Type 1 Interferon‐Stimulated Gene Expression and Disease Activity in Pediatric Rheumatic Diseases: No Composite Scores Needed?
Objective Rheumatic diseases are characterized by different patterns of immune overactivation. This study investigated the correlation of whole blood type 1 interferon (IFN) stimulated gene (ISG), IL18, and CXCL9 expression with clinical disease activity in pediatric rheumatic diseases and assessed...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2023-12-01
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| Series: | ACR Open Rheumatology |
| Online Access: | https://doi.org/10.1002/acr2.11618 |
| _version_ | 1827585786637189120 |
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| author | Christina Weiden Melanie Saers Tobias Schwarz Tanja Hinze Helmut Wittkowski Christoph Kessel Katja Masjosthusmann Michael Mohr Georg Evers Sandra Oesingmann‐Weirich Dirk Foell Claas H. Hinze |
| author_facet | Christina Weiden Melanie Saers Tobias Schwarz Tanja Hinze Helmut Wittkowski Christoph Kessel Katja Masjosthusmann Michael Mohr Georg Evers Sandra Oesingmann‐Weirich Dirk Foell Claas H. Hinze |
| author_sort | Christina Weiden |
| collection | DOAJ |
| description | Objective Rheumatic diseases are characterized by different patterns of immune overactivation. This study investigated the correlation of whole blood type 1 interferon (IFN) stimulated gene (ISG), IL18, and CXCL9 expression with clinical disease activity in pediatric rheumatic diseases and assessed the required number of ISGs to be included in a composite type 1 IFN score. Methods Whole blood‐derived RNA and clinical data were collected from 171 mostly pediatric patients with connective tissue diseases (CTDs), systemic autoinflammatory diseases (SAIDs), monogenic interferonopathies (IFNPs) and other inflammatory diseases, and from 38 controls. The expression of six previously established ISGs, IL18, and CXCL9 was assessed by real‐time polymerase chain reaction (471 samples). Individual and composite gene expression was assessed, and correlation and threshold analyses were performed. Results Correlation between ISG expression and clinical disease activity was strongest in CTD, especially in juvenile dermatomyositis (JDM) and IFNP, and modest in patients with SAID. Threshold ISG expression levels for the detection of at least mild clinical disease activity were substantially higher in patients with systemic lupus erythematosus compared with JDM. The correlation of expression levels of limited sets of ISGs and even individual ISGs with clinical disease activity were not inferior to a composite score of six ISGs. Conclusion In a real‐world cohort, individual ISG expression levels robustly reflected clinical disease activity in CTD and IFNP, especially in JDM, which would simplify such analyses in clinical routine and be more cost‐effective. Threshold levels varied across diseases, potentially reflecting different mechanisms of type 1 IFN overactivation. |
| first_indexed | 2024-03-08T23:51:26Z |
| format | Article |
| id | doaj.art-2117b7f1de6d411eb6d475dbe6e8f0fd |
| institution | Directory Open Access Journal |
| issn | 2578-5745 |
| language | English |
| last_indexed | 2024-03-08T23:51:26Z |
| publishDate | 2023-12-01 |
| publisher | Wiley |
| record_format | Article |
| series | ACR Open Rheumatology |
| spelling | doaj.art-2117b7f1de6d411eb6d475dbe6e8f0fd2023-12-13T10:36:14ZengWileyACR Open Rheumatology2578-57452023-12-0151265266210.1002/acr2.11618Type 1 Interferon‐Stimulated Gene Expression and Disease Activity in Pediatric Rheumatic Diseases: No Composite Scores Needed?Christina Weiden0Melanie Saers1Tobias Schwarz2Tanja Hinze3Helmut Wittkowski4Christoph Kessel5Katja Masjosthusmann6Michael Mohr7Georg Evers8Sandra Oesingmann‐Weirich9Dirk Foell10Claas H. Hinze11University Hospital Muenster Muenster GermanyUniversity Hospital Muenster Muenster GermanySt. Josef‐Stift Sendenhorst GermanyUniversity Hospital Muenster Muenster GermanyUniversity Hospital Muenster Muenster GermanyUniversity Hospital Muenster Muenster GermanyUniversity Hospital Muenster Muenster GermanyUniversity Hospital Muenster Muenster GermanyUniversity Hospital Muenster Muenster GermanyUniversity Hospital Muenster Muenster GermanyUniversity Hospital Muenster Muenster GermanyUniversity Hospital Muenster Muenster GermanyObjective Rheumatic diseases are characterized by different patterns of immune overactivation. This study investigated the correlation of whole blood type 1 interferon (IFN) stimulated gene (ISG), IL18, and CXCL9 expression with clinical disease activity in pediatric rheumatic diseases and assessed the required number of ISGs to be included in a composite type 1 IFN score. Methods Whole blood‐derived RNA and clinical data were collected from 171 mostly pediatric patients with connective tissue diseases (CTDs), systemic autoinflammatory diseases (SAIDs), monogenic interferonopathies (IFNPs) and other inflammatory diseases, and from 38 controls. The expression of six previously established ISGs, IL18, and CXCL9 was assessed by real‐time polymerase chain reaction (471 samples). Individual and composite gene expression was assessed, and correlation and threshold analyses were performed. Results Correlation between ISG expression and clinical disease activity was strongest in CTD, especially in juvenile dermatomyositis (JDM) and IFNP, and modest in patients with SAID. Threshold ISG expression levels for the detection of at least mild clinical disease activity were substantially higher in patients with systemic lupus erythematosus compared with JDM. The correlation of expression levels of limited sets of ISGs and even individual ISGs with clinical disease activity were not inferior to a composite score of six ISGs. Conclusion In a real‐world cohort, individual ISG expression levels robustly reflected clinical disease activity in CTD and IFNP, especially in JDM, which would simplify such analyses in clinical routine and be more cost‐effective. Threshold levels varied across diseases, potentially reflecting different mechanisms of type 1 IFN overactivation.https://doi.org/10.1002/acr2.11618 |
| spellingShingle | Christina Weiden Melanie Saers Tobias Schwarz Tanja Hinze Helmut Wittkowski Christoph Kessel Katja Masjosthusmann Michael Mohr Georg Evers Sandra Oesingmann‐Weirich Dirk Foell Claas H. Hinze Type 1 Interferon‐Stimulated Gene Expression and Disease Activity in Pediatric Rheumatic Diseases: No Composite Scores Needed? ACR Open Rheumatology |
| title | Type 1 Interferon‐Stimulated Gene Expression and Disease Activity in Pediatric Rheumatic Diseases: No Composite Scores Needed? |
| title_full | Type 1 Interferon‐Stimulated Gene Expression and Disease Activity in Pediatric Rheumatic Diseases: No Composite Scores Needed? |
| title_fullStr | Type 1 Interferon‐Stimulated Gene Expression and Disease Activity in Pediatric Rheumatic Diseases: No Composite Scores Needed? |
| title_full_unstemmed | Type 1 Interferon‐Stimulated Gene Expression and Disease Activity in Pediatric Rheumatic Diseases: No Composite Scores Needed? |
| title_short | Type 1 Interferon‐Stimulated Gene Expression and Disease Activity in Pediatric Rheumatic Diseases: No Composite Scores Needed? |
| title_sort | type 1 interferon stimulated gene expression and disease activity in pediatric rheumatic diseases no composite scores needed |
| url | https://doi.org/10.1002/acr2.11618 |
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