Tailoring the immune response to wheat gliadin by enzymatic transamidation

Luongo, Diomira; Bonavita, Roberta; Rossi, Stefano; Aufiero, Vera Rotondi; Feliciello, Nicoletta Rosaria; Maurano, Francesco; Iaquinto, Gaetano; Mazzarella, Giuseppe; Rossi, Mauro

doi:10.1016/j.cyto.2019.02.004

Cited by 11 publications

(13 citation statements)

References 38 publications

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“…In vivo experiments conducted on HLA-DQ8 transgenic mice demonstrated that treatment with transamidated gliadin produced a modification of the ratio IL10/INF γ , indicating the ability of transamidated gliadin to convert a mainly inflammatory phenotype to a mainly anti-inflammatory phenotype [ 131 ]. Similar results were obtained in human biopsy samples [ 4 ]. In addition, in a DQ2 mouse model, a transamidated purified α -gliadin fraction, and a single recombinant α -gliadin sequence were able to counteract the pro-inflammatory activity of native gliadin [ 4 , 132 ].…”

Section: Gluten Transamidation As a Detoxification Strategy For Thera...supporting

confidence: 87%

“…Similar results were obtained in human biopsy samples [ 4 ]. In addition, in a DQ2 mouse model, a transamidated purified α -gliadin fraction, and a single recombinant α -gliadin sequence were able to counteract the pro-inflammatory activity of native gliadin [ 4 , 132 ]. A possible objection to the enzymatic approaches here described is the consideration that, even if TG enzymatic transamidation targets Gln residues responsible of immunogenicity when deamidated, a number of other immunogenic epitopes that do not need deamidation to bind HLA-DQ2/8 molecules could remain unaltered.…”

Section: Gluten Transamidation As a Detoxification Strategy For Thera...supporting

confidence: 87%

“…Regarding CD, TG2 is not only the main autoantigen; it represents one of the most important pathogenetic agents in the disease, and as a consequence, it is one of the possible targets of studies aiming to develop new therapeutical strategies [ 3 ]. Moreover, TGs, and in particular TGm, are also suitable as biotechnological tools to modify gluten proteins, which are the main environmental triggers for CD [ 4 ]. In this review, we explored all aspects regarding TGs—in particular TG2—in CD, including the consolidated concept of the role of TG2 in disease pathogenesis, the new studies on the coeliac cellular phenotype, the recent discoveries with regard to targeting TG2 as a possible new therapeutic approach, and finally, the use of a food-grade TGm to detoxify gluten sequences.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Type 2 Transglutaminase in Coeliac Disease: A Key Player in Pathogenesis, Diagnosis and Therapy

Paolella

Sposito

Romanelli

et al. 2022

IJMS

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Type 2 transglutaminase (TG2) is the main autoantigen in coeliac disease (CD), a widespread inflammatory enteropathy caused by the ingestion of gluten-containing cereals in genetically predisposed individuals. As a consequence, serum antibodies to TG2 represent a very useful marker in CD diagnosis. However, TG2 is also an important player in CD pathogenesis, for its ability to deamidate some Gln residues of gluten peptides, which become more immunogenic in CD intestinal mucosa. Given the importance of TG2 enzymatic activities in CD, several studies have sought to discover specific and potent inhibitors that could be employed in new therapeutical approaches for CD, as alternatives to a lifelong gluten-free diet. In this review, we summarise all the aspects regarding TG2 involvement in CD, including its enzymatic reactions in pathogenesis, the role of anti-TG2 antibodies in disease management, and the exploration of recent strategies to reduce deamidation or to use transamidation to detoxify gluten.

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Section: Gluten Transamidation As a Detoxification Strategy For Thera...supporting

confidence: 87%

Section: Gluten Transamidation As a Detoxification Strategy For Thera...supporting

confidence: 87%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Type 2 Transglutaminase in Coeliac Disease: A Key Player in Pathogenesis, Diagnosis and Therapy

Paolella

Sposito

Romanelli

et al. 2022

IJMS

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“…Finally, there is an ongoing debate on mTG usage in bakeries. Some scientists advocate its therapeutic application [47][48][49][50] while others oppose it [3,[9][10][11][12][13]17,18,34,35,37,51,52]. Well designed, double blind, cross-over CD patients' challenges will clarify those contradictory opinions.…”

Section: Microbial Transglutaminase-gliadin Complexes Are Immunogenic In Celiac Diseasementioning

confidence: 99%

Microbial Transglutaminase Is a Very Frequently Used Food Additive and Is a Potential Inducer of Autoimmune/Neurodegenerative Diseases

Lerner

Benzvi

2021

Toxics

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Microbial transglutaminase (mTG) is a heavily used food additive and its industrial transamidated complexes usage is rising rapidly. It was classified as a processing aid and was granted the GRAS (generally recognized as safe) definition, thus escaping full and thorough toxic and safety evaluations. Despite the manufacturers claims, mTG or its cross-linked compounds are immunogenic, pathogenic, proinflammatory, allergenic and toxic, and pose a risk to public health. The enzyme is a member of the transglutaminase family and imitates the posttranslational modification of gluten, by the tissue transglutaminase, which is the autoantigen of celiac disease. The deamidated and transamidated gliadin peptides lose their tolerance and induce the gluten enteropathy. Microbial transglutaminase and its complexes increase intestinal permeability, suppresses enteric protective pathways, enhances microbial growth and gliadin peptide’s epithelial uptake and can transcytose intra-enterocytically to face the sub-epithelial immune cells. The present review updates on the potentially detrimental side effects of mTG, aiming to interest the scientific community, induce food regulatory authorities’ debates on its safety, and protect the public from the mTG unwanted effects.

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“…12 The presence of immunomodulatory properties of spf has been also shown, associated with specific components of the alpha-gliadin fraction. 14 The effectiveness of this detoxification strategy on the immune response in vivo remains to be fully elucidated. The mucosa of the upper respiratory tract represents a strategic route to induce mucosal immune responses, 15 as it requires low doses of antigen in comparison to the high doses necessary for oral sensitisation.…”

Section: Introductionmentioning

confidence: 99%

Transamidated wheat gliadin induces differential antigen recognition in the small intestine of HLA/DQ8 transgenic mice

et al. 2022

Self Cite

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Tailoring the immune response to wheat gliadin by enzymatic transamidation

Cited by 11 publications

References 38 publications

Type 2 Transglutaminase in Coeliac Disease: A Key Player in Pathogenesis, Diagnosis and Therapy

Type 2 Transglutaminase in Coeliac Disease: A Key Player in Pathogenesis, Diagnosis and Therapy

Microbial Transglutaminase Is a Very Frequently Used Food Additive and Is a Potential Inducer of Autoimmune/Neurodegenerative Diseases

Transamidated wheat gliadin induces differential antigen recognition in the small intestine of HLA/DQ8 transgenic mice

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