PMID- 27805845
OWN - NLM
STAT- MEDLINE
DCOM- 20170620
LR  - 20220408
IS  - 1945-7197 (Electronic)
IS  - 0021-972X (Linking)
VI  - 102
IP  - 1
DP  - 2017 Jan 1
TI  - Presence of Autoreactive, MHC Class I-Restricted, Calcium-Sensing Receptor 
      (CaSR)-Specific CD8+ T Cells in Idiopathic Hypoparathyroidism.
PG  - 167-175
LID - 10.1210/jc.2016-3131 [doi]
AB  - CONTEXT: 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. 
      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)-gamma enzyme-linked immunospot (ELISPOT) 
      assays. SETTING: Tertiary patient care center and National Institute of 
      Immunology, New Delhi, India. PATIENTS AND OTHER PARTICIPANTS: Forty-five 
      patients with IH attending the endocrine clinic of the All India Institute of 
      Medical Sciences and 22 healthy controls. MAIN OUTCOME MEASURES: Major 
      histocompatibility complex class-I restricted, CaSR-specific cytotoxic CD8+ 
      T-cell responses evaluated by IFN-gamma ELISPOT assay. RESULTS: Of IH patients, 82.2% 
      showed IFN-gamma-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-gamma 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.
CI  - Copyright (c) 2017 by the Endocrine Society
FAU - Mahtab, Samrina
AU  - Mahtab S
AD  - Department of Endocrinology and Metabolism, All India Institute of Medical 
      Sciences, Ansari Nagar, New Delhi 110029, India; and.
FAU - Vaish, Utpreksha
AU  - Vaish U
AD  - Molecular Immunogenetics Group, National Institute of Immunology, Aruna Asaf Ali 
      Marg, New Delhi 110067, India.
FAU - Saha, Soma
AU  - Saha S
AD  - Department of Endocrinology and Metabolism, All India Institute of Medical 
      Sciences, Ansari Nagar, New Delhi 110029, India; and.
FAU - Singh, Archana
AU  - Singh A
AD  - Molecular Immunogenetics Group, National Institute of Immunology, Aruna Asaf Ali 
      Marg, New Delhi 110067, India.
FAU - Goswami, Ravinder
AU  - Goswami R
AD  - Department of Endocrinology and Metabolism, All India Institute of Medical 
      Sciences, Ansari Nagar, New Delhi 110029, India; and.
FAU - Rani, Rajni
AU  - Rani R
AD  - Molecular Immunogenetics Group, National Institute of Immunology, Aruna Asaf Ali 
      Marg, New Delhi 110067, India.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Clin Endocrinol Metab
JT  - The Journal of clinical endocrinology and metabolism
JID - 0375362
RN  - 0 (CASR protein, human)
RN  - 0 (Epitopes, T-Lymphocyte)
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 0 (Peptide Fragments)
RN  - 0 (Receptors, Calcium-Sensing)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - Adult
MH  - Amino Acid Sequence
MH  - CD8-Positive T-Lymphocytes/*immunology
MH  - Case-Control Studies
MH  - Cells, Cultured
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Epitope Mapping
MH  - Epitopes, T-Lymphocyte/*immunology
MH  - Female
MH  - Follow-Up Studies
MH  - Histocompatibility Antigens Class I/*immunology
MH  - Humans
MH  - Hypoparathyroidism/*immunology
MH  - Interferon-gamma
MH  - Male
MH  - Peptide Fragments/immunology
MH  - Receptors, Calcium-Sensing/immunology/*metabolism
MH  - T-Lymphocytes, Cytotoxic/*immunology
EDAT- 2016/11/03 06:00
MHDA- 2017/06/21 06:00
CRDT- 2016/11/03 06:00
PHST- 2016/08/30 00:00 [received]
PHST- 2016/10/26 00:00 [accepted]
PHST- 2016/11/03 06:00 [pubmed]
PHST- 2017/06/21 06:00 [medline]
PHST- 2016/11/03 06:00 [entrez]
AID - 10.1210/jc.2016-3131 [doi]
PST - ppublish
SO  - J Clin Endocrinol Metab. 2017 Jan 1;102(1):167-175. doi: 10.1210/jc.2016-3131.