Autoantibodies to the extracellular domain of the calcium sensing receptor in patients with acquired hypoparathyroidism.
Acquired hypoparathyroidism (AH) has been considered to result from an autoimmune process but the self-antigens have not been identified. We studied 25 patients with AH, of which 17 had type I autoimmune polyglandular syndrome and 8 had AH associated with autoimmune hypothyroidism. Five of 25 (20%) AH sera reacted to a membrane-associated antigen of 120-140 kD in human parathyroid gland extracts using immunoblot analysis. This is the exact size of the calcium sensing receptor (Ca-SR). The AH sera were then tested by immunoblot using a membrane fraction of HEK-293 cells transfected with Ca-SR cDNA. Eight of 25 (32%) AH sera reacted to a 120-140-kD protein, which closely matched that recognized by the anti-Ca-SR IgG raised in rabbits. The Ca-SR cDNA was translated in vitro into two parts in order to identify the antigenic epitopes. By using this technique, 14 of 25 (56%) AH sera were positive to the extracellular domain of the Ca-SR, whereas none of the AH patients sera reacted to the intracellular domain. The reactivity of the positive sera was completely removed after pre-absorption with the Ca-SR containing membranes. Sera from 50 patients with various other autoimmune diseases as well as 22 normal controls were also tested, and none of them was positive. In conclusion, the Ca-SR has been identified as an autoantigen in AH.
Li
Y
Y
Department of Pathology and Laboratory Medicine and Pediatrics, University of Florida, Gainesville, USA.
Song
Y H
YH
Rais
N
N
Connor
E
E
Schatz
D
D
Muir
A
A
Maclaren
N
N
D001323:Autoantibodies / Q000276:immunology*; D001324:Autoantigens / Q000097:blood*; D002135:Calcium-Binding Proteins / Q000737:chemistry / Q000276:immunology*; D018604:Epitope Mapping; D005110:Extracellular Space / Q000276:immunology; D006801:Humans; D007011:Hypoparathyroidism / Q000276:immunology*; D008565:Membrane Proteins / Q000276:immunology; D008970:Molecular Weight; D010280:Parathyroid Glands / Q000276:immunology*; D044169:Receptors, Calcium-Sensing; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000276:immunology*; D011994:Recombinant Proteins / Q000276:immunology
D001323:Autoantibodies; D001324:Autoantigens; C095550:CASR protein, human; D002135:Calcium-Binding Proteins; D008565:Membrane Proteins; D044169:Receptors, Calcium-Sensing; D011956:Receptors, Cell Surface; D011994:Recombinant Proteins