title: Lack of Evidence for Molecular Mimicry in HIV-Infected Subjects.
abstract: Previous studies in HIV patients have reported autoantibodies to several human proteins, including erythropoietin (EPO), interferon-α (IFN-α), interleukin-2 (IL-2), and HLA-DR, as potential mediators of anemia or immunosuppression. The etiology of these autoantibodies has been attributed to molecular mimicry between HIV epitopes and self-proteins. Here, the Luciferase Immunoprecipitation System (LIPS) was used to investigate the presence of such autoantibodies in HIV-infected adults. High levels of antibodies to HIV proteins such as capsid (p24), matrix (p17), envelope (gp41), and reverse transcriptase (RT) were detected using LIPS in both untreated and anti-retroviral-treated HIV-infected individuals but not in uninfected controls. LIPS readily detected anti-EPO autoantibodies in serum samples from subjects with presumptive pure red cell aplasia but not in any of the samples from HIV-infected or uninfected individuals. Similarly, subjects with HIV lacked autoantibodies to IFN-α, IL-2, HLA-DR and the immunoglobulin lambda light chain; all purported targets of molecular mimicry. While molecular mimicry between pathogen proteins and self-proteins is a commonly proposed mechanism for autoantibody production, the findings presented here indicate such a process is not common in HIV disease.
authors.affiliation: Dental Clinical Research Core, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, United States of America.
authors.forename: Peter D
authors.initials: PD
authors.lastname: Burbelo
authors.affiliation: Dental Clinical Research Core, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, United States of America.
authors.forename: James S
authors.initials: JS
authors.lastname: Klimavicz
authors.affiliation: Department of Medicine, University of California, San Francisco, San Francisco, CA, United States of America.
authors.forename: Steve G
authors.initials: SG
authors.lastname: Deeks
authors.affiliation: NIH Clinical Center, National Institutes of Health, Bethesda, MD, United States of America.
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Kovacs
authors.affiliation: Office of Biological Products, OPQ, CDER, FDA, Silver Spring, MD, United States of America.
authors.forename: Jack A
authors.initials: JA
authors.lastname: Ragheb
mesh_terms: D000917:Antibody Formation / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology; D003710:Demography; D004921:Erythropoietin / Q000276:immunology; D005260:Female; D015658:HIV Infections / Q000276:immunology*; D006684:HLA-DR Antigens / Q000276:immunology; D006801:Humans; D007146:Immunoglobulin lambda-Chains / Q000276:immunology; D016898:Interferon-alpha / Q000276:immunology; D007376:Interleukin-2 / Q000276:immunology; D008297:Male; D018716:Molecular Mimicry; D014764:Viral Proteins / Q000276:immunology
chemical_list: D001323:Autoantibodies; D006684:HLA-DR Antigens; D007146:Immunoglobulin lambda-Chains; D016898:Interferon-alpha; D007376:Interleukin-2; D014764:Viral Proteins; D004921:Erythropoietin