High prevalence of serum autoantibodies against the amino terminal of α-enolase in Hashimoto's encephalopathy

Yoneda, Makoto; Fujii, Akihiro; Ito, Akira; Yokoyama, Hiromi; Nakagawa, Hiroto; Kuriyama, Masaru

doi:10.1016/j.jneuroim.2007.01.018

Cited by 148 publications

(119 citation statements)

References 17 publications

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“…␣-Enolase, a glycolytic enzyme, has been identified as an autoantigen in diseases such as MS 41 and Hashimoto's encephalopathy. 42 NSE has been used as a pathogenic marker in various neurological diseases including MS, 43 acute ischemic stroke, 44 and RA. 36,45 In addition, previous reports showed an early elevation of NSE in cerebrospinal fluid of Creutzfeldt-Jakob disease (CJD) patients, which decreased with disease duration, and this early elevation is considered to support the diagnosis of CJD.…”

Section: Discussionmentioning

confidence: 99%

Accumulation of Citrullinated Proteins by Up-Regulated Peptidylarginine Deiminase 2 in Brains of Scrapie-Infected Mice

Jang

Kim

Choi

et al. 2008

The American Journal of Pathology

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Peptidylarginine deiminases (PADs), which are a group of posttranslational modification enzymes, are involved in protein citrullination (deimination) by the conversion of peptidylarginine to peptidylcitrulline in a calcium concentration-dependent manner. Among the PADs, PAD2 is widely distributed in various tissues and is the only type that is expressed in brain. To elucidate the involvement of protein citrullination by PAD2 in the pathogenesis of brain-specific prion diseases, we examined the profiles of citrullinated proteins using the brains of scrapie-infected mice as a prion disease model. We found that, compared with controls, increased levels of citrullinated proteins of various molecular weights were detected in different brain sections of scrapie-infected mice. In support of this data, expression levels of PAD2 protein as well as its enzyme activity were significantly increased in brain sections of scrapie-infected mice, including hippocampus, brain stem, and striatum. Additionally, the expression levels of PAD2 mRNA were increased during scrapie infection. Moreover, PAD2 immunoreactivity was increased in scrapie-infected brains, with staining detected primarily in reactive astrocytes. Using two-dimensional electrophoresis and matrix-assisted laser desorption/ionization-time of flight mass spectrometry, various citrullinated proteins were identified in the brains of scrapie-infected mice, including glial fibrillary acidic protein, myelin basic protein, enolases, and aldolases. This study suggests that accumulated citrullinated proteins and abnormal activation of PAD2 may function in the pathogenesis of prion diseases and serve as potential therapeutic targets. Accumulation of misfolded proteins, posttranslational modification of proteins, alteration of free ion distribution, and perturbation of cellular redox homeostasis are general features of progressive neurodegenerative disorders. These changes have been observed consistently as part of the neuropathogenesis and neuropathology of prion diseases. Prion diseases are characterized by various neurological symptoms and common histopathological features such as spongiform degeneration of the central nervous system, reactive gliosis, neuronal loss, and, in some cases, formation of amyloid plaques. 1 It has been reported that all prion diseases are associated with the aberrant metabolism of prion protein (PrP). Conversion of the cellular prion protein (PrP C ) into an abnormal, protease-resistant and infectious isoform (PrP Sc ) is believed to be a principal molecular basis of prion diseases, 2 and the accumulation of PrP Sc in the central nervous system is thought to be responsible for neuronal loss and/or astrocytosis.

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Section: Discussionmentioning

confidence: 99%

Accumulation of Citrullinated Proteins by Up-Regulated Peptidylarginine Deiminase 2 in Brains of Scrapie-Infected Mice

Jang

Kim

Choi

et al. 2008

The American Journal of Pathology

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“…Immunotherapy was effective in one of the two positive patients and in one of the two negative patients. Anti-NAE antibody demonstrates a high specificity for Hashimoto's encephalopathy and can be a useful serological diagnostic marker for Hashimoto's encephalopathy (12), however, because the number of patients in this study was small, the utility of anti-NAE antibody could not be verified.…”

Section: Discussionmentioning

confidence: 80%

Prevalence of Autoantibodies and the Efficacy of Immunotherapy for Autoimmune Cerebellar Ataxia

et al. 2016

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Objective Autoimmune cerebellar ataxias were recently reported to be treatable. However, the proportion of patients with cortical cerebellar atrophy of unknown etiology with autoimmune-associated cerebellar ataxia and the actual effectiveness of immunotherapy in these diseases remain unknown. Methods We measured the level of autoantibodies (including anti-gliadin antibody, anti-glutamic acid decarboxylase (GAD) antibody, and anti-thyroid antibody) in 58 Japanese patients with cerebellar ataxia, excluding those with multiple system atrophy, hereditary spinocerebellar ataxia, cancer, or those who were receiving phenytoin, and the efficacy of immunotherapy was assessed. Results Thirty-one of 58 (53%) patients were positive for anti-GAD antibody, anti-gliadin antibody, or antithyroid antibody. Seven of the 12 anti-gliadin antibody-positive patients, three of the four anti-GAD antibody-positive patients, and three of the six anti-thyroid antibody-positive patients responded well to immunotherapy, indicating that 59% of patients with ataxia-associated antibody-positive cerebellar ataxia undergoing immunotherapy responded well. Conclusion Some patients with cerebellar ataxia have autoimmune conditions and diagnosing autoimmune cerebellar ataxia is therefore an important component in the care of patients with this disease entity.

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“…A new autoantibody directed against the amino (NH2)-terminal of α-enolase (NAE) has a high prevalence (68%) and high specificity for patients with Hashimoto's encephalopathy but its role in the pathogenesis is not yet elucidated [4]. In the future this might play a role in the diagnosis of the disease.…”

Section: Discussionmentioning

confidence: 99%

Hashimoto’s encephalopathy in the setting of subclinical hypothyroidism

Bota¹,

Corrigan²

2011

IJCRI

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High prevalence of serum autoantibodies against the amino terminal of α-enolase in Hashimoto's encephalopathy

Cited by 148 publications

References 17 publications

Accumulation of Citrullinated Proteins by Up-Regulated Peptidylarginine Deiminase 2 in Brains of Scrapie-Infected Mice

Accumulation of Citrullinated Proteins by Up-Regulated Peptidylarginine Deiminase 2 in Brains of Scrapie-Infected Mice

Prevalence of Autoantibodies and the Efficacy of Immunotherapy for Autoimmune Cerebellar Ataxia

Hashimoto’s encephalopathy in the setting of subclinical hypothyroidism

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