Autoantibody Response Against NALP5/MATER in Primary Ovarian Insufficiency and in Autoimmune Addison's Disease

• Published in: The journal of clinical endocrinology and metabolism Vol. 100; no. 5; pp. 1941 - 1948
• Main Authors: Brozzetti, Annalisa, Alimohammadi, Mohammad, Morelli, Silvia, Minarelli, Viviana, Hallgren, Åsa, Giordano, Roberta, De Bellis, Annamaria, Perniola, Roberto, Kämpe, Olle, Falorni, Alberto
• Format: Journal Article
• Language: English
• Published: United States Endocrine Society 01.05.2015; Copyright by The Endocrine Society
• Subjects: Addison Disease - blood; Addison Disease - immunology; Adolescent; Adult; Aged; Autoantibodies - blood; Autoantigens - immunology; Child; Child, Preschool; Female; Humans; Inhibins - immunology; Male; Medicin och hälsovetenskap; Middle Aged; Primary Ovarian Insufficiency - blood; Primary Ovarian Insufficiency - immunology; Young Adult
• ISSN: 0021-972X; 1945-7197; 1945-7197
• DOI: 10.1210/jc.2014-3571

Context: NACHT leucine-rich-repeat protein 5 (NALP5)/maternal antigen that embryo requires (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: The objectives of the study were 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) and to evaluate whether inhibin chains are a target for autoantibodies in POI. Methods: Autoantibodies against NALP5/MATER and inhibin chains-α and -βA 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 of 19 (58%) sera from APS1 patients, 12 of 172 (7%) AAD sera, 5 of 41 (12%) SCA-POI sera, 0 of 119 idiopathic POI sera and 1 of 211 healthy control sera (P < .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 chain-α/βA autoantibodies. 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.