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

2002; Wolters Kluwer; Volume: 73; Issue: 4 Linguagem: Inglês

10.1097/00007890-200202270-00016

1534-6080

Michael Eikmans, Yvo W.J. Sijpkens, Hans J. Baelde, Emile de Heer, Lorna Paul, Jan A. Bruijn,

Renal Transplantation Outcomes and Treatments

Background. A case-control study was performed to investigate whether mRNA levels of transforming growth factor-β (TGF-β) 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-β1, collagen α1(IV), collagen α1(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-β 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-β to decorin mRNA ratios between the two patient groups did not differ significantly. Conclusions. In summary, high mRNA levels for TGF-β, 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-β might have beneficial effects during acute rejection through its known antiinflammatory actions or as an inducer of tissue repair.