In vitro morphological profiling of T cells predicts clinical response to natalizumab therapy in patients with multiple sclerosis
Beatriz Chaves,
Juan Carlo Santos e Silva,
Helder Nakaya,
Nicolas Socquet-Juglard,
Florence Bucciarelli,
Guilhèn Prunier,
Matheus V. Almeida,
Claire Lacouture,
Saniya Kari,
Anne L. Astier,
Marco A. Medeiros,
João H. M. Silva,
Roland Liblau,
Vinicius Cotta- de-Almeida () and
Loïc Dupré ()
Additional contact information
Beatriz Chaves: Toulouse University
Juan Carlo Santos e Silva: University of São Paulo
Helder Nakaya: Hospital Israelita Albert Einstein
Nicolas Socquet-Juglard: Toulouse University
Florence Bucciarelli: Toulouse University
Guilhèn Prunier: Toulouse University
Matheus V. Almeida: Oswaldo Cruz Foundation (Fiocruz)
Claire Lacouture: Toulouse University
Saniya Kari: Toulouse University
Anne L. Astier: Toulouse University
Marco A. Medeiros: Oswaldo Cruz Foundation (Fiocruz)
João H. M. Silva: Oswaldo Cruz Foundation (Fiocruz)
Roland Liblau: Toulouse University
Vinicius Cotta- de-Almeida: Oswaldo Cruz Foundation (Fiocruz)
Loïc Dupré: Toulouse University
Nature Communications, 2025, vol. 16, issue 1, 1-15
Abstract:
Abstract Despite the efficacy of natalizumab, which targets the integrin VLA-4, in treating multiple sclerosis (MS), approximately 35% patients with MS present evidence of disease activity two years after treatment initiation. Individual heterogeneity of leukocyte response to VLA-4 on natalizumab-mediated blockade may underlie disparities in treatment efficacy. Here we use a high-content cell imaging (HCI) pipeline to profile the in vitro effects of natalizumab on VLA-4-stimulated PBMCs from MS patients prior to natalizumab treatment. Unsupervised clustering of image data partially discriminates non-responder MS patients based on morphology, F-actin organization and signaling-related features in CD8+ T cells. Furthermore, through a random forest approach, treatment response can be predicted with a performance of 92% for a discovery cohort and 88% for a validation cohort. Unfavorable treatment response is associated with a distinct actin remodeling response of natalizumab-exposed CD8+ T cells and a residual ability of these cells to spread on VCAM-1. Our study thus 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.
Date: 2025
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-60224-3
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DOI: 10.1038/s41467-025-60224-3
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