Elevated serum autoantibody against high mobility group box 1 as a potent surrogate biomarker for amyotrophic lateral sclerosis

Hwang, Ching-Shiang; Liu, Guan Ting; Chang, Margaret Dah‐Tsyr; Liao, I-Lin; Chang, Hsiang-Kuang

doi:10.1016/j.nbd.2013.04.013

Cited by 39 publications

(22 citation statements)

References 49 publications

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“…HMGB1 and its receptors such as TLR2, TLR4, and RAGE are increased in reactive glia, whereas they are decreased in degenerating motor neurons in patients with amyotrophic lateral sclerosis, suggesting a possible role in the progression of inflammation and motor neuron degeneration (Casula et al, 2011; Lo Coco et al, 2007). In addition, serum HMGB1 autoantibody is increased in patients with amyotrophic lateral sclerosis compared with patients with Alzheimer's disease and Parkinson's disease (Hwang et al, 2013). These findings suggest that HMGB1 autoantibody may be a biomarker for amyotrophic lateral sclerosis (Hwang et al, 2013).…”

Section: Hmgb1 and Diseasementioning

confidence: 99%

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HMGB1 in health and disease

Kang

Chen

Zhang

et al. 2014

Molecular Aspects of Medicine

795

828

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Complex genetic and physiological variations as well as environmental factors that drive emergence of chromosomal instability, development of unscheduled cell death, skewed differentiation, and altered metabolism are central to the pathogenesis of human diseases and disorders. Understanding the molecular bases for these processes is important for the development of new diagnostic biomarkers, and for identifying new therapeutic targets. In 1973, a group of non-histone nuclear proteins with high electrophoretic mobility was discovered and termed High-Mobility Group (HMG) proteins. The HMG proteins include three superfamilies termed HMGB, HMGN, and HMGA. High-mobility group box 1 (HMGB1), the most abundant and well-studied HMG protein, senses and coordinates the cellular stress response and plays a critical role not only inside of the cell as a DNA chaperone, chromosome guardian, autophagy sustainer, and protector from apoptotic cell death, but also outside the cell as the prototypic damage associated molecular pattern molecule (DAMP). This DAMP, in conjunction with other factors, thus has cytokine, chemokine, and growth factor activity, orchestrating the inflammatory and immune response. All of these characteristics make HMGB1 a critical molecular target in multiple human diseases including infectious diseases, ischemia, immune disorders, neurodegenerative diseases, metabolic disorders, and cancer. Indeed, a number of emergent strategies have been used to inhibit HMGB1 expression, release, and activity in vitro and in vivo. These include antibodies, peptide inhbitiors, RNAi, anti-coagulants, endogenous hormones, various chemical compounds, HMGB1-receptor and signaling pathway inhibition, artificial DNAs, physical strategies including vagus nerve stimulation and other surgical approaches. Future work further investigating the details of HMGB1 localizationtion, structure, post-translational modification, and identifccation of additional partners will undoubtedly uncover additional secrets regarding HMGB1’s multiple functions.

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Section: Hmgb1 and Diseasementioning

confidence: 99%

“…In addition, serum HMGB1 autoantibody is increased in patients with amyotrophic lateral sclerosis compared with patients with Alzheimer's disease and Parkinson's disease (Hwang et al, 2013). These findings suggest that HMGB1 autoantibody may be a biomarker for amyotrophic lateral sclerosis (Hwang et al, 2013). …”

Section: Hmgb1 and Diseasementioning

confidence: 99%

HMGB1 in health and disease

Kang

Chen

Zhang

et al. 2014

Molecular Aspects of Medicine

795

828

View full text Add to dashboard Cite

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“…Although the relentlessly progressing and devastating disease amyotrophic lateral sclerosis (ALS) primarily affects motor neurons [1,2], convincing observations imply concomitant sensory nervous system involvement [3,4].…”

Section: Introductionmentioning

confidence: 99%

Small-fibre neuropathy related to bulbar and spinal-onset in patients with ALS

et al. 2015

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We aimed at seeking more precise diagnostic information on the sensory nervous system involvement described in patients with amyotrophic lateral sclerosis (ALS). We investigated large myelinated nerve fibres with nerve conduction study and small-nerve fibres with Quantitative Sensory Testing (QST) (assessing thermal-pain perceptive thresholds) and skin biopsy (assessing intraepidermal nerve fibre density) in 24 consecutive patients with ALS, 11 with bulbar-onset and 13 with spinal-onset. In 23 of the 24 patients, regardless of ALS onset, nerve conduction study invariably showed large myelinated fibre sparing. In patients with bulbar-onset ALS, QST found normal thermal-pain perceptive thresholds and skin biopsy disclosed normal intraepidermal nerve fibre density. Conversely, in patients with spinal-onset, thermal-pain thresholds were abnormal and distal intraepidermal nerve fibre density was reduced. Sensory nervous system involvement in ALS differs according to disease onset. Patients with spinal-onset but not those with bulbar-onset ALS have concomitant distal small-fibre neuropathy. Neurologists should therefore seek this ALS-related non-motor feature to improve its diagnosis and treatment.

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“…High levels of high mobility group box 1 (HMGB1) autoantibody (Hwang et al, 2013), increased granzyme B (Ilzecka, 2011), higher CSF IL-8 levels (Mitchell et al, 2009) and wide-range C-reactive protein (wrCRP) (Keizman et al, 2009) correlated with disease severity as measured by ALSFRS-R. In addition, increased levels of blood MCP-1, TNF-3 and GM-CSF correlated with disease duration (Kuhle et al, 2009; Mitchell et al, 2010).…”

Section: Defining Disease Heterogeneity and Progressionmentioning

confidence: 99%

Use of biomarkers in ALS drug development and clinical trials

2015

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The past decade has seen a dramatic increase in the discovery of candidate biomarkers for ALS. These biomarkers typically can either differentiate ALS from control subjects or predict disease course (slow versus fast progression). At the same time, late-stage clinical trials for ALS have failed to generate improved drug treatments for ALS patients. Incorporation of biomarkers into the ALS drug development pipeline and the use of biologic and/or imaging biomarkers in early- and late-stage ALS clinical trials have been absent and only recently pursued in early-phase clinical trials. Further clinical research studies are needed to validate biomarkers for disease progression and develop biomarkers that can help determine that a drug has reached its target within the central nervous system. In this review we summarize recent progress in biomarkers across ALS model systems and patient population, and highlight continued research directions for biomarkers that stratify the patient population to enrich for patients that may best respond to a drug candidate, monitor disease progression and track drug responses in clinical trials. It is crucial that we further develop and validate ALS biomarkers and incorporate these biomarkers into the ALS drug development process.

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Elevated serum autoantibody against high mobility group box 1 as a potent surrogate biomarker for amyotrophic lateral sclerosis

Cited by 39 publications

References 49 publications

HMGB1 in health and disease

HMGB1 in health and disease

Small-fibre neuropathy related to bulbar and spinal-onset in patients with ALS

Use of biomarkers in ALS drug development and clinical trials

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