Duffy blood group antigens are carried on a glycoprotein that is predicted to pass through the erythrocyte membrane seven times and is a promiscuous chemokine receptor. The Fy(a- b-) phenotype is present in two-thirds of African-American Blacks but is rare in Caucasians. In Blacks, the phenotype is due to a non-functional GATA-1 motif in the FY B, which silences the gene in erythrocytes but not in other tissues, and these patients do not generally make anti-Fyb or anti-Fy3. We describe here the molecular analysis of FY in three unrelated Caucasians who were studied because they had strong anti-Fy3 in their serum. Each was found to have a point mutation that was predicted to change a tryptophan to a premature stop codon in the coding sequence. In one patient (patient 1), the nonsense mutation was at nucleotide 287 of the major transcript in FY A; in another (patient 2), it was at nucleotide 407 in the major transcript of FY B; and in a third (patient 3), it was at nucleotide 408 of the major transcript of FY A.
No adverse reactions were reported for the study groups where "suitable" blood was provided after a serologically mismatched IAT XM. No additional benefit for these patients can be claimed by performing an IAT XM over an IS XM, as a check of ABO match. The IAT XM is both costly and time-consuming. It is proposed that for these study group patients, a reduction to an IS XM can be applied and can be beneficial.
Summary
The limited supply of reagent human polyclonal antibodies to high prevalence antigens, like Jsb, is driving the search for alternative reagents. Murine immunoglobulin G (IgG) monoclonal antibodies (Mabs) and their humanized chimaeric IgM isoforms can now be used for typing patients and screening donors. Antigen typing of red blood cells (RBC) with a positive direct antiglobulin test (DAT) is also possible using these antibodies. Blood from patients with sickle cell disease and African donors were tested with reagent anti‐Jsb, murine Mab IgG anti‐Jsb [murine immunochemistry monoclonal antibody‐8 (MIMA‐8)], and humanized chimaeric IgM anti‐Jsb [human immunochemistry monoclonal antibody‐8 (HIMA‐8)] by haemagglutination and gel cards. RBC samples that were DAT positive were used to evaluate the humanized chimaeric IgM monoclonal anti‐Fya (HIMA‐19). RBC samples (n = 243) of known Jsb type were tested in parallel with MIMA‐8 and reagent anti‐Jsb, and 132 samples were tested with MIMA‐8 in gel cards and HIMA‐8 by direct tube testing. No discrepant results were obtained. DAT‐positive RBC samples (n = 27) were correctly phenotyped using HIMA‐19. We conclude that MIMA‐8 is suitable for screening donors and typing patient RBCs. Testing MIMA‐8 with gel cards containing anti‐mouse IgG enables the screening of donors by automated methods. Humanized chimaeric IgM anti‐Jsb and anti‐Fya are suitable as typing reagents by direct agglutination methods.
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