Journal of internal medicine
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A pool of immature T cells with a seemingly unrestricted repertoire of antigen specificities is generated life-long in the thymus. Amongst these cells are, however, thymocytes that express a strongly self-reactive antigen receptor and hence hold the potential to trigger autoimmunity. ⋯ Thymic epithelial cells of the medulla express for this purpose tissue-restricted self-antigens. This review will focus on the cellular and molecular mechanisms operative in the thymus to shape a repertoire of mature T cells tolerant to self-antigens.
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Review
Clinical manifestations and management of patients with autoimmune polyendocrine syndrome type I.
Autoimmune polyendocrine syndrome type I (APS-I) is a monogenic model disease of autoimmunity. Its hallmarks are chronic mucocutaneous candidosis, hypoparathyroidism and adrenal insufficiency, but many other autoimmune disease components occur less frequently. The first components usually appear in childhood, but may be delayed to adolescence or early adult life. ⋯ Antibodies against interferon-omega and -alpha have recently been shown to be sensitive and relatively specific markers for APS-I, and mutational analysis of the autoimmune regulator gene gives the diagnosis in >95% of cases. The treatment and follow-up of patients is demanding and requires the collaboration of specialists of several fields. However, the literature is especially sparse regarding information on treatment and follow-up; hence, we present here a comprehensive overview on clinical characteristics, treatment and follow-up based on personal experience and published studies.
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Autoimmune polyendocrine syndromes type 1 and 2 (APS-1 and APS-2) are diverse in regards to their component diseases and immunologic features of pathogenesis. Animal models and human studies highlight the importance of alleles of HLA (human leukocyte antigen)-like molecules determining tissue specific targeting that with the loss of tolerance leads to organ specific autoimmunity. Knowledge of the syndromes and component diseases allows clinicians to recognize and prevent illness prior to morbidity. ⋯ Once genetically susceptible individuals are identified screening for autoantibodies can be performed. Amongst autoantibody positive individuals, monitoring for physiologic decompensation, with a goal of treating prior to morbidity and in some cases mortality, follows. With continued basic and clinical research, therapies aimed at treating the underlying autoimmunity and disease prevention should become possible.