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Autoantibody "Subspecificity" in Type 1 Diabetes

Risk for organ-specific autoimmunity clusters in distinct groups

¹ Barbara Davis Center, University of Colorado Health Sciences Center, Denver, Colorado
² Department of Pediatrics, Dankook University Hospital, Cheonan, Korea
³ Department of Pathology, Louisiana State University Health Sciences Center, School of Medicine, Shreveport, Louisiana
⁴ The Children’s Hospital, Denver, Colorado
⁵ Department of Medicine and Pathology, Loma Linda University School of Medicine, Loma Linda, California

Address correspondence and reprint requests to Jennifer M. Barker, Barbara Davis Center, University of Colorado Health Sciences Center, 4200 E. 9th Ave., B140, Denver, CO 80262. E-mail: jennifer.barker{at}uchsc.edu

OBJECTIVE—Autoimmune thyroid disease (AIT), celiac disease, and Addison’s disease are characterized by the presence of autoantibodies: thyroid peroxidase antibody (TPOAb) and thyroglobulin antibody (TGAb) in AIT, tissue transglutaminase antibody (TTGAb) in celiac disease, and 21-hydroxylase antibody (21-OHAb) in Addison’s disease. The objective of this study was to define the prevalence of these autoantibodies and clinical disease in a population with type 1 diabetes.

RESEARCH DESIGN AND METHODS—We screened 814 individuals with type 1 diabetes for TPOAb, TGAb, TTGAb, and 21-OHAb. Clinical disease was defined by chart review. Factors related to the presence of autoimmunity and clinical disease including age at onset of type 1 diabetes, duration of diabetes, age at screening, sex, and the presence of autoantibodies were reviewed.

RESULTS—The most common autoantibodies expressed were TPOAb and/or TGAb (29%), followed by TTGAb (10.1%) and 21-OHAb (1.6%). Specific HLA DR/DQ genotypes were associated with the highest risk for expression of 21-OHAb (DRB1*0404-DQ8, DR3-DQ2) and TTGAb (DR3-DQ2- DR3-DQ2). The expression of thyroid autoantibodies was related to 21-OHAb but not to TTGAb. The presence of autoantibodies was associated with and predictive of disease.

CONCLUSIONS—In this large cohort of individuals with type 1 diabetes, the expression of organ-specific autoantibodies was very high. The grouping of autoantibody expression suggests common factors contributing to the clustering.

Abbreviations: 21-OHAb, 21-hydroxylase antibody • AIT, autoimmune thyroid disease • ICA, islet cell antigen • ICMA, immunochemiluminometric assay • mIAA, microinsulin autoantibody assay • TGAb, thyroglobulin antibody • TPOAb, thyroid peroxidase antibody • TSH, thyroid-stimulating hormone • TTGAb, tissue transglutaminase antibody

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