Panel of Autoimmune Markers for Noninvasive Diagnosis of Minimal-Mild Endometriosis: A Multicenter Study

Abstract

Endometriosis, characterized by the presence of endometrial-like tissue at extrauterine sites, is a common, chronic, estrogen-dependent, inflammatory condition associated with pelvic pain, subfertility, dysmenorrhea, and dyspareunia, affecting about 10% of reproductive-age women in any population. The diagnosis of endometriosis is usually delayed on an average by 8 to 11 years leading to significant consequences in terms of disease progression. The current study was aimed to validate enzyme-linked immunosorbent assay based on the epitopes of stomatin-like protein 2, tropomodulin 3 (TMOD3), and tropomyosin 3 (TPM3) for diagnosis of minimal-mild endometriosis (revised American Fertility Society Classification (rAFS) stage I-II) and to compare the performance with the reported markers: cancer antigen (CA) 125, CA19-9, α-enolase, Serine/threonine-protein kinase (PDIK1L), and syntaxin 5. This was a cross-sectional, multicenter study conducted during the year 2012 to 2015. Women with minimal-mild endometriosis (rAFS stage I-II [n = 133]) and healthy controls (n = 104) were screened for 11 novel autoimmune markers and reported markers α-enolase, PDIK1L, syntaxin 5, CA-125, and CA19-9. The sensitivity and diagnostic accuracy of serum antibodies against all the 11 epitopes were higher than that of CA-125, CA19-9, α-enolase, PDIK1L, and syntaxin 5 for diagnosis of rAFS stage I to II endometriosis. The sensitivity of 6 biomarkers (anti-TMOD3b-autoAb, anti-TMOD3c-autoAb, anti-TMOD3d-autoAb, anti-TPM3a-autoAb, anti-TPM3c-autoAb, and anti-TPM3d-autoAb) was higher at the specificity of ≥80% for diagnosis of rAFS stage I to II endometriosis as well as ultrasound-negative endometriosis. Further, logistic regression models of this panel of biomarkers showed increase in sensitivity, specificity, and diagnostic accuracy than individual biomarkers. The panel of 6 autoimmune biomarkers could be useful in setting up of noninvasive diagnostic test for detection of minimal-mild endometriosis.

Favorable prognostic role of tropomodulins in neuroblastoma

“…TMODs are also able to influence positively dendritic arbor, indeed overexpression of both TMOD1 and TMOD2 increased dendritic complexity and the branching [ 16 ]. Recently, TMODs are emerging as new protagonists in several diseases pathogenesis; TMOD2 has altered expression in fetal Down syndrome [ 17 ], mesial temporal lobe epilepsy [ 18 ], post-stroke [ 19 ] and post-methamphetamine exposure [ 20 ], while TMOD3 has been reported as a novel biomarker with high sensitivity and diagnostic accuracy in endometriosis [ 21 ]. Initial studies reported TMODs role in cancer; Kureha and colleagues [ 22 ] demonstrated that TMOD1 expression was directly regulated by NF-κB and its overexpression was associated with enhanced breast tumor growth in a mouse xenograft model.…”

Autoantibodies: Key Mediators of Autoimmune Infertility

“…However, none of the AAb biomarkers tested were effective [86]. A recent study reported better sensitivity of 6 new biomarkers [87]. With detection of AAbs to steroid producing cells and thyroglobulin in cases with concomitant adrenal or thyroid disease in PCOS, it is now considered an autoimmune disease.…”

“…Stomatin-like protein 2 [84,87] Tropomodulin 3 (TMOD3) fact that these were NAbs. These were also validated to induce aPOI in a mouse model.…”

Multifunctional roles of Tropomodulin-3 in regulating actin dynamics

“…It is also possible that some of these developmental defects may originate from earlier defects in asymmetric division during oocyte maturation, discussed above. Nevertheless, growing evidence from exploratory expression/biomarker studies demonstrates likely Tmod3 involvement in other specialized cellular phenomena (Lopez-Ubeda et al 2015;Lu et al 2017;Paez et al 2016;Qiu et al 2010) and pathologies (Gajbhiye et al 2017;Gajbhiye et al 2012;Paez et al 2016), providing evidence of Tmod3's broad and relatively unexplored roles.…”