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STUDY: Blood group antigens as tumor markers, parasitic/bacterial/viral receptors, and their association with immunologically important proteins.
JOURNAL: Clin Chim Acta 1988 Oct 14;177(2):147-155
AUTHORS: Garratty G.
ABSTRACT: Blood group antigens (BGAs) are chemical complexes on the red blood cell (RBC) membrane. Some BGAs (e.g., A, B, H, Lewis, P, I) are widely distributed throughout the body and may not be primarily erythroid antigens. It is not known if BGAs have a biological function. There are increasing reports of BGAs [e.g., Le(x) (an isomer of Le(a)), Le(y) (an isomer of Le(b)), T, Tn, "A-like"] appearing as "new" antigens on malignant tissue. Their presence and membrane density appears to correlate with the metastatic potential of the tumor. This often parallels loss of normal BGAs (e.g., ABH) from the tissue. Some of these antigens have been shown to influence the immune response and have been used in assays to determine preclinical cancer, and in tumor immunotherapy. Interactions of some parasites and bacteria with human cells have been shown to depend on the presence of certain BGAs. This interaction is the tethering stage that start the leukocytes' journey from the circulation into the tissue. Thus, there are increasing data suggesting a biological role for BGAs unrelated to the red blood cell.
COMMENTARY: In this most important article, we can see an early use of the term 'A-like' as a description of a class of tumor antigens associated with blood groups. This 'A-like' antigen is most likely a corrupted version of what is actually known as 'T' or 'Tn' an early stage tumor antigen which is normally suppressed in healthy cells, by a thick covering of neuraminic acid (NANA). Much like a rock is covered at high tide by water, in healthy cells NANA encrypts or completely covers Tn. So rare is the appearance of Tn in a healthy cell that the immune system makes antibodies against it ('anti-Tn') -a rare instance of an antibody being puposefully manufactured against a 'self' antigen.
One of the first defects to occur in most mutating cells is the loss of the enzyme neccesary to manufacture NANA. Anti-Tn essentially acts as an 'early warning system' to help tag and identify early stage mutations, thus proving the adage that 'we make cancer cells every day of our lives, except we normally kill them before they can become a problem.'
Studies have shown lower levels of anti-Tn antibodies in blood type A individuals (1), probably because the Tn antigen, by being 'A-like,' tends to discourage type A's and AB's from making large or effective ammounts of anti-Tn, since we do not like to make antibodies against things in nature which look like us, or in this case, our blood type.(2)
1. Kurtenkov O, Klaamas K, Miljukhina L. The lower level of natural anti-Thomsen-Friedenreich antigen (TFA) agglutinins in sera of patients with gastric cancer related to ABO(H) blood-group phenotype. Int J Cancer. 1995 Mar 16;60(6):781-5.
2.Springer GF. n epitope (N-acetyl-D-galactosamine alpha-O-serine/threonine) density in primary breast carcinoma: a functional predictor of aggressiveness. Mol Immunol. 1989 Jan;26(1):1-5.