Polyglandular Autoimmune Syndromes: Immunogenetics and Long-Term Follow-Up

Abstract

Polyglandular autoimmune syndromes (PAS) are rare polyendocrinopathies characterized by the failure of several endocrine glands as well as nonendocrine organs, caused by an immune-mediated destruction of endocrine tissues. This article summarizes extensive clinical, epidemiological, serological, and genetic data of a large collective of patients with PAS (n = 360). Since 1988, more than 15,000 adult patients with endocrine diseases have been screened at the endocrine center of the Mainz University, and 151 of 360 patients with PAS have regularly been followed. Type 1 diabetes, Graves' disease, Hashimoto thyroiditis, Addison's disease, vitiligo, alopecia, hypogonadism, and pernicious anemia were observed in 61%, 33%, 33%, 19%, 20%, 6%, 5%, and 5%, respectively. The most common disease combination was type 1 diabetes and autoimmune thyroid disease. In most patients, type 1 diabetes was the first manifestation of PAS (48%). The longest time intervals between manifestations of the first and second immune endocrinopathies occurred between type 1 diabetes and thyroid disease (13.3 +/- 11.8 yr) and between vitiligo and thyroid disease (16.3 +/- 13.3 yr), but a shorter time interval was observed between Addison's and thyroid diseases. Of the 471 patients with type 1 diabetes screened, 83 (17.6%) were positive for PAS. Subsequently, sera of 126 patients with PAS, 287 with type 1 diabetes, and 303 matched controls were compared for human leukocyte antigens. Patients with PAS had significantly higher frequencies of the human leukocyte antigens A24, A31, B8, B51, B62, DR3, and DR4 (relative risk, 2.35, 2.74, 2.47, 7.17, 2.22, 1.94, and 2.46) vs. controls, and for A31, B15, B52, B55, DR2, DR11, and DR13 (relative risk, 2.51, 7.96, 3.99, 5.36, 4.46, 2.89, and 3.26) vs. type 1 diabetes patients without PAS. In conclusion, patients with autoimmune endocrine disease should be followed on a regular basis. In subjects at risk for PAS, functional screening every 3 yr is warranted. If clinical disease is present, serological measurement of organ-specific antibodies should follow.