Abstract
G A A b st ra ct s zonulin using qPCR and immunohistochemistry was assessed in asymptomatic/mildly symptomatic, anti-tTG Ab negative FDRs having normal villi (Modified Marsh grade 0) and disease controls. Functional assessment of tight junctions in them was done by measuring intestinal permeability [using lactulose mannitol ratio (LMR)] in 97 asymptomatic, anti-tTG Ab negative FDRs and 75 healthy controls. Additionally, serum zonulin level was measured in 172 antitTG Ab negative FDRs and 198 controls. Results: Ultra-structural abnormalities such as dilatation of tight junction (p=0.0037) and loss of pentalaminar structure (p=0.001) were more common in FDRs than disease controls (Fig 1). The LMR was significantly increased in FDRs than controls [0.06(IQR 0.04-0.12) vs 0.03(IQR 0.02-0.08); p=0.002]. There was significant under-expression of tight junction proteins ZO-1 (p=0.006) and occludin (p= 0.019) in FDRs. There was no significant difference in serum zonulin level between FDRs and controls (p=0.154). Conclusions: Even asymptomatic, anti-tTG-Ab negative and with normal histology FDRs have both ultra-structural and functional abnormalities in tight junctions. These findings are indirect evidence of presence of tight junctions abnormalities prior to onset of the disease and may have therapeutic implications.
Published Version
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