Pathogenesis of lupus

Oelke, Kurt; Richardson, Bruce C.

doi:10.1002/art.10380

Cited by 10 publications

(2 citation statements)

References 17 publications

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“…Phagocytosis of DNA and RNA immune complexes via Fcγ receptors leads to activation of PRRs and, in particular, TLR7 and 9 as they recognize RNA and DNA, respectively [ 76 , 77 ]. In fact, TLR7 and 9 are robust activators of B cells and dendritic cells stimulating autoantibody production and IFN-α, which are both characteristic of SLE [ 78 , 79 ]. IFN-α plays a critical role in the severity and progression of SLE [ 80 ].…”

Section: Systemic Lupus Erythematosusmentioning

confidence: 99%

Pattern recognition receptors as potential therapeutic targets in inflammatory rheumatic disease

Mullen¹,

Chamberlain²,

Sacre³

2015

Arthritis Res Ther

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The pattern recognition receptors of the innate immune system are part of the first line of defence against pathogens. However, they also have the ability to respond to danger signals that are frequently elevated during tissue damage and at sites of inflammation. Inadvertent activation of pattern recognition receptors has been proposed to contribute to the pathogenesis of many conditions including inflammatory rheumatic diseases. Prolonged inflammation most often results in pain and damage to tissues. In particular, the Toll-like receptors and nucleotide-binding oligomerisation domain-like receptors that form inflammasomes have been postulated as key contributors to the inflammation observed in rheumatoid arthritis, osteoarthritis, gout and systemic lupus erythematosus. As such, there is increasing interest in targeting these receptors for therapeutic treatment in the clinic. Here the role of pattern recognition receptors in the pathogenesis of these diseases is discussed, with an update on the development of interventions to modulate the activity of these potential therapeutic targets.

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Section: Systemic Lupus Erythematosusmentioning

confidence: 99%

Pattern recognition receptors as potential therapeutic targets in inflammatory rheumatic disease

Mullen¹,

Chamberlain²,

Sacre³

2015

Arthritis Res Ther

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“…Anti-DNA autoantibodies are a hallmark of SLE, with titers correlating with disease activity ( 6 , 7 ); however, it is not clear how these anti-DNA antibodies exert their pathogenic effects. Most studies examining the pathological mechanisms mediated by IgG anti-DNA antibodies addressed the properties endowed by the variable regions, including DNA-binding activity for IC formation, nuclear-transport activity to induce apoptosis, and cross-reactivity with other self-antigens ( 35 – 37 ). Here, we showed that two 3D8 antibody formats (3D8 IgG and 3D8 scFv-Fc) induced production of inflammatory cytokines, whereas 3D8 scFv did not, despite cytosolic localization after internalization.…”

Section: Discussionmentioning

confidence: 99%

Cytosolic Internalization of Anti-DNA Antibodies by Human Monocytes Induces Production of Pro-inflammatory Cytokines Independently of the Tripartite Motif-Containing 21 (TRIM21)-Mediated Pathway

et al. 2018

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Anti-DNA autoantibodies are a hallmark of systemic lupus erythematosus (SLE). A subset of anti-DNA IgG autoantibodies is cell-internalizable; thus they can enter living cells in the form of free IgG. However, the contribution made by the Fc region of internalized free-form IgG to the cytokine response has not been studied, despite the recent discovery of tripartite motif-containing 21 (TRIM21), a cytosolic Fc receptor involved in immune signaling. This study used an internalizable IgG anti-DNA antibody (3D8) to examine the cytokine responses of human monocytes to the Fc region of cytosolic free IgG. Internalization of 3D8 IgG and a 3D8 single-chain variable fragment-Fc (scFv-Fc) induced production of IL-8 and TNF-α via activation of NF-κB. By contrast, a 3D8 scFv (comprising variable domains alone) did not. This suggests Fc-dependent cytokine signaling. A 3D8 IgG-N434D mutant that is not recognized by TRIM21 induced greater production of cytokines than 3D8 IgG. Moreover the amounts of cytokines induced by 3D8 IgG in TRIM21-knockdown THP-1 cells were higher than those in control cells, indicating that cytokine signaling is not mediated by TRIM21. The results suggest the existence of a novel Fc-dependent signaling pathway that is activated upon internalization of IgG antibodies by human monocytes.

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Serum/plasma homocysteine levels in patients with systemic lupus erythematosus: a systematic review and meta-analysis

Sam

Zhang

et al. 2020

Clin Rheumatol

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Pathogenesis of lupus

Cited by 10 publications

References 17 publications

Pattern recognition receptors as potential therapeutic targets in inflammatory rheumatic disease

Pattern recognition receptors as potential therapeutic targets in inflammatory rheumatic disease

Cytosolic Internalization of Anti-DNA Antibodies by Human Monocytes Induces Production of Pro-inflammatory Cytokines Independently of the Tripartite Motif-Containing 21 (TRIM21)-Mediated Pathway

Serum/plasma homocysteine levels in patients with systemic lupus erythematosus: a systematic review and meta-analysis

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