Molecular remission at T cell level in patients with rheumatoid arthritis

• Published in: Scientific reports Vol. 11; no. 1; pp. 16691 - 9
• Main Authors: Inamo, Jun, Suzuki, Katsuya, Takeshita, Masaru, Kondo, Yasushi, Okuzono, Yuumi, Koga, Keiko, Kassai, Yoshiaki, Takiguchi, Maiko, Kurisu, Rina, Yoshimura, Akihiko, Takeuchi, Tsutomu
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 17.08.2021; Nature Publishing Group; Nature Portfolio
• Subjects: 631/114/1305; 631/114/2413; 631/337/2019; 692/4023/1670/498; Autoimmune diseases; CD4 antigen; CD8 antigen; Disease control; Gene expression; Humanities and Social Sciences; Learning algorithms; Lymphocytes; Lymphocytes T; Molecular modelling; Monoclonal antibodies; multidisciplinary; Patients; Principal components analysis; Remission; Remission (Medicine); Rheumatoid arthritis; Science; Science (multidisciplinary)
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-021-96300-z

While numerous disease-modifying anti-rheumatic drugs (DMARDs) have brought about a dramatic paradigm shift in the management of rheumatoid arthritis (RA), unmet needs remain, such as the small proportion of patients who achieve drug-free status. The aim of this study was to explore key molecules for remission at the T cell level, which are known to be deeply involved in RA pathogenesis, and investigate the disease course of patients who achieved molecular remission (MR). We enrolled a total of 46 patients with RA and 10 healthy controls (HCs). We performed gene expression profiling and selected remission signature genes in CD4 + T cells and CD8 + T cells from patients with RA using machine learning methods. In addition, we investigated the benefits of achieving MR on disease control. We identified 9 and 23 genes that were associated with clinical remission in CD4 + and CD8 + T cells, respectively. Principal component analysis (PCA) demonstrated that their expression profiling was similar to those in HCs. For the remission signature genes in CD4 + T cells, the PCA result was reproduced using a validation cohort, indicating the robustness of these genes. A trend toward better disease control was observed during 12 months of follow-up in patients treated with tocilizumab in deep MR compared with those in non-deep MR, although the difference was not significant. The current study will promote our understanding of the molecular mechanisms necessary to achieve deep remission during the management of RA.