In Vitro Toxicity of Gluten Peptides in Coeliac Disease Assessed by Organ Culture

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Abstract
Background: We have used organ culture to investigate the in vitro toxicity of three oligopeptides corresponding to amino acids 31–49 (peptide A), 202–220 (peptide B), and 3–21 (peptide C) of A-gliadin, Frazer's fraction III (FFIII), and ovalbumin. Methods: Eight to 14 jejunal biopsy specimens were obtained from each of 8 treated and 7 untreated coeliac patients and 5 normal controls and cultured for 18 h in organ culture with test peptide (1 mg/ml) or medium alone. Mean enterocyte cell heights (ECH) were compared with paired values for specimens grown in medium alone. Results: A significant reduction in the mean of the ECH values for each of the patient groups was observed with peptide A and FFIII in both treated (p = 0.01 and 0.02, respectively) and untreated (p = 0.03 and 0.01) coeliac patients when compared with tissue incubated with medium alone. No significant changes in the mean ECH value were noted in any of the patient groups in tissue incubated with peptide B, peptide C, or ovalbumin as compared with those with medium alone. Conclusions: These results suggest that peptide A is toxic in vitro to the jejunal mucosa of both treated and untreated coeliac patients, correlating with recent findings that this peptide exacerbates coeliac disease in vivo.