ROLE OF ZONULIN IN THE INTESTINAL PERMEABILITY CHANGES TYPICAL OF THE ACUTE PHASE OF COELIAC DISEASE

Abstract

78 Introduction: The initial steps of the coeliac disease (CD) involve the opening of tight junctions (tj) by an as yet unknown mechanism, followed by the severe intestinal damage typical of CD. We have recently identified a novel family of hormones, the zonulins (ZO), that induce tj disassembly and may represent the physiological modulators of intercellular tj. Aims: The aim of this study was to establish whether ZO is involved in CD pathogenesis. Methods: We have developed an ELISA assay to measure IgA and IgG anti-ZO in sera from: 85 untreated, 23 treated celiac patients, 112 healthy controls and 102 patients with autoimmune diseases (multiple sclerosis, IDDM). In situ immunofluorescence test was used to analyze the expression of ZO on small bowel biopsies of coeliac patients and controls. Results: The results showed that 23 out of 85 (27%) celiac patients had elevated anti-ZO antibodies. On the contrary, 11 out of 108 (9.8%) healthy controls and 12 out of 102 (11.7%) patients with autoimmune diseases were tested positive for anti-ZO antibodies. Only one of the 20 treated coeliac patients was tested positive for ZO antibodies. The anti-ZO antibodies of 5 patients followed longitudinally returned to based line after 3-6 months of gluten-free diet. Immunofluorescence analysis of intestinal biopsies obtained from 5 coeliac patients during the acute phase of the disease revealed an increased expression of zonulin detected as a characteristic reticular design that was absent in specimens obtained from healthy controls. Discussion: The present study shows that the prevalence of anti-ZO antibodies in untreated coeliac patients is significantly greater than in other study groups (p<0.01). These data suggest that ZO expression is up-regulated during the acute phase of CD and may be responsible of early changes of tj permeability typical of this condition.