R B Mcgill1, F J Steyn1,2,3,4, S T Ngo2,3,4,5,6, K A Thorpe4, S Heggie4, R D Henderson3,4, P A Mccombe3,4, T M Woodruff1,2,5. 1. School of Biomedical Sciences, The University of Queensland, Brisbane, Australia. 2. Wesley Medical Research, The Wesley Hospital, Brisbane, Australia. 3. University of Queensland Centre for Clinical Research, The University of Queensland, Brisbane, Australia. 4. Department of Neurology, Royal Brisbane & Women's Hospital, Brisbane, Australia. 5. Queensland Brain Institute, The University of Queensland, Brisbane, Australia, and. 6. Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, Australia.
Abstract
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.
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.
Authors: Robert G Miller; Rongzhen Zhang; Paige M Bracci; Ari Azhir; Richard Barohn; Richard Bedlack; Michael Benatar; James D Berry; Merit Cudkowicz; Edward J Kasarskis; Hiroshi Mitsumoto; Georgios Manousakis; David Walk; Bjorn Oskarsson; Jeremy Shefner; Michael S McGrath Journal: Muscle Nerve Date: 2022-06-03 Impact factor: 3.852