Panel of Autoimmune Markers for Noninvasive Diagnosis of Minimal-Mild Endometriosis

Reprod Sci. 2017 Mar;24(3):413-420. doi: 10.1177/1933719116657190. Epub 2016 Sep 27.

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.

Keywords: SLP2; TMOD3; TPM3; biomarkers; minimal–mild endometriosis.

Publication types

  • Multicenter Study

MeSH terms

  • Adult
  • Biomarkers / blood
  • Blood Proteins
  • CA-125 Antigen / blood
  • CA-19-9 Antigen / blood
  • Cross-Sectional Studies
  • Endometriosis / blood
  • Endometriosis / diagnosis*
  • Epitopes
  • Female
  • Humans
  • Membrane Proteins / blood*
  • Phosphopyruvate Hydratase / blood
  • Protein Serine-Threonine Kinases / blood
  • Qa-SNARE Proteins / blood
  • Sensitivity and Specificity
  • Tropomodulin / blood*
  • Tropomyosin / blood*

Substances

  • Biomarkers
  • Blood Proteins
  • CA-125 Antigen
  • CA-19-9 Antigen
  • Epitopes
  • Membrane Proteins
  • Qa-SNARE Proteins
  • STOML2 protein, human
  • TMOD3 protein, human
  • TPM3 protein, human
  • Tropomodulin
  • Tropomyosin
  • PDIK1L protein, human
  • Protein Serine-Threonine Kinases
  • Phosphopyruvate Hydratase