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

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A panel of six autoimmune biomarkers targeting TMOD3 and TPM3 epitopes demonstrated higher sensitivity and accuracy for noninvasive diagnosis of minimal-mild endometriosis than previously reported markers.

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This cross-sectional, multicenter study (2012–2015) evaluated whether serum autoantibodies to epitopes of stomatin-like protein 2, tropomodulin 3 (TMOD3), and tropomyosin 3 (TPM3) could noninvasively diagnose minimal-mild endometriosis (rAFS stage I–II). Women with rAFS stage I–II endometriosis (n=133) and healthy controls (n=104) were tested for 11 novel autoimmune markers plus previously reported markers (CA-125, CA19-9, α-enolase, PDIK1L, and syntaxin 5), and the sensitivity and diagnostic accuracy of antibodies against the 11 epitopes were higher than those comparator markers. A logistic regression panel of six biomarkers showed increased sensitivity, specificity, and overall diagnostic accuracy compared with individual biomarkers, with higher sensitivity at specificity ≥80% and also in ultrasound-negative endometriosis. The paper does not state a limitation in the provided text, but diagnostic performance was assessed in a case-control design rather than in an unselected screening population; This paper is centrally about endometriosis — it develops and validates an autoimmune biomarker panel for noninvasive detection of minimal-mild (rAFS stage I–II) endometriosis.

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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.
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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. Similar content being viewed by others

References

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Author information Authors and Affiliations Corresponding author Rights and permissions About this article Cite this article Gajbhiye, R., Bendigeri, T., Ghuge, A. et al. Panel of Autoimmune Markers for Noninvasive Diagnosis of Minimal-Mild Endometriosis: A Multicenter Study. Reprod. Sci. 24, 413–420 (2017). https://doi.org/10.1177/1933719116657190 Published: Issue date: DOI: https://doi.org/10.1177/1933719116657190

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endometriosis

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Endometriosis Membrane Proteins Tropomodulin Tropomyosin Adult Biomarkers Biomarkers Blood Proteins CA-125 Antigen CA-125 Antigen CA-19-9 Antigen CA-19-9 Antigen Cross-Sectional Studies Endometriosis Endometriosis Epitopes Female Humans Membrane Proteins Phosphopyruvate Hydratase

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