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 polygl andular syndrome and 8 had AH associated with autoimmune hypothyroidis m. Five of 25 (20%) AH sera reacted to a membrane-associated antigen o f 120-140 kD in human parathyroid gland extracts using immunoblot anal ysis. This is the exact size of the calcium sensing receptor (Ca-SR). The AH sera were then tested by immunoblot using a membrane fraction o f 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 recognize d by the anti-Ca-SR Ige raised in rabbits. The Ca-SR cDNA was translat ed 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 patient ser a reacted to the intracellular domain. The reactivity of the positive sera was completely removed after pre-absorption with the Ca-SR contai ning membranes. Sera from 50 patients with various other autoimmune di seases as web as 22 normal controls were also tested, and none of them was positive. In conclusion, the Ca-SR has been identified as an auto antigen in AH.