Up‐regulation of cytokines and chemokines predates the onset of rheumatoid arthritis

Abstract

Objective. To identify whether cytokines, cytokinerelated factors, and chemokines are up-regulated prior to the development of rheumatoid arthritis (RA).Methods. A nested case-control study was performed in 86 individuals who had donated blood samples before experiencing any symptoms of disease (prepatients) and 256 matched control subjects (1:3 ratio). In 69 of the pre-patients, blood samples were also obtained at the time of the diagnosis of RA. The plasma levels of 30 cytokines, related factors, and chemokines were measured using a multiplex system.Results. The levels of several of the cytokines, cytokine receptors, and chemokines were significantly increased in individuals before disease onset compared with the levels in control subjects; i. Conclusion. Individuals in whom RA later developed had significantly increased levels of several cytokines, cytokine-related factors, and chemokines representing the adaptive immune system (Th1, Th2, and Treg cell-related factors); after disease onset, the involvement and activation of the immune system was more general and widespread.

Enhanced and persistent levels of interleukin (IL)-17+CD4+ T cells and serum IL-17 in patients with early inflammatory arthritis

“…A previous study investigated cytokine and chemokine levels in patients prior to and at onset of RA. IL-17 expression was increased in pre-patients (up to 5 years before symptom onset), although this difference was not statistically significant [29]. IL-17 levels decreased following disease onset, while MCP-1, MIP-1α, GM-CSF and G-CSF were increased significantly in pre-patients compared with control subjects, and a number of other cytokines became increased significantly versus controls in the 3 years prior to disease onset (IL-2R, IL-1β, IL-9, IL-10, eotaxin, GM-CSF).…”

Circulating fibrocytes contribute to the pathogenesis of collagen antibody–induced arthritis

“…The CCR7 ligands CCL19 and CCL21 are expressed in vascular and lymphatic endothelium in RA (24). The levels of eotaxin (CCL11) (25), monocyte chemotactic protein 1 (CCL2) (26), and macrophage inflammatory protein 1␣ (CCL3) (27) are elevated in the serum of patients with RA. Given the large number of chemo- 3590 GALLIGAN AND FISH kines expressed in the inflamed joint, the fact that circulating fibrocytes migrate to the RA joint is not surprising.…”

Roles of Reactive Oxygen Species in Rheumatoid Arthritis Pathogenesis

“…Although synovial inflammation-induced cartilage damage and destruction of bone is the dominant manifestation of clinical RA, systemic immune abnormalities that are not joint specific are already apparent many years before onset of the RA [4,66]. With advancing age, problems in the homeostasis of the T cell compartments and signaling thresholds for T cell activation lead to the loss of naïve T cells, the accumulation of inflammatory T cell populations and loss of tolerance to modified self-antigens [17,27].…”