Activating Antibodies to The Calcium-sensing Receptor in Immunotherapy-induced Hypoparathyroidism.
J Clin Endocrinol Metab
; 105(5)2020 05 01.
Article
em En
| MEDLINE
| ID: mdl-32112105
ABSTRACT
CONTEXT Immune checkpoint inhibitors (ICIs), such as programmed cell death protein-1 (PD-1), programmed cell death protein-ligand 1 (PD-L1), and cytotoxic T lymphocyte antigen-4 (CTLA-4) monoclonal antibodies, are approved for the treatment of some types of advanced cancer. Their main treatment-related side-effects are immune-related adverse events (irAEs), especially thyroid dysfunction and hypophysitis. Hypoparathyroidism, on the contrary, is an extremely rare irAE. OBJECTIVES:
The aim of the study was to investigate the etiology of autoimmune hypoparathyroidism in a lung cancer patient treated with pembrolizumab, an anti-PD-1.METHODS:
Calcium-sensing receptor (CaSR) autoantibodies, their functional activity, immunoglobulin (Ig) subclasses and epitopes involved in the pathogenesis of autoimmune hypoparathyroidism were tested.RESULTS:
The patient developed hypocalcemia after 15 cycles of pembrolizumab. Calcium levels normalized with oral calcium carbonate and calcitriol and no remission of hypocalcemia was demonstrated during a 9-month follow-up. The patient was found to be positive for CaSR-stimulating antibodies, of IgG1 and IgG3 subclasses, that were able to recognize functional epitopes on the receptor, thus causing hypocalcemia.CONCLUSION:
The finding confirms that ICI therapy can trigger, among other endocrinopathies, hypoparathyroidism, which can be caused by pathogenic autoantibodies.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
Base de dados:
MEDLINE
Assunto principal:
Autoanticorpos
/
Receptores de Detecção de Cálcio
/
Anticorpos Monoclonais Humanizados
/
Hipoparatireoidismo
/
Imunoterapia
Tipo de estudo:
Diagnostic_studies
Limite:
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
J Clin Endocrinol Metab
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Itália