Platelets may be a target for treating systemic lupus erythematosus (SLE), based on recent evidence published in Science Translational Medicine.
SLE is a rare autoimmune disease that most commonly affects women. Inflammation targets multiple organs, and the disease progression is not yet well understood. People with SLE also have elevated levels of antibodies directed against DNA.
Patients with SLE have high amounts of plasma mitochondrial DNA (mtDNA), even with low disease activity. These patients also have chronic platelet activation.
The researchers used a mouse model to understand the role of platelets and immune complexes (ICs) in SLE. They used in vitro analysis of human platelets to determine how ICs and toll-like receptor (TLR) ligands cause platelets to release mtDNA.
They used a mouse model of lupus and injected mice with ICs for in vivo studies. The researchers also prospectively recruited 74 patients with SLE and 30 healthy individuals. They analyzed blood samples for the presence of platelet activation and extracellular mitochondria.
The study authors predicted platelets would be the primary reservoir of mtDNA in blood. But in their research, they found that, in human blood, about 27% of total mtDNA is present in platelets. They also found that stimulating a unique Fcɣ receptor, FcɣRIIA, by ICs causes the release of mtDNA by activated platelets.
“This study highlights the unforeseen role of platelets as a source of mitochondrial antigens in IC-mediated disease,” the authors concluded. “The identification of the key molecular mechanisms that underlie mitochondrial release highlights potential therapeutic targets that may improve the treatment of this devastating illness.”
Melki I, Allaeys I, Tessandier N, et al. Platelets release mitochondrial antigens in systemic lupus erythematosus. Sci Transl Med. 2021;13(581):eaav5928. doi:10.1126/scitranslmed.aav5928