Evidence map›Paper›PMID 38626361›Full record

ArticleNeurology(R) neuroimmunology & neuroinflammation2024

Peripheral Immune Profiles Predict ALS Progression in an Age- and Sex-Dependent Manner.

Benjamin J Murdock, Bangyao Zhao, Kristen D Pawlowski, Joshua P Famie, Caroline E Piecuch, Ian F Webber-Davis, Samuel J Teener, Eva L Feldman, Lili Zhao, Stephen A Goutman

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neurology(R) neuroimmunology & neuroinflammation, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
4.8field-weighted citation impact, top 4% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

18 citing papers in PubMed, 13 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Sex Hormones Associate With Amyotrophic Lateral Sclerosis Risk and Survival.Annals of clinical and translational neurology · 2026
    Article
  8. Article
  9. Review
  10. Article
  11. Review
  12. Article
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  14. Article
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  17. Gut microbiota immune cross-talk in amyotrophic lateral sclerosis.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2024
    Review
  18. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 1 institution in 1 country.

Benjamin J MurdockFrom 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.
Bangyao ZhaoFrom 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.
Kristen D PawlowskiFrom 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.ORCID 0000-0002-2497-4497
Joshua P FamieFrom 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.
Caroline E PiecuchFrom 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.
Ian F Webber-DavisFrom 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.
Samuel J TeenerFrom 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.
Eva L FeldmanFrom 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.ORCID 0000-0002-9162-2694
Lili ZhaoFrom 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.
Stephen A GoutmanFrom 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.ORCID 0000-0001-8780-6637
University of Michigan · US

Funding

Michigan Institute for Clinical and Health Research (MICHR)UL1TR002240 · NCATS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI LUMENG, JULIE C, MASHOUR, GEORGE ALEXANDER · 2017 to 2022
$54.9M
Uncovering new genes and disease modifiers for ALS and related disordersU54NS092091 · NINDS · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI Michael Benatar · 2014 to 2026
$19.8M
Mapping the ALS Exposome to Gain New Insights into Disease Risk and PathogenesisR01ES030049 · NIEHS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI BATTERMAN, STUART A, FELDMAN, EVA LUCILLE · 2020 to 2024
$3.5M
Developing novel strategies for personalized treatment and prevention of ALS: Leveraging the global exposome, genome, epigenome, metabolome, and inflammasome with data science in a case/control cohortR01NS127188 · NINDS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI BATTERMAN, STUART A, FELDMAN, EVA LUCILLE · 2021 to 2024
$3.4M
Creating a foundation for personalized age- and sex-based immune-targeted therapies from an ALS longitudinal cohort by identifying peripheral and central immune signaturesR01NS120926 · NINDS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI GOUTMAN, STEPHEN, MURDOCK, BENJAMIN JOSEPH · 2021 to 2025
$3.0M
Impact of Geospatial Factors and Environmental Pollutants on Amyotrophic Lateral Sclerosis in the State of MichiganK23ES027221 · NIEHS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI GOUTMAN, STEPHEN · 2017 to 2021
$1.0M
The Role of NK Cells in ALSR21NS102960 · NINDS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI FELDMAN, EVA LUCILLE · 2018 to 2019
$388k
ATSDR CDC HHS R01 TS000327NCATS NIH HHS UL1 TR002240NIEHS NIH HHS K23 ES027221NIEHS NIH HHS R01 ES030049NINDS NIH HHS R01 NS120926NINDS NIH HHS R01 NS127188NINDS NIH HHS R21 NS102960NINDS NIH HHS U54 NS092091
6 · The paper itself

Abstract

BACKGROUND AND

objectivesAmyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease whose pathobiology associates with peripheral blood immune cell levels and activation patterns in an age and sex-dependent manner. This study's objective was to identify immune profile associations with ALS progression, whether the associations are age and sex-specific, and whether immune profiles can predict a future disease course.

methodsFlow cytometry immune profiles (a combination of 22 peripheral blood immune markers) were generated for 241 participants with ALS and linked to ALS progression, using progression-free survival, which is a composite combining the revised ALS Functional Rating Scale and survival. Participants were first grouped by immune profiles using unsupervised hierarchical clustering, and clusters were associated with subsequent progression-free survival. Next, individual immune markers were associated with progression-free survival using least absolute shrinkage and selection operator-Cox regression. Analyses were stratified by age and sex to identify demographic-specific immune mechanisms. Finally, random forest determined the predictive power of immune profiles on ALS progression in the whole population and again stratified by age and sex.

resultsProgression-free survival differed between clusters of participants with similar immune profiles, particularly reduced natural killer (NK)-cell activation associated with slower progression. Individual markers such as neutrophil levels and NK-cell NKp46 expression associated with faster ALS progression while overall NK-cell levels and NK-cell subpopulations associated with slower progression; the strength of these associations varied by age and sex. Adding these immune markers to prediction models dramatically increased short-term prediction compared with routine clinical prognostic variables alone, and the addition of NK-cell markers further improved the prediction accuracy in female participants. DISCUSSION: Specific immune profiles likely contribute to ALS progression in an age and sex-dependent manner, and peripheral immune markers enhance the prediction of short-term clinical outcomes. These findings suggest a complex milieu of immune profiles associated with ALS progression, and more detailed immunophenotyping in ALS will facilitate personalized immunotherapeutics in ALS.

Indexed as

Amyotrophic Lateral SclerosisNeurodegenerative DiseasesBiomarkersDisease ProgressionFemaleHumansMalePrognosisBiomarkers

Identifiers

PMID38626361
PMCPMC11087030
OpenAlexW4394866198

What OpenQuestion holds

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LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.