PubMed · 2213281
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H D Modanlou. 1990. ABO incompatibility.. https://pubmed.ncbi.nlm.nih.gov/2213281/
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BACKGROUND: Removal and/or "neutralization" of anti-Gal alpha1-3Gal (alphaGal) antibodies can prevent or delay the hyperacute rejection of pig organs transplanted into primates. AIM: To determine variations in (1) cytotoxicity to pig kidney (PK15) cells, (2) anti-alphaGal antibody level, and (3) specificity in adult human (n=46) and baboon (n=38) sera. METHODS: Cytotoxicity to PK15 cells was determined by adding rabbit complement to heat-inactivated serum, using a two-color fluorescent dye to distinguish live and dead cells. Anti-alphaGal antibody level was determined by ELISA using alphaGal trisaccharide type 2-BSA glycoconjugate as antigen target. Specificity determined by ELISA using four different alphaGal-BSA glycoconjugates: (disaccharide, trisaccharides type 2 and 6, and pentasaccharide). RESULTS: Cytotoxicity of human AB sera varied from 30-100% PK15 relative cell damage (%RCD), although that of baboon sera of all blood groups varied from 35-100% RCD. In human AB sera, anti-alphaGal antibody level (at a dilution of 1:80) varied from undetectable to 0.75 (OD at 405 nm), although in baboon sera of all blood groups, anti-alphaGal antibody level varied from undetectable to >2.0. There was no correlation between anti-alphaGal antibody level and serum cytotoxicity in either species. Specificity varied among individuals in both human and baboon sera. CONCLUSIONS: These studies have demonstrated (1) considerable variation in cytotoxicity and anti-alphaGal antibody level in human and baboon sera, but a lack of correlation between these two parameters; (2) considerable variation in the specificity of anti-alphaGal antibodies; (3) blood group B human and baboon sera have lower levels of anti-alphaGal antibodies; (4) no relation between blood group and specificity of anti-alphaGal antibodies. Although there are minor differences in the parameters measured, baboons would appear to be suitable surrogates for humans in the pig-to-primate xenograft model.
The seed lectin (DBL) from the leguminous plant Dolichos biflorus has a unique specificity among the members of the legume lectin family because of its high preference for GalNAc over Gal. In addition, precipitation of blood group A+H substance by DBL is slightly better inhibited by a blood group A trisaccharide (GalNAc(alpha1-3)[Fuc(alpha1-2)]Gal) containing pentasaccharide, and about 40 times better by the Forssman disaccharide (GalNAc(alpha1-3)GalNAc) than by GalNAc. We report the crystal structures of the DBL-blood group A trisaccharide complex and the DBL-Forssman disaccharide complex.A comparison with the binding sites of Gal-binding legume lectins indicates that the low affinity of DBL for Gal is due to the substitution of a conserved aromatic residue by an aliphatic residue (Leu127). Binding studies with a Leu127Phe mutant corroborate these conclusions. DBL has a higher affinity for GalNAc because the N-acetyl group compensates for the loss of aromatic stacking in DBL by making a hydrogen bond with the backbone amide group of Gly103 and a hydrophobic contact with the side-chains of Trp132 and Tyr104. Some legume lectins possess a hydrophobic binding site that binds adenine and adenine-derived plant hormones, i.e. cytokinins. The exact function of this binding site is unknown, but adenine/cytokinin-binding legume lectins might be involved in storage of plant hormones or plant growth regulation. The structures of DBL in complex with adenine and of the dimeric stem and leaf lectin (DB58) from the same plant provide the first structural data on these binding sites. Both oligomers possess an unusual architecture, featuring an alpha-helix sandwiched between two monomers. In both oligomers, this alpha-helix is directly involved in the formation of the hydrophobic binding site. DB58 adopts a novel quaternary structure, related to the quaternary structure of the DBL heterotetramer, and brings the number of know legume lectin dimer types to four.
BACKGROUND: The role of humoral immunity in acute rejection in solid organ transplantation remains controversial, although it is known that the presence of antidonor antibodies may precipitate graft rejection. We investigated the clinical relevance of antidonor humoral immunity for living donor liver transplantation (LDLT) by means of flow cytometry crossmatch (FCXM). METHODS: T cell FCXM using fresh donor peripheral lymphocytes was performed before and up to 1 month after LDLT in 58 patients. Ten patients received ABO-incompatible grafts. IgM and IgG antidonor antibodies were analyzed in relation to clinical acute rejection as defined by liver function tests with or without histological evidence. RESULTS: Pretransplantation FCXM was positive for five patients (8.6%), resulting in two cases of positive posttransplantation FCXM and two rejection episodes. Twelve patients (20.7%) showed positive posttransplantation FCXM. The incidence of acute rejection within 1 month was 100% in FCXM-positive patients and 17.4% in FCXM-negative patients (P<0.001). Thirteen (76.5%) of 17 rejection episodes in ABO-compatible cases were associated with concomitant antidonor IgM antibody. IgG antibody was also identified in six of these episodes. Antidonor antibodies disappeared after rejection treatments in all cases, but with some delay in clinical improvement. On the other hand, no antidonor antibodies were detected in any of the four rejection episodes in ABO-incompatible cases. CONCLUSIONS: Early acute rejection in LDLT is significantly associated with antidonor T cell antibody formation in ABO-compatible cases. This suggests a definite role for donor-specific humoral immunity in acute rejection. Rejection episodes without antidonor antibodies may suggest graft injury by pure cellular immunity, or possibly the presence of humoral immunity triggered by antigens not present on donor T cells.