PMID- 36059852
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220907
IS  - 2296-858X (Print)
IS  - 2296-858X (Electronic)
IS  - 2296-858X (Linking)
VI  - 9
DP  - 2022
TI  - Increased histone citrullination in juvenile idiopathic arthritis.
PG  - 971121
LID - 10.3389/fmed.2022.971121 [doi]
LID - 971121
AB  - 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-TNFalpha 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.
CI  - Copyright (c) 2022 Parackova, Zentsova, Malcova, Cebecauerova, Sediva and Horvath.
FAU - Parackova, Zuzana
AU  - Parackova Z
AD  - Department of Immunology, 2nd Faculty of Medicine, Charles University, University 
      Hospital Motol, Prague, Czechia.
FAU - Zentsova, Irena
AU  - Zentsova I
AD  - Department of Immunology, 2nd Faculty of Medicine, Charles University, University 
      Hospital Motol, Prague, Czechia.
FAU - Malcova, Hana
AU  - Malcova H
AD  - Department of Paediatric and Adult Rheumatology, University Hospital Motol, 
      Prague, Czechia.
FAU - Cebecauerova, Dita
AU  - Cebecauerova D
AD  - Department of Paediatric and Adult Rheumatology, University Hospital Motol, 
      Prague, Czechia.
FAU - Sediva, Anna
AU  - Sediva A
AD  - Department of Immunology, 2nd Faculty of Medicine, Charles University, University 
      Hospital Motol, Prague, Czechia.
FAU - Horvath, Rudolf
AU  - Horvath R
AD  - Department of Paediatric and Adult Rheumatology, University Hospital Motol, 
      Prague, Czechia.
LA  - eng
PT  - Journal Article
DEP - 20220819
PL  - Switzerland
TA  - Front Med (Lausanne)
JT  - Frontiers in medicine
JID - 101648047
PMC - PMC9437311
OTO - NOTNLM
OT  - NETosis
OT  - carbamylation
OT  - citrullination
OT  - histone
OT  - juvenile idiopathic arthritis
OT  - neutrophil
OT  - peptidyl arginine deiminases (PAD)
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2022/09/06 06:00
MHDA- 2022/09/06 06:01
PMCR- 2022/08/19
CRDT- 2022/09/05 03:44
PHST- 2022/06/16 00:00 [received]
PHST- 2022/08/03 00:00 [accepted]
PHST- 2022/09/05 03:44 [entrez]
PHST- 2022/09/06 06:00 [pubmed]
PHST- 2022/09/06 06:01 [medline]
PHST- 2022/08/19 00:00 [pmc-release]
AID - 10.3389/fmed.2022.971121 [doi]
PST - epublish
SO  - Front Med (Lausanne). 2022 Aug 19;9:971121. doi: 10.3389/fmed.2022.971121. 
      eCollection 2022.