Circulating levels of tight junction proteins in multiple sclerosis: Association with inflammation and disease activity before and after disease modifying therapy
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Background: Tight junction proteins contribute to maintenance of epithelial and endothelial barriers such as the intestinal barrier and the blood brain barrier (BBB). Increased permeability of these barriers has been linked to disease activity in MS and there is currently a lack of easily accessible biomarkers predicting disease activity in MS. Aim: To investigate whether levels of circulating tight junction proteins occludin and zonula occludens-1 (ZO-1) are associated with biomarkers of inflammation and disease activity; and to determine whether they could serve as clinical biomarkers. Methods: We prospectively included 72 newly diagnosed patients with relapsing remitting MS or clinically isolated syndrome with no prior disease modifying therapy (DMT) use and 50 healthy controls (HCs). Patients were followed with blood samples, 3 tesla MRI, and clinical evaluation for 12 months. Occludin, ZO-1, calprotectin and soluble urokinase-type plasminogen activator receptor (suPAR) were measured by ELISA; serum neurofilament light (NfL) and IL-6 by single-molecule array (SIMOA). The mRNA expression of IFNG, IL1R1, IL10, IL1B, ARG1 and TNF was measured by quantitative real time polymerase chain reaction (qPCR) in whole blood. Results: Plasma occludin levels were higher in MS patients compared with HCs. After 12 months on DMT, occludin levels were reduced by approximately 25% irrespective of 1st or 2nd line DMT (p<0.001). Furthermore, NfL and calprotectin levels were significantly reduced by 31% and 29%, respectively. Occludin and ZO-1 did not correlate with biomarkers of inflammation and did not predict disease activity at baseline or after 12 months. Conclusions: Higher levels of occludin suggest an increased permeability of the BBB and/or the intestinal barrier in MS patients. The reduction of occludin after 12 months on DMTs might reflect repair of these barriers upon treatment. However, plasma levels of ZO-1 and occludin could not predict clinical or MRI disease activity as determined by regression and ROC-curve analysis. Our results do not indicate a clear clinically relevant role for circulating tight junction proteins as biomarkers of disease activity in MS and further investigations in larger cohorts are needed to clarify this issue.
Originalsprog | Engelsk |
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Artikelnummer | 103136 |
Tidsskrift | Multiple Sclerosis and Related Disorders |
Vol/bind | 54 |
Antal sider | 7 |
ISSN | 2211-0348 |
DOI | |
Status | Udgivet - 2021 |
Bibliografisk note
Funding Information:
This research was supported by the Danish Multiple Sclerosis Society [A-38469 and A35043], Aase og Ejnar Danielsens Fond [10?002094], Overl?ge Johan Boserup og Lise Boserups Legat [J.nr. 20795?24], Grosserer A.V. Lykfeldt og Hustrus Legat, Trigon fonden, Civilingeni?r Bent B?gh og hustru Inge B?ghs fond, Carl og Ellen Hertz Legat [J.nr. 7179?2], Direkt?r Emil C. Hertz og hustru Inger Hertz' Fond, Civilingeni?r Frode V. Nyegaard og Hustrus Fond, Th. Maigaards Eftf. Fru Lily Benthine Lunds Fond, Jascha Fonden, Torben og Alice Frimodts Fond and Fonden til L?gevidenskabens Fremme [20-L-0360]. The funders did not contribute to the study design, execution, analyses, interpretation of data, or writing.
Funding Information:
This research was supported by the Danish Multiple Sclerosis Society [ A-38469 and A35043 ], Aase og Ejnar Danielsens Fond [ 10–002094 ], Overlæge Johan Boserup og Lise Boserups Legat [J.nr. 20795–24 ], Grosserer A.V. Lykfeldt og Hustrus Legat , Trigon fonden , Civilingeniør Bent Bøgh og hustru Inge Bøghs fond , Carl og Ellen Hertz Legat [J.nr. 7179–2 ], Direktør Emil C. Hertz og hustru Inger Hertz' Fond , Civilingeniør Frode V. Nyegaard og Hustrus Fond , Th. Maigaards Eftf. Fru Lily Benthine Lunds Fond , Jascha Fonden , Torben og Alice Frimodts Fond and Fonden til Lægevidenskabens Fremme [ 20-L-0360 ]. The funders did not contribute to the study design, execution, analyses, interpretation of data, or writing.
Publisher Copyright:
© 2021
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