DEGLYCOSYLATION OF SERUM VITAMIN-D-3 BINDING-PROTEIN LEADS TO IMMUNOSUPPRESSION IN CANCER-PATIENTS

Serum vitamin D-3-binding protein (Gc protein) can be converted by bet a-galactosidase of B cells and sialidase of T cells to a potent macrop hage activating factor, a protein with N-acetylgalactosamine as the re maining sugar moiety, Thus, Gc protein is the precursor of the macroph age activating factor (MAP), Treatment of Gc protein with immobilized beta-galactosidase and sialidase generates an extremely high titered M AF, Gc-MAF. When peripheral blood monocytes/macrophages of 52 patients bearing various types of cancer were incubated with 100 pg/ml of GcMA F, the monocytes/macrophages of all patients were efficiently activate d, However, the MAF precursor activity of patient plasma Gc protein wa s found to be severely reduced in about 25% of this patient population , About 45% of the patients had moderately reduced MAF precursor activ ities, Loss of the precursor activity was found to be due to deglycosy lation of plasma Gc protein by alpha-N-acetylgalactosaminidase detecte d in the patient's bloodstream, The source of the enzyme appeared to b e cancerous cells, Radiation therapy decreased plasma alpha-N-acetylga lactosaminidase activity with concomitant increase of precursor activi ty, This implies that radiation therapy decreases the number of cancer ous cells capable of secreting alpha-N-acetylgalactosaminidase. Both a lpha-N-acetylgalactosaminidase activity and MAP precursor activity of Gc protein in patient bloodstream can serve as diagnostic and prognost ic indices.