Circulatory Inflammatory Proteins as Early Diagnostic Biomarkers for Invasive Aspergillosis in Patients with Hematologic Malignancies-an Exploratory Study
© 2024. The Author(s)..
OBJECTIVES: Invasive aspergillosis (IA) is a major cause of mortality in immunocompromised patients and it is difficult to diagnose because of the lack of reliable highly sensitive diagnostics. We aimed to identify circulating immunological markers that could be useful for an early diagnosis of IA.
METHODS: We collected longitudinally serum samples from 33 cases with probable/proven IA and two matched control cohorts without IA (one with microbiological and clinical evidence of bacterial or viral non-fungal pneumonia and one without evidence of infection, all matched for neutropenia, primary underlying disease, and receipt of corticosteroids/other immunosuppressants) at a tertiary university hospital. In addition, samples from an independent cohort (n = 20 cases of proven/probable IA and 20 matched controls without infection) were obtained. A panel of 92 circulating proteins involved in inflammation was measured by proximity extension assay. A random forest model was used to predict the development of IA using biomarkers measured before diagnosis.
RESULTS: While no significant differences were observed between IA cases and infected controls, concentrations of 30 inflammatory biomarkers were different between cases and non-infected controls, of which nine were independently replicated: PD-L1, MMP-10, Interleukin(IL)-10, IL-15RA, IL-18, IL-18R1, CDCP1, CCL19 and IL-17C. From the differential abundance analysis of serum samples collected more than 10 days before diagnosis and at diagnosis, increased IL-17C concentrations in IA patients were replicated in the independent cohort.
CONCLUSIONS: An increased circulating concentration of IL-17C was detected both in the discovery and independent cohort, both at the time of diagnosis and in samples 10 days before the diagnosis of IA, suggesting it should be evaluated further as potential (early) biomarker of infection.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:189 |
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| Enthalten in: |
Mycopathologia - 189(2024), 2 vom: 26. Feb., Seite 24 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Aerts, Robina [VerfasserIn] |
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| Links: |
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| Themen: |
Antigens, Neoplasm |
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| Anmerkungen: |
Date Completed 27.02.2024 Date Revised 29.02.2024 published: Electronic Citation Status MEDLINE |
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| doi: |
10.1007/s11046-024-00831-8 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM368976432 |
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| 245 | 1 | 0 | |a Circulatory Inflammatory Proteins as Early Diagnostic Biomarkers for Invasive Aspergillosis in Patients with Hematologic Malignancies-an Exploratory Study |
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| 500 | |a Date Completed 27.02.2024 | ||
| 500 | |a Date Revised 29.02.2024 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2024. The Author(s). | ||
| 520 | |a OBJECTIVES: Invasive aspergillosis (IA) is a major cause of mortality in immunocompromised patients and it is difficult to diagnose because of the lack of reliable highly sensitive diagnostics. We aimed to identify circulating immunological markers that could be useful for an early diagnosis of IA | ||
| 520 | |a METHODS: We collected longitudinally serum samples from 33 cases with probable/proven IA and two matched control cohorts without IA (one with microbiological and clinical evidence of bacterial or viral non-fungal pneumonia and one without evidence of infection, all matched for neutropenia, primary underlying disease, and receipt of corticosteroids/other immunosuppressants) at a tertiary university hospital. In addition, samples from an independent cohort (n = 20 cases of proven/probable IA and 20 matched controls without infection) were obtained. A panel of 92 circulating proteins involved in inflammation was measured by proximity extension assay. A random forest model was used to predict the development of IA using biomarkers measured before diagnosis | ||
| 520 | |a RESULTS: While no significant differences were observed between IA cases and infected controls, concentrations of 30 inflammatory biomarkers were different between cases and non-infected controls, of which nine were independently replicated: PD-L1, MMP-10, Interleukin(IL)-10, IL-15RA, IL-18, IL-18R1, CDCP1, CCL19 and IL-17C. From the differential abundance analysis of serum samples collected more than 10 days before diagnosis and at diagnosis, increased IL-17C concentrations in IA patients were replicated in the independent cohort | ||
| 520 | |a CONCLUSIONS: An increased circulating concentration of IL-17C was detected both in the discovery and independent cohort, both at the time of diagnosis and in samples 10 days before the diagnosis of IA, suggesting it should be evaluated further as potential (early) biomarker of infection | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Aspergillosis | |
| 650 | 4 | |a Biomarkers | |
| 650 | 4 | |a IL-17 | |
| 650 | 4 | |a Invasive fungal infections | |
| 650 | 4 | |a Opportunistic infections | |
| 650 | 4 | |a Proteomics | |
| 650 | 7 | |a Interleukin-17 |2 NLM | |
| 650 | 7 | |a CDCP1 protein, human |2 NLM | |
| 650 | 7 | |a Antigens, Neoplasm |2 NLM | |
| 650 | 7 | |a Cell Adhesion Molecules |2 NLM | |
| 700 | 1 | |a Ricaño-Ponce, Isis |e verfasserin |4 aut | |
| 700 | 1 | |a Bruno, Mariolina |e verfasserin |4 aut | |
| 700 | 1 | |a Mercier, Toine |e verfasserin |4 aut | |
| 700 | 1 | |a Rosati, Diletta |e verfasserin |4 aut | |
| 700 | 1 | |a Maertens, Johan |e verfasserin |4 aut | |
| 700 | 1 | |a Kumar, Vinod |e verfasserin |4 aut | |
| 700 | 1 | |a Carvalho, Agostinho |e verfasserin |4 aut | |
| 700 | 1 | |a Netea, Mihai G |e verfasserin |4 aut | |
| 700 | 1 | |a Hoenigl, Martin |e verfasserin |4 aut | |
| 700 | 0 | |a ECMM Immunologic Markers for Treatment Monitoring and Diagnosis in Invasive Mold Infection Working Group Contributors |e verfasserin |4 aut | |
| 700 | 1 | |a Sprute, Rosanne |e investigator |4 oth | |
| 700 | 1 | |a Köhler, Philipp |e investigator |4 oth | |
| 700 | 1 | |a Grothe, Jan |e investigator |4 oth | |
| 700 | 1 | |a Lass-Flörl, Cornelia |e investigator |4 oth | |
| 700 | 1 | |a Garcia-Vidal, Carol |e investigator |4 oth | |
| 700 | 1 | |a Monoz, Patricia |e investigator |4 oth | |
| 700 | 1 | |a Gangneux, Jean-Pierre |e investigator |4 oth | |
| 700 | 1 | |a Giaccobbe, Daniele |e investigator |4 oth | |
| 700 | 1 | |a Mikulska, Malgorzata |e investigator |4 oth | |
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