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
Giudice LC, Kao LC. Endometriosis. Lancet. 2004;364(9447):1789–1799.
Gajbhiye R, Khole V. Endometriosis research in India: current scenario and challenges for future. Endo Insight Newsletter. 2013;2:4–8
Leng JH, Lang JH, Dai Y, Li HJ, Li XY. Relationship between pain symptoms and clinico-pathological features of pelvic endometriosis. Zhonghua Fu Chan KeZaZhi. 2007;42(3):165–168.
Bulletti C, Coccia M E, Battistoni S, Borini A. Endometriosis and infertility. J Assist Reprod Genet. 2010;27(8):441–447.
Bendigeri T, Warty N, Sawant R, et al. Endometriosis: clinical experience of 500 patients from India. Indian Pract. 2015;68(7):34–40.
Simoens S, Dunselman G, Dirksen C, et al. The burden of endometriosis: costs and quality of life of women with endometriosis and treated in referral centres. Hum Reprod. 2012;27(5):1292–1299.
Klein S, D’Hooghe T, Meulemanb C, Dirksenc C, Dunselmand G, Simoensa S. What is the societal burden of endometriosis-associated symptoms? A prospective Belgian study. Reprod BioMed. 2014;28(1):116–124.
Winkel C. Evaluation and management of women with endometriosis. Obstet Gynecol. 2003;102(2):397–408.
Kennedy S, Bergqvist A, Chapron C, et al. ESHRE guideline for the diagnosis and treatment of endometriosis. Hum Reprod. 2005;20(10):2698–2704.
Hadfield R, Mardon H, Barlow D, Kennedy S. Delay in the diagnosis of endometriosis: a survey of women from the USA and the UK. Hum Reprod 1996;11:878–880.
D’Hooghe TM, Mihalyi AM, Simsa P, et al. Why we need a non-invasive diagnostic test for minimal to mild endometriosis with a high sensitivity. Gynecol Obstet Invest. 2006;62(3):136–138.
Husby G, Haugen R, Moen M. Diagnostic delay in women with pain and endometriosis. Acta Obstet Gynecol Scand. 2003;82(7):649–653.
Ballard K, Lowton K, Wright J. What’s the delay? A qualitative study of women’s experiences of reaching a diagnosis of endometriosis. Fertil Steril. 2006;86(5):1296–1301.
Nnoaham K, Hummelshoj L, Webster P, et al.; World Endometriosis Research Foundation Global Study of Women’s Health consortium. Impact of endometriosis on quality of life and work productivity: a multicenter study across ten countries. Fertil Steril. 2011;96(2):366–373.
Rogers P, D’Hooghe T, Fazleabas A, et al. Defining future direction for endometriosis research: workshop report from 2011 world congress of endometriosis in Montpellier. Reprod Sci. 2013;20(5):483–499.
Vodolazkaia A, El-Aalamat Y, Popovic D, et al. Evaluation of a panel of 28 biomarkers for the non-invasive diagnosis of endometriosis. Hum Reprod. 2012;27(9):2698–2711.
Nabeta M, Abe Y, Kagawa L, et al. Identification of anti-a-enolase autoantibody as a novel serum marker for endometriosis. Proteomics Clin Appl. 2009;3(10):1201–1210.
Nabeta M, Abe Y, Haraguchi R., Kito K, Kusanagi Y, Ito M. Serum anti-PDIK1L autoantibody as a novel marker for endometriosis. Fert Steril. 2010;94(7):2552–2557.
Nabeta M, Abe Y, Takaokaa Y, Kusanagi Y, Ito M. Identification of anti-syntaxin 5 autoantibody as a novel serum marker of endometriosis. J Reprod Immunol. 2011;91(1-2):48–55.
Fassbender A, Vodolazkaia A, Saunders P, et al. Biomarkers of endometriosis. Fertil Steril. 2013;99(4):1135–1145.
Fassbender A, Burney R, Dorien F. O, D’Hooghe T, Giudice L. Update on biomarkers for the detection of endometriosis. Biomed Res Int. 2015;2015:130854.
Gajbhiye R, Suryawanshi A, Khan S, et al. Multiple endometrial antigens are targeted in autoimmune endometriosis. Reprod BioMed Online. 2008;16(6):817–824.
Gajbhiye R, Sonawani A, Khan S, et al. Identification and validation of novel serum markers for early diagnosis of endometriosis. Hum Reprod. 2012;27(2):408–417.
American Society for Reproductive Medicine. Revised American Society for Reproductive Medicine Classification of endometriosis: 1996. Fertil Steril. 1997;67(5):817–821.
Bossuyt X., Clinical performance characteristics of a laboratory test. Apractical approach in autoimmune laboratory. Autoimmune Rev. 2009;8(7):543–548.
Darah AC, Caitlin DL, Chau LA, et al. Stomatin-like protein binds cardiolipin and regulates mitochondrial biogenesis and function. Mol Cell Biol. 2011;31(18):3845–3856.
Zhang L, Ding F, Cao W, et al. Stomatin-like protein 2 is overexpressed in cancer and involved in regulating cell growth and cell adhesion in human esophageal squamous cell carcinoma. Clin Cancer Res. 2006;12(5):1639–1646.
Cui Z, Zhang L, Hua Z, Cao W, Feng W, Liu Z. Stomatin-like protein 2 is over expressed and related to cell growth in human endometrial adenocarcinoma. Oncol Re. 2007;17(4):829–833.
Kirchhof M, Chau L, Lemke C, et al. Modulation of T cell activation by stomatin-like protein 2. J Immunol. 2008;181(3):1927–2704.
Fischer RS, Fritz-Six KL, Fowler VM., Pointed-end capping by tropomodulin3 negatively regulates endothelial cell motility. J Cell Biol. 2003;161(2):371–380.
Welch S, Plank D, Witt S, et al. Cardiac-specific IGF-1 expression attenuates dilated cardiomyopathy in tropomodulin-overexpressing. Transgenic Mice Circ Res. 2002;90(6):641–648.
Das KM, Bajpai M. Tropomyosins in human diseases: ulcerative colitis. Adv Exp Med Biol. 2008;644:158–167.
O’Neill GM, Stehn J, Gunning PW. Tropomyosins as interpreters of the signalling environment to regulate the local cytoskeleton. Semin Cancer Biol. 2008;18(1):35–44.
May KE, Conduit-Hulbert SA, Villar J, Kirtley S, Kennedy SH, Becker CM. Peripheral biomarkers of endometriosis: a systematic review. Hum Reprod Update. 2010;16(6):651–674.
Mihalyi A, Gevaert O, Kyama C M, et al. Non-invasive diagnosis of endometriosis based on a combined analysis of six plasma biomarkers. Hum Reprod. 2010;25(3):654–664.
Thubert T, Santulli P, Marcellin L, et al. Measurement of hs-CRP is irrelevant to diagnose and stage endometriosis: prospective study of 834 patients. Am J Obstet Gynecol. 2014;210(6):533.e1-533.e10.
Kurdoglu Z, Gursoy R, Kurdoglu M, Erdem M, Erdem O, Erdem A. Comparison of the clinical value of CA19-9 versus CA 125 for the diagnosis of endometriosis. Fertil Steril. 2009;92(5):1761–1763.
Abrão MS, Podgaec S, Pinotti JA, de Oliveira RM. Tumor markers in endometriosis. Int J Gynaecol Obstet. 1999;66(1):19–22.
Harada T, Kubota T, Aso T. Usefulness of CA19-9 versus CA125 for the diagnosis of endometriosis. Fertil Steril. 2002;78(4):733–739.
Somigliana E, Vigano P, Tirelli AS, et al. Use of the concomitant serum dosage of CA 125, CA 19-9 and interleukin-6 to detect the presence of endometriosis. Results from a series of reproductive age women undergoing laparoscopic surgery for benign gynaecological conditions. Hum Reprod. 2004;19(8):1871–1876.
Bilibio JP, Souza CA, Rodini GP, et al. Serum prolactin and CA-125 levels as biomarkers of peritoneal endometriosis. Gynecol Obstet Invest. 2014;78(1):45–52.
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