Autoantibodies against ß₂-microglobulin-free HLA antigens in AIDS patients

Serum samples from 88 human immunodeficiency virus (HIV)-positive drug addicts have been investigated for the presence of antibodies to both ß₂-microglobulin (ß₂m)-free and ß₂m-associated HLA class I molecules. Using HIV-negative drug addicts as background control, we found that none of the Centers for Disease Control (CDC) stage II, 9.1% of CDC III, 36.4% of CDC IV A, and 45.5% of CDC IV Cl patients had significant levels of autoantibodies competing with the binding of the monoclonal antibody specific for ß₂m-free HLA I (L31 mAb). Using the mAb 01.65, recognizing the ß₂massociated form of HLA class I molecules, a similar percentage of positive samples was found in the CDC II, CDC III, and CDC IV A patient groups; conversely, the percentage of positive serum samples was lower in the CDC IV Cl group. A lower number of systemic lupus erythematosus serum samples and none of the specimens from healthy adult subjects or patients suffering from recurrent Epstein-Barr virus infections were positive in both assays. Our data demonstrate the existence of an ongoing HLA class I-specific autoimmune response during AIDS disease development, which probably reflects a molecular mimicry between autologous histocompatibility antigens and HIV components. The relationship between the prevalence of autoantibodies against ß₂m-free HLA class I and disease progression suggests a possible pathogenetic role of these antibodies in the induction of the HIV-associated immune deficiency.