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Interleukin-6 as a marker of Huntington's disease progression: Systematic review and meta-analysis
Sarah Eide1, Melissa Misztal1, Zhong-Ping Feng1
1Department of Physiology, University of Toronto, Toronto, Ontario, M5S 1A8, Canada.
Insights
Plasma Interleukin-6 (IL-6) levels are elevated in Huntington's disease (HD) patients, correlating with disease progression and motor symptom severity. This finding suggests IL-6 may serve as a useful biomarker for tracking HD progression in clinical settings.
Area of Science:
- Neuroscience
- Biomarkers
- Genetics
Background:
- Huntington's disease (HD) is an inherited neurodegenerative disorder with variable progression.
- Current diagnostic methods confirm HD but lack markers for disease progression.
- Accurate progression markers are crucial for personalized treatment plans in HD.
Purpose of the Study:
- To investigate plasma Interleukin-6 (IL-6) as a potential biomarker for Huntington's disease progression.
- To meta-analytically compare IL-6 levels between HD patients and healthy controls.
- To correlate IL-6 levels with motor and cognitive function in HD patients.
Main Methods:
- Systematic literature search of PubMed and Medline (up to October 2021).
- Inclusion of studies reporting plasma IL-6 levels in mutation-positive HD patients and controls.
- Meta-analysis of IL-6 levels and correlation with standardized cognitive and motor function measures.
Main Results:
- Plasma IL-6 levels were significantly higher in HD patients compared to controls (g = 0.73, P < 0.01).
- IL-6 levels increased significantly across disease stages, particularly from pre-manifest to manifest HD (g = 0.31, P < 0.05).
- Elevated IL-6 correlated with more severe motor impairments (r = 0.179, P = 0.008) and daily living/work task disabilities (r = -0.229, P < 0.001).
Conclusions:
- Plasma IL-6 is a viable biomarker for Huntington's disease progression.
- IL-6 levels correlate with motor symptom severity and functional decline in HD.
- Further research is needed to establish definitive IL-6 ranges for progressive HD states.
Abstract:
Huntington's disease (HD) is a rare, inherited disorder with a broad spectrum of manifestations that vary with disease severity and progression. Although genetic testing can readily confirm the initial diagnosis of HD, markers sensitive to HD progression are needed to aid the development of individual treatment plans. The current analysis aims to identify plasma Interleukin-6 (IL-6) as a marker of disease progression in HD patients. A systematic search of PubMed and Medline from conception through October 2021 was conducted. Studies reporting plasma IL-6 levels of mutation-positive HD patients and healthy controls that met inclusion criteria were selected. The search strategy collected 303 studies, 9 of which met analysis inclusion criteria. From included studies, plasma IL-6 levels of 469 individuals with the HD mutation and 206 healthy controls were collected. Plasma IL-6 levels were meta-analytically compared between healthy controls and individuals with the confirmed HD mutation at all stages of disease and correlated to performance on standardized measures of total cognitive and motor function. Plasma IL-6 was significantly increased in HD groups compared to controls (g = 0.73, 95% CI = 0.31,1.16, P < 0.01) and increased significantly throughout most stages of disease progression, notably between pre-manifest and manifest (g = 0.31, 95% CI = 0.04,0.59, P < 0.05) and early and moderate HD stages (g = 0.52, 95% CI = 0.18,0.86, P < 0.01). Significant correlations between plasma IL-6 levels and HD symptomatic progression were identified, with increased cytokine levels associated with more severe motor impairments (r = 0.179, 95% CI = 0.0479,0.304, P = 0.008) and more extreme disabilities in activities of daily living and/or work tasks (r = -0.229, 95% CI = -0.334, -0.119, P < 0.001). Conclusively, plasma IL-6 levels correlate with disease and motor symptom progression and may act as a viable marker for clinical use. Analysis is limited by small study numbers and highlights the need for future work to identify definitive ranges or rates of change of plasma IL-6 levels that correlate to progressive HD disease states.
