Extended Data Fig. 10: Association between disease stage and complement component levels and activity in the CSF and plasma of Huntington’s disease patients.
(a) Bar chart showing the concentration of complement component C1q in CSF samples from early premanifest HD patients (see Methods for inclusion criteria), late premanifest HD patients (see Methods for inclusion criteria) and early manifest HD patients (see Methods for inclusion criteria) recruited into the HDClarity study. Each dot represents a sample from a separate individual and the bar denotes the mean for each group n = 13 early premanifest HD, n = 18 late premanifest HD and n = 32 early manifest HD. Kurkasl-Wallis test (non-parametric ANOVA) p = 0.175 with early premanifest versus late premanifest HD p = >0.999, late premanifest versus early manifest HD p = 0.205 and early premanifest versus early manifest HD p = >0.999 via Dunn’s multiple comparison test. (b) Graphs showing the association between CAP score and CSF C1q concentration for all samples from Huntington’s Disease gene expansion carriers (HDGECs) as well as those just from premanifest HD patients recruited into the HDClarity study. Each dot represents a sample from a separate individual n = 63 HDGEC’s and n = 31 premanifest HD. Spearman r for HDGEC’s p = 0.267; for premanifest HD p = 0.977. (c) Bar chart showing the concentration of complement component C1q in plasma samples from early premanifest HD patients (see Methods for inclusion criteria), late premanifest HD patients (see Methods for inclusion criteria) and early manifest HD patients (see Methods for inclusion criteria) recruited into the HDClarity study. Each dot represents a sample from a separate individual and the bar denotes the mean for each group n = 13 early premanifest HD, n = 19 late premanifest HD and n = 32 early manifest HD. Kurkasl-Wallis test (non-parametric ANOVA) p = 0.133 with early premanifest versus late premanifest HD p = 0.180, late premanifest versus early manifest HD p = >0.999 and early premanifest versus early manifest HD p = 0.236 via Dunn’s multiple comparison test. (d) Graphs showing the association between CAP score and plasma C1q concentration for all samples from Huntington’s Disease gene expansion carriers (HDGECs) as well as those just from premanifest HD patients recruited into the HDClarity study. Each dot represents a sample from a separate individual n = 64 HDGEC’s and n = 32 premanifest HD. Spearman r for HDGEC’s p = 0.932; for premanifest HD p = 0.922. (e) Bar chart showing the ages of the early premanifest HD patients (see Methods for inclusion criteria), late premanifest HD patients (see Methods for inclusion criteria) and early manifest HD patients (see Methods for inclusion criteria) from the HDClarity study whose samples were assessed in this study. Each dot represents a sample from a separate individual and the bar denotes the mean for each group n = 13 early premanifest HD, n = 19 late premanifest HD and n = 32 early manifest HD. Kurkasl-Wallis test (non-parametric ANOVA) p = 0.000009 with early premanifest versus late premanifest HD p = 0.527, late premanifest versus early manifest HD p = 0.003 and early premanifest versus early manifest HD p = 0.00003 via Dunn’s multiple comparison test. (f) Bar chart showing the ‘high’ CAG repeat number of the early premanifest HD patients (see Methods for inclusion criteria), late premanifest HD patients (see Methods for inclusion criteria) and early manifest HD patients (see Methods for inclusion criteria) from the HDClarity study whose samples were assessed in this study. Each dot represents a sample from a separate individual and the bar denotes the mean for each group n = 13 early premanifest HD, n = 19 late premanifest HD and n = 32 early manifest HD. Kurkasl-Wallis test (non-parametric ANOVA) p = 0.003 with early premanifest versus late premanifest HD p = 0.002, late-premanifest versus early manifest HD p = 0.497 and early premanifest versus early manifest HD p = 0.004 via Dunn’s multiple comparison test. (g) Bar chart showing the CAP score of the early premanifest HD patients (see Methods for inclusion criteria), late premanifest HD patients (see Methods for inclusion criteria) and early manifest HD patients (see Methods for inclusion criteria) from the HDClarity study whose samples were assessed in this study. Each dot represents a sample from a separate individual and the bar denotes the mean for each group n = 13 early premanifest HD, n = 18 late premanifest HD and n = 32 early manifest HD. Kurkasl-Wallis test (non-parametric ANOVA) p = 0.0000002 with early premanifest versus late premanifest HD p = 0.025, late premanifest versus early manifest HD p = 0.016 and early premanifest versus early manifest HD p = 0.0000002 via Dunn’s multiple comparison test. (h) Graph showing the association between age and CSF C3 concentration for control (clinically normal) individuals recruited into the HDClarity study. Each dot represents a sample from a separate individual n = 32. Spearman r p = 0.022. (i) Graph showing the association between age and CSF iC3b concentration for control (clinically normal) individuals recruited into the HDClarity study. Each dot represents a sample from a separate individual n = 32. Spearman r p = 0.206. (J) Graph showing the association between age and CSF C1q concentration for control (clinically normal) individuals recruited into the HDClarity study. Each dot represents a sample from a separate individual n = 32. Spearman r p = 0.142. (k) Graph showing the association between CAP score and CSF C3 concentration (after adjustment for the effects of aging in controls) in samples from premanifest HD patients recruited into the HDClarity study. Each dot represents a sample from a separate individual n = 31 premanifest HD. Spearman r p = 0.968. (l) Bar chart showing the CSF C3 concentration (after adjustment for the effects of aging in controls) in samples from early premanifest HD and late premanifest HD patients. Each dot represents a sample from a separate individual and bars equal the mean for each group n = 13 early premanifest HD and n = 18 late premanifest HD. Kolmogorov-Smirnov test p = 0.194. (m) Graph showing the association between CAP score and CSF iC3b concentration (after adjustment for the effects of aging in controls) in samples from premanifest HD patients recruited into the HDClarity study. Each dot represents a sample from a separate individual n = 31 premanifest HD. Spearman r p = 0.060. (n) Bar chart showing the CSF iC3b concentration (after adjustment for aging in controls) in samples from early premanifest HD and late premanifest HD patients. Each dot represents a sample from a separate individual and bars equal the mean for each group n = 13 early premanifest HD and n = 18 late premanifest HD. Kolmogorov-Smirnov test p = 0.011. For bar charts, bars depict the mean. All error bars represent SEM. Stars depict level of significance with *=p < 0.05, **p = <0.01 and ***p < 0.001.
