Autoantigens in ovarian autoimmunity associated with unexplained infertility and premature ovarian failure

Abstract

Objective: To identify ovarian autoantigens associated with ovarian autoantibodies.

Design: Hypothesis-generating prospective study.

Setting: Urban infertility referral centers and academic research institution.

Patient(s): Seventy-four patients with infertility, 19 patients with premature ovarian failure (POF), and 16 healthy control women.

Intervention(s): None.

Main outcome measure(s): Identification of autoantigens.

Result(s): To identify major antigens for ovarian autoimmunity, sera from 74 women with unexplained infertility were screened for ovarian autoantibodies (AOAs) by immunoassay and one-dimensional Western blot. The majority of sera had immunoreactions at 50-56 kDa. Six representative positive infertility sera were used to identify antigens between 40 and 60 kD by two-dimensional Western blot and mass spectrometry. Antigens included aldehyde (retinal) dehydrogenases (ALDH1A1, ALDH1A2, and ALDH7A1), protein disulfide isomerase A3, vimentin, α-enolase, phosphoglycerate dehydrogenase, and selenium-binding protein 1 (SBP1). Sixty percent (24 out of 40) of infertility and POF sera were positive for recombinant ALDH1A1, SBP1, or enolase; 80.7% (21 out of 26) of AOA-positive sera had antibodies to one or more of the three antigens, and only 7% (1 out of 14) of AOA-negative sera had antibodies to recombinant proteins.

Conclusion(s): ALDH1A1 and SBP1 are unique to ovarian autoimmunity associated with infertility and POF, and may provide the basis for specific tests to identify patients with ovarian autoimmunity.