CD4+ T-cell transcription factors predict phenoconversion in idiopathic rapid eye movement sleep behavior disorder

<b>Aim:</b> Early biomarkers of phenoconversion to neurodegeneration are crucial to identify individuals at high risk. In patients with idiopathic REM sleep behavior disorder (iRBD), the strongest risk factor for neurodegeneration, CD4⁺ T cells exhibit a peculiar transcription factor pattern. <b>Objective:</b> To assess transcription factor mRNA levels in CD4⁺ T cells as predictive biomarkers of phenoconversion in iRBD patients. <b>Methods:</b> iRBD patients were followed prospectively. ROC curve analysis and Kaplan-Meier curves were used to assess the discrimination between converters and non-converters. <b>Results:</b> CD4⁺ T cells from converters had higher <i>STAT1</i>, and lower <i>GATA3</i> and <i>FOXP3</i> mRNA levels. Hazard ratio was 58.3 (95% CI: 6.2–547.1) for higher <i>STAT1</i>, 101.2 (95% CI: 16.8–609.4) for lower <i>GATA3</i> and 15.7 (2.7–91.4) for lower <i>FOXP3</i>. <b>Conclusion:</b><i>STAT1</i>, <i>GATA3</i> and <i>FOXP3</i> mRNA levels in CD4⁺ T cells are promising predictive biomarkers of phenoconversion in iRBD patients. Idiopathic REM sleep behavior disorder (iRBD) can lead to neurodegeneration, and the early identification of patients at risk would be crucial. Our research now shows that mRNA levels of some transcription factors in CD4⁺ T cells may represent early biomarkers predicting phenoconversion to established neurodegenerative conditions on average up to 3.5 years earlier. Patients with idiopathic REM sleep behavior disorder (iRBD) are at risk of progression toward established neurodegeneration, and early biomarkers of phenoconversion would be crucial to identify individuals at higher risk. This study shows that, in iRBD subjects progressing to neurodegenerative conditions, CD4⁺ T cells have higher expression of the transcription factors <i>STAT1</i>, and lower levels of <i>GATA3</i> and <i>FOXP3</i> on average 3.5 years before progression. <i>STAT1</i>, <i>GATA3</i> and <i>FOXP3</i> mRNA levels in CD4⁺ T cells are therefore promising predictive biomarkers of phenoconversion in iRBD patients.