TGF-beta expression in renal transplant biopsies: a comparative study between cyclosporin-A and tacrolimus.
BACKGROUND
Chronic rejection is a major cause of graft dysfunction after kidney transplantation. This fibroproliferative disease may be promoted by overproduction of transforming growth factor beta (TGF-beta). Previous studies have suggested that CsA might increase production of this growth factor. The current study was designed to measure the expression of TGF-beta(b) in renal transplant biopsy specimens from patients undergoing immunosuppressive therapy with either CsA or tacrolimus (FK506).


METHODS
Paraffin-embedded renal biopsy specimens were sectioned, dewaxed, and incubated with primary antibody against TGF-beta(b)1 latency-associated protein and active TGF-beta(b1). After washing, the sections were treated with secondary antibody conjugated with FITC. In each case, the sections were assessed by semi-quantitative scanning laser confocal microscopic method.


RESULTS
There was no significant difference in latent TGF-beta(b) expression between biopsy specimens from patients receiving CsA and patients receiving FK506. However, biopsy specimens from patients receiving CsA expressed significantly more active TGF-beta(b1) than biopsy specimens from patients receiving FK506 (P<0.0001, Mann-Whitney test).


CONCLUSIONS
The increased level of active TGF-beta1 expression in renal biopsy specimens of patients receiving CsA may indicate a mechanism of chronic rejection. However, these biopsies were performed to assess deranged renal function; therefore, the specimens may reflect events rather than differences in medication.
Mohamed
M A
MA
Department of Surgery, University of Newcastle, Newcastle Upon Tyne, UK. M.A.S.Mohamed@ncl.ac.uk
Robertson
H
H
Booth
T A
TA
Balupuri
S
S
Kirby
J A
JA
Talbot
D
D
D001706:Biopsy; D016572:Cyclosporine / Q000627:therapeutic use; D005455:Fluorescent Antibody Technique; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007668:Kidney / Q000378:metabolism* / Q000473:pathology; D016030:Kidney Transplantation; D018613:Microscopy, Confocal; D010446:Peptide Fragments; D011498:Protein Precursors; D011506:Proteins / Q000378:metabolism; D016559:Tacrolimus / Q000627:therapeutic use; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D053773:Transforming Growth Factor beta1
D007166:Immunosuppressive Agents; D010446:Peptide Fragments; D011498:Protein Precursors; D011506:Proteins; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D016572:Cyclosporine; D016559:Tacrolimus