Presence of Autoreactive, MHC Class I-Restricted, Calcium-Sensing Receptor (CaSR)-Specific CD8+ T Cells in Idiopathic Hypoparathyroidism.
J Clin Endocrinol Metab
; 102(1): 167-175, 2017 01 01.
Article
en En
| MEDLINE
| ID: mdl-27805845
ABSTRACT
Context Major histocompatibility complex class I allele HLA-A*2601 and human leukocyte antigen (HLA) supertype A01 (STA01) are increased in idiopathic hypoparathyroidism (IH). However, cell-mediated autoimmune responses directed against the calcium-sensing receptor (CaSR) have not been demonstrated. Objective:
To study CaSR-specific cytotoxic T-cell responses in peripheral blood mononuclear cells of IH patients.Design:
Twenty-four peptides of CaSR (RH1 to RH24) were evaluated for their ex vivo potential to stimulate PBMCs from IH patients and controls in interferon (IFN)-γ enzyme-linked immunospot (ELISPOT) assays.Setting:
Tertiary patient care center and National Institute of Immunology, New Delhi, India. Patients and OtherParticipants:
Forty-five patients with IH attending the endocrine clinic of the All India Institute of Medical Sciences and 22 healthy controls. Main OutcomeMeasures:
Major histocompatibility complex class-I restricted, CaSR-specific cytotoxic CD8+ T-cell responses evaluated by IFN-γ ELISPOT assay.Results:
Of IH patients, 82.2% showed IFN-γ-secreting cells when stimulated ex-vivo with CaSR peptides. Peptides RH7, RH9, and RH16 elicited HLA supertype A01-restricted responses in IH. RH8, RH14, RH15, RH20, and RH21 peptides induced significantly higher responses in STA01+ IH patients compared with healthy controls irrespective of their supertype A01 status.Conclusions:
Our ex vivo IFN-γ ELISPOT assays demonstrate the presence of CaSR-specific memory CD8+ T cells in the peripheral circulation of patients with IH, suggesting the role of cell-mediated autoimmune responses in the etiopathogenesis of IH.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Linfocitos T Citotóxicos
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Antígenos de Histocompatibilidad Clase I
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Linfocitos T CD8-positivos
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Epítopos de Linfocito T
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Receptores Sensibles al Calcio
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Hipoparatiroidismo
Tipo de estudio:
Observational_studies
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Prognostic_studies
Límite:
Adult
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Female
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Humans
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Male
Idioma:
En
Año:
2017
Tipo del documento:
Article