In Vitro–Deranged Intestinal Immune Response to Gliadin in Type 1 Diabetes

• Published in: Diabetes (New York, N.Y.) Vol. 53; no. 7; pp. 1680 - 1683
• Main Authors: Auricchio, Renata, Paparo, Francesco, Maglio, Maria, Franzese, Adriana, Lombardi, Francesca, Valerio, Giuliana, Nardone, Gerardo, Percopo, Selvaggia, Greco, Luigi, Troncone, Riccardo
• Format: Journal Article
• Language: English
• Published: United States American Diabetes Association 01.07.2004
• Subjects: Adolescent; Antibody Formation; Autoimmune diseases; Biopsy; Care and treatment; Case-Control Studies; Celiac disease; Child; Diabetes; Diabetes mellitus; Diabetes Mellitus, Type 1 - immunology; Female; Gliadin - immunology; Gluten; Health aspects; HLA Antigens - analysis; HLA Antigens - classification; Humans; Immunohistochemistry; Inflammation; Intestinal Mucosa - immunology; Jejunum - immunology; Jejunum - pathology; Male; Monoclonal antibodies; Organ Culture Techniques; Phosphatase; Serology; T cells; Type 1 diabetes; United States
• ISSN: 0012-1797; 1939-327X
• DOI: 10.2337/diabetes.53.7.1680

In Vitro–Deranged Intestinal Immune Response to Gliadin in Type 1 Diabetes Renata Auricchio 1 , Francesco Paparo 1 , Maria Maglio 1 , Adriana Franzese 1 , Francesca Lombardi 1 , Giuliana Valerio 1 , Gerardo Nardone 2 , Selvaggia Percopo 1 , Luigi Greco 1 and Riccardo Troncone 1 1 Department of Pediatrics and European Laboratory for the Investigation of Food-Induced Diseases, University “Federico II,” Naples, Italy 2 Department of Experimental Medicine, University “Federico II,” Naples, Italy Address correspondence and reprint requests to Dr. Renata Auricchio, Dipartimento di Pediatria, Università Federico II, via Sergio Pansini 5, I-80131 Napoli, Italy. E-mail: reauricc{at}tin.it Abstract Dietary gluten has been associated with an increased risk of type 1 diabetes. We have evaluated inflammation and the mucosal immune response to gliadin in the jejunum of patients with type 1 diabetes. Small intestinal biopsies from 17 children with type 1 diabetes without serological markers of celiac disease and from 50 age-matched control subjects were examined by immunohistochemistry. In addition, biopsies from 12 type 1 diabetic patients and 8 control subjects were cultured with gliadin or ovalbumin peptic-tryptic digest and examined for epithelial infiltration and lamina propria T-cell activation. The density of intraepithelial CD3 + and γδ + cells and of lamina propria CD25 + mononuclear cells was higher in jejunal biopsies from type 1 diabetic patients versus control subjects. In the patients’ biopsies cultured with peptic-tryptic gliadin, there was epithelial infiltration by CD3 + cells, a significant increase in lamina propria CD25 + and CD80 + cells and enhanced expression of lamina propria CD54 and crypt HLA-DR. No such phenomena were observed in control subjects, even those with celiac disease–associated HLA haplotypes. In conclusion, signs of mucosal inflammation were present in jejunal biopsies from type 1 diabetic patients, and organ culture studies indicate a deranged mucosal immune response to gliadin. CD, celiac disease Footnotes Accepted March 19, 2004. Received July 29, 2003. DIABETES