Abstrakt: |
Many antibodies that cause paroxysmal cold hemoglobinuria (Donath-Landsteiner antibodies) appear to be directed against the blood group P antigen. We recently identified this antigen as the glycosphingolipid globoside GalNAc(β, 1-3)Gal(α, 1-4)Gal(β,1-4)Glc-Cer, 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, GalNAc(α, 1-3) GalNAc(β, 1-3)Gal(α, 1-4)Gal(β,1-4)Glc-Cer, contains the globoside structure plus an additional terminal nonreducing α-GalNAc residue. All five antibodies were inhibited effectively by globoside. Two of the Donath-Landsteiner 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 agglutinin. 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 β-GalNAc 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. |