Delayed NK Cell Reconstitution and Reduced NK Activity Increased the Risks of CMV Disease in Allogeneic-Hematopoietic Stem Cell Transplantation
Cytomegalovirus (CMV) infection has a significant impact in patients after allogeneic hematopoietic stem cell transplantation (HSCT). We investigated natural killer (NK) cell reconstitution and cytotoxic/cytokine production in controlling CMV infection, especially severe CMV disease in HSCT patients...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2020-05-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/21/10/3663 |
| _version_ | 1797567256377425920 |
|---|---|
| author | Ki Hyun Park Ji Hyeong Ryu Hyunjoo Bae Sojeong Yun Joo Hee Jang Kyungja Han Byung Sik Cho Hee-Je Kim Hyeyoung Lee Eun-Jee Oh |
| author_facet | Ki Hyun Park Ji Hyeong Ryu Hyunjoo Bae Sojeong Yun Joo Hee Jang Kyungja Han Byung Sik Cho Hee-Je Kim Hyeyoung Lee Eun-Jee Oh |
| author_sort | Ki Hyun Park |
| collection | DOAJ |
| description | Cytomegalovirus (CMV) infection has a significant impact in patients after allogeneic hematopoietic stem cell transplantation (HSCT). We investigated natural killer (NK) cell reconstitution and cytotoxic/cytokine production in controlling CMV infection, especially severe CMV disease in HSCT patients. Fifty-eight patients with acute myeloid leukemia (AML) who received allo-HSCT were included. We monitored NK reconstitution and NK function at baseline, 30, 60, 90, 120, 150, and 180 days after HSCT, and compared the results in recipients stratified on post-HSCT CMV reactivation (<i>n</i> = 23), non-reactivation (<i>n</i> = 24) versus CMV disease (<i>n</i> = 11) groups. The CMV disease group had a significantly delayed recovery of CD56dim NK cells and expansion of FcRγ-CD3ζ+NK cells started post-HSCT 150 days. Sequential results of NK cytotoxicity, NK cell-mediated antibody-dependent cellular cytotoxicity (NK-ADCC), and NK-Interferon-gamma (NK-IFNγ) production for 180 days demonstrated delayed recovery and decreased levels in the CMV disease group compared with the other groups. The results within 1 month after CMV viremia also showed a significant decrease in NK function in the CMV disease group compared to the CMV reactivation group. It suggests that NK cells’ maturation and cytotoxic/IFNγ production contributes to CMV protection, thereby revealing the NK phenotype and functional NK monitoring as a biomarker for CMV risk prediction, especially CMV disease. |
| first_indexed | 2024-03-10T19:40:10Z |
| format | Article |
| id | doaj.art-de902c5c945241c288f1c6d92f69dbc4 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T19:40:10Z |
| publishDate | 2020-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-de902c5c945241c288f1c6d92f69dbc42023-11-20T01:24:11ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-05-012110366310.3390/ijms21103663Delayed NK Cell Reconstitution and Reduced NK Activity Increased the Risks of CMV Disease in Allogeneic-Hematopoietic Stem Cell TransplantationKi Hyun Park0Ji Hyeong Ryu1Hyunjoo Bae2Sojeong Yun3Joo Hee Jang4Kyungja Han5Byung Sik Cho6Hee-Je Kim7Hyeyoung Lee8Eun-Jee Oh9Department of Biomedicine & Health Sciences, Graduate School, The Catholic University of Korea, Seoul 06591, KoreaDepartment of Laboratory Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, KoreaDepartment of Biomedicine & Health Sciences, Graduate School, The Catholic University of Korea, Seoul 06591, KoreaDepartment of Biomedicine & Health Sciences, Graduate School, The Catholic University of Korea, Seoul 06591, KoreaDepartment of Biomedicine & Health Sciences, Graduate School, The Catholic University of Korea, Seoul 06591, KoreaDepartment of Laboratory Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, KoreaDepartment of Hematology, Catholic Hematology Hospital, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, KoreaDepartment of Hematology, Catholic Hematology Hospital, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, KoreaDepartment of Laboratory Medicine, Catholic Kwandong University International St. Mary’s Hospital, Incheon 22711, KoreaDepartment of Laboratory Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, KoreaCytomegalovirus (CMV) infection has a significant impact in patients after allogeneic hematopoietic stem cell transplantation (HSCT). We investigated natural killer (NK) cell reconstitution and cytotoxic/cytokine production in controlling CMV infection, especially severe CMV disease in HSCT patients. Fifty-eight patients with acute myeloid leukemia (AML) who received allo-HSCT were included. We monitored NK reconstitution and NK function at baseline, 30, 60, 90, 120, 150, and 180 days after HSCT, and compared the results in recipients stratified on post-HSCT CMV reactivation (<i>n</i> = 23), non-reactivation (<i>n</i> = 24) versus CMV disease (<i>n</i> = 11) groups. The CMV disease group had a significantly delayed recovery of CD56dim NK cells and expansion of FcRγ-CD3ζ+NK cells started post-HSCT 150 days. Sequential results of NK cytotoxicity, NK cell-mediated antibody-dependent cellular cytotoxicity (NK-ADCC), and NK-Interferon-gamma (NK-IFNγ) production for 180 days demonstrated delayed recovery and decreased levels in the CMV disease group compared with the other groups. The results within 1 month after CMV viremia also showed a significant decrease in NK function in the CMV disease group compared to the CMV reactivation group. It suggests that NK cells’ maturation and cytotoxic/IFNγ production contributes to CMV protection, thereby revealing the NK phenotype and functional NK monitoring as a biomarker for CMV risk prediction, especially CMV disease.https://www.mdpi.com/1422-0067/21/10/3663cytomegalovirushematopoietic stem cell transplantationacute myeloid leukemiaNK cellsNK cell-mediated antibody-dependent cellular cytotoxicityNK subsets |
| spellingShingle | Ki Hyun Park Ji Hyeong Ryu Hyunjoo Bae Sojeong Yun Joo Hee Jang Kyungja Han Byung Sik Cho Hee-Je Kim Hyeyoung Lee Eun-Jee Oh Delayed NK Cell Reconstitution and Reduced NK Activity Increased the Risks of CMV Disease in Allogeneic-Hematopoietic Stem Cell Transplantation International Journal of Molecular Sciences cytomegalovirus hematopoietic stem cell transplantation acute myeloid leukemia NK cells NK cell-mediated antibody-dependent cellular cytotoxicity NK subsets |
| title | Delayed NK Cell Reconstitution and Reduced NK Activity Increased the Risks of CMV Disease in Allogeneic-Hematopoietic Stem Cell Transplantation |
| title_full | Delayed NK Cell Reconstitution and Reduced NK Activity Increased the Risks of CMV Disease in Allogeneic-Hematopoietic Stem Cell Transplantation |
| title_fullStr | Delayed NK Cell Reconstitution and Reduced NK Activity Increased the Risks of CMV Disease in Allogeneic-Hematopoietic Stem Cell Transplantation |
| title_full_unstemmed | Delayed NK Cell Reconstitution and Reduced NK Activity Increased the Risks of CMV Disease in Allogeneic-Hematopoietic Stem Cell Transplantation |
| title_short | Delayed NK Cell Reconstitution and Reduced NK Activity Increased the Risks of CMV Disease in Allogeneic-Hematopoietic Stem Cell Transplantation |
| title_sort | delayed nk cell reconstitution and reduced nk activity increased the risks of cmv disease in allogeneic hematopoietic stem cell transplantation |
| topic | cytomegalovirus hematopoietic stem cell transplantation acute myeloid leukemia NK cells NK cell-mediated antibody-dependent cellular cytotoxicity NK subsets |
| url | https://www.mdpi.com/1422-0067/21/10/3663 |
| work_keys_str_mv | AT kihyunpark delayednkcellreconstitutionandreducednkactivityincreasedtherisksofcmvdiseaseinallogeneichematopoieticstemcelltransplantation AT jihyeongryu delayednkcellreconstitutionandreducednkactivityincreasedtherisksofcmvdiseaseinallogeneichematopoieticstemcelltransplantation AT hyunjoobae delayednkcellreconstitutionandreducednkactivityincreasedtherisksofcmvdiseaseinallogeneichematopoieticstemcelltransplantation AT sojeongyun delayednkcellreconstitutionandreducednkactivityincreasedtherisksofcmvdiseaseinallogeneichematopoieticstemcelltransplantation AT jooheejang delayednkcellreconstitutionandreducednkactivityincreasedtherisksofcmvdiseaseinallogeneichematopoieticstemcelltransplantation AT kyungjahan delayednkcellreconstitutionandreducednkactivityincreasedtherisksofcmvdiseaseinallogeneichematopoieticstemcelltransplantation AT byungsikcho delayednkcellreconstitutionandreducednkactivityincreasedtherisksofcmvdiseaseinallogeneichematopoieticstemcelltransplantation AT heejekim delayednkcellreconstitutionandreducednkactivityincreasedtherisksofcmvdiseaseinallogeneichematopoieticstemcelltransplantation AT hyeyounglee delayednkcellreconstitutionandreducednkactivityincreasedtherisksofcmvdiseaseinallogeneichematopoieticstemcelltransplantation AT eunjeeoh delayednkcellreconstitutionandreducednkactivityincreasedtherisksofcmvdiseaseinallogeneichematopoieticstemcelltransplantation |