Circulating Cytokine Profiles and Their Relationships with Autoantibodies, Acute Phase Reactants, and Disease Activity in Patients with Rheumatoid Arthritis

Abstract

Our objective was to analyse the relationship between circulating cytokines, autoantibodies, acute phase reactants, and disease activity in DMARDs-naïve rheumatoid arthritis (RA) patients (n = 140). All cytokines were significantly higher in the RA cohort than in healthy controls. Moderate-to-strong positive intercorrelations were observed between Th1/Th2/macrophage/fibroblast-derived cytokines. RF correlated significantly with IL-1β, IL-2, IL-4, IL-10, IL-12, G-CSF, GM-CSF, IFN-γ, and TNF (P < .0001), and aCCP and aMCV with IL-1β, IL-2, IL-4, and IL-10 (P < .0002), while IL-6 correlated best with the acute phase reactants, CRP, and SAA (P < .0001). In patients with a DAS28 score of ≥5.1, IFN-γ, IL-1β, IL-1Ra, TNF, GM-CSF, and VEGF were significantly correlated (P < .04–.001) with high disease activity (HDA). Circulating cytokines in RA reflect a multifaceted increase in immune reactivity encompassing Th1 and Th2 cells, monocytes/macrophages, and synovial fibroblasts, underscored by strong correlations between these cytokines, as well as their relationships with RF, aCCP, and aMCV, with some cytokines showing promise as biomarkers of HDA.

Effectiveness of Chloroquine and Inflammatory Cytokine Response in Patients With Early Persistent Musculoskeletal Pain and Arthritis Following Chikungunya Virus Infection

“…Except for a disproportionately low CRP level, the laboratory results showed a severe inflammatory response. The proinflammatory cytokine phenotype was as intense as that reported for RA (8). We previously observed persistent musculoskeletal pain and arthritis among patients in the community (16% at 4 months, 12% at 1 year, and 5% at 2 years).…”

Exaggerated circulating Th-1 cytokine response in early rheumatoid arthritis patients with nodules

“…Previously, we and others have shown RA patients to have higher IL-7 levels compared to healthy controls (15,16) , although reduced IL-7 levels in RA patients compared to healthy controls or osteoarthritis patients have been reported elsewhere (17).…”

Reliable and cost-effective serodiagnosis of rheumatoid arthritis

“…Multiple biomarkers of disease activity in RA have been evaluated in studies originating from both Africa [6][7][8][9][10][11] and elsewhere [12][13][14][15][16]. In addition, commercial ventures have also focused on developing multi-array test profiles that may improve cost-effective management of RA [15,17].…”

“…Combination testing of RF and ACPA had the best specificity and positive predictive value [22]  Systemic pro-inflammatory and anti-inflammatory cytokines were elevated in DMARD-naïve RA patients, some of which were strongly and positively correlated with RF, ACPA, and acute phase reactants, as well as with HDA (high disease activity) [6]  Patients unresponsive to DMARDs after 6 months of treatment are unlikely to improve at 12 months of treatment, underscoring the need for better disease management to attain LDA (low disease activity) or remission earlier in disease [23].…”