ORFeome-based identification of biomarkers for serodiagnosis of Mycobacterium tuberculosis latent infection
Abstract Background The challenges posed by Mycobacterium tuberculosis infection require the gradual removal of the pool of latent tuberculosis infection (LTBI). The current cell-immune-based diagnostic tests used to identify LTBI individuals have several irreversible drawbacks. In the present study...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2017-12-01
|
| Series: | BMC Infectious Diseases |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12879-017-2910-y |
| _version_ | 1828791804142551040 |
|---|---|
| author | Fangbin Zhou Xindong Xu Sijia Wu Xiaobing Cui Weiqing Pan |
| author_facet | Fangbin Zhou Xindong Xu Sijia Wu Xiaobing Cui Weiqing Pan |
| author_sort | Fangbin Zhou |
| collection | DOAJ |
| description | Abstract Background The challenges posed by Mycobacterium tuberculosis infection require the gradual removal of the pool of latent tuberculosis infection (LTBI). The current cell-immune-based diagnostic tests used to identify LTBI individuals have several irreversible drawbacks. In the present study, we attempted to identify novel diagnostic antigens for LTBI. Methods A high-throughput glutathione S-transferase (GST)-fusion technology was used to express over 409 TB proteins and sera from LTBI and healthy individuals was used to interrogate these GST-TB fusion proteins. Results Of 409 TB proteins, sixty-three reacted seropositive and defined the immuno-ORFeome of latent M. tuberculosis. Within the immuno-ORFeome, the rare targets were predominantly latency-associated proteins and secreted proteins, while the preferentially recognized antigens tended to be transmembrane proteins. Six of novel highly-reactive antigens had the potential to distinguish LTBI from active TB and healthy individuals. A multiple-antigen combination set was selected through analysis of various combinations. A panel of 94 archived serum samples was used to validate the diagnostic performance of the multiple-antigen combination set, which had sensitivity of 66.1% (95% CI 52.9, 77.4) and specificity of 87.5% (95% CI 70.1, 95.1). Conclusion These results provide experimental evidence of the immunogenicity of novel TB proteins that are suitable for the development of serodiagnostic tools for LTBI. |
| first_indexed | 2024-12-12T02:57:11Z |
| format | Article |
| id | doaj.art-f34bc1a8fa444eb4b8e5515c3c416aa0 |
| institution | Directory Open Access Journal |
| issn | 1471-2334 |
| language | English |
| last_indexed | 2024-12-12T02:57:11Z |
| publishDate | 2017-12-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Infectious Diseases |
| spelling | doaj.art-f34bc1a8fa444eb4b8e5515c3c416aa02022-12-22T00:40:42ZengBMCBMC Infectious Diseases1471-23342017-12-011711810.1186/s12879-017-2910-yORFeome-based identification of biomarkers for serodiagnosis of Mycobacterium tuberculosis latent infectionFangbin Zhou0Xindong Xu1Sijia Wu2Xiaobing Cui3Weiqing Pan4Institute for Infectious Diseases and Vaccine Development, Tongji University School of MedicineInstitute for Infectious Diseases and Vaccine Development, Tongji University School of MedicineInstitute for Infectious Diseases and Vaccine Development, Tongji University School of MedicineInstitute for Infectious Diseases and Vaccine Development, Tongji University School of MedicineInstitute for Infectious Diseases and Vaccine Development, Tongji University School of MedicineAbstract Background The challenges posed by Mycobacterium tuberculosis infection require the gradual removal of the pool of latent tuberculosis infection (LTBI). The current cell-immune-based diagnostic tests used to identify LTBI individuals have several irreversible drawbacks. In the present study, we attempted to identify novel diagnostic antigens for LTBI. Methods A high-throughput glutathione S-transferase (GST)-fusion technology was used to express over 409 TB proteins and sera from LTBI and healthy individuals was used to interrogate these GST-TB fusion proteins. Results Of 409 TB proteins, sixty-three reacted seropositive and defined the immuno-ORFeome of latent M. tuberculosis. Within the immuno-ORFeome, the rare targets were predominantly latency-associated proteins and secreted proteins, while the preferentially recognized antigens tended to be transmembrane proteins. Six of novel highly-reactive antigens had the potential to distinguish LTBI from active TB and healthy individuals. A multiple-antigen combination set was selected through analysis of various combinations. A panel of 94 archived serum samples was used to validate the diagnostic performance of the multiple-antigen combination set, which had sensitivity of 66.1% (95% CI 52.9, 77.4) and specificity of 87.5% (95% CI 70.1, 95.1). Conclusion These results provide experimental evidence of the immunogenicity of novel TB proteins that are suitable for the development of serodiagnostic tools for LTBI.http://link.springer.com/article/10.1186/s12879-017-2910-yMycobacterium tuberculosisLatent TB infectionSerodiagnosisRecombinant GST-TB fusion proteinsSensitivity and specificity |
| spellingShingle | Fangbin Zhou Xindong Xu Sijia Wu Xiaobing Cui Weiqing Pan ORFeome-based identification of biomarkers for serodiagnosis of Mycobacterium tuberculosis latent infection BMC Infectious Diseases Mycobacterium tuberculosis Latent TB infection Serodiagnosis Recombinant GST-TB fusion proteins Sensitivity and specificity |
| title | ORFeome-based identification of biomarkers for serodiagnosis of Mycobacterium tuberculosis latent infection |
| title_full | ORFeome-based identification of biomarkers for serodiagnosis of Mycobacterium tuberculosis latent infection |
| title_fullStr | ORFeome-based identification of biomarkers for serodiagnosis of Mycobacterium tuberculosis latent infection |
| title_full_unstemmed | ORFeome-based identification of biomarkers for serodiagnosis of Mycobacterium tuberculosis latent infection |
| title_short | ORFeome-based identification of biomarkers for serodiagnosis of Mycobacterium tuberculosis latent infection |
| title_sort | orfeome based identification of biomarkers for serodiagnosis of mycobacterium tuberculosis latent infection |
| topic | Mycobacterium tuberculosis Latent TB infection Serodiagnosis Recombinant GST-TB fusion proteins Sensitivity and specificity |
| url | http://link.springer.com/article/10.1186/s12879-017-2910-y |
| work_keys_str_mv | AT fangbinzhou orfeomebasedidentificationofbiomarkersforserodiagnosisofmycobacteriumtuberculosislatentinfection AT xindongxu orfeomebasedidentificationofbiomarkersforserodiagnosisofmycobacteriumtuberculosislatentinfection AT sijiawu orfeomebasedidentificationofbiomarkersforserodiagnosisofmycobacteriumtuberculosislatentinfection AT xiaobingcui orfeomebasedidentificationofbiomarkersforserodiagnosisofmycobacteriumtuberculosislatentinfection AT weiqingpan orfeomebasedidentificationofbiomarkersforserodiagnosisofmycobacteriumtuberculosislatentinfection |