Epitopes described in "Sequential anti-cytomegalovirus response monitoring may allow prediction of cytomegalovirus reactivation after allogeneic stem cell transplantation."

Article Authors:Sylvia Borchers; Melanie Bremm; Thomas Lehrnbecher; Elke Dammann; Brigitte Pabst; Benno Wölk; Ruth Esser; Meral Yildiz; Matthias Eder; Michael Stadler; Peter Bader; Hans Martin; Andrea Jarisch; Gisbert Schneider; Thomas Klingebiel; Arnold Ganser; Eva M Weissinger; Ulrike Koehl
Article Title:Sequential anti-cytomegalovirus response monitoring may allow prediction of cytomegalovirus reactivation after allogeneic stem cell transplantation.
Reference Detail
Reference ID:1025397
Abstract:BACKGROUND: Reconstitution of cytomegalovirus-specific CD3(+)CD8(+) T cells (CMV-CTLs) after allogeneic hematopoietic stem cell transplantation (HSCT) is necessary to bring cytomegalovirus (CMV) reactivation under control. However, the parameters determining protective CMV-CTL reconstitution remain unclear to date. DESIGN AND METHODS: In a prospective tri-center study, CMV-CTL reconstitution was analyzed in the peripheral blood from 278 patients during the year following HSCT using 7 commercially available tetrameric HLA-CMV epitope complexes. All patients included could be monitored with at least CMV-specific tetramer. RESULTS: CMV-CTL reconstitution was detected in 198 patients (71%) after allogeneic HSCT. Most importantly, reconstitution with 1 CMV-CTL per µl blood between day +50 and day +75 post-HSCT discriminated between patients with and without CMV reactivation in the R+/D+ patient group, independent of the CMV-epitope recognized. In addition, CMV-CTLs expanded more daramtaically in patients experiencing only one CMV-reactivation than those without or those with multiple CMV reactivations. Monitoring using at least 2 tetramers was possible in 63% (n = 176) of the patients. The combinations of particular HLA molecules influenced the numbers of CMV-CTLs detected. The highest CMV-CTL count obtained for an individual tetramer also changed over time in 11% of these patients (n = 19) resulting in higher levels of HLA-B*0801 (IE-1) recognizing CMV-CTLs in 14 patients. CONCLUSIONS: Our results indicate that 1 CMV-CTL per µl blood between day +50 to +75 marks the beginning of an immune response against CMV in the R+/D+ group. Detection of CMV-CTL expansion thereafter indicates successful resolution of the CMV reactivation. Thus, sequential monitoring of CMV-CTL reconstitution can be used to predict patients at risk for recurrent CMV reactivation.
Affiliations:Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany.
Reference Type:Literature
PubMed ID:23272059
Journal:PLoS One
Journal Volume:7
Article Pages:e50248
Journal ISSN:1932-6203
Article Chemical List:Antigens, CD3;Epitopes
Article MeSH List:Adolescent; Adult; Aged; Antigens, CD3(biosynthesis); CD8-Positive T-Lymphocytes(cytology); Child; Child, Preschool; Cytomegalovirus(metabolism); Cytomegalovirus Infections(diagnosis; metabolism); Epitopes(chemistry); Female; Flow Cytometry(methods); Hematopoietic Stem Cell Transplantation(methods); Humans; Infant; Kinetics; Male; Middle Aged; Prospective Studies; Risk; Transplantation, Homologous(methods)
Article Comments:ErratumIn(PLoS One. 2013;8(4). doi: 10.1371/annotation/43e9b84c-fbe3-4b39-88c8-1cde34b0afea )
Curation Last Updated:2015-06-05 03:49:19