Glial fibrillary acidic protein (GFAP) is a novel biomarker for the prediction of autoimmune diabetes

Pang, Zheng-Da; Kushiyama, Akifumi; Sun, Jing; Kikuchi, Takako; Yamazaki, Hiroki; Iwamoto, Yasuhiko; Kuroda, Hiroshi; Yoshida, Shota; Shimamura, Munehisa; Higuchi, Masayoshi; Kawano, Tetsuya; Takami, Yoichi; Rakugi, Hiromi; Morishita, Ryuichi; Nakagami, Hironori

doi:10.1096/fj.201700110r

Cited by 21 publications

(12 citation statements)

References 33 publications

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“…Several reports have described the detection of GFAP‐IgG in other diseases, including traumatic brain injury, brain tumor, autism, lead‐exposed workers, systemic lupus erythematosus, Alzheimer's disease and diabetes . However, these reports tested serum specimens, not cerebrospinal fluid (CSF), and GFAP‐IgG was detected using western blotting or enzyme‐linked immunosorbent assay.…”

Section: Gfap‐igg Detection Methodsmentioning

confidence: 99%

“…Several reports have described the detection of GFAP-IgG in other diseases, including traumatic brain injury, brain tumor, autism, lead-exposed workers, systemic lupus erythematosus, Alzheimer's disease and diabetes. [12][13][14][15][16][17][18] However, these reports tested serum specimens, not cerebrospinal fluid (CSF), and GFAP-IgG was detected using western blotting or enzyme-linked immunosorbent assay. Some patients have detectable GFAP-IgG in the serum and CSF, whereas in others it is only detected in the CSF; most patients with GFAP-IgG in the CSF (CSF GFAP-IgG) have inflammatory meningoencephalitis with or without a myelitis phenotype.…”

Section: Gfap-igg Detection Methodsmentioning

confidence: 99%

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Autoimmune glial fibrillary acidic protein astrocytopathy

Kimura

Takekoshi

Yagi

et al. 2019

Clinical & Exp Neuroim

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Autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy (GFAP‐A) was recently reported as a spectrum of autoimmune inflammatory central nervous system disorders characterized by the detection of immunoglobulin G (IgG) against GFAP in cerebrospinal fluid using tissue‐ and cell‐based testing. The most common phenotypes of GFAP‐A are meningoencephalitis with or without myelitis. Patients present with headache and fever followed by consciousness disturbance and meningeal signs. Movement disorders, ataxia, hyperreflexia and blurred vision related to optic disc edema are sometimes observed. Some patients with GFAP‐A have a neoplasm. The most commonly detected neoplasm is ovarian teratoma. Coexisting neural antibodies are also sometimes detected. N‐methyl‐D‐aspartate receptor (NMDA‐R)‐IgG is the most common coexisting antibody, and patients with coexisting N‐methyl‐D‐aspartate receptor‐IgG have a clinical course resembling N‐methyl‐D‐aspartate receptor encephalitis. Lymphocytic pleocytosis lasts for several months and brain linear perivascular radial gadolinium‐enhancement patterns, an imaging hallmark of GFAP‐A, are sometimes observed. A previous neuropathological study reported inflammatory infiltrates including T‐, B‐ and plasma cells surrounding blood vessels. Although the pathophysiological mechanisms of GFAP‐A remain to be elucidated, GFAP‐specific CD8+ T cells are likely effectors of this disorder. GFAP‐A is usually corticosteroid responsive in the acute stage. However, some patients are prone to relapse or even die. In relapsed or refractory patients, the administration of oral prednisolone or a steroid‐sparing agent might be necessary. Because the timing of corticosteroid therapy might affect patient prognosis, cerebrospinal fluid GFAP‐IgG should be examined in patients with meningoencephalitis with or without myelitis who present with characteristic clinical features.

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Section: Gfap‐igg Detection Methodsmentioning

confidence: 99%

Section: Gfap-igg Detection Methodsmentioning

confidence: 99%

Autoimmune glial fibrillary acidic protein astrocytopathy

Kimura

Takekoshi

Yagi

et al. 2019

Clinical & Exp Neuroim

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“…GFAP epitopes for autoreactive T and B cells have now been identified in non-obese diabetic (NOD) mice and humans with T1D. Serum GFAP antibodies are now used as a predictive marker for the development of T1D, and it has been shown that administration of GFAP as a vaccine delayed the progression of T1D by regulating T cell differentiation (22, 23). GFAP-expressing glial cells of the peripheral nervous system require TRPV1 expression for their proper maturation, and studies have shown that depleting TRPV1-expressing cells reduced the development of insulitis in NOD mice (16, 24).…”

Section: Gfap—not the Usual Suspect!mentioning

confidence: 99%

“…Thus, GFAP-expressing glial cells may have a protective role in maintaining the integrity of the gut, but under uncontrolled inflammatory conditions, it may lead to autoreactivity. As such, glial cell-derived protein GFAP is now an identified autoantigen in T1D and autoantibodies to GFAP has been detected in NOD mice and humans with T1D (23), thus showing the relevance of the microbiota–EGC pathways in T1D.…”

Section: Il-22 and Ens Take Control Of T1dmentioning

confidence: 99%

Dietary SCFAs, IL-22, and GFAP: The Three Musketeers in the Gut–Neuro–Immune Network in Type 1 Diabetes

Jayasimhan

Mariño

2019

Front. Immunol.

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Microbial metabolites have a profound effect on the development of type 1 diabetes (T1D). The cross-talk between the gut microbiota, the nervous system, and immune system is necessary to establish and maintain immune and gut tolerance. As quoted by Hippocrates, “All disease begins in the gut.” Although this has been recognized for 2,000 years, the connection between the gut and autoimmune T1D is not yet well-understood. Here, we outline new advances supported by our research and others that have contributed to elucidate the impact of microbial metabolites on the physiology of the pancreas and the gut through their remarkable effect on the immune and nervous system. Among many of the mechanisms involved in the gut–beta-cell–immune cross-talk, glial fibrillary acidic protein (GFAP)-expressing cells are critical players in the development of invasive insulitis. Besides, this review reveals a novel mechanism for microbial metabolites by stimulating IL-22, an essential cytokine for gut homeostasis and beta-cell survival. The close connections between the gut and the pancreas are highlighted through our review as microbial metabolites recirculate through the whole body and intimately react with the nervous system, which controls essential disorders associated with diabetes. As such, we discuss the mechanisms of action of microbial metabolites or short-chain fatty acids (SCFAs), IL-22, and GFAP on beta-cells, gut epithelial cells, neurons, and glial cells via metabolite sensing receptors or through epigenetic effects. The fine-tuned gut–neuro–immune network may be profoundly affected by SCFA deficiency related to dysbiosis and diet alterations at very early stages of the initiation of the disease. Thus, dampening the initial immune response or preventing the perpetuation of the immune response by maintaining the integrity of the gut is among the alternative approaches to prevent T1D.

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“…E ) Representative micrographs of sciatic nerve cross sections. Cross sections were stained for glial fibrillary acidic protein (green) which is a filament protein found in astrocytes and SCs and has been reported as an autoantigen candidate for type 1 diabetes and for isolectin-B4 (red), which identifies endothelial cells(42); asterisk indicates skeletal muscle. Scale bars, 200 mm.…”

mentioning

confidence: 99%

Gene therapy with the angiogenic neuropeptide secretoneurin ameliorates experimental diabetic neuropathy

Theurl¹,

Lener²,

Albrecht-Schgoer³

et al. 2018

FASEB j.

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The pathogenesis of diabetic neuropathy remains enigmatic. Damage to the vasa nervorum may be responsible for this disorder. Recently, we showed that secretoneurin (SN) induces angiogenesis in hindlimb and myocardial ischemia. Moreover, beneficial effects were observed in wound healing. We therefore hypothesized that SN therapy may ameliorate diabetic neuropathy. We used db/db mice as animal model for neuropathy. Gene therapy was accomplished by intramuscular injection of SN plasmid along the sciatic nerve. Sciatic nerve motor and sensory conduction velocities were then measured for 9 wk. Nerve conduction velocities showed normal values in heterozygous mice for the observational period, but were severely reduced in homozygous mice in which velocities were significantly improved by SN, but not by control plasmid gene therapy. The reaction time in the tail-flick test improved significantly in SN-treated animals. The induction of growth of vasa nervorum seems to be part of the underlying mechanism. In addition, SN positively affected Schwann cell function in vitro and induced activation of important signaling pathways. Our observations suggest that SN exerts beneficial effects on nerve function in vivo and on Schwann cells in vitro. It therefore may be a promising treatment option for diabetic neuropathy.-Theurl, M., Lener, D., Albrecht-Schgoer, K., Beer, A., Schgoer, W., Liu, Y., Stanzl, U., Fischer-Colbrie, R., Kirchmair, R. Gene therapy with the angiogenic neuropeptide secretoneurin ameliorates experimental diabetic neuropathy.

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Glial fibrillary acidic protein (GFAP) is a novel biomarker for the prediction of autoimmune diabetes

Cited by 21 publications

References 33 publications

Autoimmune glial fibrillary acidic protein astrocytopathy

Autoimmune glial fibrillary acidic protein astrocytopathy

Dietary SCFAs, IL-22, and GFAP: The Three Musketeers in the Gut–Neuro–Immune Network in Type 1 Diabetes

Gene therapy with the angiogenic neuropeptide secretoneurin ameliorates experimental diabetic neuropathy

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