Enhanced serum levels of soluble HLA class I molecules are induced by treatment with recombinant interferon-gamma (IFN-gamma).
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.
Third Department of Medicine, Johannes Gutenberg University, Mainz, Germany.
W E
WE
Aulitzky
H
H
Grosse-Wilde
U
U
Westhoff
H
H
Tilg
W
W
Aulitzky
G
G
Gastl
M
M
Herold
C
C
Huber
D002292:Carcinoma, Renal Cell / Q000628:therapy; D004305:Dose-Response Relationship, Drug; D004341:Drug Evaluation; D015395:Histocompatibility Antigens Class I / Q000097:blood* / Q000737:chemistry; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins; D012995:Solubility; D001613:beta 2-Microglobulin / Q000737:chemistry / Q000378:metabolism
D015395:Histocompatibility Antigens Class I; D011994:Recombinant Proteins; D001613:beta 2-Microglobulin; D007371:Interferon-gamma