Enteritis linfocítica duodenalfactores asociados, evolución y marcadores diagnósticos de enfermedad celiaca

Resum

Introduction: celiac disease (EC) is a condition which appears triggered by exposure to dietary gluten in genetically prediposed subjects. Villous atrophy in the small intestine is characteristic of celiac disease but milder forms can be seen as lymphocytic enteritis (LE). Aims: to assess mucosa recovery in celiac patients after gluten-free-diet (GFD) implementation and to evaluate factors associated with it; to analyze lymphocytic enteritis persistence. To study gluten intake in first-degree-relatives of celiac patients (FDR) and to assess its relation with clinical and histological features. To identify lymphocytic enteritis caused by celiac disease studying intestinal lymphocytic composition and quantifying serological biomarkers of intestinal damage, inflammation and immune response. Materials and methods: we designed a different study for each aim including celiac patients, FDR, patients with functional dyspepsia and healthy controls. We established more than 12 months period in GFD to take control biopsies in celiac patients. We assessed gluten intake in FDR by detecting gliadin immunogenic peptides (GIPs) in feces using the monoclonal antibody antigliadin 33-mer-G12. We evaluated the presence of Foxp3+ lymphocytes in the lamina propria by immunohistochemistry and intraepithelial lymphocytes T δγ by flow cytometry. We determined serological levels of inflammatory and immune response biomarkers (CCL28, ST2, IL2, IL17, TRX y TWEAK) and intestinal damage, apoptosis and cellular necrosis (IFABP y HMGB1). Results: After a mean follow-up of 2.93 years, 34% celiac patients had total mucosa recovery, 22.9% LE persistence and 42.9% remained with villous atrophy. The associated factors with histological response were time with symptoms, atrophy severity at diagnosis and TTGA levels at diagnosis and follow-up. GIPs levels were undetectable in 34% of FDR with a referred normal gluten intake. Thirty-four percent of them had LE and 4.7% villous atrophy in spite of a negative celiac serology. Celiac patients with GFD presented more Foxp3+ lymphocytes (18.9 ± 11.9). Control group had similar amount of Foxp3+ lymphocytes (8.5 ± 2.5) than those with functional dyspepsia (7.6 ± 2.2) and FGR (6.4 ± 2.5). Celiac patients, even those in GFD and with LE, presented a higher percentage of lymphocytes T δγ (37.4%), than functional subjects, FDR and controls (11.8%, 5.5% y 5.3% respectively (p<0,001). We observed a positive correlation between both variables (r= 0,752, p< 0,001; Spearman´s test). TWEAK, CCL28, IL17, IFABP and HMBG1 serological levels were higher in celiac patients (GFD or gluten containing diet), with a good relation with histological damage and villous atrophy. Only TRX was higher in celiac patients with GFD and Marsh 1 than those with normal mucosa. FDR with high risk HLADQ and LE had superior levels of CCL28 than those FDR without genetic risk and normal mucosa. Conclusions: despite gluten free diet, an important percentage of celiac patients remain with histological changes, LE among them. The time with symptoms before diagnosis and severity of villous atrophy are essential for the mucosa recovery. FDR make important gluten restrictions in their diet which can affect their diagnosis. Monoclonal antibody antigliadin 33-mer-G12 is a great tool to assess gluten intake. Evaluation of Foxp3+ lymphocytes infiltration in duodenal lamina propria allow to identificate celiac LE; it can be useful for its diagnosis. The biomarkers IFABP, HMGB1, TWEAK, CCL28 and IL17 could be useful in diagnosis and follow-up of celiac disease. CCL28 could be also useful in FDR with LE.