In 1973 a new antigen was reported that occurred in 5% of Indians from Bombay. Two
years later, Dr. Giles reported the Salis serum which contained an antibody to a high
frequency antigen that was antithetical to Ina, thus, it was
named Inb. A higher frequency of Ina
has been found in some Arabs (10-12%). Both of the Indian antigens can be suppressed by
the In(Lu) gene (LU). In addition, the
null phenotype, ie. "In(a-b-)", has been reported in a patient diagnosed with
congenital dyserythropoietic anemia. In this case there appears to be a silent allele
present (no protein is produced) but the exact molecular basis for this is unknown at this
time.
The gene for Indian is located on chromosome 11p13 and is named CD44.
CD44 is a 80,000 molecular weight glycoprotein that is found on many cells including white
blood cells, brain, breast, heart, kidney, liver, lungs and skin to name a few. It is
believed to be important in "lymphocyte homing". A point mutation at bp position
252 is responsible for the Indian antigens. The Ina antigen has
proline at amino acid 26 while Inb has arginine. Preliminary
data suggest that the antigen AnWj may also be carried on CD44 and that this antigen may
soon be assigned to the IN system.
Although originally investigated as a serological problem, the IN/CD44 protein is of
considerable importance in cancer. Alternative forms or sizes of the CD44 mRNA may be
produced and are called isoforms. In certain types of cancer, eg. melanoma and colonic
carcinoma, there is an over-expression of some CD44 isoforms. Thus, detection of these
alternate forms is currently under investigation as a means for early detection of some
cancers as well as new therapies for cancer.