PMID- 37331172
OWN - NLM
STAT- MEDLINE
DCOM- 20230822
LR  - 20240202
IS  - 1095-9157 (Electronic)
IS  - 0896-8411 (Print)
IS  - 0896-8411 (Linking)
VI  - 139
DP  - 2023 Sep
TI  - Antimyeloperoxidase antibodies modulate inflammatory responses and activate 
      profibrotic pathways in human monocytes.
PG  - 103060
LID - S0896-8411(23)00069-0 [pii]
LID - 10.1016/j.jaut.2023.103060 [doi]
LID - 103060
AB  - Antimyeloperoxidase (anti-MPO) and antiproteinase 3 (anti-PR3) antibodies are 
      found in anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV). We 
      investigated the effect of both anti-MPO and anti-PR3 IgG on human monocytes. 
      Peripheral blood monocytes were cultured under a range of conditions that 
      included TLR agonists, anti-MPO IgG and anti-PR3 IgG with appropriate controls. 
      Experiments included whole transcriptome profiling and an assessment of the role 
      of Fc receptors. When monocytes were stimulated with LPS or R848, anti-MPO but 
      not anti-PR3 IgG, caused a reduction in IL-10 secretion and had a profound effect 
      on cell-surface marker expression. Anti-MPO but not anti-PR3 IgG enhanced 
      monocyte survival in the absence of TLR stimulation. These effects depended on 
      the Fc receptor CD32a. With TLR stimulation, the effect of anti-MPO but not 
      anti-PR3 IgG on the transcriptional response at 6 h was variable, but we 
      identified a core set of transcripts likely to be important. Without TLR 
      stimulation, there was a robust effect of anti-MPO but not anti-PR3 IgG on the 
      transcriptional response at 24 h, and there was a highly significant enrichment 
      of genes encoding extracellular matrix and extracellular matrix-associated 
      proteins. Analysis with nCounter confirmed many of the differentially expressed 
      transcripts and supported a role for CD32a. These data show that anti-MPO, but 
      not anti-PR3 IgG, from patients with AAV has wide-ranging effects on monocytes 
      which depend on CD32a. The activation of a profibrotic transcriptional response 
      by anti-MPO but not anti-PR3 IgG may give insights into the differences in 
      disease phenotype.
CI  - Copyright (c) 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.
FAU - Florez-Barros, Fernanda
AU  - Florez-Barros F
AD  - School of Immunology and Microbial Sciences, King's College London, UK.
FAU - Bearder, Siobhan
AU  - Bearder S
AD  - School of Immunology and Microbial Sciences, King's College London, UK.
FAU - Pavlidis, Polychronis
AU  - Pavlidis P
AD  - School of Immunology and Microbial Sciences, King's College London, UK.
FAU - Robson, Michael G
AU  - Robson MG
AD  - School of Immunology and Microbial Sciences, King's College London, UK. 
      Electronic address: Michael.robson@kcl.ac.uk.
LA  - eng
GR  - MR/R004870/1/MRC_/Medical Research Council/United Kingdom
GR  - PG/17/51/32950/BHF_/British Heart Foundation/United Kingdom
GR  - DH_/Department of Health/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230616
PL  - England
TA  - J Autoimmun
JT  - Journal of autoimmunity
JID - 8812164
RN  - EC 3.4.21.76 (Myeloblastin)
RN  - 0 (Receptors, Fc)
RN  - 0 (Immunoglobulin G)
RN  - 0 (Antibodies, Antineutrophil Cytoplasmic)
RN  - EC 1.11.1.7 (Peroxidase)
SB  - IM
MH  - Humans
MH  - *Monocytes
MH  - Myeloblastin
MH  - *Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis
MH  - Receptors, Fc/genetics
MH  - Immunoglobulin G
MH  - Antibodies, Antineutrophil Cytoplasmic
MH  - Peroxidase
PMC - PMC10828547
OTO - NOTNLM
OT  - ANCA
OT  - Autoantibody
OT  - Autoimmunity
OT  - Inflammation
OT  - Monocyte
OT  - Vasculitis
COIS- Declaration of competing interest The authors have declared that no conflict of 
      interest exists.
EDAT- 2023/06/19 00:42
MHDA- 2023/08/22 06:42
PMCR- 2023/09/01
CRDT- 2023/06/18 18:05
PHST- 2023/03/20 00:00 [received]
PHST- 2023/05/05 00:00 [revised]
PHST- 2023/05/08 00:00 [accepted]
PHST- 2023/08/22 06:42 [medline]
PHST- 2023/06/19 00:42 [pubmed]
PHST- 2023/06/18 18:05 [entrez]
PHST- 2023/09/01 00:00 [pmc-release]
AID - S0896-8411(23)00069-0 [pii]
AID - 103060 [pii]
AID - 10.1016/j.jaut.2023.103060 [doi]
PST - ppublish
SO  - J Autoimmun. 2023 Sep;139:103060. doi: 10.1016/j.jaut.2023.103060. Epub 2023 Jun 
      16.