Monocyte NOTCH2 expression predicts IFN-beta immunogenicity in multiple sclerosis patients
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11110%2F18%3A10376736" target="_blank" >RIV/00216208:11110/18:10376736 - isvavai.cz</a>
Alternative codes found
RIV/00064165:_____/18:10376736
Result on the web
<a href="https://doi.org/10.1172/jci.insight.99274" target="_blank" >https://doi.org/10.1172/jci.insight.99274</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1172/jci.insight.99274" target="_blank" >10.1172/jci.insight.99274</a>
Alternative languages
Result language
angličtina
Original language name
Monocyte NOTCH2 expression predicts IFN-beta immunogenicity in multiple sclerosis patients
Original language description
Multiple sclerosis (MS) is an autoimmune disease characterized by CNS inflammation leading to demyelination and axonal damage. IFN-beta is an established treatment for MS; however, up to 30% of IFN-beta-treated MS patients develop neutralizing antidrug antibodies (nADA), leading to reduced drug bioactivity and efficacy. Mechanisms driving antidrug immunogenicity remain uncertain, and reliable biomarkers to predict immunogenicity development are lacking. Using high-throughput flow cytometry, NOTCH2 expression on CD14(+) monocytes and increased frequency of proinflammatory monocyte subsets were identified as baseline predictors of nADA development in MS patients treated with IFN-beta. The association of this monocyte profile with nADA development was validated in 2 independent cross-sectional MS patient cohorts and a prospective cohort followed before and after IFN-beta administration. Reduced monocyte NOTCH2 expression in nADA(+) MS patients was associated with NOTCH2 activation measured by increased expression of Notch-responsive genes, polarization of monocytes toward a nonclassical phenotype, and increased proinflammatory IL-6 production. NOTCH2 activation was T cell dependent and was only triggered in the presence of serum from nADA(+) patients. Thus, nADA development was driven by a proinflammatory environment that triggered activation of the NOTCH2 signaling pathway prior to first IFN-beta administration.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30103 - Neurosciences (including psychophysiology)
Result continuities
Project
<a href="/en/project/7H12016" target="_blank" >7H12016: Anti-Biopharmaceutical Immunization: Prediction and analysis of clinical relevance to minimize the risk</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2018
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
JCI Insight [online]
ISSN
2379-3708
e-ISSN
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Volume of the periodical
3
Issue of the periodical within the volume
11
Country of publishing house
US - UNITED STATES
Number of pages
17
Pages from-to
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UT code for WoS article
000434866600010
EID of the result in the Scopus database
2-s2.0-85062250225