Antigens associated with the human immunodeficiency virus: Studies in immunodeficiency and autoimmunity
Description
In investigating autoimmune patient indeterminate HIV-1 Western blot (Wb) results, it was noted that 70 kilodalton heat shock proteins (hsp70) and the B'/B polypeptide Smith autoantigens (Sm B'/B) are found as cellular contaminants on the HIV-1 Wb. Hsp70 and the Sm B'/B copurified from anion-exchange and gel-filtration sizing columns in the same fractions, and coprecipitated with antibodies to either protein suggesting that hsp70 is physically associated with the Sm B'/B complex and may be involved in pre-mRNA splicing. One or both of these proteins appear to be associated with purified HIV-1 and are found as cellular contaminants on the HIV-1 Wb. Interaction of exogenous viral proteins with hsps and Sm B'/B suggests a mechanism(s) by which self-polypeptides can become immunogenic, ultimately leading to autoimmune disease Silicone is used medically because it is considered to be biologically and immunologically inert. Yet, a portion of the women who received silicone-filled gel breast implants have complications resembling autoimmune diseases. In characterizing HIV-1 Wb indeterminate results, we found that individuals exposed to silicone produce serum antibodies reactive with the HIV-1 Wb. Characterization determined that the reactive antigen presents itself as a polymeric contaminant on Wb. We developed an immunoblot assay that specifically detects anti-polymer antibodies (APAs) and determined that they are present in almost 55% (363/667) of the individuals experiencing complications associated with silicone exposure. This percentage is significantly greater than that observed in non-silicone exposed autoimmune patients or in healthy controls ($\leq$10%, p $<$ 0.0005). Besides potential diagnostic value, APAs may be important in the pathology of the symptoms observed in silicone-exposed patients A better understanding of the mechanisms leading to systemic autoimmune diseases may be gained by studying the interplay between viral proteins, cellular proteins and other antigens present on the HIV-1 Wb. Additionally, identification and characterization of non-viral antigens on the HIV-1 Wb should help in the interpretation of indeterminate results