Increased histone citrullination in juvenile idiopathic arthritis
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00064203%3A_____%2F22%3A10446636" target="_blank" >RIV/00064203:_____/22:10446636 - isvavai.cz</a>
Alternative codes found
RIV/00216208:11130/22:10446636
Result on the web
<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=MwIr4MqNY0" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=MwIr4MqNY0</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.3389/fmed.2022.971121" target="_blank" >10.3389/fmed.2022.971121</a>
Alternative languages
Result language
angličtina
Original language name
Increased histone citrullination in juvenile idiopathic arthritis
Original language description
OBJECTIVE: Posttranslational modifications (PTMs) of proteins are crucial for regulating various biological processes. However, protein alteration via PTMs, and consequently, the creation of new epitopes, can induce abnormal autoimmune responses in predisposed individuals. Immunopathogenesis of several rheumatic diseases, including the most common childhood form, juvenile idiopathic arthritis (JIA), is associated with the generation of autoantibodies against such modified proteins. Dysregulated generation of neutrophil extracellular traps (NETs) can be a source of post-translationally altered proteins. Thus, we investigated the role of PTMs and the presence of NET-associated markers in JIA patients. METHODS: We recruited 30 pediatric patients with JIA (20 with active disease and 10 in remission) and 30 healthy donors. The serum concentrations of citrullinated histone H3 (citH3), peptidyl arginine deiminases (PADs), and NET-related products were detected using ELISA, and the number of citH3+ neutrophils was assessed using flow cytometry. RESULTS: The serum levels of citH3 and PADs were higher in active as well as in remission JIA patients than in healthy donors. Similarly, the number of citH3+ neutrophils was higher in the peripheral blood of patients with JIA, implying an enhanced process of NETosis. This was effectively reflected by elevated serum levels of NET-associated products, such as neutrophil elastase, LL37, and cell-free DNA-histone complexes. Additionally, 16.7% of active JIA patients were seropositive for carbamylated autoantibodies, the levels of which declined sharply after initiation of anti-TNFα therapy. CONCLUSION: Collectively, our data suggest that the accelerated process of NETosis and PTMs in JIA may result in the generation of anti-citrullinated/carbamylated autoantibodies against various epitopes later in life, which could be prevented by effectively regulating inflammation using immune therapy.
Czech name
—
Czech description
—
Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
—
OECD FORD branch
30226 - Rheumatology
Result continuities
Project
<a href="/en/project/NU20-05-00320" target="_blank" >NU20-05-00320: Neutrophils in juvenile idiopathic arthritis: biomarkers with potential to improve clinical treatment decisions and patient care</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
2022
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Frontiers in Medicine [online]
ISSN
2296-858X
e-ISSN
2296-858X
Volume of the periodical
9
Issue of the periodical within the volume
August
Country of publishing house
CH - SWITZERLAND
Number of pages
9
Pages from-to
971121
UT code for WoS article
000849702100001
EID of the result in the Scopus database
2-s2.0-85137754981