Characterization of the humoral immune response to the EBV proteome in extranodal NK/T-cell lymphoma
Abstract Extranodal natural killer/T-cell lymphoma (NKTCL) is an aggressive malignancy that has been etiologically linked to Epstein-Barr virus (EBV) infection, with EBV gene transcripts identified in almost all cases. However, the humoral immune response to EBV in NKTCL patients has not been well c...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2021-12-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-021-02788-w |
| _version_ | 1818723476127612928 |
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| author | Zhiwei Liu Yomani D. Sarathkumara John K. C. Chan Yok-Lam Kwong Tai Hing Lam Dennis Kai Ming Ip Brian C.-H. Chiu Jun Xu Yu-Chieh Su Carla Proietti Martha M. Cooper Kelly J. Yu Bryan Bassig Raymond Liang Wei Hu Bu-Tian Ji Anna E. Coghill Ruth M. Pfeiffer Allan Hildesheim Nathaniel Rothman Denise L. Doolan Qing Lan |
| author_facet | Zhiwei Liu Yomani D. Sarathkumara John K. C. Chan Yok-Lam Kwong Tai Hing Lam Dennis Kai Ming Ip Brian C.-H. Chiu Jun Xu Yu-Chieh Su Carla Proietti Martha M. Cooper Kelly J. Yu Bryan Bassig Raymond Liang Wei Hu Bu-Tian Ji Anna E. Coghill Ruth M. Pfeiffer Allan Hildesheim Nathaniel Rothman Denise L. Doolan Qing Lan |
| author_sort | Zhiwei Liu |
| collection | DOAJ |
| description | Abstract Extranodal natural killer/T-cell lymphoma (NKTCL) is an aggressive malignancy that has been etiologically linked to Epstein-Barr virus (EBV) infection, with EBV gene transcripts identified in almost all cases. However, the humoral immune response to EBV in NKTCL patients has not been well characterized. We examined the antibody response to EBV in plasma samples from 51 NKTCL cases and 154 controls from Hong Kong and Taiwan who were part of the multi-center, hospital-based AsiaLymph case–control study. The EBV-directed serological response was characterized using a protein microarray that measured IgG and IgA antibodies against 202 protein sequences representing the entire EBV proteome. We analyzed 157 IgG antibodies and 127 IgA antibodies that fulfilled quality control requirements. Associations between EBV serology and NKTCL status were disproportionately observed for IgG rather than IgA antibodies. Nine anti-EBV IgG responses were significantly elevated in NKTCL cases compared with controls and had ORshighest vs. lowest tertile > 6.0 (Bonferroni-corrected P-values < 0.05). Among these nine elevated IgG responses in NKTCL patients, three IgG antibodies (all targeting EBNA3A) are novel and have not been observed for other EBV-associated tumors of B-cell or epithelial origin. IgG antibodies against EBNA1, which have consistently been elevated in other EBV-associated tumors, were not elevated in NKTCL cases. We characterize the antibody response against EBV for patients with NKTCL and identify IgG antibody responses against six distinct EBV proteins. Our findings suggest distinct serologic patterns of this NK/T-cell lymphoma compared with other EBV-associated tumors of B-cell or epithelial origin. |
| first_indexed | 2024-12-17T21:11:07Z |
| format | Article |
| id | doaj.art-96c0c569af1e43a0b758847bbd7d9102 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-17T21:11:07Z |
| publishDate | 2021-12-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-96c0c569af1e43a0b758847bbd7d91022022-12-21T21:32:28ZengNature PortfolioScientific Reports2045-23222021-12-011111810.1038/s41598-021-02788-wCharacterization of the humoral immune response to the EBV proteome in extranodal NK/T-cell lymphomaZhiwei Liu0Yomani D. Sarathkumara1John K. C. Chan2Yok-Lam Kwong3Tai Hing Lam4Dennis Kai Ming Ip5Brian C.-H. Chiu6Jun Xu7Yu-Chieh Su8Carla Proietti9Martha M. Cooper10Kelly J. Yu11Bryan Bassig12Raymond Liang13Wei Hu14Bu-Tian Ji15Anna E. Coghill16Ruth M. Pfeiffer17Allan Hildesheim18Nathaniel Rothman19Denise L. Doolan20Qing Lan21Division of Cancer Epidemiology and Genetics, 9609 Medical Center Drive, National Cancer InstituteCentre for Molecular Therapeutics, Australian Institute of Tropical Health of Medicine, James Cook UniversityDepartment of Pathology, Queen Elizabeth HospitalQueen Mary Hospital, The University of Hong KongSchool of Public Health, Faculty of Medicine, Li Ka Shing (LKS), The University of Hong KongSchool of Public Health, Faculty of Medicine, Li Ka Shing (LKS), The University of Hong KongDepartment of Public Health Sciences, University of ChicagoSchool of Public Health, Faculty of Medicine, Li Ka Shing (LKS), The University of Hong KongDepartment of Medicine, School of Medicine, I-Shou UniversityCentre for Molecular Therapeutics, Australian Institute of Tropical Health of Medicine, James Cook UniversityCentre for Molecular Therapeutics, Australian Institute of Tropical Health of Medicine, James Cook UniversityDivision of Cancer Epidemiology and Genetics, 9609 Medical Center Drive, National Cancer InstituteDivision of Cancer Epidemiology and Genetics, 9609 Medical Center Drive, National Cancer InstituteHong Kong Sanatorium & HospitalDivision of Cancer Epidemiology and Genetics, 9609 Medical Center Drive, National Cancer InstituteDivision of Cancer Epidemiology and Genetics, 9609 Medical Center Drive, National Cancer InstituteCancer Epidemiology Program, Division of Population Sciences, H. Lee Moffitt Cancer Center and Research InstituteDivision of Cancer Epidemiology and Genetics, 9609 Medical Center Drive, National Cancer InstituteDivision of Cancer Epidemiology and Genetics, 9609 Medical Center Drive, National Cancer InstituteDivision of Cancer Epidemiology and Genetics, 9609 Medical Center Drive, National Cancer InstituteCentre for Molecular Therapeutics, Australian Institute of Tropical Health of Medicine, James Cook UniversityDivision of Cancer Epidemiology and Genetics, 9609 Medical Center Drive, National Cancer InstituteAbstract Extranodal natural killer/T-cell lymphoma (NKTCL) is an aggressive malignancy that has been etiologically linked to Epstein-Barr virus (EBV) infection, with EBV gene transcripts identified in almost all cases. However, the humoral immune response to EBV in NKTCL patients has not been well characterized. We examined the antibody response to EBV in plasma samples from 51 NKTCL cases and 154 controls from Hong Kong and Taiwan who were part of the multi-center, hospital-based AsiaLymph case–control study. The EBV-directed serological response was characterized using a protein microarray that measured IgG and IgA antibodies against 202 protein sequences representing the entire EBV proteome. We analyzed 157 IgG antibodies and 127 IgA antibodies that fulfilled quality control requirements. Associations between EBV serology and NKTCL status were disproportionately observed for IgG rather than IgA antibodies. Nine anti-EBV IgG responses were significantly elevated in NKTCL cases compared with controls and had ORshighest vs. lowest tertile > 6.0 (Bonferroni-corrected P-values < 0.05). Among these nine elevated IgG responses in NKTCL patients, three IgG antibodies (all targeting EBNA3A) are novel and have not been observed for other EBV-associated tumors of B-cell or epithelial origin. IgG antibodies against EBNA1, which have consistently been elevated in other EBV-associated tumors, were not elevated in NKTCL cases. We characterize the antibody response against EBV for patients with NKTCL and identify IgG antibody responses against six distinct EBV proteins. Our findings suggest distinct serologic patterns of this NK/T-cell lymphoma compared with other EBV-associated tumors of B-cell or epithelial origin.https://doi.org/10.1038/s41598-021-02788-w |
| spellingShingle | Zhiwei Liu Yomani D. Sarathkumara John K. C. Chan Yok-Lam Kwong Tai Hing Lam Dennis Kai Ming Ip Brian C.-H. Chiu Jun Xu Yu-Chieh Su Carla Proietti Martha M. Cooper Kelly J. Yu Bryan Bassig Raymond Liang Wei Hu Bu-Tian Ji Anna E. Coghill Ruth M. Pfeiffer Allan Hildesheim Nathaniel Rothman Denise L. Doolan Qing Lan Characterization of the humoral immune response to the EBV proteome in extranodal NK/T-cell lymphoma Scientific Reports |
| title | Characterization of the humoral immune response to the EBV proteome in extranodal NK/T-cell lymphoma |
| title_full | Characterization of the humoral immune response to the EBV proteome in extranodal NK/T-cell lymphoma |
| title_fullStr | Characterization of the humoral immune response to the EBV proteome in extranodal NK/T-cell lymphoma |
| title_full_unstemmed | Characterization of the humoral immune response to the EBV proteome in extranodal NK/T-cell lymphoma |
| title_short | Characterization of the humoral immune response to the EBV proteome in extranodal NK/T-cell lymphoma |
| title_sort | characterization of the humoral immune response to the ebv proteome in extranodal nk t cell lymphoma |
| url | https://doi.org/10.1038/s41598-021-02788-w |
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