PubMed · 4998415
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J Schneider. 1970-05-29. [Immunoglobulin prophylaxis].. https://pubmed.ncbi.nlm.nih.gov/4998415/
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The B-subunits of cholera toxin (CTB) and Escherichia coli heat-labile enterotoxin (LTB) are structurally and functionally related. However, the carbohydrate binding specificities of the two proteins differ. While both CTB and LTB bind to the GM1 ganglioside, LTB also binds to N-acetyllactosamine-terminated glycoconjugates. The structural basis of the differences in carbohydrate recognition has been investigated by a systematic exchange of amino acids between LTB and CTB. Thereby, a CTB/LTB hybrid with a gain-of-function mutation resulting in recognition of blood group A and B determinants was obtained. Glycosphingolipid binding assays showed a specific binding of this hybrid B-subunit, but not CTB or LTB, to slowly migrating non-acid glycosphingolipids of human and animal small intestinal epithelium. A binding-active glycosphingolipid isolated from cat intestinal epithelium was characterized by mass spectrometry and proton NMR as GalNAcalpha3(Fucalpha2)Galbeta4(Fucalpha3)Glc NAcbeta3Galbeta4Glc NAcbeta3Galbeta4Glcbeta1Cer. Comparison with reference glycosphingolipids showed that the minimum binding epitope recognized by the CTB/LTB hybrid was Galalpha3(Fucalpha2)Galbeta4(Fucalpha3)GlcNAc beta. The blood group A and B determinants bind to a novel carbohydrate binding site located at the top of the B-subunit interfaces, distinct from the GM1 binding site, as found by docking and molecular dynamics simulations.
The kinetics and thermodynamics of Ulex europeas agglutinin 1-H-antigenic determinant was studied by monitoring the binding of the lectin to H-antigenic fucolipid incorporated in liposomes tethered to the sensor surface by surface plasmon resonance. The second-order rate constants for the interactions are several order of magnitude slower than the diffusion controlled reactions. Analyses of activation parameters reveals that these slow second-order rate constants are a consequence of an unfavorable activation enthalpy term.
We have performed ten pediatric kidney transplantations from living-related ABO-incompatible donors. All patients underwent preoperative plasmapheresis with or without immunoadsorption to reduce isoagglutinin. Primary immunosuppression consisted of methyl-prednisolone, cyclosporin or tacrolimus, azathioprine, anti-lymphocyte globulin, and/or deoxyspergualin. At transplantation splenectomy was simultaneously performed in all patients. Median follow-up is 65 months (range 4-95 months). The patient and graft survival rates are 100% to date. Post-transplantation isoagglutinin titers did not increase more than 1:32, except for 1 patient, without uncontrollable vascular rejection episodes. Despite the heavy immunosuppressive regimen, cytomegalovirus infection occurred in only three patients, who were successfully treated with ganciclovir and cytomegalovirus high-titer gamma globulin. Our small series clearly shows that the preoperative reduction of isoagglutinin, splenectomy, and strict immunosuppressive therapy lead to successful long-term results in children.