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REVIEWS  7th INTERNATIONAL CONFERENCE ON TRANSGLUTAMINASES AND PROTEIN CROSSLINKING REACTIONS
Ferrara (Italy), September 14-17, 2002
 

Minerva Biotecnologica 2002 June;14(2):177-80

Copyright © 2003 EDIZIONI MINERVA MEDICA

lingua: Inglese

The role of tissue transglutaminase in the pathophysiology of coeliac disease

Troncone R. 1, Esposito C. 2, Auricchio S. 1

1 Department of Pediatrics and European Laboratory for the Investigation of Food-Induced Diseases, University Federico II, Naples, Italy; 2 Department of Chemistry, University of Salerno, Salerno, Italy


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Coeliac Dis­ease (CD) is a mul­ti­fac­to­ri­al dis­ease con­sid­ered to be the ­result of a dys­reg­u­lat­ed T ­cell muco­sal ­immune ­response to ­wheat gli­a­din and relat­ed pro­la­mines of oth­er tox­ic ­cereals. It has ­been dem­on­strat­ed ­that glu­ten-spe­cif­ic intes­ti­nal T ­cells ­from CD ­patients rec­og­nise pro­la­mine pep­tides ­only ­after ­they ­have under­gone deam­i­da­tion, the lat­ter ­being medi­at­ed by the ­enzyme tis­sue trans­glu­tam­i­nase (tTG). Recent­ly, ­such ­enzyme has ­been iden­ti­fied as the prom­i­nent if not ­sole endo­my­sial auto­an­ti­gen. ­Since it has ­been dem­on­strat­ed ­that tTG-gli­a­din com­plex­es ­could be ­formed in ­vitro it has ­been sug­gest­ed ­that ­these com­plex­es may con­tain neo­epi­topes ­that trig­ger muco­sal T ­cells and abol­ish tol­er­ance. tTG pro­tein lev­els and activ­ity are ­increased in spe­cif­ic are­as of the untreat­ed ­coeliac muco­sa. In ­fact, tTG is heav­i­ly ­expressed in the sub­epi­the­lial ­region ­just ­below the ­basal mem­brane; tTG ­appears con­cen­trat­ed in the ­extra-cel­lu­lar ­matrix, as ­well as in the ente­roc­y­tes ­both at ­brush bor­der and cyto­plasm lev­els. ­These find­ings sug­gest ­that tTG ­plays a ­role in the remod­el­ling of extra­cel­lu­lar ­matrix occur­ring in untreat­ed CD as ­result of acti­vat­ed muco­sal ­cell medi­at­ed immu­nity.

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