Erika De Francesco1, Michele Terzaghi2, Elisa Storelli1, Luca Magistrelli3,4, Cristoforo Comi1,3, Massimiliano Legnaro1, Marco Mauri5, Franca Marino1,6, Maurizio Versino5, Marco Cosentino1,6. 1. Center of Research in Medical Pharmacology, University of Insubria, Varese, Italy. 2. Unit of Sleep Medicine and Epilepsy, IRCCS Mondino Foundation, Pavia, Italy. 3. Movement Disorders Centre, Neurology Unit, Department of Translational Medicine, University of Piemonte Orientale, Novara, Italy. 4. PhD Program in Clinical and Experimental Medicine and Medical Humanities, University of Insubria, Varese, Italy. 5. Department of Medicine and Surgery, University of Insubria, Varese, Italy. 6. Center of Research in Neuroscience, University of Insubria, Varese, Italy.
Abstract
BACKGROUND: CD4+ T-cell dysregulation occurs in Parkinson's disease (PD); however, it is unknown whether it contributes to PD development. The objective of this study was to investigate transcription factor gene expression in CD4+ T cells in idiopathic rapid eye movement sleep behavior disorder, the strongest risk factor for prodromal PD. METHODS: Expression of transcription factors (TBX21, STAT1, STAT3, STAT4, STAT6, RORC, GATA3, FOXP3, and NR4A2) was measured in CD4+ T cells from 33 polysomnographically confirmed idiopathic rapid eye movement sleep behavior disorder subjects and compared with expression in cells from matched healthy subjects and antiparkinson drugs-naive PD patients. RESULTS: Compared with healthy subjects, idiopathic rapid eye movement sleep behavior disorder subjects and PD patients had lower TBX21, STAT3, and STAT4, and higher FOXP3 expression. TBX21 expression discriminated healthy subjects from idiopathic rapid eye movement sleep behavior disorder subjects and PD patients, but not idiopathic rapid eye movement sleep behavior disorder subjects with PD. CONCLUSIONS: In idiopathic rapid eye movement sleep behavior disorder subjects CD4+ T cells exhibit a peculiar molecular signature strongly resembling cells from PD patients, suggesting early involvement of peripheral immunity in PD.
BACKGROUND:CD4+ T-cell dysregulation occurs in Parkinson's disease (PD); however, it is unknown whether it contributes to PD development. The objective of this study was to investigate transcription factor gene expression in CD4+ T cells in idiopathic rapid eye movement sleep behavior disorder, the strongest risk factor for prodromal PD. METHODS: Expression of transcription factors (TBX21, STAT1, STAT3, STAT4, STAT6, RORC, GATA3, FOXP3, and NR4A2) was measured in CD4+ T cells from 33 polysomnographically confirmed idiopathic rapid eye movement sleep behavior disorder subjects and compared with expression in cells from matched healthy subjects and antiparkinson drugs-naive PDpatients. RESULTS: Compared with healthy subjects, idiopathic rapid eye movement sleep behavior disorder subjects and PDpatients had lower TBX21, STAT3, and STAT4, and higher FOXP3 expression. TBX21 expression discriminated healthy subjects from idiopathic rapid eye movement sleep behavior disorder subjects and PDpatients, but not idiopathic rapid eye movement sleep behavior disorder subjects with PD. CONCLUSIONS: In idiopathic rapid eye movement sleep behavior disorder subjects CD4+ T cells exhibit a peculiar molecular signature strongly resembling cells from PDpatients, suggesting early involvement of peripheral immunity in PD.
Authors: Elena Contaldi; Luca Magistrelli; Anna Vera Milner; Marco Cosentino; Franca Marino; Cristoforo Comi Journal: J Parkinsons Dis Date: 2021 Impact factor: 5.568