Altered gastrointestinal motility involving autoantibodies in the experimental autoimmune encephalomyelitis model of multiple sclerosis

Spear, Estelle; Holt, Emily A.; Joyce, Emily J.; Haag, Melody M; Mawe, Seamus; Hennig, Grant W.; Lavoie, Brigitte; Applebee, Angela; Teuscher, Cory; Mawe, Gary M.

doi:10.1111/nmo.13349

Cited by 53 publications

(68 citation statements)

References 38 publications

(52 reference statements)

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“…The majority of mice with EAE had ENS-reactive autoantibodies, while antibodies against a component of the ENS could be detected in 10 of 33 human MS patients. These results were corroborated by another study showing accelerated gastric emptying and reduced colonic motility in EAE mice, accompanied by immunoreactivity against the ENS in sera (Spear et al, 2018).…”

Section: Transmittersupporting

confidence: 76%

The enteric nervous system: “A little brain in the gut”

Annaházi

Schemann²

2020

Neuroforum

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AbstractThe gut’s own autonomous nervous system, the enteric nervous system (ENS), has fascinated scientists for more than 100 years. It functions, in the true sense of the word, autonomously, by performing complex tasks and controlling vital functions independently of extrinsic inputs. At the same time, the ENS is bombarded with signals from other cells in the gut wall and lumen and has to integrate all of these inputs. We describe the main functions of the ENS under physiological conditions and give a few examples of its role in gut diseases. The ENS has received increasing attention recently as scientists outside the field of Neurogastroenterology realize its important role in the pathogenesis of Parkinson’s, autism and multiple sclerosis.

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Section: Transmittersupporting

confidence: 76%

The enteric nervous system: “A little brain in the gut”

Annaházi

Schemann²

2020

Neuroforum

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“…As pointed out by Drachman, this will confirm the specific pathogenic role of the antibody and will rule out a cell-mediated disease mechanism [60]. GI dysmotility occurs in experimental autoimmune encephalomyelitis (EAE), a murine model of multiple sclerosis (MS) [61,62]. Delayed colonic motility is exhibited in wild type mice induced with EAE but is absent in B celldeficient mice, suggesting that the observed dysmotility is antibody mediated [61].…”

Section: Autoantibodies (Aabs)mentioning

confidence: 70%

Autoimmune gastrointestinal dysmotility: the interface between clinical immunology and neurogastroenterology

Nakane

Mukaino

Ihara

et al. 2020

Immunological Medicine

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Autoimmune gastrointestinal dysmotility (AGID), an idiopathic or paraneoplastic phenomenon, is a clinical form of limited autoimmune dysautonomia. The symptoms of AGID and gastrointestinal manifestations in patients with autoimmune rheumatic diseases are overlapping. Antineuronal autoantibodies are often detected in patients with AGID. Autoantibodies play a key role in GI dysmotility; however, whether they cause neuronal destruction is unknown. Hence, the connection between the presence of these autoantibodies and the specific interference in synaptic transmission in the plexus ganglia of the enteric nervous system has to be determined. The treatment options for AGID are not well-defined. However, theoretically, immunomodulatory therapies have been shown to be effective and are therefore used as the first line of treatment. Nonetheless, diverse combined immunomodulatory therapies should be considered for intractable cases of AGID. We recommend comprehensive autoimmune evaluation and cancer screening for clinical diagnosis of AGID. Univocal diagnostic criteria, treatment protocols, and outcome definitions for AGID are required for prompt diagnosis and treatment and appropriate management of immunotherapy, which will circumvent the need for surgeries and improve patient outcome. In conclusion, AGID, a disease at the interface of clinical immunology and neurogastroenterology, requires further investigations and warrants cooperation among specialists, especially clinical immunologists, gastroenterologists, and neurologists.

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“…47 Both endpoints have been used by our laboratory and others in mice. 48,49 Statistics.-For each group of data, a Kruskal-Wallis one-way ANOVA with Dunn post hoc test was used for P value calculations with P ≤ .05 considered significant. GraphPad Prism (version 7.0, GraphPad Software, La Jolla, CA) was used for statistical analysis.…”

Section: Methodsmentioning

confidence: 99%

No Gastrointestinal Dysmotility in Transgenic Mouse Models of Migraine

et al. 2019

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Objective.-To determine whether transgenic mouse models of migraine exhibit upper gastrointestinal dysmotility comparable to those observed in migraine patients.Background.-There is considerable evidence supporting the comorbidity of gastrointestinal dysmotility and migraine. Gastrointestinal motility, however, has never been investigated in transgenic mouse models of migraine.Methods.-Three transgenic mouse strains that express pathogenic gene mutations linked to monogenic migraine-relevant phenotypes were studied: CADASIL (Notch3-Tg88), FASP (CSNK1D-T44A), and FHM1 (CACNA1A-S218L). Upper gastrointestinal motility was quantified by measuring gastric emptying and small intestinal transit in mutant and control animals. Gastrointestinal motility was measured at baseline and after pretreatment with 10 mg/kg nitroglycerin (NTG).Results. -No significant differences were observed for gastric emptying or small intestinal transit at baseline for any of the 3 transgenic strains when compared to appropriate controls or after pretreatment with NTG when compared to vehicle.Conclusions.-We detected no evidence of upper gastrointestinal dysmotility in mice that express mutations in genes linked to monogenic migraine-relevant phenotypes. Future studies seeking to understand why humans with migraine experience delayed gastric emptying may benefit from pursuing other modifiers of gastrointestinal motility, such as epigenetic or microbiome-related factors.Abbreviations: CADASIL cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, FASP familial advanced sleep phase, FHM familial hemiplegic migraine, IBS irritable bowel syndrome, IG idiopathic gastroparesis, NTG nitroglycerin (Headache 2020;60:396-404) Headache

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Altered gastrointestinal motility involving autoantibodies in the experimental autoimmune encephalomyelitis model of multiple sclerosis

Cited by 53 publications

References 38 publications

The enteric nervous system: “A little brain in the gut”

The enteric nervous system: “A little brain in the gut”

Autoimmune gastrointestinal dysmotility: the interface between clinical immunology and neurogastroenterology

No Gastrointestinal Dysmotility in Transgenic Mouse Models of Migraine

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