One third of HLA DQ2 homozygous patients with type 1 diabetes express celiac disease-associated transglutaminase autoantibodies

Type 1 diabetes and celiac disease are both immunologic disorders where spe cific HLA alleles are associated with disease risk. We have developed a rad ioassay for autoantibodies to tissue transglutaminase (tTG) following the r eport that this enzyme is 'the' endomysial autoantigen (EMA) of celiac dise ase. The radioassay for transglutaminase autoantibodies is similar to that utilized for detecting anti-islet autoantibodies. The 'cut-off' for the IgA autoantibody assay was established as 3 x 100th percentile of 184 healthy control subjects at an index of 0.05. Ninety-eight of 847 patients with typ e 1 diabetes (11.6%) had tissue transglutaminase autoantibodies (tTG). All EMA-positive patients were positive (49/49) for transglutaminase autoantibo dies, as were 49/540 EMA-negative patients. Twenty transglutaminase-positiv e patients consented to intestinal biopsy and 15 biopsies were positive for celiac disease. All patients with a transglutaminase level greater than 0. 70 (13/13) had a positive biopsy, while none (0/3) with a level <0.3 had a positive biopsy. The prevalence of transglutaminase autoantibodies was high er in diabetic patients with HLA DQ2 or DQ8. One third of DQ2 homozygous pa tients (22/68) expressed transglutaminase autoantibodies vs. less than 2% o f patients lacking DQ2 or DQ8. A simple radioassay for IgA transglutaminase autoantibodies detects all endomysial antibody positive patients and detec ts transglutaminase autoantibodies in 5% of endomysial autoantibody negativ e patients. The prevalence of transglutaminase autoantibodies is associated with DQ2 and DQ8 and in particular DQ2 homozygosity. Autoimmunity to trans glutaminase is remarkably prevalent amongst patients with type 1 diabetes e xpressing certain class II HLA alleles. (C) 1999 Academic Press.