Majority of children with type 1 diabetes produce and deposit anti-tissue transglutaminase antibodies in the small intestine.
OBJECTIVE
Anti-tissue transglutaminase (TG2) antibodies are the serological marker of celiac disease. Given the close association between celiac disease and type 1 diabetes, we investigated the production and deposition of anti-TG2 antibodies in the jejunal mucosa of type 1 diabetic children.


METHODS
Intestinal biopsies were performed in 33 type 1 diabetic patients with a normal mucosal architecture: 14 had high levels (potential celiac disease patients) and 19 had normal levels of serum anti-TG2 antibodies. All biopsy specimens were investigated for intestinal deposits of IgA anti-TG2 antibodies by double immunofluorescence. In addition, an antibody analysis using the phage display technique was performed on the intestinal biopsy specimens from seven type 1 diabetic patients, of whom four had elevated and three had normal levels of serum anti-TG2 antibodies.


RESULTS
Immunofluorescence studies showed that 11 of 14 type 1 diabetic children with elevated levels and 11 of 19 with normal serum levels of anti-TG2 antibodies presented with mucosal deposits of such autoantibodies. The phage display analysis technique confirmed the intestinal production of the anti-TG2 antibodies; however, whereas the serum-positive type 1 diabetic patients showed a preferential use of the VH5 antibody gene family, in the serum-negative patients the anti-TG2 antibodies belonged to the VH1 and VH3 families, with a preferential use of the latter.


CONCLUSIONS
Our findings demonstrate that there is intestinal production and deposition of anti-TG2 antibodies in the jejunal mucosa of the majority of type 1 diabetic patients. However, only those with elevated serum levels of anti-TG2 antibodies showed the VH usage that is typical of the anti-TG2 antibodies that are produced in patients with celiac disease.
Maglio
Mariantonia
M
Department of Pediatrics and European Laboratory for the Investigation of Food-Induced Diseases, University Federico II, Naples, Italy.
Florian
Fiorella
F
Vecchiet
Monica
M
Auricchio
Renata
R
Paparo
Francesco
F
Spadaro
Raffaella
R
Zanzi
Delia
D
Rapacciuolo
Luciano
L
Franzese
Adriana
A
Sblattero
Daniele
D
Marzari
Roberto
R
Troncone
Riccardo
R
D000293:Adolescent; D001323:Autoantibodies / Q000096:biosynthesis*; D001706:Biopsy; D002446:Celiac Disease / Q000150:complications / Q000276:immunology / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000201:enzymology* / Q000276:immunology*; D019204:GTP-Binding Proteins; D006680:HLA Antigens / Q000276:immunology; D006650:Histocompatibility Testing; D006801:Humans; D007150:Immunohistochemistry; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology; D007413:Intestinal Mucosa / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D007583:Jejunum / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases / Q000276:immunology*; D055815:Young Adult
D001323:Autoantibodies; D006680:HLA Antigens; D053645:Interleukin-2 Receptor alpha Subunit; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins