Background and Objectives: Inflammatory interstitial fibrosis and tubular atrophy (i-IFTA) is an inflammation in the area of tubular atrophy and fibrosis. i-IFTA is poorly associated with graft outcome and associated with infiltration of inflammatory mononuclear cells. A cytotoxic T cell is a granzyme B
+CD8
+CD3
+ T cell, mainly secret granzyme B. Granzyme B is a serine protease that may mediate allograft injury and inflammatory interstitial fibrosis and tubular atrophy (i-IFTA). However, there is no report identifying the association of granzyme B with i-IFTA after a long post-transplant interval.
Material and Methods: In this study, we have measured the cytotoxic T-cell frequency with flow cytometry, serum and PBMCs culture supernatants granzyme-B levels with ELISA and intragraft granzyme-B mRNA transcript expression with the RT-PCR in RTRs in 30 patients with biopsy-proven i-IFTA and 10 patients with stable graft function.
Result: The frequency of cytotoxic T cells (CD3
+CD8
+ granzyme B
+) in SGF vs. i-IFTA was (27.96 ± 4.86 vs. 23.19 ± 3.85%,
p = 0.011), the serum granzyme-B level was (100.82 ± 22.41 vs. 130.32 ± 46.60,
p = 0.038 pg/mL) and the intragraft granzyme-B mRNA transcript expression was (1.01 ± 0.048 vs. 2.10 ± 1.02,
p < 0.001 fold). The frequency of CD3
+ T cells in SGF vs. i-IFTA was (66.08 ± 6.8 vs. 65.18 ± 9.35%;
p = 0.68) and that of CD3
+CD8
+ T cells was (37.29 ± 4.11 vs. 34.68 ± 5.43%;
p = 0.28), which were similar between the 2 groups. CTLc frequency was negatively correlated with urine proteinuria (r = −0.51,
p < 0.001), serum creatinine (r = −0.28,
p = 0.007) and eGFR (r = −0.28,
p = 0.037). Similarly, the PBMC culture supernatants granzyme-B level was negatively correlated with urine proteinuria (r = −0.37,
p < 0.001) and serum creatinine (r = −0.31,
p = 0.002), while the serum granzyme-B level (r = 0.343,
p = 0.001) and intragraft granzyme-B mRNA transcript expression (r = 0.38,
p < 0.001) were positively correlated with proteinuria.
Conclusions: A decrease in the CTLc frequency in circulation and an increased serum granzyme-B level and intragraft granzyme-B mRNA expression shows that cytotoxic T cells may mediate the allograft injury in RTRs with i-IFTA by releasing granzyme B in serum and intragraft tissue.
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