Damiano Marastoni, Ermanna Turano, Agnese Tamanti, Elisa Colato, Anna Isabella Pisani, Arianna Scartezzini, Silvia Carotenuto, Valentina Mazziotti, Valentina Camera, Daniela Anni, Stefano Ziccardi, Maddalena Guandalini, Francesca B Pizzini, Federica Virla, Raffaella Mariotti, Roberta Magliozzi, Bruno Bonetti, Lawrence Steinman, Massimiliano Calabrese
{"title":"CSF 骨蛋白水平与早期多发性硬化症皮质萎缩和残疾的关系","authors":"Damiano Marastoni, Ermanna Turano, Agnese Tamanti, Elisa Colato, Anna Isabella Pisani, Arianna Scartezzini, Silvia Carotenuto, Valentina Mazziotti, Valentina Camera, Daniela Anni, Stefano Ziccardi, Maddalena Guandalini, Francesca B Pizzini, Federica Virla, Raffaella Mariotti, Roberta Magliozzi, Bruno Bonetti, Lawrence Steinman, Massimiliano Calabrese","doi":"10.1212/NXI.0000000000200265","DOIUrl":null,"url":null,"abstract":"<p><strong>Background and objectives: </strong>To evaluate CSF inflammatory markers with accumulation of cortical damage as well as disease activity in patients with early relapsing-remitting MS (RRMS).</p><p><strong>Methods: </strong>CSF levels of osteopontin (OPN) and 66 inflammatory markers were assessed using an immune-assay multiplex technique in 107 patients with RRMS (82 F/25 M, mean age 35.7 ± 11.8 years). All patients underwent regular clinical assessment and yearly 3T MRI scans for 2 years while 39 patients had a 4-year follow-up. White matter lesion number and volume, cortical lesions (CLs) and volume, and global cortical thickness (CTh) were evaluated together with the 'no evidence of disease activity' (NEDA-3) status, defined by no relapses, no disability worsening, and no MRI activity, including CLs.</p><p><strong>Results: </strong>The random forest algorithm selected OPN, CXCL13, TWEAK, TNF, IL19, sCD30, sTNFR1, IL35, IL16, and sCD163 as significantly associated with changes in global CTh. OPN and CXCL13 were most related to accumulation of atrophy after 2 and 4 years. In a multivariate linear regression model on CSF markers, OPN (<i>p</i> < 0.001), CXCL13 (<i>p</i> = 0.001), and sTNFR1 (<i>p</i> = 0.024) were increased in those patients with accumulating atrophy (adjusted R-squared 0.615). The 10 markers were added in a model that included all clinical, demographic, and MRI variables: OPN (<i>p</i> = 0.002) and IL19 (<i>p</i> = 0.022) levels were confirmed to be significantly increased in patients developing more CTh change over the follow-up (adjusted R-squared 0.619). CXCL13 and OPN also revealed the best association with NEDA-3 after 2 years, with OPN significantly linked to disability accumulation (OR 2.468 [1.46-5.034], <i>p</i> = 0.004) at the multivariate logistic regression model.</p><p><strong>Discussion: </strong>These data confirm and expand our knowledge on the prognostic role of the CSF inflammatory profile in predicting changes in cortical pathology and disease activity in early MS. The data emphasize a crucial role of OPN.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"11 5","pages":"e200265"},"PeriodicalIF":7.8000,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11203401/pdf/","citationCount":"0","resultStr":"{\"title\":\"Association of Levels of CSF Osteopontin With Cortical Atrophy and Disability in Early Multiple Sclerosis.\",\"authors\":\"Damiano Marastoni, Ermanna Turano, Agnese Tamanti, Elisa Colato, Anna Isabella Pisani, Arianna Scartezzini, Silvia Carotenuto, Valentina Mazziotti, Valentina Camera, Daniela Anni, Stefano Ziccardi, Maddalena Guandalini, Francesca B Pizzini, Federica Virla, Raffaella Mariotti, Roberta Magliozzi, Bruno Bonetti, Lawrence Steinman, Massimiliano Calabrese\",\"doi\":\"10.1212/NXI.0000000000200265\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background and objectives: </strong>To evaluate CSF inflammatory markers with accumulation of cortical damage as well as disease activity in patients with early relapsing-remitting MS (RRMS).</p><p><strong>Methods: </strong>CSF levels of osteopontin (OPN) and 66 inflammatory markers were assessed using an immune-assay multiplex technique in 107 patients with RRMS (82 F/25 M, mean age 35.7 ± 11.8 years). All patients underwent regular clinical assessment and yearly 3T MRI scans for 2 years while 39 patients had a 4-year follow-up. White matter lesion number and volume, cortical lesions (CLs) and volume, and global cortical thickness (CTh) were evaluated together with the 'no evidence of disease activity' (NEDA-3) status, defined by no relapses, no disability worsening, and no MRI activity, including CLs.</p><p><strong>Results: </strong>The random forest algorithm selected OPN, CXCL13, TWEAK, TNF, IL19, sCD30, sTNFR1, IL35, IL16, and sCD163 as significantly associated with changes in global CTh. OPN and CXCL13 were most related to accumulation of atrophy after 2 and 4 years. In a multivariate linear regression model on CSF markers, OPN (<i>p</i> < 0.001), CXCL13 (<i>p</i> = 0.001), and sTNFR1 (<i>p</i> = 0.024) were increased in those patients with accumulating atrophy (adjusted R-squared 0.615). The 10 markers were added in a model that included all clinical, demographic, and MRI variables: OPN (<i>p</i> = 0.002) and IL19 (<i>p</i> = 0.022) levels were confirmed to be significantly increased in patients developing more CTh change over the follow-up (adjusted R-squared 0.619). CXCL13 and OPN also revealed the best association with NEDA-3 after 2 years, with OPN significantly linked to disability accumulation (OR 2.468 [1.46-5.034], <i>p</i> = 0.004) at the multivariate logistic regression model.</p><p><strong>Discussion: </strong>These data confirm and expand our knowledge on the prognostic role of the CSF inflammatory profile in predicting changes in cortical pathology and disease activity in early MS. The data emphasize a crucial role of OPN.</p>\",\"PeriodicalId\":19472,\"journal\":{\"name\":\"Neurology® Neuroimmunology & Neuroinflammation\",\"volume\":\"11 5\",\"pages\":\"e200265\"},\"PeriodicalIF\":7.8000,\"publicationDate\":\"2024-09-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11203401/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Neurology® Neuroimmunology & Neuroinflammation\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1212/NXI.0000000000200265\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/6/25 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"CLINICAL NEUROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Neurology® Neuroimmunology & Neuroinflammation","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1212/NXI.0000000000200265","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/6/25 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
Association of Levels of CSF Osteopontin With Cortical Atrophy and Disability in Early Multiple Sclerosis.
Background and objectives: To evaluate CSF inflammatory markers with accumulation of cortical damage as well as disease activity in patients with early relapsing-remitting MS (RRMS).
Methods: CSF levels of osteopontin (OPN) and 66 inflammatory markers were assessed using an immune-assay multiplex technique in 107 patients with RRMS (82 F/25 M, mean age 35.7 ± 11.8 years). All patients underwent regular clinical assessment and yearly 3T MRI scans for 2 years while 39 patients had a 4-year follow-up. White matter lesion number and volume, cortical lesions (CLs) and volume, and global cortical thickness (CTh) were evaluated together with the 'no evidence of disease activity' (NEDA-3) status, defined by no relapses, no disability worsening, and no MRI activity, including CLs.
Results: The random forest algorithm selected OPN, CXCL13, TWEAK, TNF, IL19, sCD30, sTNFR1, IL35, IL16, and sCD163 as significantly associated with changes in global CTh. OPN and CXCL13 were most related to accumulation of atrophy after 2 and 4 years. In a multivariate linear regression model on CSF markers, OPN (p < 0.001), CXCL13 (p = 0.001), and sTNFR1 (p = 0.024) were increased in those patients with accumulating atrophy (adjusted R-squared 0.615). The 10 markers were added in a model that included all clinical, demographic, and MRI variables: OPN (p = 0.002) and IL19 (p = 0.022) levels were confirmed to be significantly increased in patients developing more CTh change over the follow-up (adjusted R-squared 0.619). CXCL13 and OPN also revealed the best association with NEDA-3 after 2 years, with OPN significantly linked to disability accumulation (OR 2.468 [1.46-5.034], p = 0.004) at the multivariate logistic regression model.
Discussion: These data confirm and expand our knowledge on the prognostic role of the CSF inflammatory profile in predicting changes in cortical pathology and disease activity in early MS. The data emphasize a crucial role of OPN.
期刊介绍：
Neurology Neuroimmunology & Neuroinflammation is an official journal of the American Academy of Neurology. Neurology: Neuroimmunology & Neuroinflammation will be the premier peer-reviewed journal in neuroimmunology and neuroinflammation. This journal publishes rigorously peer-reviewed open-access reports of original research and in-depth reviews of topics in neuroimmunology & neuroinflammation, affecting the full range of neurologic diseases including (but not limited to) Alzheimer's disease, Parkinson's disease, ALS, tauopathy, and stroke; multiple sclerosis and NMO; inflammatory peripheral nerve and muscle disease, Guillain-Barré and myasthenia gravis; nervous system infection; paraneoplastic syndromes, noninfectious encephalitides and other antibody-mediated disorders; and psychiatric and neurodevelopmental disorders. Clinical trials, instructive case reports, and small case series will also be featured.
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