Wei Su,1,2,* Yang Xiao,1,2,* Xiaohong Chen,1,2,* Yan Wu,1,2 Bitao Wu,1,2 Qiang Yang,1,2 Bi Peng,3 Jie Tang,4,5 Yuwei Yang1,2 

1Department of Medicine Laboratory, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang, Sichuan, People’s Republic of China; 2Department of Medicine Laboratory, NHC Key Laboratory of Nuclear Technology Medical Transformation (Mianyang Central Hospital), Mianyang, Sichuan, People’s Republic of China; 3Department of Medicine Laboratory, The Third Hospital of Mianyang, Sichuan Mental Health Center, Mianyang, Sichuan, People’s Republic of China; 4Department of Blood Transfusion, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang, Sichuan, People’s Republic of China; 5Department of Blood Transfusion, NHC Key Laboratory of Nuclear Technology Medical Transformation (Mianyang Central Hospital), Mianyang, Sichuan, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Yuwei Yang, Email yyw318@sc-mch.cn Jie Tang, Email tjandbetty@sc-mch.cn

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.

Keywords: cytokine release, rheumatoid arthritis, clinical remission, prediction, pattern