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Anti-type 2 transglutaminase antibodies as modulators of type 2 transglutaminase functions: a possible pathological role in celiac disease

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Abstract

Auto-antibodies to the ubiquitous enzyme type-2 transglutaminase (TG2) are a specific hallmark of celiac disease (CD), a widely diffused, multi-factorial disease, affecting genetically predisposed subjects. In CD an inflammatory response, at the intestinal level, is triggered by diet consumption of gluten-containing cereals. Intestinal mucosa displays various degrees of atrophy and hyperplasia, with consequent global intestinal dysfunction and other relevant extra-intestinal symptoms. Through deamidation of specific glutamines of gluten-derived gliadin peptides, TG2 strongly enhances gliadin immunogenicity. In addition, TG2 cross-linking activity may generate complexes between TG2 itself and gliadin peptides, and these complexes seem to cause the auto-immune response by means of an apten-carrier-like mechanism of antigen presentation. Anti-TG2 antibodies can be early detected in the intestinal mucosa of celiac patients and are also abundantly present into the serum, thus potentially reaching other organs and tissues by blood circulation. Recently, the possible pathogenetic role of auto-antibodies to TG2 in CD has been investigated. Here, we report an overview about the genesis of these antibodies, their specificity, their modulating ability toward TG2 enzymatic or non-enzymatic activities and their biological effects exerted by interacting with extracellular TG2 or with cell-surface TG2. We also discuss the auto-immune response occurring in CD against other TG members (i.e. type 3 and type 6) and analyze the occurrence of anti-TG2 antibodies in other auto-immune CD-related diseases. Data now available let us to suppose that, even if antibodies to TG2 do not represent the triggering molecules in CD, they could be important players in disease progression and manifestations.

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Abbreviations

TG2:

Type-2 transglutaminase

CD:

Celiac disease

TG:

Transglutaminase

HLA:

Human leukocyte antigens

DH:

Dermatitis herpetiformis

TG3:

Type 3 transglutaminase

TG6:

Type 6 transglutaminase

T1D:

Type 1 diabetes

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  1. Stefania Martucciello and Gaetana Paolella contributed equally to the manuscript.

Authors and Affiliations

  1. Department of Chemistry and Biology, University of Salerno, via Giovanni Paolo II, 132, 84084, Fisciano (SA), Italy

    Stefania Martucciello, Gaetana Paolella, Carla Esposito, Marilena Lepretti & Ivana Caputo

  2. Interuniversity Centre “European Laboratory for the Investigation of Food-Induced Diseases” (ELFID), University of Salerno, Fisciano (SA), Italy

    Carla Esposito & Ivana Caputo

Authors
  1. Stefania Martucciello
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  2. Gaetana Paolella
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  3. Carla Esposito
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  4. Marilena Lepretti
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  5. Ivana Caputo
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Correspondence to Ivana Caputo.

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Martucciello, S., Paolella, G., Esposito, C. et al. Anti-type 2 transglutaminase antibodies as modulators of type 2 transglutaminase functions: a possible pathological role in celiac disease. Cell. Mol. Life Sci. 75, 4107–4124 (2018). https://doi.org/10.1007/s00018-018-2902-0

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