Anti-i cold agglutinins in a patient with Wiskott-Aldrich syndrome binding study with membrane glycosphingolipids.

An unusual isohemagglutinin caused blood incompatibility in a patient with the Wiskott-Aldrich syndrome after nine transfusions. The patient's serum agglutinated erythrocytes of all the donors examined. The antibodies were cold agglutinins which agglutinated adult and cord erythrocytes equally. The binding of these antibodies to glycosphingolipids was analyzed by thin-layer chromatogram immunostaining and solid phase radioimmunoassay. The results indicate that the antibodies in the patient's serum bound specifically to lactonorhexaosylceramide and sialosyllactonorhexaosylceramide, glycolipids known to carry the i antigenic determinant. The antibodies did not bind to neolactotetraosylceramide, sialosylneolactotetraosylceramide or lactoisooctaosylceramide (I-active glycolipid). The patient's serum immunostained several components in the acidic glycolipids from OI erythrocytes. The antibody activity was predominantly present in IgG but the IgM showed similar binding specificity. Hemagglutination of OI erythrocytes with the patient's serum could be inhibited with lactonorhexaosylceramide. These results showed that the patient's antibodies recognized the i determinants carried by membrane surface glycolipids. The production of anti-i antibodies in the patient is intriguing in view of the decreased antibody response to carbohydrate antigens and deficient isohemagglutinins which have been generally observed in the Wiskott-Aldrich syndrome.