Serine proteinase inhibitor-9, an endogenous blocker of granzyme B/perforin lytic pathway, is hyperexpressed during acute rejection of renal allografts

Transplantation. 2003 May 15;75(9):1565-70. doi: 10.1097/01.TP.0000058230.91518.2F.


Background: Serine proteinase inhibitor (PI)-9 with a reactive center P1 (Glu)-P1' is a natural antagonist of granzyme B and is expressed in high levels in cytotoxic T lymphocytes (CTL). In view of the role of CTL in acute rejection, we explored the hypothesis that PI-9 would be hyperexpressed during acute rejection. Because PI-9 can protect CTL from its own fatal arsenal and potentially enhance the vitality of CTL, we examined whether PI-9 levels correlate with the severity of rejection as well as predict subsequent graft function.

Methods: We obtained 95 urine specimens from 87 renal allograft recipients. RNA was isolated from the urinary cells and mRNA encoding PI-9, granzyme B, or perforin and a constitutively expressed 18S rRNA was measured with the use of real-time quantitative polymerase chain reaction assay, and the level of expression was correlated with allograft status.

Results: The levels of PI-9 (P=0.001), granzyme B (P<0.0001), and perforin mRNAs (P<0.0001), but not the levels of 18S rRNA (P=0.54), were higher in the urinary cells from the 29 patients with a biopsy-confirmed acute rejection than in the 58 recipients without acute rejection. PI-9 levels were significantly higher in patients with type II or higher acute rejection changes compared with those with less than type II changes (P=0.01). Furthermore, PI-9 levels predicted subsequent graft function (r=0.43, P=0.01).

Conclusions: PI-9 mRNA levels in urinary cells are diagnostic of acute rejection, predict renal allograft histology grade, and predict functional outcome following an acute rejection episode.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acute Disease
  • Adult
  • Aged
  • Female
  • Graft Rejection / metabolism*
  • Granzymes
  • Humans
  • Kidney Transplantation / immunology*
  • Male
  • Membrane Glycoproteins / antagonists & inhibitors*
  • Membrane Glycoproteins / genetics
  • Middle Aged
  • Perforin
  • Pore Forming Cytotoxic Proteins
  • RNA, Messenger / analysis
  • Serine Endopeptidases* / genetics
  • Serpins / biosynthesis*
  • Serpins / genetics
  • T-Lymphocytes, Cytotoxic / immunology
  • Transplantation, Homologous


  • Membrane Glycoproteins
  • Pore Forming Cytotoxic Proteins
  • RNA, Messenger
  • SERPINB9 protein, human
  • Serpins
  • Perforin
  • GZMB protein, human
  • Granzymes
  • Serine Endopeptidases