The high prevalence of autoantibodies to tissue transglutaminase in first-degree relatives of patients with type 1 diabetes is not associated with islet autoimmunity.
OBJECTIVE
To determine the extent of celiac autoimmunity in type 1 diabetic patients and the overlap between islet and celiac autoimmunity in their nondiabetic relatives.


METHODS
IgA antibodies to tissue transglutaminase were determined in serum taken from 433 type 1 diabetic patients and 1,442 nondiabetic first-degree relatives. Samples with transglutaminase antibodies above the 97.5th percentile of 347 schoolchildren were also assayed for IgA anti-endomysial antibodies (EMAs). Markers of islet autoimmunity (islet cell antibodies and autoantibodies to insulin, glutamate decarboxylase. and protein tyrosine phosphatase IA-2) had previously been measured in all relatives.


RESULTS
In the absence of known celiac disease, the prevalence of transglutaminase antibody levels above the 97.5th percentile of the schoolchildren was 13.4% in diabetic patients and 7.0% in nondiabetic relatives. ENMAs were found in addition to transglutaminase antibodies in 2.6% of probands and in 1.9% of first-degree relatives, but none of the schoolchildren. Transglutaminase antibodies were found to persist in 10 of 30 patients and in 30 of 59 relatives with follow-up samples taken at least 2 years after the initial sample. Of 186 nondiabetic relatives with islet autoantibodies, only 10 also had transglutaminase antibodies.


CONCLUSIONS
We found a high prevalence of celiac autoimmunity in patients and first-degree relatives of children with type 1 diabetes, but we found limited overlap between islet and celiac autoimmunity in nondiabetic relatives. The high prevalence of celiac autoimmunity may be explained by shared genetic susceptibility and identifies a population within which screening for the disease may be justified.
Williams
A J
AJ
Diabetes and Metabolism Division of Medicine, University of Bristol, UK.
Norcross
A J
AJ
Lock
R J
RJ
Unsworth
D J
DJ
Gale
E A
EA
Bingley
P J
PJ
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D001323:Autoantibodies / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000235:genetics* / Q000276:immunology*; D005260:Female; D019204:GTP-Binding Proteins / Q000276:immunology*; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood*; D007223:Infant; D007515:Islets of Langerhans / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009679:Nuclear Family; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases / Q000276:immunology*
D001323:Autoantibodies; D015415:Biomarkers; D007070:Immunoglobulin A; C024211:islet cell antibody; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins