Benjamin J Murdock, Bangyao Zhao, Ian F Webber-Davis, Samuel J Teener, Kristen D Pawlowski, Joshua P Famie, Caroline E Piecuch, Dae Gyu Jang, Eva L Feldman, Lili Zhao, Stephen A Goutman
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引用次数: 0
Abstract
Background: 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.
Methods: 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.
Findings: 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.
Conclusions: 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.
期刊介绍：
Med is a flagship medical journal published monthly by Cell Press, the global publisher of trusted and authoritative science journals including Cell, Cancer Cell, and Cell Reports Medicine. Our mission is to advance clinical research and practice by providing a communication forum for the publication of clinical trial results, innovative observations from longitudinal cohorts, and pioneering discoveries about disease mechanisms. The journal also encourages thought-leadership discussions among biomedical researchers, physicians, and other health scientists and stakeholders. Our goal is to improve health worldwide sustainably and ethically.
Med publishes rigorously vetted original research and cutting-edge review and perspective articles on critical health issues globally and regionally. Our research section covers clinical case reports, first-in-human studies, large-scale clinical trials, population-based studies, as well as translational research work with the potential to change the course of medical research and improve clinical practice.
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