Pré-Publication, Document De Travail Année : 2024

Morphological profiling of T cells predicts clinical response to VLA-4-targeting natalizumab therapy in patients with multiple sclerosis

Résumé

Abstract Despite the efficacy of natalizumab in Multiple Sclerosis (MS) treatment, approximately 30% of patients do not respond favorably. Individual heterogeneity of T-cell response to VLA-4 natalizumab-mediated blockade may underlie disparities in treatment efficacy. Here, a high-content cell imaging (HCI) pipeline was implemented to profile the in vitro effects of natalizumab on VLA-4-stimulated leukocytes from MS patients prior to treatment. Unsupervised clustering of image data partially discriminated non-responder MS patients based on morphology, F-actin organization, and signaling-related features in CD8+ T cells. Treatment response was assessed through a Random Forest approach with predictive performance of 91% for a discovery cohort and 70% for a validation cohort. Unfavorable treatment response was associated with the inefficacy of natalizumab to impair the ability of pretreated CD8+ T cells to spread over VCAM-1. Our study unveils that CD8+ T cells from individual MS patients display heterogeneous susceptibility to natalizumab in vitro and highlights the potential of HCI-based pretreatment monitoring to assist individualized treatment prescription.

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Immunologie
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Dates et versions

inserm-04728349 , version 1 (09-10-2024)

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Beatriz Chaves, Juan Carlo Santos E Silva, Helder Nakaya, Matheus Almeida, Florence Bucciarelli, et al.. Morphological profiling of T cells predicts clinical response to VLA-4-targeting natalizumab therapy in patients with multiple sclerosis. 2024. ⟨inserm-04728349⟩
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