Cytotoxic effector molecule gene expression in acute renal allograft rejection: correlation with clinical outcome; histopathology and function of the allograft.
BACKGROUND
Cytotoxic effector molecule expression in human renal allograft biopsies has been closely associated with acute rejection. Here we studied whether intragraft expression of perforin, granzyme B, and Fas ligand correlates with long-term clinical outcome of acute rejection episodes. Furthermore, we examined the relation to histopathology and function of the allograft during rejection.


METHODS
Twenty-two human renal biopsies were quantified for mRNA expression of perforin, granzyme B, Fas ligand, and Fas with reverse transcription-polymerase chain reaction. Expression levels were correlated with clinical outcome after 12 months, Banff rejection grades, and allograft function in the course of acute rejection.


RESULTS
Only Fas ligand, but not perforin or granzyme B, showed significantly higher up-regulation in seven samples with therapy-resistant acute rejections versus eight samples with therapy-sensitive acute rejection. We found no relation between cytotoxic marker expression and Banff rejection grades or serum creatinine peak levels.


CONCLUSIONS
Fas ligand may be useful as an early marker of therapy-resistant acute rejection. Cells that express Fas ligand but not classical soluble cytotoxic molecules might influence clinical outcome of acute rejection episodes.
Nickel
P
P
Institute of Medical Immunology, Charité-Campus Mitte, Charité-Medical School of Humboldt-University of Berlin, D-10098 Berlin, Germany.
Lacha
J
J
Ode-Hakim
S
S
Sawitzki
B
B
Babel
N
N
Frei
U
U
Volk
H D
HD
Reinke
P
P
D000208:Acute Disease; D003404:Creatinine / Q000097:blood; D004351:Drug Resistance; D015870:Gene Expression; D006084:Graft Rejection / Q000097:blood / Q000235:genetics* / Q000473:pathology; D053804:Granzymes; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007668:Kidney / Q000473:pathology; D016030:Kidney Transplantation; D008562:Membrane Glycoproteins / Q000235:genetics; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D012697:Serine Endopeptidases / Q000235:genetics; D014184:Transplantation, Homologous; D015854:Up-Regulation; D019014:fas Receptor / Q000235:genetics*
D007166:Immunosuppressive Agents; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D019014:fas Receptor; D054353:Perforin; D003404:Creatinine; C509213:GZMB protein, human; D053804:Granzymes; D012697:Serine Endopeptidases