This preprint is under consideration at Arthritis Research & Therapy. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research article
Molecular Remission at T cell level in Patients with Rheumatoid Arthritis
Tsutomu Takeuchi
Keio University School of Medicine
Corresponding Author
ORCiD: https://orcid.org/0000-0003-1111-8218
License:
This work is licensed under a CC BY 4.0 License. Read Full License
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.
Keywords
Rheumatoid arthritis, T cells, molecular remission
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
This is a list of supplementary files associated with this preprint. Click to download.
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Under Review
Version 2
Posted 28 Sep, 2020
No community comments so far
Review #2 received
Received 11 Jan, 2021
Reviewer #2 agreed
On 05 Jan, 2021
Reviewer #1 agreed
On 25 Sep, 2020
Review #1 received
Received 25 Sep, 2020
Editor assigned
On 24 Sep, 2020
Reviewers invited
Invitations sent on 24 Sep, 2020
Submission checks complete
On 23 Sep, 2020
Editor invited
On 23 Sep, 2020
No comments provided
Editorial decision: Major revision
On 22 Sep, 2020
Review #1 received
Received 07 Sep, 2020
Reviewer #2 agreed
On 05 Sep, 2020
Reviewer #1 agreed
On 03 Sep, 2020
Reviewers invited
Invitations sent on 02 Sep, 2020
Editor assigned
On 31 Jul, 2020
First submitted
On 30 Jul, 2020
Submission checks complete
On 30 Jul, 2020
Editor invited
On 30 Jul, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Rheumatology
Learn more about our company.
This preprint is under consideration at Arthritis Research & Therapy. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research article
Molecular Remission at T cell level in Patients with Rheumatoid Arthritis
Tsutomu Takeuchi
Keio University School of Medicine
Corresponding Author
ORCiD: https://orcid.org/0000-0003-1111-8218
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Under Review
Version 2
Posted 28 Sep, 2020
No community comments so far
Review #2 received
Received 11 Jan, 2021
Reviewer #2 agreed
On 05 Jan, 2021
Reviewer #1 agreed
On 25 Sep, 2020
Review #1 received
Received 25 Sep, 2020
Editor assigned
On 24 Sep, 2020
Reviewers invited
Invitations sent on 24 Sep, 2020
Submission checks complete
On 23 Sep, 2020
Editor invited
On 23 Sep, 2020
No comments provided
Editorial decision: Major revision
On 22 Sep, 2020
Review #1 received
Received 07 Sep, 2020
Reviewer #2 agreed
On 05 Sep, 2020
Reviewer #1 agreed
On 03 Sep, 2020
Reviewers invited
Invitations sent on 02 Sep, 2020
Editor assigned
On 31 Jul, 2020
First submitted
On 30 Jul, 2020
Submission checks complete
On 30 Jul, 2020
Editor invited
On 30 Jul, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Rheumatology
License:
This work is licensed under a CC BY 4.0 License. Read Full License
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