High transforming growth factor-beta and extracellular matrix mRNA response in renal allografts during early acute rejection is associated with absence of chronic rejection.
BACKGROUND
A case-control study was performed to investigate whether mRNA levels of transforming growth factor-beta (TGF-beta) and various extracellular matrix molecules in renal transplant biopsy specimens, taken during acute rejection episodes within 6 months of transplantation, discriminate between patients who show deterioration of graft function and develop chronic rejection (CR+ group), and those who do not develop chronic rejection (CR- group).


METHODS
Patients in both the CR+ group (n=10) and the CR- group (n=18) had at least one biopsy-proven acute rejection episode within the first 6 months after transplantation. The two groups were similar with respect to donor-, recipient-, and transplantation-related clinical variables. Histologic changes (Banff classification) and the timing of the acute rejection episodes in the biopsies studied did not differ between groups. Renal cortical mRNA levels of TGF-beta1, collagen alpha1(IV), collagen alpha1(I), decorin, and the household gene glyceraldehyde-3-phosphate dehydrogenase in biopsy specimens taken during acute rejection episodes were quantified by real-time polymerase chain reaction.


RESULTS
The mean TGF-beta mRNA level in the CR- group was 3.4 times higher than that in the CR+ group (P<0.04). The mean collagen IV, collagen I, and decorin mRNA levels in the CR- group were 4.2 times (P<0.05), 5.1 times (not significant), and 3.2 times (P<0.05) higher, respectively, than those in the CR+ group. The mean TGF-beta to decorin mRNA ratios between the two patient groups did not differ significantly.


CONCLUSIONS
In summary, high mRNA levels for TGF-beta, collagen IV, and decorin, but not histopathologic changes, in biopsies taken during acute rejection episodes early after kidney transplantation are associated with absence of chronic rejection. We hypothesize that TGF-beta might have beneficial effects during acute rejection through its known antiinflammatory actions or as an inducer of tissue repair.
Eikmans
Michael
M
Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands. M.Eikmans@LUMC.NL
Sijpkens
Yvo W J
YW
Baelde
Hans J
HJ
de Heer
Emile
E
Paul
Leendert C
LC
Bruijn
Jan A
JA
D000208:Acute Disease; D000328:Adult; D016022:Case-Control Studies; D002908:Chronic Disease; D003094:Collagen / Q000235:genetics; D058575:Decorin; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D006084:Graft Rejection / Q000473:pathology*; D006650:Histocompatibility Testing; D006801:Humans; D007677:Kidney Function Tests; D016030:Kidney Transplantation / Q000276:immunology / Q000473:pathology / Q000502:physiology*; D016133:Polymerase Chain Reaction; D011509:Proteoglycans / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D012189:Retrospective Studies; D014158:Transcription, Genetic; D016212:Transforming Growth Factor beta / Q000235:genetics*
C546878:DCN protein, human; D058575:Decorin; D016326:Extracellular Matrix Proteins; D011509:Proteoglycans; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D003094:Collagen