CAPITOLO 4: Sensitività al glutine non celiaca (NCGS)
4.9 Tendenze attuali e future
L‘accresciuto interesse verso la NCGS è testimoniato dalla diminuzione del rapporto tra pubblicazioni sulla NCGS e sulla CD, passato da 1:438 nel periodo 1950-1970 a 1:10 nel periodo 2010-13 (Tabella 6).
Tabella 6
Tenuto conto della letteratura limitata sull‘argomento, non deve sorprendere il fatto che numerose domande sulla NCGS siano tuttora aperte. Il range riportato nella letteratura è compreso tra lo 0,5% e il 6%, ma è basato su studi limitati e su definizioni della malattia ampiamente variabili da un rapporto all‘altro. Solo recenti studi, condotti a regola d‘arte, in doppio cieco e controllo con placebo, stanno fornendo dati supportati da prove sulla prevalenza della NCGS in condizioni cliniche specifiche, in particolare IBS. Vi è una forte
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necessità di sforzi maggiormente coordinati per eseguire studi multicentrici di ampia portata sulle condizioni, inclusi autismo e schizofrenia, in cui la NCGS è stata indicata come possibile causa in un sottogruppo di pazienti. L‘assenza di biomarcatori confermati per una diagnosi che non sia basata su criteri di esclusione è ritenuta un aspetto di importanza fondamentale da molti esperti del settore. Proprio a tale scopo è attualmente in corso un ampio studio multicentrico controllato con placebo, con l‘auspicio che possa fornire gli strumenti per una diagnosi più corretta, nonché per l‘esecuzione di studi più rigorosi onde stabilire la prevalenza della NCGS in condizioni specifiche e nella popolazione generale. Recenti studi hanno sollevato l‘ipotesi che, oltre al glutine e agli inibitori dell‘amilasi/tripsina del frumento, i carboidrati a catena corta, scarsamente fermentabili e a basso assorbimento possano contribuire ai sintomi (almeno quelli legati all‘IBS) riscontrati nei pazienti colpiti da NCGS. Queste nuove scoperte necessitano di conferme tramite ulteriori studi condotti su un numero più ampio di soggetti. L‘eventuale conferma di queste nuove scoperte spingerebbe probabilmente verso un cambiamento della nomenclatura, da NCGS a “sensibilità al frumento“, riflettendo il fatto che, oltre al glutine, altri componenti del frumento possono essere responsabili dei sintomi segnalati dai pazienti colpiti da NCGS [110].
CONCLUSIONI
La TG2 ha indiscutibilmente un ruolo importante nello sviluppo della celiachia in virtù della sua attività enzimatica. Di contro l’assenza di biomarkers e in molti casi la inadeguatezza delle procedure diagnostiche rendono difficilmente stimabile la prevalenza e le caratteristiche della NCGS. Nonostante i notevoli progressi nella comprensione del ruolo patogeno di tTG nella malattia celiaca, molti problemi devono ancora essere chiariti. Questi includono il regolamento intracellulare di tTG, il meccanismo della sua esternalizzazione, il ruolo degli enterociti come siti primari di modifica di gliadina da tTG, l'effetto degli anticorpi anti-tTG sulla sua attività di transamidazione, e la connessione tra le diverse funzioni esercitate da questo enzima: primo, come bersaglio di anticorpi malattia-specifici; e in secondo luogo come un enzima di deamidazione che può potenziare l'effetto immunostimolante del glutine. Prendendo in considerazione la possibilità di terapie basate su tTG messe a disposizione dalla caratterizzazione strutturale e funzionale dell’enzima in anni recenti, è possibile predire che tTG creerà ulteriore notizia nel prossimo futuro.
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