Open AccessThe exposure of autoantigens by microparticles underlies the formation of potent inflammatory components: the microparticle‐associated immune complexes
Author(s) -
Cloutier Nathalie,
Tan Sisareuth,
Boudreau Luc H.,
Cramb Catriona,
Subbaiah Roopashree,
Lahey Lauren,
Albert Alexandra,
Shnayder Ruslan,
Gobezie Reuben,
Nigrovic Peter A.,
Farndale Richard W.,
Robinson William H.,
Brisson Alain,
Lee David M.,
Boilard Eric
Publication year - 2013
Publication title -
embo molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.923
H-Index - 107
eISSN - 1757-4684
pISSN - 1757-4676
DOI - 10.1002/emmm.201201846
Subject(s) - immunology , immune system , arthritis , inflammation , neutrophil extracellular traps , synovial fluid , platelet , antibody , immune complex , flow cytometry , fibrinogen , chemistry , medicine , osteoarthritis , pathology , alternative medicine , biochemistry
Immunoglobulins, antigens and complement can assemble to form immune complexes (IC). ICs can be detrimental as they propagate inflammation in autoimmune diseases. Like ICs, submicron extracellular vesicles termed microparticles (MP) are present in the synovial fluid from patients affected with autoimmune arthritis. We examined MPs in rheumatoid arthritis (RA) using high sensitivity flow cytometry and electron microscopy. We find that the MPs in RA synovial fluid are highly heterogeneous in size. The observed larger MPs were in fact MP‐containing ICs (mpICs) and account for the majority of the detectable ICs. These mpICs frequently express the integrin CD41, consistent with platelet origin. Despite expression of the Fc receptor FcγRIIa by platelet‐derived MPs, we find that the mpICs form independently of this receptor. Rather, mpICs display autoantigens vimentin and fibrinogen, and recognition of these targets by anti‐citrullinated peptide antibodies contributes to the production of mpICs. Functionally, platelet mpICs are highly pro‐inflammatory, eliciting leukotriene production by neutrophils. Taken together, our data suggest a unique role for platelet MPs as autoantigen‐expressing elements capable of perpetuating formation of inflammatory ICs.