Immunoreactivity to astrocytes in different forms of dementia: High prevalence of autoantibodies to GFAP

Barthel, Paula Charlotte; Staabs, Finja; Li, Lucie Y.; Buthut, Maria; Otto, Carolin; Ruprecht, Klemens; Prüß, Harald; Höltje, Markus

doi:10.1016/j.bbih.2023.100609

Cited by 3 publications

(1 citation statement)

References 46 publications

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“…The list of potential “dementia autoantibodies” is continuously growing and further contains autoantibodies against GFAP ( 11 , 12 ), alpha1-adrenergic receptors ( 13 ), NMDA receptors ( 14–17 ), and multiple neuronal antigens in cancer patients with cognitive impairment ( 18 ). Initiation of immunotherapy in patients with LGI1 and IgLON5 autoantibodies can partially reverse the cognitive impairment, underscoring both, the need for and the potential of early autoantibody diagnostics in presumed neurodegenerative diseases.…”

Section: Introductionmentioning

confidence: 99%

Brain-targeting autoantibodies in patients with dementia

Staabs,

Foverskov Rasmussen,

Buthut

et al. 2024

Front. Neurol.

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Autoantibodies against proteins in the brain are increasingly considered as a potential cause of cognitive decline, not only in subacute autoimmune encephalopathies but also in slowly progressing impairment of memory in patients with classical neurodegenerative dementias. In this retrospective cohort study of 161 well-characterized patients with different forms of dementia and 34 controls, we determined the prevalence of immunoglobulin (Ig) G and IgA autoantibodies to brain proteins using unbiased immunofluorescence staining of unfixed murine brain sections. Autoantibodies were detected in 21.1% of dementia patients and in 2.9% of gender-matched controls, with higher frequencies in vascular dementia (42%), Alzheimer’s disease (30%), dementia of unknown cause (25%), and subjective cognitive impairment (16.7%). Underlying antigens involved glial fibrillary acidic protein (GFAP), glycine receptor, and Rho GTPase activating protein 26 (ARHGAP26), but also a range of yet undetermined epitopes on neurons, myelinated fiber tracts, choroid plexus, glial cells, and blood vessels. Antibody-positive patients were younger than antibody-negative patients but did not differ in the extent of cognitive impairment, epidemiological and clinical factors, or comorbidities. Further research is needed to understand the potential contribution to disease progression and symptomatology, and to determine the antigenic targets of dementia-associated autoantibodies.

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Section: Introductionmentioning

confidence: 99%

Brain-targeting autoantibodies in patients with dementia

Staabs,

Foverskov Rasmussen,

Buthut

et al. 2024

Front. Neurol.

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View full text Add to dashboard Cite

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Prediction of clinical progression in nervous system diseases: plasma glial fibrillary acidic protein (GFAP)

Zheng,

Yang,

Hou

et al. 2024

Eur J Med Res

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Glial fibrillary acidic protein (GFAP), an intracellular type III intermediate filament protein, provides structural support and maintains the mechanical integrity of astrocytes. It is predominantly found in the astrocytes which are the most abundant subtypes of glial cells in the brain and spinal cord. As a marker protein of astrocytes, GFAP may exert a variety of physiological effects in neurological diseases. For example, previous published literatures showed that autoimmune GFAP astrocytopathy is an inflammatory disease of the central nervous system (CNS). Moreover, the studies of GFAP in brain tumors mainly focus on the predictive value of tumor volume. Furthermore, using biomarkers in the early setting will lead to a simplified and standardized way to estimate the poor outcome in traumatic brain injury (TBI) and ischemic stroke. Recently, observational studies revealed that cerebrospinal fluid (CSF) GFAP, as a valuable potential diagnostic biomarker for neurosyphilis, had a sensitivity of 76.60% and specificity of 85.56%. The reason plasma GFAP could serve as a promising biomarker for diagnosis and prediction of Alzheimer's disease (AD) is that it effectively distinguished AD dementia from multiple neurodegenerative diseases and predicted the individual risk of AD progression. In addition, GFAP can be helpful in differentiating relapsing–remitting multiple sclerosis (RRMS) versus progressive MS (PMS). This review article aims to provide an overview of GFAP in the prediction of clinical progression in neuroinflammation, brain tumors, TBI, ischemic stroke, genetic disorders, neurodegeneration and other diseases in the CNS and to explore the potential therapeutic methods.

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Circulating Brain-Reactive Autoantibody Profiles in Military Breachers Exposed to Repetitive Occupational Blast

Rhind,

Shiu,

Vartanian

et al. 2024

IJMS

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Military breachers are routinely exposed to repetitive low-level blast overpressure, placing them at elevated risk for long-term neurological sequelae. Mounting evidence suggests that circulating brain-reactive autoantibodies, generated following CNS injury, may serve as both biomarkers of cumulative damage and drivers of secondary neuroinflammation. In this study, we compared circulating autoantibody profiles in military breachers (n = 18) with extensive blast exposure against unexposed military controls (n = 19). Using high-sensitivity immunoassays, we quantified IgG and IgM autoantibodies targeting glial fibrillary acidic protein (GFAP), myelin basic protein (MBP), and pituitary (PIT) antigens. Breachers exhibited significantly elevated levels of anti-GFAP IgG (p < 0.001) and anti-PIT IgG (p < 0.001) compared to controls, while anti-MBP autoantibody levels remained unchanged. No significant differences were observed for any IgM autoantibody measurements. These patterns suggest that repetitive blast exposure induces a chronic, adaptive immune response rather than a short-lived acute phase. The elevated IgG autoantibodies highlight the vulnerability of astrocytes, myelin, and the hypothalamic–pituitary axis to ongoing immune-mediated injury following repeated blast insults, likely reflecting sustained blood–brain barrier disruption and neuroinflammatory processes. Our findings underscore the potential of CNS-targeted IgG autoantibodies as biomarkers of cumulative brain injury and immune dysregulation in blast-exposed populations. Further research is warranted to validate these markers in larger, more diverse cohorts, and to explore their utility in guiding interventions aimed at mitigating neuroinflammation, neuroendocrine dysfunction, and long-term neurodegenerative risks in military personnel and similarly exposed groups.

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Immunoreactivity to astrocytes in different forms of dementia: High prevalence of autoantibodies to GFAP

Cited by 3 publications

References 46 publications

Brain-targeting autoantibodies in patients with dementia

Brain-targeting autoantibodies in patients with dementia

Prediction of clinical progression in nervous system diseases: plasma glial fibrillary acidic protein (GFAP)

Circulating Brain-Reactive Autoantibody Profiles in Military Breachers Exposed to Repetitive Occupational Blast

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