Sera of patients with Addison's disease contain autoantibodies recogni
zing antigen(s) in the adrenal cortex. In the present study we have ex
amined the antigen expression in normal (n = 6) and pathological human
adrenal tissues (n = 24) and also in the human steroid-producing adre
nocortical cell line NCI-H295. Sera from two patients with Addison's d
isease were selected as they strongly stained the human adrenal gland
and identified a 54 kDa autoantigen previously demonstrated as 21-hydr
oxylase. These sera reacted with normal human adrental cortex (n = 6),
all hyperplasias (n = 5) and all the adrenocortical cancers (n = 9),
whereas slight or no reactivity was observed in the adenomas without a
ny detectable excess of peripheral steroids (n = 4). Both patient sera
reacted in an identical manner with each tissue specimen and they als
o reacted strongly with the steroid-producing cell line. The data demo
nstrate that the expression of the Addisonian autoantigen cor-relates
with the functional activity of adrenocortical neoplasms. Furthermore
they suggest, that immunohistochemical stainings for steroid-producing
enzymes may be clinically useful in the characterization of adrenal l
esions.