Early Immune System Changes in Amyotrophic Lateral Sclerosis Correlate With Later Disease Progression.

Details

• Alternative Title:
  Med (New York, N.Y.), 2025, v. 6, no. 8: Early Immune System Changes in Amyotrophic Lateral Sclerosis Correlate With Later Disease Progression.
• Journal Article:
  Med (New York, N.Y.)
• Personal Author:
  Murdock, Benjamin J. ; Zhao, Bangyao ; Webber-Davis, Ian F. ; Teener, Samuel J. ; Pawlowski, Kristen D. ; Famie, Joshua P. ; Piecuch, Caroline E. ; Jang, Dae Gyu ; Feldman, Eva L. ; Zhao, Lili ; Goutman, Stephen A.
• Description:
  Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disease with no cure and limited treatment options. The immune system is implicated in disease pathology, unlocking a potential therapeutic avenue. However, it is unclear whether immune changes are a cause or consequence of disease progression.
  
  Peripheral immune cells were longitudinally measured at monthly intervals in 55 ALS and 50 control participants. 22 peripheral immune markers in the blood were assessed using flow cytometry, and clinical progression was assessed using the revised ALS functional rating scale (ALSFRS-R). Individual immune markers, their trajectories, and overall variability were compared in ALS versus control participants; ALS participants were also stratified by clinical progression rates and assessed similarly across progression groups. Finally, a novel, lagged linear regression model correlated the rate of immune changes to subsequent downstream ALSFRS-R changes.
  
  Numerous immune markers were dysregulated in ALS versus control participants, with altered levels, trajectories, or variability in immune populations and surface markers. ALS participants had increased immune variability relative to control participants; within ALS participants, faster progressors overall had decreased marker variability. Finally, natural killer (NK) cell numbers, NK cell subpopulations, and NK cell surface markers were significantly associated with downstream ALS progression.
  
  The immune system is dysregulated in ALS and more consistently dysregulated in faster ALS progression, and immune dysregulation occurs upstream of clinical changes. These findings suggest that the immune system is a causal factor of ALS progression in human patients.
  
  CReATe Consortium, NIH, Target ALS, DoD, ALSA.
• Content Notes:
  Author manuscript
• Subjects:
  • Amyotrophic Lateral Sclerosis
  • Disease Progression
  • Case-Control Studies
  • Biomarkers
  • Flow Cytometry
  • Longitudinal Studies
  • Immunity, Cellular
  • Humans
  • Male
  • Female
  More +
• Keywords:
  • Immune system
  • amyotrophic lateral sclerosis
  • ALS
  • NK cells
  • neuroinflammation
• Source:
  Med (New York, N.Y.), 2025, v. 6, no. 8
• DOI:
  https://doi.org/10.1016/j.medj.2025.100673
• ISSN:
  2666-6359 ; 2666-6340
• Pubmed ID:
  40286795
• Pubmed Central ID:
  PMC12335928
• Document Type:
  Text
• Funding:
  U54 NS092091/NS/NINDS NIH HHSUnited States/ ; R01 TS000339/TS/ATSDR CDC HHSUnited States/ ; R01 NS120926/NS/NINDS NIH HHSUnited States/ ; R01 NS127188/NS/NINDS NIH HHSUnited States/ ; R01 ES030049/ES/NIEHS NIH HHSUnited States/ ; R21 NS102960/NS/NINDS NIH HHSUnited States/
• Genre:
  Journal Article
• Pages in Document:
  100673 (28 pdf pages)
• Volume:
  6
• Issue:
  8
• Download URL:
  https://stacks.cdc.gov/view/cdc/261453/cdc_261453_DS1.pdf
• File Type:
  [PDF - 1.62 MB]
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha-512:acb79e6a765185c02cc0b40e1d3d5ff34ebedde734c0b5a38cbe634c2d1fd32e0268dca6232b21f394adad38bdc5cff2d777c3b3147afddd6311d295e56ea1c1