Advances in Nonresponsive and Refractory Celiac Disease.

Nonresponsive celiac disease (CeD) is relatively common. It is generally attributed to persistent gluten exposure and resolves after correction of diet errors. However, other complications of CeD and disorders clinically mimicking CeD need to be excluded. Novel therapies are being evaluated to facilitate mucosal recovery, which might benefit patients with nonresponsive CeD. Refractory CeD (RCeD) is rare and is divided into 2 types. The etiology of type I RCeD is unclear. A switch to gluten-independent autoimmunity is suspected in some patients. In contrast, type II RCeD represents a low-grade intraepithelial lymphoma. Type I RCeD remains a diagnosis of exclusion, requiring ruling out gluten intake and other nonmalignant causes of villous atrophy. Diagnosis of type II RCeD relies on the demonstration of a clonal population of neoplastic intraepithelial lymphocytes with an atypical immunophenotype. Type I RCeD and type II RCeD generally respond to open-capsule budesonide, but the latter has a dismal prognosis due to severe malnutrition and frequent progression to enteropathy-associated T-cell lymphoma; more efficient therapy is needed.

Increased risk of gastric cancer in relation with pernicious anaemia in patients with primary antibody deficiency: A nationwide case control study.

BACKGROUND/AIM: We aimed to assess gastrointestinal cancers risks in a large cohort of individuals with primary antibody deficiency (PAD) and their association with risk of autoimmune and inflammatory gastrointestinal diseases. METHODS: Investigating a French national database of inpatient admissions between 2010 and 2018, we identified 12,748 patients with PAD and 38,244 control non-exposed individuals. We performed multiple exposed-non-exposed studies using conditional logistic regression. RESULTS: In comparison with non-exposed patients, PAD patients had increased risk of in situ gastric carcinoma (Odds Ratio (OR) =10.5 [95 % CI 2.2; 50.5]), malignant gastric tumor (OR=3.2 [95 % CI 2.2; 4.4]) and colorectal cancer (OR=1.2 [95 % CI 1; 1.5]). PAD patients had also increased risk of pernicious anaemia (OR=8 |95 % CI 5.6; 11.5]), Crohn's disease (OR= 4.4 [95 % CI 3.5; 5.6]), ulcerative colitis (OR=2.9 [95 % CI 2.4; 3.6]) and coeliac disease (OR=13.3 [95 % CI 9.1; 19.5]). Within patients with gastric cancer, those with PAD had increased risk of pernicious anaemia (OR=8.4 [95 % CI 1.5; 215]; p = 0.01) but not of H. pylori infection. CONCLUSIONS: Risk of gastric cancer is particularly high in PAD patients and notably risk of in situ gastric carcinoma in association with pernicious anaemia. It supports indication of early endoscopic screening in these patients.

Cellular and molecular basis of proximal small intestine disorders.

The proximal part of the small intestine, including duodenum and jejunum, is not only dedicated to nutrient digestion and absorption but is also a highly regulated immune site exposed to environmental factors. Host-protective responses against pathogens and tolerance to food antigens are essential functions in the small intestine. The cellular ecology and molecular pathways to maintain those functions are complex. Maladaptation is highlighted by common immune-mediated diseases such as coeliac disease, environmental enteric dysfunction or duodenal Crohn's disease. An expanding spectrum of more than 100 rare monogenic disorders inform on causative molecular mechanisms of nutrient absorption, epithelial homeostasis and barrier function, as well as inflammatory immune responses and immune regulation. Here, after summarizing the architectural and cellular traits that underlie the functions of the proximal intestine, we discuss how the integration of tissue immunopathology and molecular mechanisms can contribute towards our understanding of disease and guide diagnosis. We propose an integrated mechanism-based taxonomy and discuss the latest experimental approaches to gain new mechanistic insight into these disorders with large disease burden worldwide as well as implications for therapeutic interventions.