Autoantibody response against NALP5/MATER in primary ovarian insufficiency and in autoimmune Addison’s disease

Context: NALP5/MATER is an autoantigen in hypoparathyroidism associated with autoimmune polyendocrine syndrome type 1 (APS1), but is also expressed in the ovary. Mater is an autoantigen in experimental autoimmune oophoritis. Objectives: To determine the frequency of NALP5/MATER autoantibodies (NALP5/MATER-Ab) in women with premature ovarian insufficiency (POI) and in patients with autoimmune Addison’s disease (AAD). To evaluate whether inhibin chains are target for autoantibodies in POI. Methods: Autoantibodies against NALP5/MATER and inhibin chains  and A were determined by radiobinding assays in 172 patients with AAD, without clinical signs of gonadal insufficiency, 41 women with both AAD and autoimmune POI (steroidogenic cell autoimmune POI, SCA-POI), 119 women with idiopathic POI, 19 patients with APS1 and 211 healthy control subjects. Results: NALP5/MATER-Ab were detected in 11/19 (58%) sera from APS1 patients, 12/172 (7%) AAD sera, 5/41 (12%) SCA-POI sera, 0/119 idiopathic POI sera and 1/211 healthy control sera (p<0.001). None of 160 POI sera, including 41 sera from women with SCA-POI and 119 women with idiopathic POI, and none of 211 healthy control sera were positive for inhibin /A-Ab. Conclusions: NALP5/MATER-Ab are associated with hypoparathyroidism in APS1, but are present also in patients with AAD and in women with SCA-POI without hypoparathyroidism. Inhibin chains do not appear to be likely candidate targets of autoantibodies in human POI.