Related Experiment Video
Updated: Jan 12, 2026
Determining Immune System Suppression versus CNS Protection for Pharmacological Interventions in Autoimmune Demyelination
Published on: September 12, 2016
Immune checkpoint-based biomarkers for therapeutic response in patients with multiple sclerosis
MariPaz López-Molina1, Gabriel Torres Iglesias1, Gonzalo Sáenz de Santa María-Diez2
1Neurological Sciences and Cerebrovascular Research Laboratory, Department of Neurology, Neurology and Cerebrovascular Disease Group, Neuroscience Area of Hospital La Paz Institute for Health Research IdiPAZ, La Paz University Hospital, Universidad Autónoma de Madrid, Madrid, Spain.
Introduction:
Although numerous disease-modifying treatments have been introduced for multiple sclerosis (MS), approximately 25% of patients experience therapeutic failure. This underscores the urgent need for reliable, minimally invasive biomarkers to predict treatment response at early stages. This study aimed to investigate 22 circulating immune cell subpopulations and their immune checkpoint (IC) expression profiles to identify early immunological biomarkers indicative of therapeutic failure in MS patients.
Methods:
In this observational and prospective study, 119 patients with relapsing-remitting MS were enrolled, including 69 responders and 50 non-responders, and 29 healthy controls. Spectral flow cytometry was used to immunophenotype 22 immune cell subpopulations and quantify the expression of co-stimulatory and co-inhibitory ICs before and at three months post-treatment initiation. Their correlation with therapeutic response over 12 months in MS patients was also analyzed. The response to treatment was evaluated using the No Evidence of Disease Activity composite, which includes clinical relapses, new lesions on MRI and progression of motor disability.
Results:
We identified differential IC expression patterns between MS patients and healthy controls, revealing specific ICs involved in the disease. Within the MS cohort, we observed differences between treatment responders and non-responders. Responders exhibited higher CD70 expression on Natural Killerbright cells. Additionally, elevated inhibitory CTLA-4 levels on CD20-CD27+ B cells may serve as biomarker for disability progression. BTLA expression on CD20+CD27- B cells was associated with relapse events, and PD-L1 expression on Natural Killerbright cells appeared to be a potential biomarker for progression independent of relapse activity (PIRA).
Discussion:
These findings highlight that specific immune cell subpopulations and their IC expression profiles can serve as valuable, early, and minimally invasive immunological markers for predicting therapeutic response in MS patients.
Insights
Predicting multiple sclerosis treatment failure is crucial. This study identified specific immune cell markers, like CD70 on Natural Killer cells, that can predict treatment response early, aiding personalized medicine for MS patients.
Area of Science:
- Immunology
- Neuroimmunology
- Biomarker Discovery
Background:
- Multiple sclerosis (MS) treatments have limitations, with ~25% of patients experiencing therapeutic failure.
- Predictive biomarkers are needed for early identification of non-responders to optimize MS treatment strategies.
Purpose of the Study:
- To identify early immunological biomarkers for predicting therapeutic failure in MS patients.
- To investigate immune checkpoint (IC) expression profiles on circulating immune cell subpopulations.
Main Methods:
- Observational, prospective study of 119 relapsing-remitting MS patients and 29 healthy controls.
- Spectral flow cytometry used to immunophenotype 22 immune cell subpopulations and quantify IC expression.
- Correlation of IC profiles with treatment response (No Evidence of Disease Activity) over 12 months.
Main Results:
- Differential IC expression patterns observed between MS patients and healthy controls.
- Responders showed higher CD70 on Natural Killerbright cells; elevated CTLA-4 on CD20-CD27+ B cells linked to disability progression.
- BTLA on CD20+CD27- B cells associated with relapses; PD-L1 on Natural Killerbright cells potentially predicts progression independent of relapse activity (PIRA).
Conclusions:
- Specific immune cell subpopulations and their IC expression profiles serve as valuable, early, and minimally invasive immunological markers.
- These biomarkers can predict therapeutic response and guide personalized treatment strategies in MS.
