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Identification of CD4+ T cell biomarkers for predicting the response of patients with relapsing?remitting multiple sclerosis to natalizumab treatment.

ABSTRACT: Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system of autoimmune etiopathogenesis, and is characterized by various neurological symptoms. Glatiramer acetate and interferon?? are administered as first?line treatments for this disease. In non?responsive patients, several second?line therapies are available, including natalizumab; however, a percentage of MS patients does not respond, or respond partially. Therefore, it is of the utmost importance to develop a diagnostic test for the prediction of drug response in patients suffering from complex diseases, such as MS, where several therapeutic options are already available. By a machine learning approach, the UnCorrelated Shrunken Centroid algorithm was applied to identify a subset of genes of CD4+ T cells that may predict the pharmacological response of relapsing?remitting MS patients to natalizumab, before the initiation of therapy. The results from the present study may provide a basis for the design of personalized therapeutic strategies for patients with MS.

SUBMITTER: Fagone P

PROVIDER: S-EPMC6580020 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Identification of CD4+ T cell biomarkers for predicting the response of patients with relapsing‑remitting multiple sclerosis to natalizumab treatment.

Fagone Paolo P Mazzon Emanuela E Mammana Santa S Di Marco Roberto R Spinasanta Flaminia F Basile Maria Sofia MS Petralia Maria Cristina MC Bramanti Placido P Nicoletti Ferdinando F Mangano Katia K

Molecular medicine reports 20190523 1

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system of autoimmune etiopathogenesis, and is characterized by various neurological symptoms. Glatiramer acetate and interferon‑β are administered as first‑line treatments for this disease. In non‑responsive patients, several second‑line therapies are available, including natalizumab; however, a percentage of MS patients does not respond, or respond partially. Therefore, it is of the utmost importance to develop a d ...[more]

PMID: 31180553

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Project description:Background and purposeThe considerable clinical effect of natalizumab in patients with relapsing-remitting multiple sclerosis might be explained by its possible beneficial effect on axonal functioning. In this longitudinal study, the effect of natalizumab on absolute concentrations of total N-acetylaspartate, a marker for neuronal integrity, and other brain metabolites is investigated in patients with relapsing-remitting multiple sclerosis by using MR spectroscopic imaging.Materials and methodsIn this explorative observational study, 25 patients with relapsing-remitting multiple sclerosis initiating natalizumab treatment were included and scanned every 6 months for 18 months. Additionally 18 matched patients with relapsing-remitting multiple sclerosis continuing treatment with interferon-β or glatiramer acetate were included along with 12 healthy controls. Imaging included short TE 2D-MR spectroscopic imaging with absolute metabolite quantification of total N-acetylaspartate, creatine and phosphocreatine, choline-containing compounds, myo-inositol, and glutamate. Concentrations were determined for lesional white matter, normal-appearing white matter, and gray matter.ResultsAt baseline in both patient groups, lower concentrations of total N-acetylaspartate and creatine and phosphocreatine were found in lesional white matter compared with normal-appearing white matter and additionally lower glutamate in lesional white matter of patients receiving natalizumab. In those patients, a significant yearly metabolite increase was found for lesional white matter total N-acetylaspartate (7%, P < .001), creatine and phosphocreatine (6%, P = .042), and glutamate (10%, P = .028), while lesion volumes did not change. In patients receiving interferon-β/glatiramer acetate, no significant change was measured in lesional white matter for any metabolite, while whole-brain normalized lesion volumes increased.ConclusionsPatients treated with natalizumab showed an increase in total N-acetylaspartate, creatine and phosphocreatine, and glutamate in lesional white matter. These increasing metabolite concentrations might be a sign of enhanced axonal metabolism.

Dataset Information

Identification of CD4+ T cell biomarkers for predicting the response of patients with relapsing?remitting multiple sclerosis to natalizumab treatment.

Publications

Identification of CD4+ T cell biomarkers for predicting the response of patients with relapsing‑remitting multiple sclerosis to natalizumab treatment.

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