Identification and validation of novel serum markers for early diagnosis of endometriosis

• Published in: Human reproduction (Oxford) 2012-02, Vol.27 (2), p.408-417
• Main Authors: Gajbhiye, R., Sonawani, A., Khan, S., Suryawanshi, A., Kadam, S., Warty, N., Raut, V., Khole, V.
• Format: Article
• Language: English
• Subjects: Adult; Antibody Specificity; Autoantibodies - analysis; Autoantigens - blood; Autoantigens - chemistry; Biological and medical sciences; Biomarkers - blood; Biomarkers - chemistry; Blood Proteins - chemistry; Cohort Studies; Cross-Sectional Studies; Early Diagnosis; Endometriosis - blood; Endometriosis - diagnosis; Endometriosis - physiopathology; Female; Gynecology. Andrology. Obstetrics; Humans; Immunodominant Epitopes - analysis; Immunodominant Epitopes - chemistry; Medical sciences; Membrane Proteins - blood; Membrane Proteins - chemistry; Peptide Fragments - analysis; Peptide Fragments - chemistry; Peptide Mapping; Sensitivity and Specificity; Severity of Illness Index; Tropomodulin - blood; Tropomodulin - chemistry; Tropomyosin - blood; Tropomyosin - chemistry; Young Adult
• ISSN: 0268-1161; 1460-2350
• DOI: 10.1093/humrep/der410

BACKGROUND Non-invasive diagnosis of endometriosis is urgently required to prevent the long delay between the onset of symptoms and diagnosis. A biomarker that possesses both high sensitivity and specificity is greatly required. Here, we describe the use of a proteomic approach to identify potential novel endometrial antigens using sera from endometriosis patients and healthy controls, with evaluation of biomarkers for non-invasive diagnosis of endometriosis. METHODS A cross-sectional study was conducted to identify specific endometrial antigens using 1D and 2D western blots in women with early endometriosis (n = 17), advanced endometriosis (n = 23) and without endometriosis (n = 30). Five immunoreactive spots were analyzed using matrix-assisted laser desorption/ionization-time-of-flight/mass spectrometry with MASCOT analysis. ELISAs were established for specific epitopes and autoantibody titres were estimated in an independent cohort comprising women with early endometriosis (n = 18), advanced endometriosis (n = 32) and without endometriosis (n = 27) for validation. RESULTS The 2D western blot analysis resulted in the identification of three endometrial antigens, tropomyosin 3 (TPM3), stomatin-like protein 2 (SLP2) and tropomodulin 3 (TMOD3). Serum levels of antibodies against the epitopes from the immunodominant region of proteins TPM3, SLP2 and TMOD3 were significantly elevated in endometriosis patients when compared with controls. Sensitivity and specificity of serum anti-TPM3a-autoAb (61%, 93%), anti-TPM3c-autoAb (44%, 93%), anti-TPM3d-autoAb (78%, 89%), anti-SLP2a-autoAb (50%, 96%), anti-SLP2c-autoAb (61%, 93%), anti-TMOD3b-autoAb (61%, 96%), serum anti-TMOD3c-autoAb (78%, 93%) and anti-TMOD3d-autoAb (78%, 96%) were better than those of serum CA125 levels (21%, 89%) in the detection of early stages of endometriosis. CONCLUSIONS Serum anti-TPM3a-autoAb, anti-TPM3c-autoAb, anti-TPM3d-autoAb, anti-SLP2a-autoAb, anti-SLP2c-autoAb, anti-TMOD3b-autoAb, anti-TMOD3c-autoAb and anti-TMOD3d-autoAb could be new markers for the early diagnosis of endometriosis.