Immunoglobulin isotype profile of tissue transglutaminase autoantibodies is correlated with the clinical presentation of coeliac disease.
Coeliac disease (CD) is characterized by the appearance of autoantibodies against tissue transglutaminase (tTG-Ab). Immunoglobulin A (IgA) tTG-Ab have been described as excellent diagnostic markers, but the Ig subclass distribution and the importance of isotype tTG-Ab have not yet been established. In this study, using newly developed isotype- and subclass-specific radioligand assays, we examined anti-tTG IgA1, IgA2, IgG1, IgG4 and IgE antibodies in 30 symptomatic, untreated patients with CD and 22 subjects suspected to suffer from silent CD (sCD). Among 30 patients with CD, 27 (90.0%) were positive for IgA1 tTG-Ab, whereas only 12 (40.0%) had autoantibodies of the IgA2 subclass (P <0.001). IgG1, IgG4 and IgE tTG-Ab were detected in 17 (56.6%), 0 and 3 (10.0%) individuals, respectively. IgA1 was also the predominant anti-tTG subclass in patients with sCD (n=20, 90.1%), followed by IgA2 antibodies (n=7, 31.8%), IgG1 antibodies (n=4, 18.2%), IgG4 antibodies (n=1, 4.5%) and IgE antibodies (n=1, 4.5%). The comparison between both groups revealed a significantly higher prevalence of IgG1 antibodies in patients with symptomatic CD (P <0.01). In 10 of 11 subjects undergoing an intestinal biopsy, the diagnosis of an sCD was confirmed. In this subgroup, there was a positive association between the presence of IgA2 and IgG1 tTG-Ab and severe (Marsh 2-3) mucosal abnormalities. In conclusion, patients with symptomatic and sCD predominantly have IgA1 tTG-Ab. IgG1 tTG-Ab are associated with symptomatic disease and, when present in patients with sCD, are correlated with a severe mucosal destruction. These data suggest that tTG-Ab subclasses could reflect inflammatory events associated with epithelial destruction.
Schilling
J
J
German Diabetes Clinic, German Diabetes Center, Leibniz-Institute at the Heinrich-Heine-University, Dusseldorf, Germany.
Spiekerkoetter
U
U
Wohlrab
U
U
Wendel
U
U
Seissler
J
J
D000293:Adolescent; D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000276:immunology*; D001706:Biopsy; D002446:Celiac Disease / Q000201:enzymology / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood / Q000276:immunology; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007130:Immunoglobulin Idiotypes / Q000276:immunology*; D007413:Intestinal Mucosa / Q000276:immunology; D007583:Jejunum / Q000276:immunology; D008297:Male; D008875:Middle Aged; D011503:Transglutaminases / Q000276:immunology*
D001323:Autoantibodies; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007130:Immunoglobulin Idiotypes; D007073:Immunoglobulin E; D011503:Transglutaminases