Reaction of antibodies that cause paroxysmal cold hemoglobinuria (PCH) with globoside and Forssman glycosphingolipids.

Many antibodies that cause paroxysmal cold hemoglobinuria (Donath-Landstelner antibodies) appear to be directed against the blood group P antigen. We recently Identified this antigen as the glycosphingolipld globoside GaINAc(fl, 1-’3)Gal(a, 1-’4)Gal(fl, 1-’4)GlcCer, and we examined the reaction of four Donath-Landsteiner antibodies with anti-P specificity, and an anti-P acId autoagglutinin, with globoside and Forssman glycolipids. Forssman glycolipid, GaINAc(a, 1-3) GaINAc(fl, 1-’3)Gal(a, 1-’4)Gal(fi, 1-’4)GIc-Cer, contains the globoside structure plus an additional terminal nonreducing cr-GaINAc residue. All five antibodies were Inhibited effectively by globoside. Two of the DonathLandstelner antibodies were InhIbited much more effectively by globoside than Forssman glycolipid, and the other two antibodies were inhibited more effectively by Forssman glycolipid. The two glycolipids were approximately equally effective in Inhibiting the acid anti-P agglutinln. We suggest that the populations of antibodies that react with both glycolipids are directed against an aspect of the globoside structure that is accessible in the Forssman compound, whereas the antibodies that react best with globoside are probably directed against the terminal fiGaINAc residue of this glycolipid. Some human “anti-P” antibodies are probably elicited by immunization against Forssman antigens that are widespread In animal tissues and in microorganisms.