Identification of the main gonadal autoantigens in patients with adrenal insufficiency and associated ovarian failure
O Winqvist, G Gebre-Medhin, J Gustafsson, EM Ritzen, O Lundkvist, FA Karlsson and O Kampe
Department of Medicine, University Hospital, Uppsala, Sweden.
Autoimmune adrenal insufficiency is associated with premature ovarian
failure at frequencies of 10-20%. In these patients a reactivity against an
unknown steroid cell antigen in both the adrenal glands and gonads has been
described. We have recently identified the cytochrome P450 enzyme
21-hydroxylase and the side-chain cleavage enzyme (SCC) as the major
adrenal autoantigens in Addison's disease and the rare autoimmune
polyendocrine syndrome type I (APS-I), respectively. In an attempt to
identify the steroid cell antigen, sera from patients with Addison's
disease (n = 13) and APS-I (n = 7) that reacted with Leydig cells were
selected. Preparations of isolated human granulosa cells, isolated rat
Leydig cells, and fractions of human placenta were used in Western blots.
All sera were also tested against bacterially expressed 21-hydroxylase,
SCC, and 17 alpha-hydroxylase. The SCC was recognized by sera from patients
with Addison's disease and those with APS-I. In addition, a majority of the
sera (n = 12) reacted with a novel 51- kilodalton autoantigen present in
granulosa cells and placenta. The results show that the steroid cell
autoantigen consists mainly of the SCC and a novel protein of unknown
function.
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