Autoantibody response against NALP5/MATER in primary ovarian insufficiency and in autoimmune Addison's disease.
BACKGROUND
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.


OBJECTIVE
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.
Department of Internal Medicine (A.B., S.M., V.M., A.F.), University of Perugia, 06126 Perugia, Italy; Department of Medical Sciences (M.A., O.K.), Science for Life Laboratory, Uppsala University, 750 03 Uppsala, Sweden; Centre of Molecular Medicine (M.A., A.H., O.K.), Department of Medicine (Solna), Karolinska Institutet, 171 76 Stockholm, Sweden; Division of Endocrinology, Diabetology, and Metabolism (R.G.), Department of Medical Sciences, University of Turin, 10126 Turin, Italy; Department of Cardio-Thoracic and Respiratory Science (A.D.B.), Endocrinology Unit, Second University of Naples, 80132 Naples, Italy; and Department of Pediatrics-Neonatal Intensive Care (R.P.), V. Fazzi Regional Hospital, 73100 Lecce, Italy.
Annalisa
A
Brozzetti
Mohammad
M
Alimohammadi
Silvia
S
Morelli
Viviana
V
Minarelli
Åsa
Å
Hallgren
Roberta
R
Giordano
Annamaria
A
De Bellis
Roberto
R
Perniola
Olle
O
Kämpe
Alberto
A
Falorni
D000224:Addison Disease / Q000097:blood / Q000276:immunology*; D000293:Adolescent; D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000097:blood*; D001324:Autoantigens / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007265:Inhibins / Q000276:immunology; D008297:Male; D008875:Middle Aged; D024101:Mitochondrial Proteins; D009687:Nuclear Proteins; D016649:Primary Ovarian Insufficiency / Q000097:blood / Q000276:immunology*; D055815:Young Adult
D001323:Autoantibodies; D001324:Autoantigens; D024101:Mitochondrial Proteins; C527221:NLRP5 protein, human; D009687:Nuclear Proteins; D007265:Inhibins