1. Nat. Rev. Rheumatol. doi:10.1038/nrrheum.2018.38
Figure 2 Platelet activation pathways and putative effects of activated platelets in SLE pathogenesis
Figure 2 | Platelet activation pathways and putative effects of activated platelets in SLE pathogenesis. a | Immune complexes (ICs) activate platelets via the Fc receptor FcγRIIA131,210. Complement protein C1q potentiates platelet activation by ICs, but complement is also involved in IC clearance, suggesting a balance between complement-mediated IC clearance and platelet activation. Anti-phospholipid antibodies (aPL) also contribute to the IC load and promote C4d deposition and complement activation on platelets in systemic lupus erythematosus (SLE), leading to platelet activation. Additionally, platelets can be activated through various Toll-like receptors (TLRs). b | IL-1β produced by SLE platelets promotes endothelial upregulation of intercellular adhesion molecule 1 (ICAM1; also known as CD54) and chemokines. Expression of E-selectin, vascular cell adhesion molecule 1 (VCAM1; also known as CD106) and ICAM1 on activated endothelium enables platelet adhesion. Increased levels of circulating platelet–leukocyte aggregates are detected in patients with SLE, and platelet CD40L (including soluble CD40L (sCD40L)) activates endothelial cells and also induces adaptive immune responses, by supporting T cell-mediated B cell responses including antibody production and germinal centre (GC) formation. Platelet-derived microparticles, containing cytokines, transcription factors, microRNA and mRNA, can contribute to the circulatory autoantigenic load in SLE and have been linked to disease activity. Mitochondria extruded from platelets are also a source of danger associated molecular patterns (DAMPs) as well as potential autoantigens in SLE. A number of soluble mediators produced by platelets, such as S100A8/A9 proteins (also called calprotectin), serotonin, sCD40L and high mobility group protein B1 (HMGB1), have been associated with SLE pathogenesis. The increased risk of thrombosis in SLE could be linked to FcγRIIA ligation, increased complement deposition on platelets and aPL. S100A9 could also be a prothrombotic factor in SLE. mtDNA, mitochondrial DNA; NET, neutrophil extracellular trap.
Linge, P. et al. (2018) The non-haemostatic role of platelets in systemic lupus erythematosus
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