Naturally occurring alpha-galactosyl antibodies in human sera display polyreactivity

Anti-gal is a dominant autoantibody constituting nearly 1% of total circulating IgG in humans and old world primates. Raised levels of anti-gal have been demonstrated in parasitic diseases such as malaria, leishmaniasis and Chagas disease and in a variety of autoimmune diseases. It has also been implicated as a primary cause of rejection of xenogeneic cells and organs transplanted in old world primates since Gal-alpha 1,3 Gal is thought to be the major antigenic epitope to which xenoreactive natural antibodies bind. Since polyreactive antibodies have also been widely implicated in xenotransplantation 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 were assayed in 72 human sera and compared with DNA-binding antibodies. A significant positive correlation was found between anti-gal and DNA-binding antibodies. 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 were found to be reactive to DNA, actin, myosin and tubulin indicating the polyreactive 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 Americans were also found to react with DNA. The demonstration of polyreactivity of anti-gal indicates a much wider biological role for this autoantibody in humans and old world primates.