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

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.

Keywords:

• Amyotrophic lateral sclerosis
• myeloid
• monocyte
• CD14
• HLA-DR
• ALSFRS-R

Acknowledgments

The authors would like to thank the patients with ALS who donated their time to this research and Megan McStea for statistical support. The authors are also grateful to A/Prof. Marc Ruitenberg for critical reading and helpful suggestions on the manuscript.

Declaration of interest

No potential competing interest was reported by the author(s). STN acknowledges support through the Scott Sullivan MND Research Fellowship, and is currently supported by a FightMND Mid-Career Research Fellowship.

Data availability statement

Data are available on reasonable request.

Additional information

Funding

This study was supported by funding from the Queensland Government and MND and Me Foundation (Advance Queensland Innovation Partnership [AQIP01216]), FightMND [02_TRG_2017], Wesley Medical Research [2016-31], and the National Health and Medical Research Council [1082271].