Presence of Autoreactive, MHC Class I-Restricted, Calcium-Sensing Receptor (CaSR)-Specific CD8+ T Cells in Idiopathic Hypoparathyroidism.
Major histocompatibility complex class I allele HLA-A*26:01 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.



To study CaSR-specific cytotoxic T-cell responses in peripheral blood mononuclear cells of IH patients.



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.



Tertiary patient care center and National Institute of Immunology, New Delhi, India.



Forty-five patients with IH attending the endocrine clinic of the All India Institute of Medical Sciences and 22 healthy controls.



Major histocompatibility complex class-I restricted, CaSR-specific cytotoxic CD8+ T-cell responses evaluated by IFN-γ ELISPOT assay.



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.



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.
Department of Endocrinology and Metabolism, All India Institute of Medical Sciences, Ansari Nagar, New Delhi 110029, India; and.
Samrina
S
Mahtab
Molecular Immunogenetics Group, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi 110067, India.
Utpreksha
U
Vaish
Department of Endocrinology and Metabolism, All India Institute of Medical Sciences, Ansari Nagar, New Delhi 110029, India; and.
Soma
S
Saha
Molecular Immunogenetics Group, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi 110067, India.
Archana
A
Singh
Department of Endocrinology and Metabolism, All India Institute of Medical Sciences, Ansari Nagar, New Delhi 110029, India; and.
Ravinder
R
Goswami
Molecular Immunogenetics Group, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi 110067, India.
Rajni
R
Rani
D000328:Adult; D000595:Amino Acid Sequence; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D016022:Case-Control Studies; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D018604:Epitope Mapping; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005260:Female; D005500:Follow-Up Studies; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D007011:Hypoparathyroidism / Q000276:immunology*; D007371:Interferon-gamma; D008297:Male; D010446:Peptide Fragments / Q000276:immunology; D044169:Receptors, Calcium-Sensing / Q000276:immunology / Q000378:metabolism*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
C095550:CASR protein, human; D018984:Epitopes, T-Lymphocyte; D015395:Histocompatibility Antigens Class I; D010446:Peptide Fragments; D044169:Receptors, Calcium-Sensing; D007371:Interferon-gamma