Current Developments

Molecular Genetics

Although the ABO system was discovered over 90 years ago, new knowledge and advances continue to occur. For example we now know that A,B,O genes are on chromosome 9, whereas Hh and Sese are closely linked on chromosome 19; also molecular genetic methods have shown that A and B genes differ from each other by seven single base substitutions and that the O gene differs from the A gene by a single base deletion.

Monoclonal Antisera

At a practical level, use of monoclonal antisera has resolved some ABO typing problems such as weak subgroups (due to high sensitivity) and extra antigens (due to high specificity), e.g., T-activation.

However, monoclonal reagents have also caused some problems, such as an increase in detecting acquired B phenomenon with monoclonal ES4 anti-B (discussed earlier), as well as phenomena such as B(A) and A₁(B) . B(A) phenomenon has been observed in about 1 in 1,000 B persons. Apparently the B transferase can transfer small amounts of A sugar to the red cell and, when it is increased in some individuals, there may be enough A sugar on red cells to be detected by potent monoclonal anti-A. Thus, people previously typed as group B may now appear to be group AB. The B(A) problem may be identified by using human polyclonal typing sera.

The A₁(B) phenomenon involves persons who previously grouped as A now typing as AB with some monoclonal anti-B antisera. Similarly to the case with B(A), but the reverse, the A transferase can transfer small amounts of B sugar to the red cell and, when it is increased in some individuals, there may be enough B sugar on red cells to be detected by potent monoclonal anti-B.

Designer Red Cells

On the research front, one group of workers is exploring the enzymatic conversion of group B red cells to group O. The enzyme [alpha]-galactosidase (purified from coffee beans) is used to remove galactose residues from B cells; the enzymatically converted O cells have been shown to survive normally in healthy volunteers. If successful, designer red cells may one day be used routinely.

Enrichment Activity 7

Read designer red cells, a Medline abstract of a study about converting group B red cells to group O cells.

1. This paper describes the results of a Phase 1 clinical trial involving blood transfusion. Go to this hospital site, which explains phase 1, 2, and 3 clinical trials as they relate to cancer therapy. Speculate on what type of study would be required next for a phase 2 clinical trial of the designer red cells. E-mail comments to the class mailing list.

2. Also e-mail a general comment or question to the class mailing list about the advent of designer red cells. For example, comment on the relevance of converting group B cells as opposed to red cells of other groups.

3. Finally, e-mail a response to the class list about another student's comments or questions.

Current Developments