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Increased Plasma Microbial tDR-1 in At-Risk Individuals Is Associated With Decreased Conversion to Clinical
Anastasiia Phothisane1, Tulsi K Joishy1, Carolina Ramirez-Becerra1
1Vanderbilt University Medical Center, Nashville, Tennessee.
Arthritis & Rheumatology (Hoboken, N.J.)
|June 23, 2026
Summary
Higher levels of microbial tRNA-derived RNA-1 (tDR-1) in at-risk individuals were linked to a lower likelihood of developing rheumatoid arthritis (RA). This microbial RNA may influence RA development by downregulating immune response genes.
Area of Science:
- Microbiology
- Immunology
- Rheumatology
Background:
- Microbial small RNAs (sRNAs) can influence human gene expression.
- Elevated plasma tRNA-derived RNA-1 (tDR-1) was previously linked to reduced rheumatoid arthritis (RA) disease activity.
- The role of tDR-1 in RA development among at-risk individuals requires further investigation.
Purpose of the Study:
- To determine if tDR-1 plasma concentrations differ in anti-CCP3+ individuals who later develop RA versus those who do not.
- To assess if tDR-1 can predict RA conversion beyond established risk factors.
- To investigate the in vitro effects of tDR-1 on immune cells.
Main Methods:
- Plasma tDR-1 concentrations were measured in 60 anti-CCP3+ at-risk individuals (ARI).
- Logistic regression and ROC analysis were used to evaluate tDR-1's predictive ability for RA development.
- Gene expression analysis was performed on human macrophages treated with tDR-1 in vitro.
Main Results:
- Higher baseline plasma tDR-1 concentrations were observed in non-converters compared to converters (5.4-fold difference).
- The addition of tDR-1 significantly improved the prediction of RA development (AUROC increased from 0.722 to 0.902).
- In vitro, tDR-1 downregulated numerous type 1 interferon response genes in THP-1 monocyte-derived macrophages.
Conclusions:
- Increased plasma tDR-1 concentrations are associated with a lower risk of developing clinical RA in CCP3+ ARI.
- tDR-1 may influence RA pathogenesis by modulating the type 1 interferon response.
- Microbial sRNAs like tDR-1 represent potential biomarkers and therapeutic targets for RA.
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