Clinical and Immunological Features of Celiac Disease in Patients With Type 1 Diabetes Mellitus

Umberto Volta; Francesco Tovoli; Giacomo Caio


Expert Rev Gastroenterol Hepatol. 2011;5(4):479-487. 

In This Article

Immune Linkage Between CD & T1DM

There is an evident immune linkage between T1DM and CD since these two autoimmune disorders share an abnormal immune response of the intestinal mucosa, intestinal inflammation with variable grade of enteropathy and production of tTGA.[32] Experimental studies have shown that rectal gluten challenge induces a significant increase in CD3+ and γ/δ lymphocytes in the rectum mucosa of T1DM patients, as well as that of CD patients, whereas these immunohistochemical changes were not found in controls.[33] Moreover, small intestinal biopsies of patients with T1DM as well as of CD patients, cultured in vitro with gliadin, demonstrated a significant increase of CD3+ T lymphocytes in the epithelium and CD25+ mononuclear cells and CD80+ cells in the lamina propria, together with an enhanced expression of HLA-DR molecules in the crypts. These signs of immune activation were not observed in the intestinal biopsies of T1DM patients cultured with food proteins other than gliadin and were also absent in HLA-DQ2 nondiabetic subjects. Moreover, a higher density of IL-1- and IL-4-positive cells was found in the lamina propria of duodenal mucosa in patients with T1DM, irrespective of the morphology of the small intestine.[34]

In the duodenal biopsies of NOD mice, an increased synthesis of tTGA has been demonstrated but still with an unclear underlying mechanism.[12] Furthermore, IgA deposits of tTGA, which are predictive markers of CD onset, have been found in the small intestinal biopsy of the majority of T1DM patients.[35] Studies performed in NOD mice and in patients with T1DM and no CD have shown that islet-infiltrating autoreactive cells express gut-associated homing receptor, thus suggesting that lymphocytes may recirculate between the gut and the pancreas.[36,37]

The frequent coexistence of CD and T1DM seems to be more than a simple association, suggesting a unifying hypothesis on the development of both disorders with a central role of gluten in their pathogenesis.[32] In this respect, removal of dietary gluten after CD diagnosis is associated with a lower frequency of T1DM. It is likely that undiagnosed CD, leading to activation of the gut immune system and increased permeability of the intestinal barrier to large proteins and also enteral viruses, especially coxsackievirus B, may contribute to the onset of T1DM.[2] Moreover, experimental data have shown that a gluten-free diet (GFD) delayed, and to a large extent prevented, diabetes in NOD mice that had never been exposed to gluten.[38]


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