A Critical Evaluation of Inflammatory Markers in Huntington’s Disease Plasma

BACKGROUND: Huntington’s Disease (HD) is a hereditary, progressive neurodegenerative disorder characterised by both neurological and systemic symptoms. In HD, immune changes can be observed before the onset of overt clinical features raising the possibility that immune markers in plasma could be used to track disease progression. It has previously been demonstrated that a widespread, progressive innate immune response is detectable in plasma throughout the course of HD. OBJECTIVE: The aim of the present study was to investigate the potential of several components of innate immunity as plasma biomarkers in HD. METHODS: We utilised antibody-based detection technologies as well as mass spectrometric quantification, multiple reaction monitoring (MRM-MS). RESULTS: Levels of several markers previously described as altered in HD, such as clusterin, complement component 4, complement component 9 and α-2 macroglobulin did not differ between healthy controls and HD subjects as measured by Luminex, ELISA or MRM-MS. C-reactive protein was decreased in early HD, while the other immune markers tested were unaltered. CONCLUSIONS: Of the immune markers tested in this study, none showed potential to track with HD disease progression

Hormone levels in control, premanifest and stage II/III HD cohorts.

<p>P-value = p-value from linear regression of specified variable on age and gender (or else by gender as indicated), L indicates that logs were taken of the specified variable prior to linear regression; P indicates Freedman and Lane permutation tests were performed to account to non-normality, LP indicates Freedman and Lane permutation tests were performed after taking logs of the specified variable. In all cases, age and gender were adjusted for.</p><p>Data are presented as Mean ±SD for normally distributed data and as median [minimum–maximum] for skewed data.</p

Analysis of GH in control, premanifest and stage II/III HD cohorts.

<p>A: Mean GH concentrations over 24 hour sampling period in the three groups. B: FT analysis of GH plotting strength/power (%) against frequency (minutes) of GH oscillations for the three groups.</p

Analysis of LH in control, premanifest and stage II/III HD cohorts.

<p>A: Mean LH concentrations over 24 hour sampling period for female subjects in the three groups. B: Mean LH concentrations over 24 hour sampling period for male subjects in the three groups. C: FT analysis of LH plotting strength/power (%) against frequency (minutes) of LH oscillations for the three groups.</p

Analysis of ACTH and cortisol in control, premanifest and stage II/III HD cohorts.

<p>A: Mean ACTH concentrations over 24 hour sampling period in the three groups. B: Mean ACTH concentrations over 24 hour sampling period in the three groups. C: FT analysis of ACTH plotting strength/power (%) against frequency (minutes) of ACTH oscillations for the three groups. D: FT analysis of cortisol plotting strength/power (%) against frequency (minutes) of cortisol oscillations for the three groups. E: Mean molar cortisol:ACTH ratio over 24 hour sampling period in the three groups.</p

Demographic characteristics and clinical features of controls, pre-manifest and stage II/III HD cohorts.

<p>Data presented as median (range).</p

Mean blood glucose levels at different time points during a glucose tolerance test in controls, premanifest and moderate HD patients and the corresponding mean insulin (A), growth hormone (B) and cortisol (C) concentrations.

<p>Mean blood glucose levels at different time points during a glucose tolerance test in controls, premanifest and moderate HD patients and the corresponding mean insulin (A), growth hormone (B) and cortisol (C) concentrations.</p

A Metabolic Study of Huntington’s Disease

Data produced as part of a study of metabolic factors in Huntington’s disease gene carriers. The study sought to determine whether various metabolic variables are linked to disease state in a cross-sectional study of cohorts of HD gene carriers and controls. The study team examined carbohydrate, lipid and protein metabolites as well as hormones related to energy metabolism in plasma samples from well-characterised cohorts of premanifest and moderate HD subjects and healthy controls