Tissue Transglutaminase Antibodies in Individuals with Celiac Disease Bind to Thyroid Follicles and Extracellular Matrix and May Contribute to Thyroid Dysfunction

Naiyer, Afzal J.; Shah, Jayesh; Hernandez, Lincoln; Kim, Soo-Youl; Ciaccio, Edward J.; Cheng, Jianfeng; Manavalan, Sanil; Bhagat, Govind; Green, Peter H. R.

doi:10.1089/thy.2008.0110

Cited by 51 publications

(46 citation statements)

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“…However, current allergic asthma therapy is not satisfactory. TGase 2 is associated with a variety of diseases (Sanchez et al, 2000;Citron et al, 2001;Junn et al, 2003;Picarelli et al, 2003;Roberts et al, 2003;Andrings et al, 2004;Kim et al, 2005;Cho et al, 2008;Naiyer et al, 2008;Hwang et al, 2009;Park et al, 2009a) including human allergic asthma (Hallstrand et al, 2010). R2 peptide inhibits TGase 2 to block inflammation in an allergic conjunctivitis model in guinea pigs (Sohn et al, 2003).…”

Section: Discussionmentioning

confidence: 99%

“…TGase 2 is aberrantly activated in tissues and cells and contributes to neurodegenerative diseases, such as Alzheimer's disease (Citron et al, 2001), Parkinson's disease (Junn et al, 2003;Andrings et al, 2004), neuro-AIDS (Roberts et al, 2003), Huntington's diseases (Kim et al, 2005), hippocampal CA 1 ischemia (Hwang et al, 2009), celiac disease (Naiyer et al, 2008), lupus (Sanchez et al, 2000), autoimmune diseases like rheumatic arthritis (Picarelli et al, 2003), human atherosclerotic coronary arteries (Cho et al, 2008), breast cancers (Park et al, 2009a) and drug resistance in variety of cancer cells Park et al, 2009bPark et al, , 2010. TGase 2 expression is increased in inflammatory diseases such as activation of microglia, a hallmark of brain inflammation (Park et al, 2004), idiopathic inflammatory myopathies (Kim, 2006) and allergic asthma (Hallstrand et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

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Anti‐inflammatory effects of the R2 peptide, an inhibitor of transglutaminase 2, in a mouse model of allergic asthma, induced by ovalbumin

Kim

Park

Hong

et al. 2010

British J Pharmacology

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BACKGROUND AND PURPOSETransglutaminase 2 (TGase 2) expression is increased in inflammatory diseases, and TGase 2 inhibitors block these increases. We examined whether the R2 peptide inhibited the expression of TGase 2 in a mouse model of inflammatory allergic asthma. EXPERIMENTAL APPROACHC57BL/6 mice were sensitized and challenged by ovalbumin (OVA) to induce asthma. OVA-specific serum IgE and leukotrienes (LTs) levels were measured by enzyme-linked immunosorbent assay. Recruitment of inflammatory cells into bronchoalveolar lavage (BAL) fluid or lung tissues and goblet cell hyperplasia were assessed histologically. Airway hyperresponsiveness was determined in a barometric plethysmographic chamber. Expression of TGase 2, eosinophil major basic protein (EMBP), the adhesion molecule vascular cell adhesion molecule-1, Muc5ac and phospholipase A2 (PLA2) protein were determined by Western blot. Expression of mRNAs of Muc5ac, cytokines, matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs) were measured by reverse transcriptase-polymerase chain reaction and nuclear factor-kB (NF-kB) by electrophoretic mobility shift assay. KEY RESULTSR2 peptide reduced OVA-specific IgE levels; the number of total inflammatory cells, macrophages, neutrophils, lymphocytes and eosinophils in BAL fluid and the number of goblet cells. Airway hyperresponsiveness, TGase 2 and EMBP levels, mRNA levels of interleukin (IL)-4, IL-5, IL-6, IL-8, IL-13, RANTES, tumour necrosis factor-a, and MMP2/9, Muc5ac, NF-kB activity, PLA2 activity and expressions, and LT levels in BAL cells and lung tissues were all reduced by R2 peptide. R2 peptide also restored expression of TIMP1/2. CONCLUSION AND IMPLICATIONSR2 peptide reduced allergic responses by regulating NF-kB/TGase 2 activity in a mouse model of allergic asthma. This peptide may be useful in the treatment of allergic asthma. AbbreviationsBAL, bronchoalveolar lavage; ELISA, enzyme-linked immunosorbent assay; EMBP, eosinophil major basic protein; EMSA, electrophoretic mobility shift assay; MMP, matrix metalloproteinase; NF-kB, nuclear factor-kappa B; OVA, ovalbumin; PAS, periodic acid-Schiff; PBS, phosphate buffered saline; PLA2, phospholipase A2; RT-PCR, reverse transcriptase-polymerase chain reaction; TGase 2, transglutaminase 2; TIMP, tissue inhibitor of matrix metalloproteinase BJP British Journal of Pharmacology

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Anti‐inflammatory effects of the R2 peptide, an inhibitor of transglutaminase 2, in a mouse model of allergic asthma, induced by ovalbumin

Kim

Park

Hong

et al. 2010

British J Pharmacology

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“…Although the exact mechanisms for the induction of these autoimmunities are not definitively known, there is a growing body of evidence indicating that these diseases may result from molecular mimicry between gliadin or transglutaminase and various tissue antigens, including nervous system proteins [8,[41][42][43]48]. Interestingly, the celiac peptide VVKVGGSSSLGW shares more than 30% homology with the transglutaminase peptide 476-487 (RIRVGQSMNMGS) [8].…”

Section: Cross-reaction Between α-Gliadin and Different Tissue Antigensmentioning

confidence: 99%

Cross-Reaction between Gliadin and Different Food and Tissue Antigens

Vojdani¹,

Tarash²

2013

FNS

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A subgroup of coeliac disease patients continues to experience symptoms even on a gluten-free diet (GFD). We attempted to determine whether these symptoms could be due to either cross-contamination with gluten-containing foods or cross-reactivity between α-gliadin and non-gluten foods consumed on a GFD. We measured the reactivity of affinity-purified polyclonal and monoclonal α-gliadin 33-mer peptide antibodies against gliadin and additional food antigens commonly consumed by patients on a GFD using ELISA and dot-blot. We also examined the immune reactivity of these antibodies with various tissue antigens. We observed significant immune reactivity when these antibodies were applied to cow's milk, milk chocolate, milk butyrophilin, whey protein, casein, yeast, oats, corn, millet, instant coffee and rice. To investigate whether there was cross-reactivity between α-gliadin antibody and different tissue antigens, we measured the degree to which this antibody bound to these antigens. The most significant binding occurred with asialoganglioside, hepatocyte, glutamic acid decarboxylase 65, adrenal 21-hydroxylase, and various neural antigens. The specificity of anti-α-gliadin binding to different food and tissue antigens was demonstrated by absorption and inhibition studies. We also observed significant cross-reactivity between α-gliadin 33-mer and various food antigens, but some of these reactions were associated with the contamination of non-gluten foods with traces of gluten. The consumption of cross-reactive foods as well as gluten-contaminated foods may be responsible for the continuing symptoms presented by a subgroup of patients with coeliac disease. The lack of response of some CD patients may also be due to antibody cross-reactivity with non-gliadin foods. These should then be treated as gluten-like peptides and should also be excluded from the diet when the GFD seems to fail.

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“…For instance, celiac disease-specific autoantibodies recognize TG2 in bone, 90 thyroidal gland 91 and heart muscle tissues, 92 and furthermore, celiac disease has been associated with osteoporotic fractures and with thyroidal and cardiac autoimmunity and dysfunction. [90][91][92] Currently, we can only speculate that the disease-specific autoantibodies may have an active role in the pathophysiology of these conditions; although this suggestion is attractive, its validity awaits verification.…”

Section: Antibodies In Celiac Diseasementioning

confidence: 99%

Antibodies in celiac disease: implications beyond diagnostics

et al. 2011

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Tissue Transglutaminase Antibodies in Individuals with Celiac Disease Bind to Thyroid Follicles and Extracellular Matrix and May Contribute to Thyroid Dysfunction

Abstract: Anti-TGase II antibodies bind to TGase II in thyroid tissue, and titers correlate with TPO antibody titers. These findings suggest that anti-TGase II antibodies could contribute to the development of thyroid disease in celiac disease.

Cited by 51 publications

References 50 publications

Anti‐inflammatory effects of the R2 peptide, an inhibitor of transglutaminase 2, in a mouse model of allergic asthma, induced by ovalbumin

Anti‐inflammatory effects of the R2 peptide, an inhibitor of transglutaminase 2, in a mouse model of allergic asthma, induced by ovalbumin

Cross-Reaction between Gliadin and Different Food and Tissue Antigens

Antibodies in celiac disease: implications beyond diagnostics

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