Expression of α-Defensins, CD20+ B-lymphocytes, and Intraepithelial CD3+ T-lymphocytes in the Intestinal Mucosa of Patients with Liver Cirrhosis: Emerging Mediators of Intestinal Barrier Function

Dig Dis Sci. 2018 Oct;63(10):2582-2592. doi: 10.1007/s10620-018-5146-9. Epub 2018 Jun 7.

Abstract

Aim: The present study investigates the role of innate and adaptive immune system of intestinal mucosal barrier function in cirrhosis.

Methods: Forty patients with decompensated (n = 40, group A), 27 with compensated cirrhosis (n = 27, group B), and 27 controls (n = 27, group C) were subjected to duodenal biopsy. Expression of α-defensins 5 and 6 at the intestinal crypts was evaluated by immunohistochemistry and immunofluorescence. Serum endotoxin, intestinal T-intraepithelial, and lamina propria B-lymphocytes were quantified.

Results: Cirrhotic patients presented higher endotoxin concentrations (p < 0.0001) and diminished HD5 and HD6 expression compared to healthy controls (p = 0.000287, p = 0.000314, respectively). The diminished HD5 and HD6 expressions were also apparent among the decompensated patients compared to compensated group (p = 0.025, p = 0.041, respectively). HD5 and HD6 expressions were correlated with endotoxin levels (r = -0.790, p < 0.0001, r = - 0.777, p < 0.0001, respectively). Although intraepithelial T-lymphocytes were decreased in group A compared to group C (p = 0.002), no notable alterations between groups B and C were observed. The B-lymphocytic infiltrate did not differ among the investigated groups.

Conclusions: These data demonstrate that decreased expression of antimicrobial peptides may be considered as a potential pathophysiological mechanism of intestinal barrier dysfunction in liver cirrhosis, while remodeling of gut-associated lymphoid tissue as an acquired immune response to bio-pathogens remains an open field to illuminate.

Keywords: Antimicrobial peptides; Bacterial translocation; Endotoxin; Gut-associated lymphoid tissue; Mucosal defense; Paneth cells.

MeSH terms

  • Endotoxins / blood
  • Female
  • Humans
  • Immunity, Mucosal*
  • Liver Cirrhosis / immunology*
  • Liver Cirrhosis / metabolism
  • Lymphocytes
  • Lymphoid Tissue / cytology
  • Male
  • Middle Aged
  • Paneth Cells / metabolism*
  • Prospective Studies
  • alpha-Defensins / metabolism*

Substances

  • Endotoxins
  • alpha-Defensins