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.