Molecular Profiling Reveals Characteristic and Decisive Signatures in Patients after Allogeneic Stem Cell Transplantation Suffering from Invasive Pulmonary Aspergillosis
Despite available diagnostic tests and recent advances, diagnosis of pulmonary invasive aspergillosis (IPA) remains challenging. We performed a longitudinal case-control pilot study to identify host-specific, novel, and immune-relevant molecular candidates indicating IPA in patients post allogeneic...
| Main Authors: | , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-02-01
|
| Series: | Journal of Fungi |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2309-608X/8/2/171 |
| _version_ | 1797478907833745408 |
|---|---|
| author | Tamara Zoran Bastian Seelbinder Philip Lewis White Jessica Sarah Price Sabrina Kraus Oliver Kurzai Joerg Linde Antje Häder Claudia Loeffler Goetz Ulrich Grigoleit Hermann Einsele Gianni Panagiotou Juergen Loeffler Sascha Schäuble |
| author_facet | Tamara Zoran Bastian Seelbinder Philip Lewis White Jessica Sarah Price Sabrina Kraus Oliver Kurzai Joerg Linde Antje Häder Claudia Loeffler Goetz Ulrich Grigoleit Hermann Einsele Gianni Panagiotou Juergen Loeffler Sascha Schäuble |
| author_sort | Tamara Zoran |
| collection | DOAJ |
| description | Despite available diagnostic tests and recent advances, diagnosis of pulmonary invasive aspergillosis (IPA) remains challenging. We performed a longitudinal case-control pilot study to identify host-specific, novel, and immune-relevant molecular candidates indicating IPA in patients post allogeneic stem cell transplantation (alloSCT). Supported by differential gene expression analysis of six relevant in vitro studies, we conducted RNA sequencing of three alloSCT patients categorized as probable IPA cases and their matched controls without <i>Aspergillus</i> infection (66 samples in total). We additionally performed immunoassay analysis for all patient samples to gain a multi-omics perspective. Profiling analysis suggested <i>LGALS2</i>, <i>MMP1</i>, IL-8, and caspase-3 as potential host molecular candidates indicating IPA in investigated alloSCT patients. MMP1, IL-8, and caspase-3 were evaluated further in alloSCT patients for their potential to differentiate possible IPA cases and patients suffering from COVID-19-associated pulmonary aspergillosis (CAPA) and appropriate control patients. Possible IPA cases showed differences in IL-8 and caspase-3 serum levels compared with matched controls. Furthermore, we observed significant differences in IL-8 and caspase-3 levels among CAPA patients compared with control patients. With our conceptual work, we demonstrate the potential value of considering the human immune response during <i>Aspergillus</i> infection to identify immune-relevant molecular candidates indicating IPA in alloSCT patients. These human host candidates together with already established fungal biomarkers might improve the accuracy of IPA diagnostic tools. |
| first_indexed | 2024-03-09T21:38:18Z |
| format | Article |
| id | doaj.art-86fbb2e9ff97466fa51d8bb8feb3bb70 |
| institution | Directory Open Access Journal |
| issn | 2309-608X |
| language | English |
| last_indexed | 2024-03-09T21:38:18Z |
| publishDate | 2022-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Fungi |
| spelling | doaj.art-86fbb2e9ff97466fa51d8bb8feb3bb702023-11-23T20:37:57ZengMDPI AGJournal of Fungi2309-608X2022-02-018217110.3390/jof8020171Molecular Profiling Reveals Characteristic and Decisive Signatures in Patients after Allogeneic Stem Cell Transplantation Suffering from Invasive Pulmonary AspergillosisTamara Zoran0Bastian Seelbinder1Philip Lewis White2Jessica Sarah Price3Sabrina Kraus4Oliver Kurzai5Joerg Linde6Antje Häder7Claudia Loeffler8Goetz Ulrich Grigoleit9Hermann Einsele10Gianni Panagiotou11Juergen Loeffler12Sascha Schäuble13Department of Internal Medicine II, University Hospital Wuerzburg, 97080 Wuerzburg, GermanySystems Biology and Bioinformatics Unit, Leibniz Institute for Natural Product Research and Infection Biology—Hans Knoell Institute, 07745 Jena, GermanyPublic Health Wales, Microbiology Cardiff, UHW, Cardiff CF14 4XW, UKPublic Health Wales, Microbiology Cardiff, UHW, Cardiff CF14 4XW, UKDepartment of Internal Medicine II, University Hospital Wuerzburg, 97080 Wuerzburg, GermanyResearch Group Fungal Septomics, Leibniz Institute for Natural Product Research and Infection Biology—Hans Knoell Institute, 07745 Jena, GermanyFriedrich—Loeffler Institute, Institute of Bacterial Infections and Zoonoses, 07743 Jena, GermanyResearch Group Fungal Septomics, Leibniz Institute for Natural Product Research and Infection Biology—Hans Knoell Institute, 07745 Jena, GermanyDepartment of Internal Medicine II, University Hospital Wuerzburg, 97080 Wuerzburg, GermanyDepartment of Internal Medicine II, University Hospital Wuerzburg, 97080 Wuerzburg, GermanyDepartment of Internal Medicine II, University Hospital Wuerzburg, 97080 Wuerzburg, GermanySystems Biology and Bioinformatics Unit, Leibniz Institute for Natural Product Research and Infection Biology—Hans Knoell Institute, 07745 Jena, GermanyDepartment of Internal Medicine II, University Hospital Wuerzburg, 97080 Wuerzburg, GermanySystems Biology and Bioinformatics Unit, Leibniz Institute for Natural Product Research and Infection Biology—Hans Knoell Institute, 07745 Jena, GermanyDespite available diagnostic tests and recent advances, diagnosis of pulmonary invasive aspergillosis (IPA) remains challenging. We performed a longitudinal case-control pilot study to identify host-specific, novel, and immune-relevant molecular candidates indicating IPA in patients post allogeneic stem cell transplantation (alloSCT). Supported by differential gene expression analysis of six relevant in vitro studies, we conducted RNA sequencing of three alloSCT patients categorized as probable IPA cases and their matched controls without <i>Aspergillus</i> infection (66 samples in total). We additionally performed immunoassay analysis for all patient samples to gain a multi-omics perspective. Profiling analysis suggested <i>LGALS2</i>, <i>MMP1</i>, IL-8, and caspase-3 as potential host molecular candidates indicating IPA in investigated alloSCT patients. MMP1, IL-8, and caspase-3 were evaluated further in alloSCT patients for their potential to differentiate possible IPA cases and patients suffering from COVID-19-associated pulmonary aspergillosis (CAPA) and appropriate control patients. Possible IPA cases showed differences in IL-8 and caspase-3 serum levels compared with matched controls. Furthermore, we observed significant differences in IL-8 and caspase-3 levels among CAPA patients compared with control patients. With our conceptual work, we demonstrate the potential value of considering the human immune response during <i>Aspergillus</i> infection to identify immune-relevant molecular candidates indicating IPA in alloSCT patients. These human host candidates together with already established fungal biomarkers might improve the accuracy of IPA diagnostic tools.https://www.mdpi.com/2309-608X/8/2/171host responseinvasive pulmonary aspergillosisalloSCT patientsgalectin-2caspase-3matrix metallopeptidase-1 |
| spellingShingle | Tamara Zoran Bastian Seelbinder Philip Lewis White Jessica Sarah Price Sabrina Kraus Oliver Kurzai Joerg Linde Antje Häder Claudia Loeffler Goetz Ulrich Grigoleit Hermann Einsele Gianni Panagiotou Juergen Loeffler Sascha Schäuble Molecular Profiling Reveals Characteristic and Decisive Signatures in Patients after Allogeneic Stem Cell Transplantation Suffering from Invasive Pulmonary Aspergillosis Journal of Fungi host response invasive pulmonary aspergillosis alloSCT patients galectin-2 caspase-3 matrix metallopeptidase-1 |
| title | Molecular Profiling Reveals Characteristic and Decisive Signatures in Patients after Allogeneic Stem Cell Transplantation Suffering from Invasive Pulmonary Aspergillosis |
| title_full | Molecular Profiling Reveals Characteristic and Decisive Signatures in Patients after Allogeneic Stem Cell Transplantation Suffering from Invasive Pulmonary Aspergillosis |
| title_fullStr | Molecular Profiling Reveals Characteristic and Decisive Signatures in Patients after Allogeneic Stem Cell Transplantation Suffering from Invasive Pulmonary Aspergillosis |
| title_full_unstemmed | Molecular Profiling Reveals Characteristic and Decisive Signatures in Patients after Allogeneic Stem Cell Transplantation Suffering from Invasive Pulmonary Aspergillosis |
| title_short | Molecular Profiling Reveals Characteristic and Decisive Signatures in Patients after Allogeneic Stem Cell Transplantation Suffering from Invasive Pulmonary Aspergillosis |
| title_sort | molecular profiling reveals characteristic and decisive signatures in patients after allogeneic stem cell transplantation suffering from invasive pulmonary aspergillosis |
| topic | host response invasive pulmonary aspergillosis alloSCT patients galectin-2 caspase-3 matrix metallopeptidase-1 |
| url | https://www.mdpi.com/2309-608X/8/2/171 |
| work_keys_str_mv | AT tamarazoran molecularprofilingrevealscharacteristicanddecisivesignaturesinpatientsafterallogeneicstemcelltransplantationsufferingfrominvasivepulmonaryaspergillosis AT bastianseelbinder molecularprofilingrevealscharacteristicanddecisivesignaturesinpatientsafterallogeneicstemcelltransplantationsufferingfrominvasivepulmonaryaspergillosis AT philiplewiswhite molecularprofilingrevealscharacteristicanddecisivesignaturesinpatientsafterallogeneicstemcelltransplantationsufferingfrominvasivepulmonaryaspergillosis AT jessicasarahprice molecularprofilingrevealscharacteristicanddecisivesignaturesinpatientsafterallogeneicstemcelltransplantationsufferingfrominvasivepulmonaryaspergillosis AT sabrinakraus molecularprofilingrevealscharacteristicanddecisivesignaturesinpatientsafterallogeneicstemcelltransplantationsufferingfrominvasivepulmonaryaspergillosis AT oliverkurzai molecularprofilingrevealscharacteristicanddecisivesignaturesinpatientsafterallogeneicstemcelltransplantationsufferingfrominvasivepulmonaryaspergillosis AT joerglinde molecularprofilingrevealscharacteristicanddecisivesignaturesinpatientsafterallogeneicstemcelltransplantationsufferingfrominvasivepulmonaryaspergillosis AT antjehader molecularprofilingrevealscharacteristicanddecisivesignaturesinpatientsafterallogeneicstemcelltransplantationsufferingfrominvasivepulmonaryaspergillosis AT claudialoeffler molecularprofilingrevealscharacteristicanddecisivesignaturesinpatientsafterallogeneicstemcelltransplantationsufferingfrominvasivepulmonaryaspergillosis AT goetzulrichgrigoleit molecularprofilingrevealscharacteristicanddecisivesignaturesinpatientsafterallogeneicstemcelltransplantationsufferingfrominvasivepulmonaryaspergillosis AT hermanneinsele molecularprofilingrevealscharacteristicanddecisivesignaturesinpatientsafterallogeneicstemcelltransplantationsufferingfrominvasivepulmonaryaspergillosis AT giannipanagiotou molecularprofilingrevealscharacteristicanddecisivesignaturesinpatientsafterallogeneicstemcelltransplantationsufferingfrominvasivepulmonaryaspergillosis AT juergenloeffler molecularprofilingrevealscharacteristicanddecisivesignaturesinpatientsafterallogeneicstemcelltransplantationsufferingfrominvasivepulmonaryaspergillosis AT saschaschauble molecularprofilingrevealscharacteristicanddecisivesignaturesinpatientsafterallogeneicstemcelltransplantationsufferingfrominvasivepulmonaryaspergillosis |