IDENTIFICATION OF 3-BETA-HYDROXYSTEROID DEHYDROGENASE AS A NOVEL TARGET OF STEROID CELL AUTOANTIBODIES - ASSOCIATION OF ANTOANTIBODIES WITHENDOCRINE AUTOIMMUNE-DISEASE
S. Arif et al., IDENTIFICATION OF 3-BETA-HYDROXYSTEROID DEHYDROGENASE AS A NOVEL TARGET OF STEROID CELL AUTOANTIBODIES - ASSOCIATION OF ANTOANTIBODIES WITHENDOCRINE AUTOIMMUNE-DISEASE, The Journal of clinical endocrinology and metabolism, 81(12), 1996, pp. 4439-4445
Autoantibodies directed against steroid hormone-producing cells (SCA)
detectable by immunofluorescence are typically found in a small propor
tion of patients with premature ovarian failure (POF) as well as in ot
her 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 libr
ary was screened using SCA-positive serum, and the steroid enzyme 3 be
ta-hydroxysteroid dehydrogenase (3 beta HSD) was identified. Only 1 of
48 (2%) patients with idiopathic POF, not preselected for the presenc
e of other autoimmune diseases, had SCA by immunofluorescence, whereas
10 of 48 (21%) had anti-3 beta HSD autoantibodies detectable by immun
oblot using recombinant human enzyme compared with 6 of 115 (5%) contr
ol subjects (P = 0.002). Absorption of SCA-positive serum with recombi
nant human 3 beta HSD abolished the immunofluorescence pattern. We als
o examined the prevalence of anti-3 beta HSD autoantibodies in other e
ndocrine autoimmune diseases. Two of 112 (2%) diabetic patients, but n
one of the thyroid or Addisonian patients, had SCA by immunofluorescen
ce. 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 s
teroid cell autoantigen defined at the molecular level to be associate
d with idiopathic POF occurring in the absence of other polyglandular
diseases. Autoantibodies to 3 beta HSD in patients with other organ-sp
ecific autoimmune diseases indicate that the enzyme behaves as a typic
al target of polyendocrine autoimmunity. Anti-3 beta HSD autoantibodie
s in patients with POF may provide a marker of those subjects whose ov
arian failure is autoimmune in origin and, as recent studies suggest,
may be salvageable with glucocorticoid treatment.