PMID- 36311714
OWN - NLM
STAT- MEDLINE
DCOM- 20221101
LR  - 20221102
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 13
DP  - 2022
TI  - The role of organ-deposited IgG in the pathogenesis of multi-organ and tissue 
      damage in systemic lupus erythematosus.
PG  - 924766
LID - 10.3389/fimmu.2022.924766 [doi]
LID - 924766
AB  - Systemic lupus erythematosus (SLE), often known simply as lupus, is a severe 
      chronic autoimmune disease that is characterized by multi-organ and tissue damage 
      and high levels of autoantibodies in serum. We have recently investigated, using 
      animal models, the role of organ-deposited IgG autoantibodies in the pathogenesis 
      of organ and tissue damage in SLE. We found that intra-organ injection of serum 
      from mice with lupus (i.e., lupus mice) into healthy mice triggered inflammation 
      in tissue and organs but that serum from other healthy mice did not, and that the 
      severity of inflammation was related to the dose of serum injected. 
      Immunohistochemistry showed that a large number of IgG molecules are deposited at 
      the site of organ and tissue damage in lupus mice, and that IgG is a major 
      contributor to the development of tissue inflammation triggered by serum from 
      lupus mice or patients. The development of tissue inflammation induced by IgG in 
      serum from lupus mice requires the presence of monocytes/macrophages, but not of 
      lymphocytes or neutrophils; tumor necrosis factor (TNF)/tumor necrosis factor 
      receptor 1 (TNFR1) and interleukin 1 (IL-1) also play essential roles in the 
      development of tissue inflammation triggered by IgG. In addition, it has been 
      found that TNFR1 inhibitors can suppress skin injury in lupus mice and that 
      spleen tyrosine kinase (Syk) inhibitors, which can block the signaling 
      transduction of IgG/Fc gamma receptors (FcgammaRs), can prevent and treat skin injury 
      and kidney damage in lupus mice. We have also observed that lupus IgG might 
      protect against bone erosion. Based on these results, we conclude that IgG plays 
      a crucial role in the development of organ and tissue damage in SLE and in 
      protecting bone erosion and arthritis, and we suggest that the IgG/FcgammaR signaling 
      pathway is an important therapeutic target in SLE.
CI  - Copyright (c) 2022 Qiu, Yu and Deng.
FAU - Qiu, Wenlin
AU  - Qiu W
AD  - Department of Rheumatology and Immunology, Union Hospital, Tongji Medical 
      College, Huazhong University of Science and Technology, Wuhan, China.
FAU - Yu, Tong
AU  - Yu T
AD  - Department of Rheumatology and Immunology, Union Hospital, Tongji Medical 
      College, Huazhong University of Science and Technology, Wuhan, China.
FAU - Deng, Guo-Min
AU  - Deng GM
AD  - Department of Rheumatology and Immunology, Union Hospital, Tongji Medical 
      College, Huazhong University of Science and Technology, Wuhan, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20221013
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
RN  - 0 (Receptors, Tumor Necrosis Factor, Type I)
RN  - 0 (Autoantibodies)
RN  - 0 (Immunoglobulin G)
SB  - IM
MH  - Mice
MH  - Animals
MH  - *Receptors, Tumor Necrosis Factor, Type I
MH  - *Lupus Erythematosus, Systemic
MH  - Autoantibodies
MH  - Inflammation/pathology
MH  - Immunoglobulin G
PMC - PMC9609414
OTO - NOTNLM
OT  - FcgammaR
OT  - IgG
OT  - SLE
OT  - autoantibody
OT  - macrophage
OT  - organ damage
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- 2022/11/01 06:00
MHDA- 2022/11/02 06:00
PMCR- 2022/01/01
CRDT- 2022/10/31 04:26
PHST- 2022/04/20 00:00 [received]
PHST- 2022/09/14 00:00 [accepted]
PHST- 2022/10/31 04:26 [entrez]
PHST- 2022/11/01 06:00 [pubmed]
PHST- 2022/11/02 06:00 [medline]
PHST- 2022/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2022.924766 [doi]
PST - epublish
SO  - Front Immunol. 2022 Oct 13;13:924766. doi: 10.3389/fimmu.2022.924766. eCollection 
      2022.