Complexities of the Dombrock blood group system revealed

Abstract

The Do(a) antigen was discovered after I began my career in immunohematology and I have been fortunate to be involved in several fascinating discoveries in the Dombrock blood group system. The Do(a) antigen and its antithetical antigen, Do(b), have a prevalence that makes them useful as genetic markers. The paucity of reliable anti-Do(a) and anti-Do(b) has prevented this potential from being realized; however, our ability to type for DO alleles at the DNA level has made it possible to test cohorts from different populations. In 1992, the Dombrock blood group system was expanded to include three phenotypically related antigens, Gy(a), Hy, and Jo(a), when it was discovered that the Gy(a-) phenotype was the null of the Dombrock system. Based on the knowledge that the Dombrock glycoprotein is attached to the RBC membrane via a glycosylphosphatidylinositol linkage and subsequent to the assignment of the corresponding gene to the short arm of chromosome 12, expressed sequence tags from terminally differentiating human erythroid cells were analyzed in silico to identify the DO gene. This allowed determination of the molecular basis of the various Do phenotypes and the realization that DO is identical to the gene encoding a mono-ADP-ribosyltransferase, ART4. No enzymatic activity in RBCs has been demonstrated and the function of this glycoprotein, on the outside surface of RBCs, has yet to be determined. This review is a synthesis of our current knowledge of the Dombrock blood group system.

Dombrock Blood Group System

“…ART4 , a gene encoding a member of a family of mono -ADP -ribosyltransferases, was identifi ed as a candidate for DO [8] . This would give a mature protein of 240 amino acids [9] . ART4 spans 14 kb and contains 3 exons that appear to encode a protein of 314 amino acids with fi ve putative N -glycosylation sites and six cysteine residues (including one in the signal peptide).…”

Transfusion in the age of molecular diagnostics

“…RBC typing for Do a , Do b , Hy and Jo a antigens is notoriously difficult because the corresponding antibodies, although potentially of clinical significance, are often weakly reactive, available only in small volume, and present in sera containing other alloantibodies 19. At the New York Blood Center, for over a decade we have used PCR-RFLP LDTs to type donors selected to lack certain combinations of antigens [eg, C–, E–, K–, Fy(a–), Jk(b–)] for DO*A, DO*B, DO*HY and DO*JO for patients who have antibodies to multiple antigens, in addition to the Dombrock system antibody.…”

Applications and Experience with PCR-Based Assays to Predict Blood Group Antigens

“…[28] At the New York Blood Center, for over a decade we have used PCR-RFLP LDTs to type donors selected to lack certain combinations of antigens [e.g., C–, E–, K–, Fy(a–), Jk(b–)] for DO*A and DO*B for patients who have antibodies to multiple antigens, in addition to anti-Do a or anti-Do b . We also test donors whose RBCs react weakly or do not react with human polyclonal anti-Gy a for DO*HY and DO*JO , which has provided us with a larger inventory of valuable Hy– and Jo(a–) donors.…”