Autoimmune Polyglandular Syndrome Type 2

  • George J. Kahaly
  • Manuela Dittmar
Part of the Contemporary Endocrinology book series (COE)


The nature of autoimmune polyglandular syndrome type 2 (APS-2) has been based on the presence of lymphocyte infiltration in the affected gland, organ-specific antibodies (Abs) in the serum, cellular immune defects, and an association with the human leukocyte antigen (HLA)-DR/DQ genes or immune-response genes. Autoantibodies to the various endocrine and non-endocrine tissues not only offer a diagnostic clue to the autoimmune nature of diseases but also can be used to identify asymptomatic individuals who are at risk of developing other component diseases of the syndrome. Although target tissues or glands differ, several common threads link the diseases of the APS. The autoimmune destruction of most target glands appears to be a slow process with a long preclinical prodrome that may last for years. During this period, autoantibodies, lymphocyte abnormalities, and subclinical endocrine defects are usually present. As knowledge of target antigens has progressed, it appears that despite polyendocrine disease, within each gland, specific antigens are the targets of the autoimmune process. A defect resides in one of the genes of the HLA locus, which, in concert with other gene(s), results in susceptibility. Genetic susceptibility is necessary but not sufficient to produce the disorder. This is illustrated by the lack of 100% concordance of disease in identical twins. When the genetic defects and environmental influences of organ-specific autoimmunity are better understood, it may be possible to devise specific replacement or corrective therapies. Given the similar features of many of the organ-specific autoimmune disorders, it is likely that if immunotherapeutic modalities are successful in one disease, they may be of benefit in related disorders. With respect to the significant morbidity and potential mortality of the disease, the main diagnostic objective is to detect APS-2 at an early stage, with the advantage of less frequent complications, effective therapy, and better prognosis. This requires that patients at risk be regularly screened for subclinical endocrinopathies before clinical manifestation occurs. Regarding the possible large time interval between manifestation of the first and further endocrinopathies, regular and long-term follow-up of patients with endocrine autoimmune disorders is warranted. Considering the high incidence of one or more endocrinopathies in first-degree relatives of patients with APS-2, family members of patients should be regularly screened, because they may develop autoimmune endocrinopathies in the future.


Autoimmune polyglandular syndrome type 2 polyglandular autoimmunity epidemiology diagnosis genetics pathogenesis 


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© Humana Press Inc. 2007

Authors and Affiliations

  • George J. Kahaly
  • Manuela Dittmar

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