Anti-Fucosyltransferase 3 polyclonal antibody

Calculations of blood group antigen immunogenicity have been based on antigen and antibody frequencies in transfused populations, with the assumption of a single red blood cell (RBC) unit exposure per patient. Given that patients are usually transfused >1 RBC unit, antigen exposures will be greater than assumed, resulting in inaccurate immunogenicity calculations. As such, the goal of this study was to modify the calculation to correct for RBC exposures. To further improve accuracy, we used an empirically-derived immunogenicity for the reference antigen, K, in calculations of absolute immunogencity and eliminated anamnestic and pre-existing antibodies (i.e., antibodies induced outside the study site) from the calculation. Alloantibody numbers for the top 12 specificities and mean RBCs (MRBC) transfused per patient were obtained from the records of a hospital transfusion service. A revised immunogenicity calculation, incorporating a correction for MRBC, was developed. This correction resulted in up to a 4-fold increase in the immunogenicity of relatively high frequency antigens, with smaller increases for lower frequency antigens, yielding the following revised immunogenicity ranking: K>Jk(a)>Lu-a>E>P1>c>M>Le(b)>C>Le(a)>Fy(a)>S. Use of an empirical value for K immunogenicity resulted in a 19-fold increase in absolute immunogenicities for all antigens. In summary, the calculation of blood group antigen immunogenicity has been further refined.

Burkholderia arnbifana is an opportunistic respiratory pathogen belonging to the Burkholderia cepacia complex, a collection of species responsible for the rapidly fatal cepacia syndrome in cystic fibrosis patients. A fucose-binding lectin identified in the B. ambifaria genome, BambL, is able to adhere to lung tissue, and may play a role in respiratory infection. X-ray crystallography has revealed the bound complex structures for four fucosylated human blood group epitopes (blood group B. H type 1, H type 2, and Lex determinants). The present study employed computational approaches, including docking and molecular dynamics (MD), to extend the structural analysis of BambL-oligosaccharide complexes to include four additional blood group saccharides (A, Le(a), Le(b), and Le(y)) and a library of blood-group-related carbohydrates. Carbohydrate recognition is dominated by interactions with fucose via a hydrogen-bonding network involving Arg15, Glu26, Ala38, and Trp79 and a stacking interaction with Trp74. Additional hydrogen bonds to non-fucose residues are formed with Asp30, Tyr35, Thr36, and Trp74. BambL recognition is dominated by interactions with fucose, but also features interactions with other parts of the ligands that may modulate specificity or affinity. The detailed computational characterization of the BambL carbohydrate-binding site provides guidelines for the future design of lectin inhibitors.