Molecular Remission at T cell level in Patients with Rheumatoid Arthritis
Background. While numerous disease-modifying anti-rheumatic drugs (DMARDs) has brought about a dramatic paradigm shift in the management of rheumatoid arthritis (RA), unmet needs remain such as small proportion of achievement drug-free patients. The aim of this study is to explore key molecules for remission at T cell level, which is known to involve the pathogenesis of RA deeply, and investigate disease course of patients who achieved molecular remission (MR).
Methods. 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 of patients with RA using machine learning methods. In addition, we investigated the benefit of achieving MR on disease control thereafter.
Results. We identified 9 and 23 genes that were associated with clinical remission in CD4+ and CD8+ T cells. Principal component analysis (PCA) demonstrated expression profiling of them was similar with HCs. As to remission signature genes in CD4+ T cells, PCA result was reproduced using validation cohort, indicating their robustness. There was a trend towards better disease control during 12 months follow-up in patients treated with tocilizumab in deep MR than those in non-deep MR, although it was not significant.
Conclusion. We identified robust genes which represented remission status in CD4+ T cells using machine learning techniques. The current study will promote our understandings about molecular mechanism to achieve deep remission in the management of RA.
Trial registration: Not required.
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Posted 28 Sep, 2020
Received 11 Jan, 2021
On 05 Jan, 2021
On 25 Sep, 2020
Received 25 Sep, 2020
On 24 Sep, 2020
Invitations sent on 24 Sep, 2020
On 23 Sep, 2020
On 23 Sep, 2020
On 22 Sep, 2020
Received 07 Sep, 2020
On 05 Sep, 2020
On 03 Sep, 2020
Invitations sent on 02 Sep, 2020
On 31 Jul, 2020
On 30 Jul, 2020
On 30 Jul, 2020
On 30 Jul, 2020
Molecular Remission at T cell level in Patients with Rheumatoid Arthritis
Posted 28 Sep, 2020
Received 11 Jan, 2021
On 05 Jan, 2021
On 25 Sep, 2020
Received 25 Sep, 2020
On 24 Sep, 2020
Invitations sent on 24 Sep, 2020
On 23 Sep, 2020
On 23 Sep, 2020
On 22 Sep, 2020
Received 07 Sep, 2020
On 05 Sep, 2020
On 03 Sep, 2020
Invitations sent on 02 Sep, 2020
On 31 Jul, 2020
On 30 Jul, 2020
On 30 Jul, 2020
On 30 Jul, 2020
Background. While numerous disease-modifying anti-rheumatic drugs (DMARDs) has brought about a dramatic paradigm shift in the management of rheumatoid arthritis (RA), unmet needs remain such as small proportion of achievement drug-free patients. The aim of this study is to explore key molecules for remission at T cell level, which is known to involve the pathogenesis of RA deeply, and investigate disease course of patients who achieved molecular remission (MR).
Methods. 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 of patients with RA using machine learning methods. In addition, we investigated the benefit of achieving MR on disease control thereafter.
Results. We identified 9 and 23 genes that were associated with clinical remission in CD4+ and CD8+ T cells. Principal component analysis (PCA) demonstrated expression profiling of them was similar with HCs. As to remission signature genes in CD4+ T cells, PCA result was reproduced using validation cohort, indicating their robustness. There was a trend towards better disease control during 12 months follow-up in patients treated with tocilizumab in deep MR than those in non-deep MR, although it was not significant.
Conclusion. We identified robust genes which represented remission status in CD4+ T cells using machine learning techniques. The current study will promote our understandings about molecular mechanism to achieve deep remission in the management of RA.
Trial registration: Not required.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5