PMID- 35886575
OWN - NLM
STAT- MEDLINE
DCOM- 20220728
LR  - 20220830
IS  - 1660-4601 (Electronic)
IS  - 1661-7827 (Print)
IS  - 1660-4601 (Linking)
VI  - 19
IP  - 14
DP  - 2022 Jul 18
TI  - Changes in Tumor Necrosis Factor alpha (TNFalpha) and Peptidyl Arginine Deiminase 4 
      (PAD-4) Levels in Serum of General Treated Psoriatic Patients.
LID - 10.3390/ijerph19148723 [doi]
LID - 8723
AB  - Psoriasis is an autoimmune disease in which the disturbed dependencies between 
      lymphocytes, dendritic cells, keratinocytes and neutrophils play the most 
      important role. One of them is the overproduction of neutrophil extracellular 
      traps (NETs). The release of NETs can be induced by pathogens, as well as 
      antibodies and immune complexes, cytokines and chemokines, including TNFalpha. The 
      first step of the NET creation is the activation of peptidyl arginine deiminase 4 
      (PAD-4). PAD-4 seems to be responsible for citrullination of histones and 
      chromatin decondensation, but the data on PAD-4 in NETs is inconclusive. Thus, 
      the current study aimed to determine PAD-4 and TNFalpha levels in the serum of 
      psoriatic patients by ELISA and observe the response of these factors to systemic 
      (anti-17a, anti-TNFalpha and methotrexate) therapies. Increased levels of both PAD-4 
      and its main stimulus factor TNFalpha in pre-treatment patients have been reported 
      along with the concentrations of proteins correlated with disease severity (PASI, 
      BSA). Before treatment, the irregularities in the case of anti-nuclear antibodies 
      level (ANA) were also observed. All of the applied therapies led to a decrease in 
      PAD-4 and TNFalpha levels after 12 weeks. The most significant changes, both in 
      protein concentrations as well as in scale scores, were noted with anti-TNFalpha 
      therapy (adalimumab and infliximab). This phenomenon may be associated with the 
      inhibition of TNFalpha production at different stages of psoriasis development, 
      including NET creation. The obtained data suggest the participation of PAD-4 in 
      the activation of neutrophils to produce NETs in psoriasis, which may create 
      opportunities for modern therapies with PAD inhibitors. However, further 
      exploration of gene and protein expression in psoriatic skin is needed.
FAU - Czerwinska, Joanna
AU  - Czerwinska J
AUID- ORCID: 0000-0001-6371-8130
AD  - Department of Dermatology, Sexually Transmitted Diseases and Clinical Immunology, 
      School of Medicine, University of Warmia and Mazury in Olsztyn, 10-719 Olsztyn, 
      Poland.
FAU - Kasprowicz-Furmanczyk, Marta
AU  - Kasprowicz-Furmanczyk M
AUID- ORCID: 0000-0002-4177-8404
AD  - Department of Dermatology, Sexually Transmitted Diseases and Clinical Immunology, 
      School of Medicine, University of Warmia and Mazury in Olsztyn, 10-719 Olsztyn, 
      Poland.
FAU - Placek, Waldemar
AU  - Placek W
AD  - Department of Dermatology, Sexually Transmitted Diseases and Clinical Immunology, 
      School of Medicine, University of Warmia and Mazury in Olsztyn, 10-719 Olsztyn, 
      Poland.
FAU - Owczarczyk-Saczonek, Agnieszka
AU  - Owczarczyk-Saczonek A
AUID- ORCID: 0000-0002-8372-0438
AD  - Department of Dermatology, Sexually Transmitted Diseases and Clinical Immunology, 
      School of Medicine, University of Warmia and Mazury in Olsztyn, 10-719 Olsztyn, 
      Poland.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220718
PL  - Switzerland
TA  - Int J Environ Res Public Health
JT  - International journal of environmental research and public health
JID - 101238455
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 3.- (Hydrolases)
RN  - EC 3.5.3.15 (PADI4 protein, human)
RN  - EC 3.5.3.15 (Protein-Arginine Deiminase Type 4)
SB  - IM
MH  - *Extracellular Traps/metabolism
MH  - Humans
MH  - Hydrolases/metabolism
MH  - Neutrophils/metabolism
MH  - *Protein-Arginine Deiminase Type 4/blood/metabolism
MH  - *Psoriasis/drug therapy/metabolism
MH  - *Tumor Necrosis Factor-alpha/blood/metabolism
PMC - PMC9324472
OTO - NOTNLM
OT  - NETs
OT  - PAD-4
OT  - adalimumab
OT  - methotrexate
OT  - psoriasis
OT  - secukinumab
OT  - systemic therapy
COIS- The authors declare no conflict of interest.
EDAT- 2022/07/28 06:00
MHDA- 2022/07/29 06:00
PMCR- 2022/07/18
CRDT- 2022/07/27 01:20
PHST- 2022/06/10 00:00 [received]
PHST- 2022/07/11 00:00 [revised]
PHST- 2022/07/15 00:00 [accepted]
PHST- 2022/07/27 01:20 [entrez]
PHST- 2022/07/28 06:00 [pubmed]
PHST- 2022/07/29 06:00 [medline]
PHST- 2022/07/18 00:00 [pmc-release]
AID - ijerph19148723 [pii]
AID - ijerph-19-08723 [pii]
AID - 10.3390/ijerph19148723 [doi]
PST - epublish
SO  - Int J Environ Res Public Health. 2022 Jul 18;19(14):8723. doi: 
      10.3390/ijerph19148723.