Pathological and clinical significance of increased intraepithelial lymphocytes (IELs) in small bowel mucosa

Abstract

Intestinal intraepithelial lymphocytes (IELs) belong to a unique T-cell population interspersed between epithelial cells of both the small and large intestine. It is becoming increasingly recognised that an increased number of IELs with a normal villous architecture is within the wide spectrum of histological abnormalities observed in coeliac disease. An increased number of IELs is the earliest pathological change following gluten challenge and a high IEL count may be the only sign of gluten sensitivity. Therefore, the finding of a raised IEL count with normal villous architecture is of sufficient clinical importance to be reported in routine small bowel biopsies. However, it is evident that not all small intestinal biopsy specimens showing increased IELs are explained by gluten sensitivity. Increased IELs in small bowel mucosa have also been associated with autoimmune disorders, tropical sprue, food protein intolerance, Helicobacter pylori-associated gastritis, peptic duodenitis, parasitic and viral infections, as well as the development of intestinal lymphoma. Histological examination of a biopsy specimen of the small bowel remains the diagnostic gold standard for coeliac disease. There will be an ever increasing demand for histological confirmation of gluten sensitivity in patients in whom the classic microscopic appearance of flattened villi may not have fully developed. The more widespread recognition by histopathologists of the pattern of injury manifested by increased numbers of IELs in intestinal biopsy specimens will certainly help in early diagnosis of coeliac disease, lessen diagnostic confusion and influence the modern practice of gastrointestinal tract medicine. This review discusses some of the recent developments in clinical pathology pertaining to increased IELs in small bowel mucosal biopsies.

Anti-tissue transglutaminase antibodies (IgA and IgG) in both Crohn's disease and autoimmune diabetes

“…Large numbers of villous IELs was described during an episode of active Crohn's enteritis (29). However, Wright et al (30) found a similar IEL density in the duodenum of Crohn's disease patients with normal radiographic and endoscopic findings in agreement with our results.…”

Duodenal intraepithelial lymphocytosis is common in children without coeliac disease, and is not meaningfully influenced by Helicobacter pylori infection

“…Helicobacter pylori infection has no major influence on the intraepithelial lymphocyte counts in children with recurrent abdominal pain or children with coeliac disease. [6][7][8][9] Increased IELs are also present in~70% of patients with noncoeliac enteropathy. 10 Furthermore, mild intraepithelial lymphocytosis has also been described in healthy individuals with varying prevalence in different studies.…”

IL-36 receptor is expressed by human blood and intestinal T lymphocytes and is dose–dependently activated via IL-36β and induces CD4+ lymphocyte proliferation

“…Intra-epithelial lymphocyte populations are known to increase in patients with various intestinal disorders [22] but the model we have used denudes the intestinal epithelium which would also preclude intra-epithelial lymphocytes from the CD4/IL-36-R population we have measured. Our results, therefore, most likely indicate that CD4+ lymphocytes maintain IL-36R expression as they enter peripheral tissue from the blood.…”