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Reference | Study design | Patient characteristics | Immunodiagnostic findings | Graft outcomes | Conclusions/additional comments |
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Muthukumar et al. [49] | Prospective | 83 total pts (36 pts with graft dysfunction and BPAR) | Increased Foxp3 transcripts in urinary cells in pts with BPAR | Better kidney function and lower risk of graft failure in pts with BPAR and higher levels of Foxp3 transcripts | Demonstration of potential role of the measurement of Foxp3 transcripts for diagnosis of rejection and outcomes prediction |
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Wang et al. [50] | Prospective | 10 living-donor transplant pts with BPAR | Increased Foxp3 transcripts in peripheral blood associated with BPAR | | Measurement of Foxp3 transcripts in peripheral blood may aid the immunodiagnosis of rejection in living-donor transplantation/sample size too small to be conclusive, but findings are encouraging |
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Martin et al. [51] | Retrospective | 11 of 17 pts with acute BPAR | | Patients with Foxp3+ infiltrates had better kidney function and lower rates of graft loss at 1-year posttransplantation | Tregs infiltration in graft might correlate with favourable graft outcomes/sample size too small to be conclusive and some patients who lost their graft had evidence of humoral rejection |
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Aquino-Dias et al. [52] | Prospective | 35 pts with DGF (total 48 biopsies: 20 with BPAR and 28 with ATN) | Increased Foxp3 transcripts in kidney tissue, peripheral blood and urinary cells correlated with BPAR when compared to ATN | | Measurement of Foxp3 transcripts may aid the early identification of rejection for pts with DGF |
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Grimbert et al. [53] | Cross-sectional | 26 pts with kidney dysfunction (15 pts with borderline rejection and 11 with type IA acute TCMR) | Higher ratios for the transcripts of Foxp3/granzyme B were found in pts with borderline rejection in comparision with pts with type IA acute TCMR | | Tregs could play a protective role ameliorating inflammation and preventing the progression to frank rejection |
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Mansour et al. [54] | Retrospective | 46 pts with borderline rejection | Increased Foxp3 transcripts in pts with stable creatinine compared to pts who progressed to BPAR | No difference found in kidney function at 2 years in both pts with treated BPAR and pts with stable creatinine | Measurement of Foxp3 transcripts may have prognostic value in borderline rejection |
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Bestard et al. [56] | Retrospective | 37 pts with SCR from 170 protocol biopsies | Fewer Tregs were observed in pts on ciclosporin | The presence of Treg infiltrates correlated with better graft function at 2- and 3-years posttransplantation | Presence of Tregs infiltration could prevent the progression from SCR to clinical rejection |
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Bestard et al. [18] | Retrospective | 37 pts with SCR | Number of infiltrating Tregs in pts with SCR correlated with Foxp3 demethylation at the Treg-specific demethylation region | The presence of Treg infiltrates correlated with better graft function and survival up to 5-year posttransplantation | Presence of Tregs infiltration in rejection associates with better graft outcomes/the Banff classification alone is insufficient for immunodiagnosis and prognostication purposes |
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Xu et al. [57] | Retrospective | 125 pts with protocol biopsies with presence of T cell infiltrates (14 with SCR, 32 with borderline rejection, 79 with no rejection) | Higher ratios for the transcripts of Foxp3/granzyme B correlated with lower risk for rejection | Higher ratios for the transcripts of Foxp3/granzyme B predicted better kidney function and graft survival up to 5-year posttransplantation | Tregs could play a protective role reducing rejection risk and improving graft outcomes/unable to provide conclusions for pts without T cell infiltrates |
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Zuber et al. [58] | Retrospective | 67 pts (34 with acute TCMR, 33 with chronic TCMR) | Higher number and ratio of Tregs over total T cells were observed in patients with chronic rejection than with acute rejection | The greater the Treg infiltrate in inflamed scarred areas, the better the graft survival | Tregs might be protective in chronic rejection |
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