The Granzyme B Inhibitor SERPINB9 (Protease Inhibitor 9) Circulates in Blood and Increases on Primary Cytomegalovirus Infection after Renal Transplantation

Rowshani, Ajda T.
Strik, Merel C. M.
Molenaar, Rosalie
Yong, Si-La
Wolbink, Angela M.
Bemelman, Frederike J.
Hack, Erik C.
ten Berge, Ineke J. M.

Divisions of
¹Clinical Immunology and Rheumatology and
²Nephrology, Department of Internal Medicine, and
³Department of Experimental Immunology, Academic Medical Center,
⁴Department of Immunopathology, Sanquin Research at the Central Laboratory Bloodbank, and
⁵Department of Clinical Chemistry, Free University Medical Center, Amsterdam, The Netherlands

Reprints or correspondence: Dr. Ajda T. Rowshani, Academic Medical Center, University of Amsterdam, Div. of Clinical Immunology and Rheumatology, Dept. of Internal Medicine, PO Box 22700, 1100 DE Amsterdam, The Netherlands ([email protected]).

Received 6 March 2005; revised 30 May 2005; accepted 20 June 2005.

Potential conflicts of interest: none reported.

Financial support: Academic Medical Center, University of Amsterdam.

Journal of Infectious Diseases 192(11):p 1908-1911, December 1, 2005. | DOI: 10.1086/497606

SERPINB9 is the only known human intracellular inhibitor of granzyme B (GrB), the effector molecule in immunity against cytomegalovirus (CMV) and in renal allograft rejection. Therefore, using specific enzyme-linked immunosorbent assays, we addressed the presence of circulating SERPINB9 during primary CMV infection, subclinical rejection, acute rejection, and uncomplicated posttransplantation course. Soluble (s) SERPINB9 circulates in blood and increases on primary CMV infection. This increase was significantly higher in symptomatic than in asymptomatic patients. In contrast, sSERPINB9 levels did not change in response to subclinical or acute rejection. We demonstrated the presence of circulating sSERPINB9/sGrB complexes, which suggests that SERPINB9 has extracellular functions as well.