Sera of Patients With Celiac Disease and Neurologic Disorders Evoke a Mitochondrial-Dependent Apoptosis In Vitro

Cervio, Elisabetta; Volta, Umberto; Verri, Manuela; Boschi, Federica; Pastoris, Ornella; Granito, Alessandro; Barbara, Giovanni; Parisi, Claudia; Felicani, Cristina; Tonini, Marcello; Giorgio, Roberto De

doi:10.1053/j.gastro.2007.04.070

Cited by 62 publications

(46 citation statements)

References 44 publications

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“…TG2-reactive autoantibodies produced in celiac disease could therefore influence TG2 function. Indications of such an effect have been observed by the addition of celiac disease antibodies to cell culture systems (36)(37)(38)(39)(40)(41). The mechanisms underlying the various biological effects reported are not well understood.…”

Section: Discussionmentioning

confidence: 99%

Activity-regulating structural changes and autoantibody epitopes in transglutaminase 2 assessed by hydrogen/deuterium exchange

Iversen

Mysling

Hnida

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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The multifunctional enzyme transglutaminase 2 (TG2) is the target of autoantibodies in the gluten-sensitive enteropathy celiac disease. In addition, the enzyme is responsible for deamidation of gluten peptides, which are subsequently targeted by T cells. To understand the regulation of TG2 activity and the enzyme's role as an autoantigen in celiac disease, we have addressed structural properties of TG2 in solution by using hydrogen/deuterium exchange monitored by mass spectrometry. We demonstrate that Ca 2+ binding, which is necessary for TG2 activity, induces structural changes in the catalytic core domain of the enzyme. Cysteine oxidation was found to abolish these changes, suggesting a mechanism whereby disulfide bond formation inactivates the enzyme. Further, by using TG2-specific human monoclonal antibodies generated from intestinal plasma cells of celiac disease patients, we observed that binding of TG2 by autoantibodies can induce structural changes that could be relevant for the pathogenesis. Detailed mapping of two of the main epitopes targeted by celiac disease autoantibodies revealed that they are located adjacent to each other in the N-terminal part of the TG2 molecule.

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Section: Discussionmentioning

confidence: 99%

Activity-regulating structural changes and autoantibody epitopes in transglutaminase 2 assessed by hydrogen/deuterium exchange

Iversen

Mysling

Hnida

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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“…Up to 10% of patients with CD have neurologic al symptoms ranging from polyneuropathy, epilepsy, myoclonus, multifocal leukoencephalopathy, dementia, chorea, migraine, memory/attention impairment and peripheral axonal and demyelinating neuropathies as well as ac etylc holine-antibody positive myasthenia gravis [78] . Autoimmunity may ac t as a mec hanism triggering neurologic al dysfunc tion [79] , and anti-neuronal, anti-gliadin and tTG antibodies may c ontribute to neurologic al impairment through Apaf-1 ac tivation with Bax and c ytoc hrome C transloc ation, leading to impairment of mitoc hondrialdependent apoptosis. There is no statistically significant association between CD and subsequent development of Parkinson's disease, Alzheimer's disease, hereditary ataxia, symptoms of ataxia, Huntington's disease, or spinal musc ular atrophy [80] .…”

Section: Clinical Associationsmentioning

confidence: 99%

Recent advances in celiac disease

Freeman

Chopra²,

Clandinin³

et al. 2011

WJG

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Celiac disease now affects about one person in a hundred in Europe and North America. In this review, we consider a number of important and exciting recent developments, such as clinical associations, HLA-DQ2 and HLA-DQ8 predispositions, the concept of potential celiac disease, the use of new imaging/endoscopy techniques, and the development of refractory disease. This review will be of use to all internists, pediatricians and gastroenterologists.

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“…One patient (atypical-female) had ophthalmoplegia, extrapyramidal symptoms (dystonia and basal ganglion involvement), demyelinating neuropathy, sensorineural hearing loss, and white matter lesions may be seen in relation with CD 6,7,[19][20][21] . Also sera from patients with CD and neurological manifestations also evoke a mitochondrial-dependent apoptosis in vitro, suggesting that neurotoxic antibodies might be present 22 .…”

Section: Discussionmentioning

confidence: 99%

Neurological findings spectrum in Celiac disease

et al. 2016

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We aimed to provide early diagnosis by determining possible Celiac disease related subclinical or symptomatic neurological abnormalities in children in order to decrease risk of mortality and morbidity.Children with Celiac disease were assessed with neurological examination, neurophysiological tests and neuroimaging.A total of 65 patients were included in the study. The neurological examination was abnormal in 4 patients. There were EEG abnormalities in 5 patients, VEP was abnormal in 7 patients, BAER was abnormal in 1 patient, ENMG was abnormal in 8 patients, and there were abnormal findings on neuroimaging in 2 patients.The Celiac disease related neurological complications that manifest in adulthood usually lay their foundations in childhood. Therefore, it must be kept in mind that subclinical neurological abnormalities may be related to Celiac disease, and Celiac disease may be the underlying cause in the patients with overt neurological abnormalities in childhood.

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Sera of Patients With Celiac Disease and Neurologic Disorders Evoke a Mitochondrial-Dependent Apoptosis In Vitro

Cited by 62 publications

References 44 publications

Activity-regulating structural changes and autoantibody epitopes in transglutaminase 2 assessed by hydrogen/deuterium exchange

Activity-regulating structural changes and autoantibody epitopes in transglutaminase 2 assessed by hydrogen/deuterium exchange

Recent advances in celiac disease

Neurological findings spectrum in Celiac disease

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