Cytokine Signatures as Biomarkers of Clinical Remission in Rheumatoid Arthritis

Abstract

Objective: Variations in cytokine levels have been observed in patients with rheumatoid arthritis (RA), which contribute to immune dysfunction. This study aimed to investigate the potential of intricate cytokine networks for predicting the clinical remission of RA. Methods: In total, 164 patients with RA and 69 healthy individuals were included in this study. We investigated the levels of interleukins (ILs, including IL1β, IL2, IL4, IL5, IL6, IL8, IL10, IL12P70, and IL17), interferons (IFNs, including IFNα and IFNγ), tumor necrosis factor-alpha (TNFα), and immunoinflammatory markers, and subsequently analyzed their association and diagnostic potential in RA remission. Results: In all patients with RA, the prevalence of the release of more than six or seven cytokines was 25.0% or 18.9%, respectively, and presented nearly or the highest consistency with the prevalence of non-remission RA (Kappa=0.678 or 0.682, respectively, P<0.001). All the 12 cytokines examined were significantly associated with non-remission of RA in both Spearman correlation analysis (ρ=0.28~0.58, P<0.017) and univariate logistic regression analysis (OR=1.005~1.546, all P<0.05). However, multivariate analysis identified only IL-6, IL12P70, and TNFα as independently associated with non-remission RA (OR=1.003~1.460, all P<0.05). For the diagnosis of clinical remission of RA, the release patterns of these three cytokines yielded areas under the curve of 0.941 and 0.926 in the modeling and validation groups, respectively, with sensitivities of 88.9% and 87.0% and specificities of 87.5% and 87.9%, respectively. Conclusion: Our study suggests that IL6, TNFα, and IL12P70 may plot a cytokine release pattern for non-remission of RA, and are associated with its initiation, progression, and manifestation.