Extracellular vesicles are associated with the systemic inflammation of patients with seropositive rheumatoid arthritis

Abstract

Patients with rheumatoid arthritis (RA) and autoantibodies, such as rheumatoid factor and those against cyclic citrullinated peptides, are designated as seropositive and have a more severe disease with worse prognosis than seronegative RA patients. Understanding the factors that participate in systemic inflammation, in addition to articular commitment, would allow better treatment approaches for prevention of RA comorbidities and disease reactivation. We evaluated whether monocyte subsets and extracellular vesicles (EVs) could contribute to this phenomenon. Seropositive patients had higher levels of proinflammatory cytokines than those of seronegative patients and healthy controls (HCs); however, this systemic inflammatory profile was unrelated to disease activity. High frequencies of circulating EVs positive for IgG, IgM, CD41a, and citrulline, together with altered counts and receptor expression of intermediate monocytes, were associated with systemic inflammation in seropositive patients; these alterations were not observed in seronegative patients, which seem to be more similar to HCs. Additionally, the EVs from seropositive patients were able to activate mononuclear phagocytes in vitro, and induced proinflammatory cytokines that were comparable to the inflammatory response observed at the systemic level in seropositive RA patients; therefore, all of these factors may contribute to the greater disease severity that has been described in these patients.

Differential Profile of Systemic Extracellular Vesicles From Sporadic and Familial Alzheimer’s Disease Leads to Neuroglial and Endothelial Cell Degeneration

“…Extracellular vesicles were isolated from citrate-induced anticoagulated peripheral blood and cerebrospinal fluid (CSF), as previously was described in our recent investigations (Burbano et al, 2018a(Burbano et al, ,b, 2019Villar-Vesga et al, 2019). Briefly, blood samples were centrifuged immediately after collection at 1,800 × g for 10 min at 21 • C to separate the plasma.…”

Johnny on the Spot-Chronic Inflammation Is Driven by HMGB1

“…In autoimmunity, platelet EVs seem to influence the course of disease, being present in high levels in patients with RA (96–98), SLE (98, 99), Grave's disease (100) and systemic sclerosis (101). In RA, EVs can act through several different pathways, presenting antigens to the immune system, degrading extracellular matrix, carrying miRNA and autoantigens, such as citrullinated proteins, resulting in induction of inflammation, as well as perpetuating it by formation of bioactive immunocomplexes (ICs) (23, 98).…”

Endothelial activation and injury by microparticles in patients with systemic lupus erythematosus and rheumatoid arthritis

“…For patients with RA, the median and age range were 56 (39–66) years, three patients had active (aRA) and six patients had inactive (iRA) disease; they were classified according to the Disease Activity Score 28 (in iRA < 2.6 or aRA ≥ 2.6) [32]. The patients with SLE [33] and RA [34] included in this study belong to previously published cohorts, in which MPs were characterized in detail. As HCs, we included six women of similar ages according to the median age of each study group.…”

“…MPs-ICs pools were those that formed ≥ 28% of ICs in patients with RA and ≥ 38% in patients with SLE; MP pools were those that formed < 6% of ICs in controls and patients (Additional file 1: Figure S1B). These thresholds were established according to the distribution of the circulating MPs-ICs frequency in a population of patients with SLE [33] and RA [34], which was previously studied by us (for a detailed explanation of this analysis, please refer to the legend of Additional file 1: Figure S1C). Each pool was counted by flow cytometry as we previously described [33].…”