Patients with multiple sclerosis who develop immunogenicity to interferon-beta have distinct transcriptomic and proteomic signatures prior to treatment which are associated with disease severity
Identifikátory výsledku
Kód výsledku v IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00064165%3A_____%2F24%3A10484206" target="_blank" >RIV/00064165:_____/24:10484206 - isvavai.cz</a>
Nalezeny alternativní kódy
RIV/00216208:11110/24:10484206
Výsledek na webu
<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=ighHyBoZz9" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=ighHyBoZz9</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.clim.2024.110339" target="_blank" >10.1016/j.clim.2024.110339</a>
Alternativní jazyky
Jazyk výsledku
angličtina
Název v původním jazyce
Patients with multiple sclerosis who develop immunogenicity to interferon-beta have distinct transcriptomic and proteomic signatures prior to treatment which are associated with disease severity
Popis výsledku v původním jazyce
Anti-drug antibodies (ADA) reduce the efficacy of immunotherapies in multiple sclerosis (MS) and are associated with increased disease progression risk. Blood biomarkers predicting immunogenicity to biopharmaceuticals represent an unmet clinical need. Patients with relapsing remitting (RR)MS were recruited before (baseline), three, and 12 (M12) months after commencing interferon-beta treatment. Neutralising ADA-status was determined at M12, and patients were stratified at baseline according to their M12 ADA-status (ADA-positive/ADAnegative). Patients stratified as ADA-positive were characterised by an early dampened response to interferonbeta (prior to serum ADA detection) and distinct proinflammatory transcriptomic/proteomic peripheral blood signatures enriched for 'immune response activation' including phosphoinositide 3-kinase-gamma and NF kappa B-signalling pathways both at baseline and throughout the treatment course, compared to ADA-negative patients. These immunogenicity-associated proinflammatory signatures significantly overlapped with signatures of MS disease severity. Thus, whole blood molecular profiling is a promising tool for prediction of ADA-development in RRMS and could provide insight into mechanisms of immunogenicity.
Název v anglickém jazyce
Patients with multiple sclerosis who develop immunogenicity to interferon-beta have distinct transcriptomic and proteomic signatures prior to treatment which are associated with disease severity
Popis výsledku anglicky
Anti-drug antibodies (ADA) reduce the efficacy of immunotherapies in multiple sclerosis (MS) and are associated with increased disease progression risk. Blood biomarkers predicting immunogenicity to biopharmaceuticals represent an unmet clinical need. Patients with relapsing remitting (RR)MS were recruited before (baseline), three, and 12 (M12) months after commencing interferon-beta treatment. Neutralising ADA-status was determined at M12, and patients were stratified at baseline according to their M12 ADA-status (ADA-positive/ADAnegative). Patients stratified as ADA-positive were characterised by an early dampened response to interferonbeta (prior to serum ADA detection) and distinct proinflammatory transcriptomic/proteomic peripheral blood signatures enriched for 'immune response activation' including phosphoinositide 3-kinase-gamma and NF kappa B-signalling pathways both at baseline and throughout the treatment course, compared to ADA-negative patients. These immunogenicity-associated proinflammatory signatures significantly overlapped with signatures of MS disease severity. Thus, whole blood molecular profiling is a promising tool for prediction of ADA-development in RRMS and could provide insight into mechanisms of immunogenicity.
Klasifikace
Druh
J<sub>imp</sub> - Článek v periodiku v databázi Web of Science
CEP obor
—
OECD FORD obor
30103 - Neurosciences (including psychophysiology)
Návaznosti výsledku
Projekt
—
Návaznosti
V - Vyzkumna aktivita podporovana z jinych verejnych zdroju
Ostatní
Rok uplatnění
2024
Kód důvěrnosti údajů
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Údaje specifické pro druh výsledku
Název periodika
Clinical Immunology
ISSN
1521-6616
e-ISSN
1521-7035
Svazek periodika
267
Číslo periodika v rámci svazku
October
Stát vydavatele periodika
US - Spojené státy americké
Počet stran výsledku
11
Strana od-do
110339
Kód UT WoS článku
001297557800001
EID výsledku v databázi Scopus
2-s2.0-85201158358