PMID- 36319843
OWN - NLM
STAT- MEDLINE
DCOM- 20221103
LR  - 20221230
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 12
IP  - 1
DP  - 2022 Nov 1
TI  - Serum extracellular traps associate with the activation of myeloid cells in SLE 
      patients with the low level of anti-DNA antibodies.
PG  - 18397
LID - 10.1038/s41598-022-23076-1 [doi]
LID - 18397
AB  - Neutrophil extracellular traps (NETs) are involved in systemic lupus 
      erythematosus (SLE). We sought to cluster SLE patients based on serum NET levels. 
      Serum NET levels were higher in SLE patients than healthy controls. Frequencies 
      of pleuritis and myositis were increased in patients with high serum NET levels. 
      Serum NET levels negatively correlated with anti-double stranded DNA (anti-dsDNA) 
      antibody titers and C1q-binding immune complexes, but positively correlated with 
      C-reactive protein (CRP) and monocyte counts. Neutrophil transcriptome analysis 
      demonstrated no difference in NET-associated signatures, irrespective of serum 
      NET levels, suggesting anti-dsDNA antibody-mediated clearance of NETs. In serum, 
      NET levels were significantly correlated with myeloid cell-derived inflammatory 
      molecules. Serum NET-based cluster analysis revealed 3 groups of patients based 
      on serum NET and CRP levels, anti-dsDNA antibody titers, and monocyte count. 
      Monocytes were consistently activated following NET-containing immune complex 
      (NET-IC) stimulation. In conclusion, SLE patients with high serum NET levels had 
      lower anti-dsDNA antibody titers and higher inflammatory responses. 
      NET-IC-stimulated monocytes might associate with an inflammatory response 
      characterized by elevated CRP levels. These findings can apply to precision 
      medicine, as inflammatory processes, rather than antibody-dependent processes, 
      can be targeted in specific subpopulations of SLE patients.
CI  - (c) 2022. The Author(s).
FAU - Hanata, Norio
AU  - Hanata N
AD  - Department of Allergy and Rheumatology, Graduate School of Medicine, The 
      University of Tokyo, Tokyo, Japan.
FAU - Ota, Mineto
AU  - Ota M
AD  - Department of Allergy and Rheumatology, Graduate School of Medicine, The 
      University of Tokyo, Tokyo, Japan.
AD  - Department of Functional Genomics and Immunological Diseases, Graduate School of 
      Medicine, The University of Tokyo, Tokyo, Japan.
FAU - Tsuchida, Yumi
AU  - Tsuchida Y
AD  - Department of Allergy and Rheumatology, Graduate School of Medicine, The 
      University of Tokyo, Tokyo, Japan.
FAU - Nagafuchi, Yasuo
AU  - Nagafuchi Y
AD  - Department of Allergy and Rheumatology, Graduate School of Medicine, The 
      University of Tokyo, Tokyo, Japan.
AD  - Department of Functional Genomics and Immunological Diseases, Graduate School of 
      Medicine, The University of Tokyo, Tokyo, Japan.
FAU - Okamura, Tomohisa
AU  - Okamura T
AD  - Department of Functional Genomics and Immunological Diseases, Graduate School of 
      Medicine, The University of Tokyo, Tokyo, Japan.
FAU - Shoda, Hirofumi
AU  - Shoda H
AD  - Department of Allergy and Rheumatology, Graduate School of Medicine, The 
      University of Tokyo, Tokyo, Japan. SHODAH-INT@h.u-tokyo.ac.jp.
FAU - Fujio, Keishi
AU  - Fujio K
AD  - Department of Allergy and Rheumatology, Graduate School of Medicine, The 
      University of Tokyo, Tokyo, Japan.
LA  - eng
GR  - 20K17439/Japan Society for the Promotion of Science/
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20221101
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (Antibodies, Antinuclear)
RN  - 0 (anti-dsDNA autoantibody)
RN  - 0 (Antigen-Antibody Complex)
RN  - 0 (Autoantibodies)
SB  - IM
MH  - Humans
MH  - *Extracellular Traps/metabolism
MH  - Antibodies, Antinuclear
MH  - *Lupus Erythematosus, Systemic
MH  - Neutrophils/metabolism
MH  - Antigen-Antibody Complex
MH  - Autoantibodies
PMC - PMC9626644
COIS- N.H. has received grants from GlaxoSmithKline. M.O. belongs to the Social 
      Cooperation Program, Department of functional genomics and immunological 
      diseases, supported by Chugai Pharmaceutical, and has received speaking fees from 
      BMS, MSD, and Chugai. Y.T. has received grants from GlaxoSmithKline and speaking 
      fees from GlaxoSmithKline and Chugai. Y.N. belongs to the Social Cooperation 
      Program, Department of functional genomics and immunological diseases, supported 
      by Chugai Pharmaceutical, and has received financial support or fees from BMS, 
      Chugai, GlaxoSmithKline, Kissei, Mitsubishi Tanabe, and Pfizer. T.O. belongs to 
      the Social Cooperation Program, Department of functional genomics and 
      immunological diseases, supported by Chugai Pharmaceutical. H.S. has received 
      speaking fees and grants from Takeda, BMS, Asahi Kasei, Sanofi, Eli Lilly, 
      Janssen, Astellas, Pfizer, Chugai, UCB, Abbvie, Eisai, Boehringer Ingelheim, 
      Gilead, Novartis, and Daiichi-Sankyo. K.F. has received speaking fees, and/or 
      honoraria from Tanabe Mitsubishi, Bristol Myers, Eli Lilly, Chugai, Jansen, 
      Pfizer, Ono, AbbVie, Ayumi, Astellas, Sanofi, Novartis, Daiichi Sankyo, Eisai, 
      Asahi Kasei, Japan Blood Products Organization, and Kowa, and has received 
      research grants from Tanabe Mitsubishi, Bristol Myers, Eli Lilly, Chugai, AbbVie, 
      Ayumi, Astellas, Sanofi, Eisai, Tsumura and Co., and Asahi Kasei.
EDAT- 2022/11/03 06:00
MHDA- 2022/11/04 06:00
PMCR- 2022/11/01
CRDT- 2022/11/02 00:37
PHST- 2022/06/15 00:00 [received]
PHST- 2022/10/25 00:00 [accepted]
PHST- 2022/11/02 00:37 [entrez]
PHST- 2022/11/03 06:00 [pubmed]
PHST- 2022/11/04 06:00 [medline]
PHST- 2022/11/01 00:00 [pmc-release]
AID - 10.1038/s41598-022-23076-1 [pii]
AID - 23076 [pii]
AID - 10.1038/s41598-022-23076-1 [doi]
PST - epublish
SO  - Sci Rep. 2022 Nov 1;12(1):18397. doi: 10.1038/s41598-022-23076-1.