The granzyme B inhibitor SERPINB9 (protease inhibitor 9) circulates in blood and increases on primary cytomegalovirus infection after renal transplantation.
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.
Rowshani
Ajda T
AT
Division of Clinical Immunology and Rheumatology, Department of Internal Medicine, Academic Medical Center, Amsterdam, The Netherlands. t.rowshani@amc.uva.nl
Strik
Merel C M
MC
Molenaar
Rosalie
R
Yong
Si-La
SL
Wolbink
Angela M
AM
Bemelman
Frederike J
FJ
Hack
C Erik
CE
Ten Berge
Ineke J M
IJ
D000328:Adult; D000368:Aged; D003587:Cytomegalovirus / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology; D003586:Cytomegalovirus Infections / Q000097:blood* / Q000503:physiopathology / Q000821:virology; D004279:DNA, Viral / Q000097:blood; D005260:Female; D006084:Graft Rejection; D053804:Granzymes; D006801:Humans; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D012697:Serine Endopeptidases / Q000378:metabolism*; D015843:Serpins / Q000097:blood* / Q000378:metabolism
D004279:DNA, Viral; C102316:SERPINB9 protein, human; D015843:Serpins; C509213:GZMB protein, human; D053804:Granzymes; D012697:Serine Endopeptidases