Gluten, Transglutaminase, Celiac Disease and IgA Nephropathy

Lerner, Aaron; Berthelot, Laureline; Jeremias, Patricia; Tenbusch, Matthias; Abbad, Lilia; Monteiro, Renato C.

doi:10.4172/2155-9899.1000499

Cited by 8 publications

(6 citation statements)

References 52 publications

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“…Celiac disease, dermatitis herpetiformis and celiac ataxia are induced by gluten-containing food products [ 1 , 2 , 3 ]. Many other autoimmune diseases might benefit from a gluten-free diet [ 5 , 14 , 15 , 16 ] or other restrictive dietary regimens [ 17 ]. Even an autoimmune neurological disease like polyradiculoneuropathy has been induced by porcine brains, although in this case the exposure of the affected abattoir workers was through aerosolized antigens and not per oral intake [ 18 ].…”

Section: Introductionmentioning

confidence: 99%

Cross-Reactivity and Sequence Homology Between Alpha-Synuclein and Food Products: A Step Further for Parkinson’s Disease Synucleinopathy

Vojdani

Lerner

Vojdani³

2021

Cells

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Introduction: Parkinson’s disease is characterized by non-motor/motor dysfunction midbrain neuronal death and α-synuclein deposits. The accepted hypothesis is that unknown environmental factors induce α-synuclein accumulation in the brain via the enteric nervous system. Material and Methods: Monoclonal antibodies made against recombinant α-synuclein protein or α-synuclein epitope 118–123 were applied to the antigens of 180 frequently consumed food products. The specificity of those antibody-antigen reactions was confirmed by serial dilution and inhibition studies. The Basic Local Alignment Search Tool sequence matching program was used for sequence homologies. Results: While the antibody made against recombinant α-synuclein reacted significantly with 86/180 specific food antigens, the antibody made against α-synuclein epitope 118–123 reacted with only 32/180 tested food antigens. The food proteins with the greatest number of peptides that matched with α-synuclein were yeast, soybean, latex hevein, wheat germ agglutinin, potato, peanut, bean agglutinin, pea lectin, shrimp, bromelain, and lentil lectin. Conclusions: The cross-reactivity and sequence homology between α-synuclein and frequently consumed foods, reinforces the autoimmune aspect of Parkinson’s disease. It is hypothesized that luminal food peptides that share cross-reactive epitopes with human α-synuclein and have molecular similarity with brain antigens are involved in the synucleinopathy. The findings deserve further confirmation by extensive research.

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Section: Introductionmentioning

confidence: 99%

Cross-Reactivity and Sequence Homology Between Alpha-Synuclein and Food Products: A Step Further for Parkinson’s Disease Synucleinopathy

Vojdani

Lerner

Vojdani³

2021

Cells

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“…It is suggested that the overexpression of tTG may lead to the retrotranscythosis of IgAbearing gliadin with increase IgA deposits. FcαRI/CD89 is probably involved in this mechanism by the direct interaction with gliadin and participation in the formation of IgA-sCD89 complexes [50]. Our previous studies [28,29] revealed the correlation between the intensity of CD89 cutaneous expression and anti-npG IgA detected with ELISA in DH, indicating that there is a single, shared pathway of DH-type IgA-mediated immune response to npG, tTG, and eTG.…”

Section: Discussionmentioning

confidence: 90%

Evaluation of a Bi-Analyte Immunoblot as a Useful Tool for Diagnosing Dermatitis Herpetiformis

et al. 2021

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Immune responses to tissue transglutaminase (tTG) and nonapeptides of gliadin (npG) are associated with dermatitis herpetiformis (DH), a gluten-related dermatosis. Recently, a bi-analyte immunoblot (b-aIB) was introduced to detect IgA antibodies in response to tTG and npG. We compared the utility of ELISA and b-aIB with tTG in serological diagnoses of DH and their agreement with direct immunofluorescence (DIF). In total, 55 sera (27 DIF-positive DH patients, 4 DIF-negative DH patients and 24 healthy controls) were examined. ELISA for anti-tTG IgA, b-aIB for anti-npG and anti-tTG IgA, and statistical analysis were performed. The b-aIB with tTG showed 78% sensitivity, 100% specificity, 100% positive predictive value, and 82% negative predictive value in relation to ELISA. A better rate of agreement (Cohen’s kappa values) in IgA detection was observed in the pair tTG ELISA and b-aIB with npG (0.85) than in pairs tTG ELISA and b-aIB with tTG (0.78) or b-aIB with tTG and b-aIB with npG (0.78). No degree of agreement was found between serological tests and DIF. Both serological tests may be used to detect the anti-tTG IgA in DH patients. Still, DH diagnosing requires careful consideration of clinical data as well as results of tissue imaging (crucial DIF) and immunoserological techniques detecting DH-type features.

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“…IgA nephropathy (IgAN) is the most common primary glomerulonephritis [1], and deteriorates to uraemia in up to 40% of patients within ~20 years [2,3]. Recent studies have further characterised IgAN as an autoimmune disease with a multi‐hit pathogenetic process [4–6]. Clinically, although immunosuppressive drugs have been used to treat some IgAN patients, their efficacy in preserving renal function and reducing proteinuria in IgAN is insufficient and remains controversial.…”

Section: Introductionmentioning

confidence: 99%

LCC18, a benzamide‐linked small molecule, ameliorates IgA nephropathy in mice

Yang

Hua

Takahata

et al. 2021

The Journal of Pathology

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IgA nephropathy (IgAN), an immune complex‐mediated process and the most common primary glomerulonephritis, can progress to end‐stage renal disease in up to 40% of patients. Accordingly, a therapeutic strategy targeting a specific molecular pathway is urgently warranted. Aided by structure characterisation and target identification, we predicted that a novel ring‐fused 6‐(2,4‐difluorophenyl)‐3‐(3‐(trifluoromethyl)phenyl)‐2H‐benzo[e][1,3]oxazine‐2,4(3H)‐dione (LCC18) targets the NLRP3 inflammasome, which participates in IgAN pathogenesis. We further developed biomarkers for the disease. We used two complementary IgAN models in C57BL/6 mice, involving TEPC‐15 hybridoma‐derived IgA, and in gddY mice. Moreover, we created specific cell models to validate therapeutic effects of LCC18 on IgAN and to explain its underlying mechanisms. IgAN mice benefited significantly from treatment with LCC18, showing dramatically improved renal function, including greatly reduced proteinuria and renal pathology. Mechanistic studies showed that the mode of action specifically involved: (1) blocking of the MAPKs/COX‐2 axis‐mediated priming of the NLRP3 inflammasome; (2) inhibition of ASC oligomerisation and NLRP3 inflammasome assembly by inhibiting NLRP3 binding to PKR, NEK7 and ASC; and (3) activation of autophagy. LCC18 exerts therapeutic effects on murine IgAN by differentially regulating NLRP3 inflammasome activation and autophagy induction, suggesting this new compound as a promising drug candidate to treat IgAN. © 2020 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

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Gluten, Transglutaminase, Celiac Disease and IgA Nephropathy

Cited by 8 publications

References 52 publications

Cross-Reactivity and Sequence Homology Between Alpha-Synuclein and Food Products: A Step Further for Parkinson’s Disease Synucleinopathy

Cross-Reactivity and Sequence Homology Between Alpha-Synuclein and Food Products: A Step Further for Parkinson’s Disease Synucleinopathy

Evaluation of a Bi-Analyte Immunoblot as a Useful Tool for Diagnosing Dermatitis Herpetiformis

LCC18, a benzamide‐linked small molecule, ameliorates IgA nephropathy in mice

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