Ganglioside-focused Glycan Array Reveals Abnormal Anti-GD1b Auto-antibody in Plasma of Preclinical Huntington’s Disease

Huntington’s disease (HD) is a progressive and devastating neurodegenerative disease marked by inheritable CAG nucleotide expansion. For offspring of HD patients carrying abnormal CAG expansion, biomarkers that predict disease onset are crucially important but still lacking. Alteration of brain gang...

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Bibliographic Details
Published in:Molecular neurobiology 2023-07, Vol.60 (7), p.3873-3882
Main Authors: Lin, Tien-Wei, Chang, Jung-Kai, Wu, Yih-Ru, Sun, Tsung-Hsien, Cheng, Yang-Yu, Ren, Chien-Tai, Pan, Mei-Hung, Wu, Jin-Lin, Chang, Kuo-Hsuan, Yang, Hwai-I, Chen, Chiung-Mei, Wu, Chung-Yi, Chen, Yun-Ru
Format: Article
Language:English
Subjects:
Antibodies
Autoantibodies
Biomarkers
Biomedical and Life Sciences
Biomedicine
Brain - pathology
Cell Biology
Humans
Huntington Disease - pathology
Huntington's disease
Huntingtons disease
Neurobiology
Neurodegenerative diseases
Neurodegenerative Diseases - pathology
Neurology
Neurosciences
Polyglutamine
Trinucleotide repeat diseases
Trinucleotide repeats
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Summary:Huntington’s disease (HD) is a progressive and devastating neurodegenerative disease marked by inheritable CAG nucleotide expansion. For offspring of HD patients carrying abnormal CAG expansion, biomarkers that predict disease onset are crucially important but still lacking. Alteration of brain ganglioside patterns has been observed in the pathology of patients carrying HD. Here, by using a novel and sensitive ganglioside-focused glycan array, we examined the potential of anti-glycan auto-antibodies for HD. In this study, we collected plasma from 97 participants including 42 control (NC), 16 pre-manifest HD (pre-HD), and 39 HD cases and measured the anti-glycan auto-antibodies by a novel ganglioside-focused glycan array. The association between plasma anti-glycan auto-antibodies and disease progression was analyzed using univariate and multivariate logistic regression. The disease-predictive capacity of anti-glycan auto-antibodies was further investigated by receiver operating characteristic (ROC) analysis. We found that anti-glycan auto-antibodies were generally higher in the pre-HD group when compared to the NC and HD groups. Specifically, anti-GD1b auto-antibody demonstrated the potential for distinguishing between pre-HD and control groups. Moreover, in combination with age and the number of CAG repeat, the level of anti-GD1b antibody showed excellent predictability with an area under the ROC curve (AUC) of 0.95 to discriminate between pre-HD carriers and HD patients. With glycan array technology, this study demonstrated abnormal auto-antibody responses that showed temporal changes from pre-HD to HD.
ISSN:0893-7648
1559-1182
DOI:10.1007/s12035-023-03307-w