Identification of 3 beta-hydroxysteroid dehydrogenase as a novel target of steroid cell autoantibodies: association of autoantibodies with endocrine autoimmune disease.
Autoantibodies directed against steroid hormone-producing cells (SCA) detectable by immunofluorescence are typically found in a small proportion of patients with premature ovarian failure (POF) as well as in other endocrine autoimmune diseases. The SCA pattern stains cells in the outer zones of the adrenal cortex, ovary, and testis. To identify the molecular target of SCA, an adrenal complementary DNA expression library was screened using SCA-positive serum, and the steroid enzyme 3 beta-hydroxysteroid dehydrogenase (3 beta HSD) was identified. Only 1 of 48 (2%) patients with idiopathic POF, not pre-selected for the presence of other autoimmune diseases, had SCA by immunofluorescence, whereas 10 of 48 (21%) had anti-3 beta HSD autoantibodies detectable by immunoblot using recombinant human enzyme compared with 6 of 115 (5%) control subjects (P = 0.002). Absorption of SCA-positive serum with recombinant human 3 beta HSD abolished the immunofluorescence pattern. We also examined the prevalence of anti-3 beta HSD autoantibodies in other endocrine autoimmune diseases. Two of 112 (2%) diabetic patients, but none of the thyroid or Addisonian patients, had SCA by immunofluorescence. Twenty-six (23%) diabetic subjects (P < 0.001 vs. controls), 3 of 18 thyroid patients (P > 0.05 vs. controls), and none of 4 Addisonian patients had anti-3 beta HSD autoantibodies. 3 beta HSD is the first steroid cell autoantigen defined at the molecular level to be associated with idiopathic POF occurring in the absence of other polyglandular diseases. Autoantibodies to 3 beta HSD in patients with other organ-specific autoimmune diseases indicate that the enzyme behaves as a typical target of polyendocrine autoimmunity. Anti-3 beta HSD autoantibodies in patients with POF may provide a marker of those subjects whose ovarian failure is autoimmune in origin and, as recent studies suggest, may be salvageable with glucocorticoid treatment.
Arif
S
S
Department of Immunology, King's College School of Medicine, London, United Kingdom.
Vallian
S
S
Farzaneh
F
F
Zanone
M M
MM
James
S L
SL
Pietropaolo
M
M
Hettiarachchi
S
S
Vergani
D
D
Conway
G S
GS
Peakman
M
M
D015096:3-Hydroxysteroid Dehydrogenases / Q000276:immunology*; D000293:Adolescent; D000328:Adult; D001323:Autoantibodies / Q000097:blood*; D001327:Autoimmune Diseases / Q000276:immunology*; D005260:Female; D005455:Fluorescent Antibody Technique; D005968:Glutamate Decarboxylase / Q000276:immunology; D006801:Humans; D015151:Immunoblotting; D008297:Male; D016649:Primary Ovarian Insufficiency / Q000276:immunology*
D001323:Autoantibodies; D015096:3-Hydroxysteroid Dehydrogenases; D005968:Glutamate Decarboxylase