Dopaminergic receptors and adrenoceptors in circulating lymphocytes as putative biomarkers for the early onset and progression of multiple sclerosis

• Subjects with CIS may convert to clinically established MS, however no biomarker may predict the individual risk.
• Lymphocyte dopaminergic receptors (DR)- and adrenoceptors (AR)-operated pathways are dysregulated in MS and may predict the response to IFN-β.
• We now show that lymphocyte expression of several DR and AR mRNAs are upregulated in CIS subjects.
• DR D3, α2A-AR, and DR D5 mRNA after first neurologic event correlate with conversion to MS at 12 months, contributing to predict the risk of MS.

Clinically isolated syndrome (CIS) is a first, usually recovering, episode of neurological disturbance(s) suggestive of multiple sclerosis (MS). CIS subjects might benefit from early disease-modifying drugs, provided that those at high risk of developing MS can be identified. Gene expression for dopaminergic receptors (DR) and adrenoceptors (AR) is dysregulated in lymphocytes of MS patients and is affected by treatment with interferon (IFN)-β. In particular, lymphocyte DR D5 mRNA might be a marker of IFN-β response in MS patients. No information exists so far in CIS subjects. We investigated DR and AR gene expression in peripheral blood mononuclear cells (PBMC) and in CD4 + T effector (Teff) and regulatory (Treg) cells from CIS subjects, and assessed their relationship with MS progression after 12 months. Expression of several DR and AR are upregulated in PBMC, Teff and Treg from CIS subjects. DR D3 and α2A-AR mRNA in PBMC, and DR D5 mRNA in Treg correlate with the risk of MS at 12 months. Results show the involvement of dopaminergic and adrenergic pathways in CIS as well as in MS pathogenesis, supporting the evaluation of dopaminergic and adrenergic agents in MS.

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