Immunologic endocrine disorders - 11/08/11

Doi : 10.1016/j.jaci.2009.09.053

Aaron W. Michels, MD ^a,^⁎ , George S. Eisenbarth, MD, PhD ^b,^c
^a Department of Medicine, Barbara Davis Center for Childhood Diabetes, University of Colorado Denver, Aurora, Colo
^b Department of Pediatrics, Barbara Davis Center for Childhood Diabetes, University of Colorado Denver, Aurora, Colo
^c Department of Immunology, Barbara Davis Center for Childhood Diabetes, University of Colorado Denver, Aurora, Colo

Reprint requests: Aaron W. Michels, MD, Barbara Davis Center for Childhood Diabetes, University of Colorado Denver, 1775 Aurora Ct, MS B140, PO BOX 6511, Aurora, CO 80045.

Abstract

Autoimmunity affects multiple glands in the endocrine system. Animal models and human studies highlight the importance of alleles in HLA-like molecules determining tissue-specific targeting that, with the loss of tolerance, leads to organ-specific autoimmunity. Disorders such as type 1A diabetes, Graves disease, Hashimoto thyroiditis, Addison disease, and many others result from autoimmune-mediated tissue destruction. Each of these disorders can be divided into stages beginning with genetic susceptibility, environmental triggers, active autoimmunity, and finally metabolic derangements with overt symptoms of disease. With an increased understanding of the immunogenetics and immunopathogenesis of endocrine autoimmune disorders, immunotherapies are becoming prevalent, especially in patients with type 1A diabetes. Immunotherapies are being used more in multiple subspecialty fields to halt disease progression. Although therapies for autoimmune disorders stop the progress of an immune response, immunomodulatory therapies for cancer and chronic infections can also provoke an unwanted immune response. As a result, there are now iatrogenic autoimmune disorders arising from the treatment of chronic viral infections and malignancies.

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Key words : Type 1 diabetes, HLA, autoantibodies, immunotherapy, Addison disease, autoimmune polyendocrine syndrome type 1, autoimmune polyendocrine syndrome type 2, Graves disease, polyendocrine autoimmunity, iatrogenic autoimmunity

Abbreviations used : ACTH, AIRE, APS-1, APS-2, CGMS, CTLA, FOXP3, GAD, GO, HT, IA-2, IPEX, NOD, POEMS, POF, PTPN22, TGA, TPO, TSH, TSHR, TSI, ZnT8

Plan

Supported by grants from the National Institutes of Health (DK32083, DK32493, and DK057538) Autoimmunity Prevention Center (AI50964), Diabetes Endocrine Research Center (P30 DK57516), and Clinical Research Centers (MO1 RR00069 and MO1 RR00051); the Immune Tolerance Network (AI15416); the American Diabetes Association; the Juvenile Diabetes Research Foundation; the Brehm Coalition, and the Children’s Diabetes Foundation.

Disclosure of potential conflict of interest: The authors have declared that they have no conflict of interest.