Monocyte CD14 and HLA-DR expression increases with disease duration and severity in amyotrophic lateral sclerosis

Amyotroph Lateral Scler Frontotemporal Degener. 2022 Aug;23(5-6):430-437. doi: 10.1080/21678421.2021.1964531. Epub 2021 Aug 16.


Objective: To investigate changes in immune markers and frequencies throughout disease progression in patients with amyotrophic lateral sclerosis (ALS). Methods: In this longitudinal study, serial blood samples were collected from 21 patients with ALS over a time period of up to 16 months. Flow cytometry was used to quantitate CD14, HLA-DR, and CD16 marker expression on monocyte subpopulations and neutrophils, as well as their cell population frequencies. A Generalized Estimating Equation model was used to assess the association between changes in these immune parameters and disease duration and the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R). Results: CD14 expression on monocyte subpopulations increased with both disease duration and a decrease in ALSFRS-R score in patients with ALS. HLA-DR expression on monocyte subpopulations also increased with disease severity and/or duration. The expression of CD16 did not change relative to disease duration or ALSFRS-R. Finally, patients had a reduction in non-classical monocytes and an increase in the classical to non-classical monocyte ratio throughout disease duration. Conclusion: The progressive immunological changes observed in this study provide further support that monocytes are implicated in ALS pathology. Monocytic CD14 and HLA-DR surface proteins may serve as a therapeutic target or criteria for the recruitment of patients with ALS into clinical trials for immunomodulatory therapies.

Keywords: ALSFRS-R; Amyotrophic lateral sclerosis; CD14; HLA-DR; monocyte; myeloid.

MeSH terms

  • Amyotrophic Lateral Sclerosis* / genetics
  • Amyotrophic Lateral Sclerosis* / metabolism
  • Biomarkers / metabolism
  • Flow Cytometry
  • HLA-DR Antigens* / metabolism
  • Humans
  • Lipopolysaccharide Receptors* / metabolism
  • Longitudinal Studies
  • Monocytes* / metabolism


  • Biomarkers
  • CD14 protein, human
  • HLA-DR Antigens
  • Lipopolysaccharide Receptors