What Are Blood Groups For - Do They Play A Biological Role?

George Garratty began the lecture by reviewing some statistical data relevant to blood groups. The selective feeding of the mosquito Anopheles gambiae is higher in group O compared to A₁. However, the mean IQ is also higher in group O individuals. Cancer and thrombosis occur at a higher rate in group A while peptic ulcer and bleeding are higher in group O.

Next, Dr. Garratty discussed the association of blood groups and tumor. Malignancy can affect cellular antigen either in the loss of normal antigens or in the appearance of new antigens such as tumor antigens and fetal antigens (illegitimate antigens). Tumor markers with blood group activity include "A-like" and A, T, Tn, Le^x, and Le^y. Many "new" antigens on malignant cells are "A-like" (or A). Group O red cells are more likely to recognize and attack these new epitopes. T and Tn are crypt antigens and are not detected on normal cells. However, they are present on malignant cells. The amount of cellular T/Tn correlates with the histologic grade and invasive potential of the tumor. Anti-T, which is a normally occurring antibody in the serum, is lower in the sera of patients with malignancy. T/Tn antigens also stimulate humoral and cellular immune responses.

Dr. Garratty then moved into the topic of blood group antigens as receptors for bacteria and parasites. Anti-A and anti-B are bacterial antibodies; anti-B can lyse E. coli in the presence of complement. ABO polymorphism can be traced to epidemics. For example, Yersinia pestis (plague) is rich in H antigen and smallpox is rich in A antigen. The Anton blood group antigen is the erythrocyte receptor for Haemophilius influenza. Le^b mediates H. pylori attachment to gastric mucosa, leading to ulcer. The P blood group system is associated with E. coli. Additionally, the P blood group is associated with Parvovirus B19 and with HIV. P, P¹, P^k are blood group antigens on glycosphingolipids (GSLs) which are implicated in HIV-host-cell-fusion.

Another well known association is the Duffy blood group and malaria. P. vivax attaches to but do not invade Fy(a–b–) RBCs. Glycophorin C is a receptor for P. falciparum, and CR1 is involved in P. falciparum rosetting. Knops null and Sl(a–) red cells have no or reduced rosetting. The Duffy blood group antigen is also the receptor for IL-8 and melanoma growth stimulating activity (MGSA). IL-8 binds minimally to Fy(a–b–) RBCs. Anti-Fy6 blocks binding of IL-8; and IL-8 and MGSA blocks parasite binding to red cells.

The number of red cell antigens can increase or decrease in disease. For example, the i antigen increases in disease. Depressed or lack of common antigens and red cell abnormalities include stomatocytosis/hemolytic anemia in Rhmod/Rh_null; acanthocytosis and muscle defects in McLeod; elliptocytosis in Ge_null (Leach type); and PNH III RBCs in Cr/Yt/JMH/Hy/Do.

Some red cell antigens function to transport. Examples include CO and AQP-1 (water); Di/Wr^b and Band 3 (anion); Rh (RHAG) and ammonia; and Jk and urea. Enzymes are associated with red cells. Examples include acetylcholinesterase and YT; zinc-metalloproteinase and Kell; and ADP-ribosyltransferase and DO.

Dr. Garratty concluded that red cells have many jobs to do and quoted D.M. Luban: "It is a good time to be an immunohematologist. Knowledge of the structure and function of the molecules carrying blood group antigens is taking us to a new level of scientific understanding and promises new techniques for use in clinical transfusion medicine."