Surface modifications in the platelets of a patient with alpha-N-acetyl-D-galactosamine residues, the Tn-syndrome.

Abstract

The Tn-syndrome is an acquired disorder characterized by the polyagglutination of blood cells and the pathological exposure of a-N-acetyl-D-galactosamine residues (Tn-antigen) at the cell surface. We now report studies on the platelets of a patient (Ba.) of which 81% reacted positively with a fluorescein con- jugate of Helix pomatia agglutinin (HPA). The surface proteins of Ba. platelets were labeled with 125I by the lactoperoxidase-catalyzed procedure; single and two- dimensional electrophoresis on sodium dodecyl sulfate (SDS)-polyacrylamide gels was followed by autora- diography that revealed normal '251-labeling of the major membrane glycoproteins (GP) but that GP lb had a faster than normal migration. The abnormal GP lb of Ba. platelets was strongly labeled when platelet suspensions were treated sequentially with neuramin- idase, galactose oxidase, and sodium [3H]borohydride. Unlike the GP Ib of normal human platelets, it was also strongly labeled when Ba. platelets were treated with galactose oxidase and sodium [3H]borohydride alone. Both the alloantigen, PHAl, and quinidine-dependent antibody receptor activity were normally ex- pressed by Ba. platelets, which also bound a mono- clonal antibody (AN51) to GP lb. Analysis of Ba. platelets by crossed immunoelectrophoresis using a rabbit anti-human platelet antibody preparation revealed the presence of an immunoprecipitate in the GP lb position that had an abnormal appearance and migration in the second dimension. An altered position of the precipitate given by Factor VIIIR:Ag was also noted. Incorporation of HPA into the agarose gel during the first dimension electrophoresis resulted in the specific precipitation of the abnormal GP lb of Ba. platelets.