Enhanced serum levels of soluble HLA class I molecules are induced by treatment with recombinant interferon-gamma (IFN-γ)

In order to investigate serum levels of soluble HLA class I antigens after single injection of various doses of recombinant IFN-gamma (rIFN-gamma) and to correlate the changes observed to beta-2-microglobulin serum levels, we studied five patients with metastasizing renal cell carcinoma. Each patient received three treatment cycles of 10, 100 and 500 micrograms rIFN-gamma three times at weekly intervals. The treatment cycles were separated by a therapy-free interval of 2 weeks. The order of dose levels was randomly assigned to each patient. Serum levels of soluble HLA class I proteins were measured by an ELISA in samples drawn immediately before and 4, 24, 48, 72 and 168 h after each administration of rIFN-gamma. Beta-2-microglobulin was assessed in parallel using a commercially available radioimmunoassay. Significant induction of soluble HLA class I protein serum levels was observed after treatment with 100 and 500 micrograms rIFN-gamma. The increments peaked after 2-4 days and remained elevated for up to more than 7 days. A significant correlation between increments of soluble HLA class I proteins and beta-2-microglobulin was observed. We conclude that measurement of soluble HLA serum levels is practical for monitoring induction of HLA class I synthesis in patients treated with rIFN-gamma. The correlation observed between induction of beta-2-microglobulin and soluble HLA class I proteins indicates that measurement of beta-2-microglobulin might be sufficient for the biological response monitoring in clinical studies.