Alternative biomarkers of tuberculosis infection in patients with immune-mediated inflammatory diseases
Copyright © 2023 Petruccioli, Petrone, Najafi-Fard, Navarra, Vanini, Cuzzi, Cantini, Gualano, Palmieri and Goletti..
Introduction: IFN-γ release assays (IGRAs) are one of the referral tests for diagnosing tuberculosis infection (TBI). To improve IGRAs accuracy, several markers have been investigated. Patients with immune-mediated inflammatory diseases (IMID), taking biological drugs, have a higher risk to progress to TB-disease compared to the general population. In several guidelines, annual TBI screening is recommended for patients undergoing biological therapy. Aim of this study was to investigate, within the QuantiFERON-TB-Plus (QFT-Plus) platform, if beside IFN-γ, alternative biomarkers help to diagnose TBI-IMID patients.
Methods: We enrolled 146 subjects: 46 with TB disease, 20 HD, 35 with TBI and 45 with TBI and IMID. Thirteen IMID subjects with a QFT-Plus negative result were diagnosed as TBI based on radiological evidence of TBI. We evaluated the IP-10 level in response to TB1 and TB2 peptides of QFT-Plus assay and we compared these results with the standardized assay based on IFN-γ. Multiplex immune assay was performed on plasma from TB1 and TB2 tubes and results were analyzed by a gradient boosting machine (GBM) as learning technique.
Results: TBI-IMID showed a significant decreased IP-10 level in response to TB1 and TB2 stimulation compared to TBI-NO IMID (p < 0.0001 and p = 0.0002). The TBI-IMID showed a moderate agreement between the IP-10-based assay and QFT-Plus scores. In TBI-IMID, QFT-Plus showed 70% sensitivity for TBI detection whereas the IP-10-based assay reached 61%. Tests combination increased the sensitivity for TBI diagnosis up to 77%. By a GBM, we explored alternative biomarkers for diagnosing TBI in IMID population reaching 89% sensitivity. In particular, the signature based on IL-2, IP-10, and IL-9 detection was associated with TB status (infection/disease). However, by applying the cut-off identified by ROC analysis, comparing TB and TBI with the HD group, within the IMID population, we did not improve the accuracy for TBI-diagnosis. Similarly, this signature did not improve TBI diagnosis in IMID with radiological evidence of TBI but negative QFT-Plus score.
Discussion: To develop alternative strategies for TBI immune-diagnosis, future studies are needed to evaluate the memory response of TBI defined by radiological tools. These results may help in tuberculosis management of patients taking lifelong immune-suppressive drugs.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:10 |
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| Enthalten in: |
Frontiers in medicine - 10(2023) vom: 19., Seite 1271632 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Petruccioli, Elisa [VerfasserIn] |
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| Links: |
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| Themen: |
Diagnosis |
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| Anmerkungen: |
Date Revised 11.12.2023 published: Electronic-eCollection Citation Status PubMed-not-MEDLINE |
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| doi: |
10.3389/fmed.2023.1271632 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM365670502 |
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| 245 | 1 | 0 | |a Alternative biomarkers of tuberculosis infection in patients with immune-mediated inflammatory diseases |
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| 520 | |a Copyright © 2023 Petruccioli, Petrone, Najafi-Fard, Navarra, Vanini, Cuzzi, Cantini, Gualano, Palmieri and Goletti. | ||
| 520 | |a Introduction: IFN-γ release assays (IGRAs) are one of the referral tests for diagnosing tuberculosis infection (TBI). To improve IGRAs accuracy, several markers have been investigated. Patients with immune-mediated inflammatory diseases (IMID), taking biological drugs, have a higher risk to progress to TB-disease compared to the general population. In several guidelines, annual TBI screening is recommended for patients undergoing biological therapy. Aim of this study was to investigate, within the QuantiFERON-TB-Plus (QFT-Plus) platform, if beside IFN-γ, alternative biomarkers help to diagnose TBI-IMID patients | ||
| 520 | |a Methods: We enrolled 146 subjects: 46 with TB disease, 20 HD, 35 with TBI and 45 with TBI and IMID. Thirteen IMID subjects with a QFT-Plus negative result were diagnosed as TBI based on radiological evidence of TBI. We evaluated the IP-10 level in response to TB1 and TB2 peptides of QFT-Plus assay and we compared these results with the standardized assay based on IFN-γ. Multiplex immune assay was performed on plasma from TB1 and TB2 tubes and results were analyzed by a gradient boosting machine (GBM) as learning technique | ||
| 520 | |a Results: TBI-IMID showed a significant decreased IP-10 level in response to TB1 and TB2 stimulation compared to TBI-NO IMID (p < 0.0001 and p = 0.0002). The TBI-IMID showed a moderate agreement between the IP-10-based assay and QFT-Plus scores. In TBI-IMID, QFT-Plus showed 70% sensitivity for TBI detection whereas the IP-10-based assay reached 61%. Tests combination increased the sensitivity for TBI diagnosis up to 77%. By a GBM, we explored alternative biomarkers for diagnosing TBI in IMID population reaching 89% sensitivity. In particular, the signature based on IL-2, IP-10, and IL-9 detection was associated with TB status (infection/disease). However, by applying the cut-off identified by ROC analysis, comparing TB and TBI with the HD group, within the IMID population, we did not improve the accuracy for TBI-diagnosis. Similarly, this signature did not improve TBI diagnosis in IMID with radiological evidence of TBI but negative QFT-Plus score | ||
| 520 | |a Discussion: To develop alternative strategies for TBI immune-diagnosis, future studies are needed to evaluate the memory response of TBI defined by radiological tools. These results may help in tuberculosis management of patients taking lifelong immune-suppressive drugs | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a IFN-γ | |
| 650 | 4 | |a IGRA | |
| 650 | 4 | |a IP-10 | |
| 650 | 4 | |a diagnosis | |
| 650 | 4 | |a latency | |
| 650 | 4 | |a tuberculosis infection | |
| 700 | 1 | |a Petrone, Linda |e verfasserin |4 aut | |
| 700 | 1 | |a Najafi-Fard, Saeid |e verfasserin |4 aut | |
| 700 | 1 | |a Navarra, Assunta |e verfasserin |4 aut | |
| 700 | 1 | |a Vanini, Valentina |e verfasserin |4 aut | |
| 700 | 1 | |a Cuzzi, Gilda |e verfasserin |4 aut | |
| 700 | 1 | |a Cantini, Fabrizio |e verfasserin |4 aut | |
| 700 | 1 | |a Gualano, Gina |e verfasserin |4 aut | |
| 700 | 1 | |a Palmieri, Fabrizio |e verfasserin |4 aut | |
| 700 | 1 | |a Goletti, Delia |e verfasserin |4 aut | |
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