CONCLUSIONS: 1) A soluble and smaller form of membrane CCR5 is present in plasma detected by ELISA dual antibody sandwich assay. 2) In Ethiopians, higher expression of membrane CCR5 is associated with lower prevalence of sCCR5. 3) HIV infection is accompanied by lower sCCR5 prevalence and lower plasma [beta]-chemokine levels. 4) sCCR5 may have a protective role against HIV infection, though our study of sCCR5 in HIV highly exposed non-infected couples does not support such a role.

Keywords: AEGIS, HIV Infections, Plasma, Macrophage Inflammatory Protein-1, Chemokines, CC, HIV Seropositivity, Disease Susceptibility, Enzyme-Linked Immunosorbent Assay, Ethiopia, Africa, IsraelKWDaegis,hivinfections,plasma,macrophageinflammatoryprotein-1,chemokines,cc,hivseropositivity,diseasesusceptibility,enzyme-linkedimmunosorbentassay,ethiopia,africa,israel

020707
A10069

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