Interferon and interferon-induced cytokines as markers of impending clinical progression in ANA+ individuals without a systemic autoimmune rheumatic disease diagnosis
Abstract Background Elevated levels of interferons (IFNs) are a characteristic feature of systemic autoimmune rheumatic diseases (SARDs) and may be useful in predicting impending symptomatic progression in anti-nuclear antibody-positive (ANA+) individuals lacking a SARD diagnosis. Typically, these a...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-02-01
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| Series: | Arthritis Research & Therapy |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13075-023-02997-w |
| _version_ | 1811165755523203072 |
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| author | Sonya T. Kim Carolina Muñoz-Grajales Shannon E. Dunn Raphael Schneider Sindhu R. Johnson Zahi Touma Zareen Ahmad Dennisse Bonilla Eshetu G. Atenafu Linda T. Hiraki Arthur Bookman Joan Wither |
| author_facet | Sonya T. Kim Carolina Muñoz-Grajales Shannon E. Dunn Raphael Schneider Sindhu R. Johnson Zahi Touma Zareen Ahmad Dennisse Bonilla Eshetu G. Atenafu Linda T. Hiraki Arthur Bookman Joan Wither |
| author_sort | Sonya T. Kim |
| collection | DOAJ |
| description | Abstract Background Elevated levels of interferons (IFNs) are a characteristic feature of systemic autoimmune rheumatic diseases (SARDs) and may be useful in predicting impending symptomatic progression in anti-nuclear antibody-positive (ANA+) individuals lacking a SARD diagnosis. Typically, these are measured by their effect on gene expression in the blood, which has limited their utility in clinical settings. Here, we assessed whether the measurement of serum IFN-α or selected IFN-induced cytokines accurately mirrors IFN-induced gene expression in ANA+ individuals and investigated their utility as biomarkers of clinical progression. Methods A total of 280 subjects were studied, including 50 ANA− healthy controls, 160 ANA+ individuals without a SARD diagnosis (96 asymptomatic, 64 with undifferentiated connective tissue disease), and 70 SARD patients. IFN-induced gene expression was measured by nanoString and cytokine levels by ELISA or Simoa. ANA+ individuals lacking a SARD diagnosis who had the new onset of SARD criteria over the subsequent 2 years were defined as progressors. Results Measurement of IFN-α levels by high-sensitivity ELISA or Simoa correlated much better with IFN-induced gene expression than measurement of CXCL-10 or Galectin-9 levels. Despite this, high CXCL-10 and Galectin-9 levels were better predictors of subsequent progression in ANA+ individuals than measures of IFN-α or IFN-induced gene expression with the optimal combination of predictive cytokines (CXCL-10 and IFN-α as measured by ELISA), resulting in a specificity and positive predictive value of 100%. Conclusion Easily performed ELISA assays for CXCL-10 and IFN-α can be used to predict ANA+ individuals at high risk of imminent symptomatic progression. |
| first_indexed | 2024-04-10T15:41:44Z |
| format | Article |
| id | doaj.art-241de6a9469845f18b5d902d52244ca8 |
| institution | Directory Open Access Journal |
| issn | 1478-6362 |
| language | English |
| last_indexed | 2024-04-10T15:41:44Z |
| publishDate | 2023-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Arthritis Research & Therapy |
| spelling | doaj.art-241de6a9469845f18b5d902d52244ca82023-02-12T12:18:47ZengBMCArthritis Research & Therapy1478-63622023-02-0125111110.1186/s13075-023-02997-wInterferon and interferon-induced cytokines as markers of impending clinical progression in ANA+ individuals without a systemic autoimmune rheumatic disease diagnosisSonya T. Kim0Carolina Muñoz-Grajales1Shannon E. Dunn2Raphael Schneider3Sindhu R. Johnson4Zahi Touma5Zareen Ahmad6Dennisse Bonilla7Eshetu G. Atenafu8Linda T. Hiraki9Arthur Bookman10Joan Wither11Schroeder Arthritis Institute, Krembil Research Institute, University Health NetworkSchroeder Arthritis Institute, Krembil Research Institute, University Health NetworkDepartment of Immunology, Faculty of Medicine, University of TorontoKeenan Research Centre for Biomedical Science, St. Michael’s HospitalDepartment of Medicine, Faculty of Medicine, University of TorontoDepartment of Medicine, Faculty of Medicine, University of TorontoDepartment of Medicine, Faculty of Medicine, University of TorontoSchroeder Arthritis Institute, Krembil Research Institute, University Health NetworkBiostatistics Department, Princess Margaret Cancer Center, University Health NetworkDivision of Rheumatology, The Hospital for Sick Children, and Department of Paediatrics, University of TorontoDepartment of Medicine, Faculty of Medicine, University of TorontoSchroeder Arthritis Institute, Krembil Research Institute, University Health NetworkAbstract Background Elevated levels of interferons (IFNs) are a characteristic feature of systemic autoimmune rheumatic diseases (SARDs) and may be useful in predicting impending symptomatic progression in anti-nuclear antibody-positive (ANA+) individuals lacking a SARD diagnosis. Typically, these are measured by their effect on gene expression in the blood, which has limited their utility in clinical settings. Here, we assessed whether the measurement of serum IFN-α or selected IFN-induced cytokines accurately mirrors IFN-induced gene expression in ANA+ individuals and investigated their utility as biomarkers of clinical progression. Methods A total of 280 subjects were studied, including 50 ANA− healthy controls, 160 ANA+ individuals without a SARD diagnosis (96 asymptomatic, 64 with undifferentiated connective tissue disease), and 70 SARD patients. IFN-induced gene expression was measured by nanoString and cytokine levels by ELISA or Simoa. ANA+ individuals lacking a SARD diagnosis who had the new onset of SARD criteria over the subsequent 2 years were defined as progressors. Results Measurement of IFN-α levels by high-sensitivity ELISA or Simoa correlated much better with IFN-induced gene expression than measurement of CXCL-10 or Galectin-9 levels. Despite this, high CXCL-10 and Galectin-9 levels were better predictors of subsequent progression in ANA+ individuals than measures of IFN-α or IFN-induced gene expression with the optimal combination of predictive cytokines (CXCL-10 and IFN-α as measured by ELISA), resulting in a specificity and positive predictive value of 100%. Conclusion Easily performed ELISA assays for CXCL-10 and IFN-α can be used to predict ANA+ individuals at high risk of imminent symptomatic progression.https://doi.org/10.1186/s13075-023-02997-wSystemic autoimmune rheumatic diseasesPre-clinicalInterferonCytokines |
| spellingShingle | Sonya T. Kim Carolina Muñoz-Grajales Shannon E. Dunn Raphael Schneider Sindhu R. Johnson Zahi Touma Zareen Ahmad Dennisse Bonilla Eshetu G. Atenafu Linda T. Hiraki Arthur Bookman Joan Wither Interferon and interferon-induced cytokines as markers of impending clinical progression in ANA+ individuals without a systemic autoimmune rheumatic disease diagnosis Arthritis Research & Therapy Systemic autoimmune rheumatic diseases Pre-clinical Interferon Cytokines |
| title | Interferon and interferon-induced cytokines as markers of impending clinical progression in ANA+ individuals without a systemic autoimmune rheumatic disease diagnosis |
| title_full | Interferon and interferon-induced cytokines as markers of impending clinical progression in ANA+ individuals without a systemic autoimmune rheumatic disease diagnosis |
| title_fullStr | Interferon and interferon-induced cytokines as markers of impending clinical progression in ANA+ individuals without a systemic autoimmune rheumatic disease diagnosis |
| title_full_unstemmed | Interferon and interferon-induced cytokines as markers of impending clinical progression in ANA+ individuals without a systemic autoimmune rheumatic disease diagnosis |
| title_short | Interferon and interferon-induced cytokines as markers of impending clinical progression in ANA+ individuals without a systemic autoimmune rheumatic disease diagnosis |
| title_sort | interferon and interferon induced cytokines as markers of impending clinical progression in ana individuals without a systemic autoimmune rheumatic disease diagnosis |
| topic | Systemic autoimmune rheumatic diseases Pre-clinical Interferon Cytokines |
| url | https://doi.org/10.1186/s13075-023-02997-w |
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