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Peripheral Immune Profiles Predict ALS Progression in an Age- and Sex-Dependent Manner
Benjamin J Murdock1, Bangyao Zhao1, Kristen D Pawlowski1
1From the Department of Neurology (B.J.M., K.D.P., J.P.F., C.E.P., I.F.W.-D., S.J.T., E.L.F., S.A.G.); and School of Public Health (B.Z., L.Z.), Biostatistics Department, University of Michigan, Ann Arbor.
Immune cell profiles in amyotrophic lateral sclerosis (ALS) vary by age and sex, impacting disease progression. Specific immune markers, especially natural killer (NK) cells, can predict ALS outcomes and may guide personalized treatments.
Area of Science:
- Neuroimmunology
- Neurodegenerative Diseases
Background:
- Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease.
- Peripheral blood immune cell profiles are implicated in ALS pathobiology.
- Immune associations with ALS progression may be age and sex-dependent.
Purpose of the Study:
- To identify immune profile associations with ALS progression.
- To determine if these associations are age and sex-specific.
- To assess the predictive power of immune profiles for ALS disease course.
Main Methods:
- Flow cytometry generated immune profiles (22 markers) from 241 ALS participants.
- Unsupervised hierarchical clustering identified immune profile groups.
- Least absolute shrinkage and selection operator-Cox regression and random forest models analyzed associations and predictive power, stratified by age and sex.
Main Results:
- Distinct immune profiles correlated with ALS progression-free survival.
- Reduced natural killer (NK)-cell activation was linked to slower progression.
- Neutrophil and NKp46 expression associated with faster progression, while overall NK-cell levels and subpopulations correlated with slower progression, with demographic variations.
- Immune markers significantly improved short-term ALS progression prediction, particularly in females with NK-cell markers.
Conclusions:
- Specific immune profiles influence ALS progression in an age and sex-dependent manner.
- Peripheral immune markers enhance short-term clinical outcome prediction in ALS.
- Detailed immunophenotyping may enable personalized immunotherapeutics for ALS.
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