title: Humoral Antibody Responses to HIV Viral Proteins and to CD4 Among HIV Controllers, Rapid and Typical Progressors in an HIV-Positive Patient Cohort.
abstract: The purpose of this study was to assess humoral antibody responses as a function of disease progression (DP) in a well-defined HIV+cohort. We quantified antibodies to HIV-1 gp120, Gag, and CD4 receptor by enzyme-linked immunosorbent assay in sera from a cohort of 97 HIV+subjects at defined stages of DP. We also measured antibody-dependent cellular cytotoxicity (ADCC) as a function of the clinical status of the patients. We purified antibodies to CD4 and gp120 and assessed them for specificity, ability to block gp120 binding to target cells, ability to block virus infection, and ability to facilitate ADCC. All of the HIV+patient samples were positive for antibodies to HIV gp120 and p24 and 80% showed evidence of hypergammaglobulinemia. Approximately 10% of cohort members were positive for antibodies to CD4, but we noted no significant correlation relevant to DP. There were statistically significant differences between the groups concerning the level of humoral response to gp120 and Gag. However, we observed no distinction in ability of anti-gp120 antibodies purified from each group to neutralize infection. In addition, there was a statistically significant difference in ADCC, with elite controllers exhibiting significantly lower levels of ADCC than the other five groups. We detected IgA anti-gp120 antibodies, but did not correlate their presence with either DP or ADCC levels. The results are consistent with the interpretation that the humoral antibody response to the antigens assessed here represents a signature of the level of viremia but does not correlate with clinical status of HIV infection.
authors: 1 Department of Immunology and Microbial Science, The Scripps Research Institute , La Jolla, California.
authors: Elizabeth
authors: E
authors: Fink
authors: 1 Department of Immunology and Microbial Science, The Scripps Research Institute , La Jolla, California.
authors: Katherine
authors: K
authors: Fuller
authors: 2 Infectious Disease Clinical Research Program, Uniformed Services University of the Health Sciences , Bethesda, Maryland.|3 Henry M. Jackson Foundation for the Advancement of Military Medicine , Bethesda, Maryland.
authors: Brian
authors: B
authors: Agan
authors: 4 Laboratory of Viral Diseases, National Institutes of Allergy and Infectious Diseases, The National Institutes of Health , Bethesda, Maryland.
authors: Edward A
authors: EA
authors: Berger
authors: 1 Department of Immunology and Microbial Science, The Scripps Research Institute , La Jolla, California.
authors: Andrew
authors: A
authors: Saphire
authors: 5 Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health Sciences , Bethesda, Maryland.
authors: Gerald V
authors: GV
authors: Quinnan
authors: 1 Department of Immunology and Microbial Science, The Scripps Research Institute , La Jolla, California.
authors: John H
authors: JH
authors: Elder
mesh_terms: D000917:Antibody Formation; D001323:Autoantibodies / Q000097:blood* / Q000276:immunology; D015704:CD4 Antigens / Q000276:immunology*; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015483:HIV Antibodies / Q000097:blood* / Q000276:immunology; D015658:HIV Infections / Q000276:immunology* / Q000473:pathology; D054298:Human Immunodeficiency Virus Proteins / Q000276:immunology*; D006801:Humans; D008297:Male; D011446:Prospective Studies; D013997:Time Factors
chemical_list: D001323:Autoantibodies; D015704:CD4 Antigens; D015483:HIV Antibodies; D054298:Human Immunodeficiency Virus Proteins
keywords: ADCC; HIV; HIV clinical outcomes research; envelope