Naturally occurring alpha-galactosyl antibodies in human sera display polyreactivity

Anti-gal is a dominant autoantibody constituting nearly 1% of total circula ting IgG in humans and old world primates. Raised levels of anti-gal have b een demonstrated in parasitic diseases such as malaria, leishmaniasis and C hagas disease and in a variety of autoimmune diseases. It has also been imp licated as a primary cause of rejection of xenogeneic cells and organs tran splanted in old world primates since Gal-alpha. 1,3 Gal is thought to be th e major antigenic epitope to which xenoreactive natural antibodies bind. Si nce polyreactive antibodies have also been widely implicated in xenotranspl antation and anti-gal is yet to be demonstrated to be polyreactive, we have attempted to study this property of anti-gal antibodies. Anti-gal levels w ere assayed in 72 human sera and compared with DNA-binding antibodies. A si gnificant positive correlation was found between anti-gal and DNA-binding a ntibodies. Absorption of sera with fresh rabbit erythrocytes (which express abundant alpha-galactose on their surface) resulted in significant removal of both anti-gal and DNA-binding antibodies. Affinity purified anti-gal we re found to be reactive to DNA, actin, myosin and tubulin indicating the po lyreactive nature of naturally occurring anti-gal antibodies in human sera. The observed polyreactivity was not an exclusive feature of sera collected from tropical countries-anti-gal affinity purified from sera of North Amer icans were also found to react with DNA. The demonstration of polyreactivit y of anti-gal indicates a much wider biological role for this autoantibody in humans and old world primates. (C) 1999 Elsevier Science B.V. All rights reserved.