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Serine Proteinase inhibitor-9, an Endogenous Blocker of Granzyme B/perforin Lytic Pathway, Is Hyperexpressed During Acute Rejection of Renal Allografts

Serine Proteinase inhibitor-9, an Endogenous Blocker of Granzyme B/perforin Lytic Pathway, Is Hyperexpressed During Acute Rejection of Renal Allografts

Thangamani Muthukumar, Ruchuang Ding, Darshana Dadhania, Mara Medeiros, Baogui Li, Vijay K Sharma, Choli Hartono, David Serur, Surya V Seshan, Hans-Dieter Volk, Petra Reinke, Sandip Kapur, Manikkam Suthanthiran

Transplantation. 2003 May 15;75(9):1565-70.

PMID: 12792516

Abstract:

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP1622426134	Serine Hydrolase Inhibitor-9		1622426-13-4	Price

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