CSF levels of Chitinase3like1 correlate with early response to cladribine in multiple sclerosis
BackgroundCladribine has been introduced as a high-efficacy drug for treating relapsing-remitting multiple sclerosis (RRMS). Initial cohort studies showed early disease activity in the first year after drug initiation. Biomarkers that can predict early disease activity are needed.AimTo estimate cere...
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Frontiers Media S.A.
2024-02-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1343892/full |
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| author | Damiano Marastoni Matteo Foschi Matteo Foschi Chiara Eccher Francesco Crescenzo Valentina Mazziotti Agnese Tamanti Albulena Bajrami Valentina Camera Stefano Ziccardi Maddalena Guandalini Francesca Bosello Daniela Anni Federica Virla Federica Virla Ermanna Turano Ermanna Turano Michele Romoli Raffaella Mariotti Francesca Benedetta Pizzini Bruno Bonetti Massimiliano Calabrese |
| author_facet | Damiano Marastoni Matteo Foschi Matteo Foschi Chiara Eccher Francesco Crescenzo Valentina Mazziotti Agnese Tamanti Albulena Bajrami Valentina Camera Stefano Ziccardi Maddalena Guandalini Francesca Bosello Daniela Anni Federica Virla Federica Virla Ermanna Turano Ermanna Turano Michele Romoli Raffaella Mariotti Francesca Benedetta Pizzini Bruno Bonetti Massimiliano Calabrese |
| author_sort | Damiano Marastoni |
| collection | DOAJ |
| description | BackgroundCladribine has been introduced as a high-efficacy drug for treating relapsing-remitting multiple sclerosis (RRMS). Initial cohort studies showed early disease activity in the first year after drug initiation. Biomarkers that can predict early disease activity are needed.AimTo estimate cerebrospinal fluid (CSF) markers of clinical and radiological responses after initiation of cladribine.MethodsForty-two RRMS patients (30F/12M) treated with cladribine were included in a longitudinal prospective study. All patients underwent a CSF examination at treatment initiation, clinical follow-up including Expanded Disability Status Scale (EDSS) assessment, and a 3T MRI scan after 6,12 and 24 months, including the evaluation of white matter (WM) and cortical lesions (CLs). CSF levels of 67 inflammatory markers were assessed with immune-assay multiplex techniques. The ‘no evidence of disease activity’ (NEDA-3) status was assessed after two years and defined by no relapses, no disability worsening measured by EDSS and no MRI activity, including CLs.ResultsThree patients were lost at follow-up. At the end of follow-up, 19 (48%) patients remained free from disease activity. IFNgamma, Chitinase3like1, IL32, Osteopontin, IL12(p40), IL34, IL28A, sTNFR2, IL20 and CCL2 showed the best association with disease activity. When added in a multivariate regression model including age, sex, and baseline EDSS, Chitinase 3 like1 (p = 0.049) significantly increased in those patients with disease activity. Finally, ROC analysis with Chitinase3like1 added to a model with EDSS, sex, age previous relapses, WM lesion number, CLs, number of Gad enhancing lesions and spinal cord lesions provided an AUC of 0.76 (95%CI 0.60-0.91).ConclusionsCSF Chitinase 3 like1 might provide prognostic information for predicting disease activity in the first years after initiation of cladribine. The drug’s effect on chronic macrophage and microglia activation deserves further evaluation. |
| first_indexed | 2024-03-08T04:01:50Z |
| format | Article |
| id | doaj.art-9d9749d94e1345dbaab41d85453fce9a |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-03-08T04:01:50Z |
| publishDate | 2024-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-9d9749d94e1345dbaab41d85453fce9a2024-02-09T14:45:16ZengFrontiers Media S.A.Frontiers in Immunology1664-32242024-02-011510.3389/fimmu.2024.13438921343892CSF levels of Chitinase3like1 correlate with early response to cladribine in multiple sclerosisDamiano Marastoni0Matteo Foschi1Matteo Foschi2Chiara Eccher3Francesco Crescenzo4Valentina Mazziotti5Agnese Tamanti6Albulena Bajrami7Valentina Camera8Stefano Ziccardi9Maddalena Guandalini10Francesca Bosello11Daniela Anni12Federica Virla13Federica Virla14Ermanna Turano15Ermanna Turano16Michele Romoli17Raffaella Mariotti18Francesca Benedetta Pizzini19Bruno Bonetti20Massimiliano Calabrese21Neurology B, Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Verona, ItalyNeurology Unit, Department of Neuroscience, Multiple Sclerosis Center, S. Maria delle Croci Hospital, AUSL, Romagna, Ravenna, ItalyDepartment of Biotechnological and Applied Clinical Sciences, University of L’Aquila, L’Aquila, ItalyNeurology B, Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Verona, ItalyNeurology Unit, “Mater Salutis” Hospital, Scaligera AULSS 9, Verona, ItalyNeurology B, Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Verona, ItalyNeurology B, Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Verona, ItalyNeurology B, Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Verona, ItalyNeurology B, Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Verona, ItalyNeurology B, Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Verona, ItalyNeurology B, Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Verona, ItalyEye Clinic, Department of Surgery, Dentistry, Maternity, and Infant, University of Verona, Verona, ItalyNeurology B, Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Verona, ItalyNeurology B, Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Verona, ItalyDepartment of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Verona, ItalyNeurology B, Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Verona, ItalyDepartment of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Verona, ItalyNeurology and Stroke Unit, Ospedale “Bufalini”, Cesena, ItalyDepartment of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Verona, ItalyRadiology and Neuroradiology Unit, Azienda Ospedaliera Universitaria Integrata, Verona, ItalyNeurology A, Azienda Ospedaliera Universitaria Integrata, Verona, ItalyNeurology B, Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Verona, ItalyBackgroundCladribine has been introduced as a high-efficacy drug for treating relapsing-remitting multiple sclerosis (RRMS). Initial cohort studies showed early disease activity in the first year after drug initiation. Biomarkers that can predict early disease activity are needed.AimTo estimate cerebrospinal fluid (CSF) markers of clinical and radiological responses after initiation of cladribine.MethodsForty-two RRMS patients (30F/12M) treated with cladribine were included in a longitudinal prospective study. All patients underwent a CSF examination at treatment initiation, clinical follow-up including Expanded Disability Status Scale (EDSS) assessment, and a 3T MRI scan after 6,12 and 24 months, including the evaluation of white matter (WM) and cortical lesions (CLs). CSF levels of 67 inflammatory markers were assessed with immune-assay multiplex techniques. The ‘no evidence of disease activity’ (NEDA-3) status was assessed after two years and defined by no relapses, no disability worsening measured by EDSS and no MRI activity, including CLs.ResultsThree patients were lost at follow-up. At the end of follow-up, 19 (48%) patients remained free from disease activity. IFNgamma, Chitinase3like1, IL32, Osteopontin, IL12(p40), IL34, IL28A, sTNFR2, IL20 and CCL2 showed the best association with disease activity. When added in a multivariate regression model including age, sex, and baseline EDSS, Chitinase 3 like1 (p = 0.049) significantly increased in those patients with disease activity. Finally, ROC analysis with Chitinase3like1 added to a model with EDSS, sex, age previous relapses, WM lesion number, CLs, number of Gad enhancing lesions and spinal cord lesions provided an AUC of 0.76 (95%CI 0.60-0.91).ConclusionsCSF Chitinase 3 like1 might provide prognostic information for predicting disease activity in the first years after initiation of cladribine. The drug’s effect on chronic macrophage and microglia activation deserves further evaluation.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1343892/fullrelapsing multiple sclerosiscytokineschemokinescladribinedisease activitybiomarkers |
| spellingShingle | Damiano Marastoni Matteo Foschi Matteo Foschi Chiara Eccher Francesco Crescenzo Valentina Mazziotti Agnese Tamanti Albulena Bajrami Valentina Camera Stefano Ziccardi Maddalena Guandalini Francesca Bosello Daniela Anni Federica Virla Federica Virla Ermanna Turano Ermanna Turano Michele Romoli Raffaella Mariotti Francesca Benedetta Pizzini Bruno Bonetti Massimiliano Calabrese CSF levels of Chitinase3like1 correlate with early response to cladribine in multiple sclerosis Frontiers in Immunology relapsing multiple sclerosis cytokines chemokines cladribine disease activity biomarkers |
| title | CSF levels of Chitinase3like1 correlate with early response to cladribine in multiple sclerosis |
| title_full | CSF levels of Chitinase3like1 correlate with early response to cladribine in multiple sclerosis |
| title_fullStr | CSF levels of Chitinase3like1 correlate with early response to cladribine in multiple sclerosis |
| title_full_unstemmed | CSF levels of Chitinase3like1 correlate with early response to cladribine in multiple sclerosis |
| title_short | CSF levels of Chitinase3like1 correlate with early response to cladribine in multiple sclerosis |
| title_sort | csf levels of chitinase3like1 correlate with early response to cladribine in multiple sclerosis |
| topic | relapsing multiple sclerosis cytokines chemokines cladribine disease activity biomarkers |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1343892/full |
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