title: Association of human cytomegalovirus DNAaemia and specific granzyme B responses in lung transplant recipients.
abstract: In lung transplant recipients (LTRs), human cytomegalovirus (HCMV) DNAaemia could be associated with HCMV disease and reduced allograft survival. In the present study we analysed whether or not HCMV-specific granzyme B (Grz-B) responses indicating CD8(+) T cell cytotoxicity exert an impact on HCMV DNAaemia and relate to specific interferon (IFN)-γ secretion. HCMV-specific Grz-B responses were quantitated by enzyme-linked immunosorbent assay (ELISA) in 70 samples from 39 HCMV seropositive LTRs who were prospectively investigated for HCMV DNA plasma levels and IFN-γ kinetics using a standardized CD8(+) T cell assay (QuantiFERON®-CMV assay). In all LTRs who were protected from HCMV DNAaemia by early and persistent IFN-γ responses, Grz-B responses were also detected. In LTRs who developed episodes of HCMV DNAaemia, the Grz-B responses which were detected prior to viral DNA detection differed significantly in patients who experienced episodes with high (exceeding 1000 copies/ml) and low plasma DNA levels (P = 0·0290, Fisher's exact test). Furthermore, the extent of Grz-B release prior to viral DNAaemia correlated statistically with the detected levels of IFN-γ (P < 0·0001, Spearman's rank test). Of note, simultaneous detection of Grz-B and IFN-γ secretion was associated significantly with protection from high HCMV DNA plasma levels during the subsequent follow-up (P = 0·0057, Fisher's exact test), and this association was stronger than for IFN-γ detection alone. We conclude that, in addition to IFN-γ responses, Grz-B secretion by CD8(+) T cells is essential to control HCMV replication and a simultaneous measurement of IFN-γ and Grz-B could contribute to the immune monitoring of LTRs.
authors.affiliation: Department of Virology, Medical University of Vienna, Vienna, Austria.
authors.forename: L
authors.initials: L
authors.lastname: Weseslindtner
authors.forename: H
authors.initials: H
authors.lastname: Kerschner
authors.forename: D
authors.initials: D
authors.lastname: Steinacher
authors.forename: M
authors.initials: M
authors.lastname: Kundi
authors.forename: P
authors.initials: P
authors.lastname: Jaksch
authors.forename: B
authors.initials: B
authors.lastname: Simon
authors.forename: L
authors.initials: L
authors.lastname: Hatos-Agyi
authors.forename: A
authors.initials: A
authors.lastname: Scheed
authors.forename: W
authors.initials: W
authors.lastname: Klepetko
authors.forename: E
authors.initials: E
authors.lastname: Puchhammer-Stöckl
mesh_terms: D000328:Adult; D000368:Aged; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D003587:Cytomegalovirus / Q000235:genetics* / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000276:immunology* / Q000821:virology*; D004279:DNA, Viral / Q000097:blood; D005260:Female; D053804:Granzymes / Q000097:blood / Q000378:metabolism*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis / Q000097:blood; D016040:Lung Transplantation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D019562:Viral Load
chemical_list: D004279:DNA, Viral; D007371:Interferon-gamma; D053804:Granzymes
keywords: DNAaemia; HCMV; cytomegalovirus; granzyme B; lung transplant recipients