Soluble NKG2D ligands in hepatic autoimmune diseases and in benign diseases involved in marker metabolism.
BACKGROUND
Proteolytic shedding of the immunostimulatory NKG2D ligands MICA and MICB from cancer cells constitutes a novel immune escape strategy that diminishes antitumor reactivity by NKG2D-bearing cytotoxic lymphocytes. In consequence, serum levels of soluble MICA and MICB are frequently found to be elevated in cancer disease.


METHODS
As the diagnostic potential depends strongly on the organ-specific benign diseases and is affected by diseases involved in marker metabolism, both markers were analyzed by ELISA in sera of 141 patients with hepatic autoimmune diseases (34 autoimmune hepatitis, 35 primary sclerosing cholangitis, 72 primary biliary cirrhosis), 18 patients with acute bacterial infections, 21 patients with renal insufficiency, 13 patients with cholestasis and 62 healthy individuals.


RESULTS
Similarly to healthy controls (median sMICA < 30 pg/mL; sMICB < 30 pg/mL), low levels of both markers were generally found in sera of patients with hepatic autoimmune diseases. In contrast, significantly elevated concentrations of sMICA and sMICB were observed in sera of patients with acute infections (median sMICA 890 pg/mL; sMICB 111 pg/mL), in those with renal insufficiency (sMICA 195 pg/mL; sMICB 50 pg/mL), and in those with cholestasis (sMICA 1058 pg/mL; sMICB 146 pg/mL).


CONCLUSIONS
While hepatic autoimmune diseases have no general impact on the amount of circulating sMICA and sMICB, acute bacterial infections, renal insufficiency and cholestasis can lead to notably elevated serum levels of the NKG2D ligands.
Holdenrieder
Stefan
S
Institute of Clinical Chemistry, University Hospital of Munich, 81377 Munich, Germany. Stefan.Holdenrieder@med.uni-muenchen.de
Eichhorn
Peter
P
Beuers
Ulrich
U
Samtleben
Walter
W
Stieber
Petra
P
Nagel
Dorothea
D
Peterfi
Andrea
A
Steinle
Alexander
A
Salih
Helmut Rainer
HR
D001327:Autoimmune Diseases / Q000097:blood*; D015415:Biomarkers / Q000097:blood*; D004797:Enzyme-Linked Immunosorbent Assay; D015395:Histocompatibility Antigens Class I / Q000097:blood*; D006801:Humans; D008024:Ligands; D008107:Liver Diseases / Q000097:blood* / Q000175:diagnosis; D055655:NK Cell Lectin-Like Receptor Subfamily K; D011971:Receptors, Immunologic / Q000378:metabolism; D055607:Receptors, Natural Killer Cell
D015415:Biomarkers; D015395:Histocompatibility Antigens Class I; C527085:KLRK1 protein, human; D008024:Ligands; D055655:NK Cell Lectin-Like Receptor Subfamily K; D011971:Receptors, Immunologic; D055607:Receptors, Natural Killer Cell