High transforming growth factor-?? and extracellular matrix mRNA response in renal allografts during early acute rejection is associated with absence of chronic rejection1

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.