Sequential anti-cytomegalovirus response monitoring may allow prediction of cytomegalovirus reactivation after allogeneic stem cell transplantation.
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...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2012-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3521740?pdf=render |
| _version_ | 1818623731640041472 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Sylvia Borchers |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-16T18:45:44Z |
| format | Article |
| id | doaj.art-bdf6dcdb333545438a14205a09ee30cf |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-16T18:45:44Z |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-bdf6dcdb333545438a14205a09ee30cf2022-12-21T22:20:51ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-01712e5024810.1371/journal.pone.0050248Sequential anti-cytomegalovirus response monitoring may allow prediction of cytomegalovirus reactivation after allogeneic stem cell transplantation.Sylvia BorchersMelanie BremmThomas LehrnbecherElke DammannBrigitte PabstBenno WölkRuth EsserMeral YildizMatthias EderMichael StadlerPeter BaderHans MartinAndrea JarischGisbert SchneiderThomas KlingebielArnold GanserEva M WeissingerUlrike KoehlBACKGROUND: 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.http://europepmc.org/articles/PMC3521740?pdf=render |
| spellingShingle | 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 Sequential anti-cytomegalovirus response monitoring may allow prediction of cytomegalovirus reactivation after allogeneic stem cell transplantation. PLoS ONE |
| title | Sequential anti-cytomegalovirus response monitoring may allow prediction of cytomegalovirus reactivation after allogeneic stem cell transplantation. |
| title_full | Sequential anti-cytomegalovirus response monitoring may allow prediction of cytomegalovirus reactivation after allogeneic stem cell transplantation. |
| title_fullStr | Sequential anti-cytomegalovirus response monitoring may allow prediction of cytomegalovirus reactivation after allogeneic stem cell transplantation. |
| title_full_unstemmed | Sequential anti-cytomegalovirus response monitoring may allow prediction of cytomegalovirus reactivation after allogeneic stem cell transplantation. |
| title_short | Sequential anti-cytomegalovirus response monitoring may allow prediction of cytomegalovirus reactivation after allogeneic stem cell transplantation. |
| title_sort | sequential anti cytomegalovirus response monitoring may allow prediction of cytomegalovirus reactivation after allogeneic stem cell transplantation |
| url | http://europepmc.org/articles/PMC3521740?pdf=render |
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