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Autoimmune Hypoparathyroidism

  • E. Helen Kemp
  • Anthony P. WeetmanEmail author
Chapter

Abstract

Autoimmunity is important with regard to the etiology and pathogenesis of hypoparathyroidism, and in this chapter, evidence for the involvement of autoimmune responses in the development of the disease will be discussed. Autoimmune hypoparathyroidism may occur as a sporadic disease or as the major endocrine disorder of autoimmune polyendocrine syndrome type 1 (APS1). In idiopathic hypoparathyroidism, lymphocytic infiltration of and autoantibodies against the parathyroid gland have been reported, although it is as yet unclear what proportion of patients have an autoimmune basis for their condition. In addition, there is a strong association of HLA-A*26:01 with idiopathic hypoparathyroidism, suggesting an important role in its pathogenesis for major histocompatibility complex (MHC) class I-mediated presentation of autoantigenic peptides to CD8+ cytotoxic T cells. Furthermore, MHC class II HLA-DRB1*01 and HLA-DRB1*09 alleles are more frequent in patients with idiopathic hypoparathyroidism than in controls, and this too supports an autoimmune basis for the disease. In APS1, a monogenic disease caused by mutations in the AIRE (autoimmune regulator) gene, autoantibodies against parathyroid-expressed targets including the calcium-sensing receptor and NALP5 (NACHT leucine-rich-repeat protein 5) are prevalent. T cell reactivity against the parathyroid in APS1 is less well studied, although autoreactive T lymphocytes that have escaped clonal deletion due to the lack of AIRE gene expression in thymic medullary epithelial cells may target and damage the parathyroid leading to hypoparathyroidism, the hallmark of APS1.

Keywords

Autoantibody Autoantigen Autoimmune hypoparathyroidism Autoimmune polyendocrine syndrome Calcium-sensing receptor NALP5 Parathyroid 

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Copyright information

© Springer-Verlag Italia 2015

Authors and Affiliations

  1. 1.Department of Human Metabolism, Faculty of Medicine, Dentistry and HealthUniversity of Sheffield, The Medical SchoolSheffield South YorkshireUK

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