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SELECTIVE INHIBITION OF GLIADIN IMMUNE REACTIVITY BY TRANSAMIDATION OF WHEAT FLOUR WITH MICROBIAL TRANSGLUTAMINASE
Author(s) -
Iaquinto Gaetano,
Lombardi Emanuela,
Bergamo Paolo,
Maurano Francesco,
Bozzella Giuseppina,
Luongo Diomira,
Mazzarella Giuseppe,
Aufiero Vera Rotondi,
Rossi Mauro
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.645.9
Subject(s) - gliadin , tissue transglutaminase , gluten , chemistry , immunogenicity , immune system , enteropathy , in vitro , small intestine , biochemistry , microbiology and biotechnology , enzyme , immunology , biology , medicine , disease
Celiac disease (CD) is an immune‐mediated enteropathy caused by the ingestion of wheat gluten. The modification of gluten by intestinal tissue transglutaminase (tTGase) plays a crucial role in CD pathogenesis. In this study, we observed that extensive transamidation of wheat flour with lysine ethyl ester (K‐C 2 H 5 ) by microbial TGase (mTGase) yielded water‐soluble (spf) and insoluble transamidated gliadin (K‐gliadins) fractions. Using DQ8 transgenic (tg) mice as a model of gluten sensitivity, we observed a dramatic reduction in IFNγ production in gliadin‐specific spleen cells challenged with spf and K‐gliadins in vitro (N=12; median values: 813 vs. 29 and 99; control vs. spf and K‐gliadins, P =0.012 for spf, P =0.003 for K‐gliadins). We also observed an increase in the IL‐10/IFNγ protein ratio (N=12; median values: 0.3 vs. 4.7, control vs. spf, P =0.005). In intestinal biopsies from untreated CD patients challenged in vitro with gliadins (N=10), K‐gliadins dramatically reduced the levels of antigen‐specific IFNγ mRNA in all specimens responsive to native gliadins (4/10; P <0.05). In addition, the analysis of glutathione‐S transferase (GST) and caspase‐3 activities in the enterocytic Caco‐2 cells showed that neither activities were modified by flour transamidation. In conclusion, we found that K‐C 2 H 5 cross‐linking via mTGase specifically affected gliadin immunogenicity, reversing the inducible inflammatory response in models of gluten sensitivity without influencing the cytotoxic properties of gliadins.