Panel of Autoimmune Markers for Noninvasive Diagnosis of Minimal

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

biomarkers minimal–mild endometriosis SLP2 TMOD3 TPM3

Get full access to this article

View all access options for this article.

References

Giudice

Kao

. Endometriosis. Lancet. 2004;364(9447):1789–1799.

Gajbhiye

Khole

. Endometriosis research in India: current scenario and challenges for future. Endo Insight Newsletter. 2013;2:4–8

Leng

Lang

Dai

. Relationship between pain symptoms and clinico-pathological features of pelvic endometriosis. Zhonghua Fu Chan KeZaZhi. 2007;42(3):165–168.

Bulletti

Coccia

M E

Battistoni

Borini

. Endometriosis and infertility. J Assist Reprod Genet. 2010;27(8):441–447.

Bendigeri

Warty

Sawant

. Endometriosis: clinical experience of 500 patients from India. Indian Pract. 2015;68(7):34–40.

Simoens

Dunselman

Dirksen

. 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

D’Hooghe

Meulemanb

Dirksenc

Dunselmand

Simoensa

. What is the societal burden of endometriosis-associated symptoms? A prospective Belgian study. Reprod BioMed. 2014;28(1):116–124.

Winkel

. Evaluation and management of women with endometriosis. Obstet Gynecol. 2003;102(2):397–408.

Kennedy

Bergqvist

Chapron

. ESHRE guideline for the diagnosis and treatment of endometriosis. Hum Reprod. 2005;20(10):2698–2704.

10.

Hadfield

Mardon

Barlow

Kennedy

. Delay in the diagnosis of endometriosis: a survey of women from the USA and the UK. Hum Reprod 1996;11:878–880.

11.

D’Hooghe

Mihalyi

Simsa

. 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.

12.

Husby

Haugen

Moen

. Diagnostic delay in women with pain and endometriosis. Acta Obstet Gynecol Scand. 2003;82(7):649–653.

13.

Ballard

Lowton

Wright

. What’s the delay? A qualitative study of women’s experiences of reaching a diagnosis of endometriosis. Fertil Steril. 2006;86(5):1296–1301.

14.

Nnoaham

Hummelshoj

Webster

; 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.

15.

Rogers

D’Hooghe

Fazleabas

. Defining future direction for endometriosis research: workshop report from 2011 world congress of endometriosis in Montpellier. Reprod Sci. 2013;20(5):483–499.

16.

Vodolazkaia

El-Aalamat

Popovic

. Evaluation of a panel of 28 biomarkers for the non-invasive diagnosis of endometriosis. Hum Reprod. 2012;27(9):2698–2711.

17.

Nabeta

Abe

Kagawa

. Identification of anti-a-enolase autoantibody as a novel serum marker for endometriosis. Proteomics Clin Appl. 2009;3(10):1201–1210.

18.

Nabeta

Abe

Haraguchi

Kito

Kusanagi

Ito

. Serum anti-PDIK1L autoantibody as a novel marker for endometriosis. Fert Steril. 2010;94(7):2552–2557.

19.

Nabeta

Abe

Takaokaa

Kusanagi

Ito

. Identification of anti-syntaxin 5 autoantibody as a novel serum marker of endometriosis. J Reprod Immunol. 2011;91(1-2):48–55.

20.

Fassbender

Vodolazkaia

Saunders

. Biomarkers of endometriosis. Fertil Steril. 2013;99(4):1135–1145.

21.

Fassbender

Burney

Dorien

F. O

D’Hooghe

Giudice

. Update on biomarkers for the detection of endometriosis. Biomed Res Int. 2015;2015:130854.

22.

Gajbhiye

Suryawanshi

Khan

. Multiple endometrial antigens are targeted in autoimmune endometriosis. Reprod BioMed Online. 2008;16(6):817–824.

23.

Gajbhiye

Sonawani

Khan

. Identification and validation of novel serum markers for early diagnosis of endometriosis. Hum Reprod. 2012;27(2):408–417.

24.

American Society for Reproductive Medicine. Revised American Society for Reproductive Medicine Classification of endometriosis: 1996. Fertil Steril. 1997;67(5):817–821.

25.

Bossuyt

Clinical performance characteristics of a laboratory test. Apractical approach in autoimmune laboratory. Autoimmune Rev. 2009;8(7):543–548.

26.

Darah

Caitlin

Chau

Stomatin-like protein binds cardiolipin and regulates mitochondrial biogenesis and function. Mol Cell Biol. 2011;31(18):3845–3856.

27.

Zhang

Ding

Cao

. 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.

28.

Cui

Zhang

Hua

Cao

Feng

Liu

. Stomatin-like protein 2 is over expressed and related to cell growth in human endometrial adenocarcinoma. Oncol Re. 2007;17(4):829–833.

29.

Kirchhof

Chau

Lemke

. Modulation of T cell activation by stomatin-like protein 2. J Immunol. 2008;181(3):1927–2704.

30.

Fischer

Fritz-Six

Fowler

VM.

Pointed-end capping by tropomodulin3 negatively regulates endothelial cell motility. J Cell Biol. 2003;161(2):371–380.

31.

Welch

Plank

Witt

. Cardiac-specific IGF-1 expression attenuates dilated cardiomyopathy in tropomodulin-overexpressing. Transgenic Mice Circ Res. 2002;90(6):641–648.

32.

Das

Bajpai

. Tropomyosins in human diseases: ulcerative colitis. Adv Exp Med Biol. 2008;644:158–167.

33.

O’Neill

Stehn

Gunning

. Tropomyosins as interpreters of the signalling environment to regulate the local cytoskeleton. Semin Cancer Biol. 2008;18(1):35–44.

34.

May

Conduit-Hulbert

Villar

Kirtley

Kennedy

Becker

. Peripheral biomarkers of endometriosis: a systematic review. Hum Reprod Update. 2010;16(6):651–674.

35.

Mihalyi

Gevaert

Kyama

C M

. Non-invasive diagnosis of endometriosis based on a combined analysis of six plasma biomarkers. Hum Reprod. 2010;25(3):654–664.

36.

Thubert

Santulli

Marcellin

. 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.

37.

Kurdoglu

Gursoy

Kurdoglu

Erdem

. Comparison of the clinical value of CA19-9 versus CA 125 for the diagnosis of endometriosis. Fertil Steril. 2009;92(5):1761–1763.

38.

Abrão

Podgaec

Pinotti

de Oliveira

. Tumor markers in endometriosis. Int J Gynaecol Obstet. 1999;66(1):19–22.

39.

Harada

Kubota

Aso

. Usefulness of CA19-9 versus CA125 for the diagnosis of endometriosis. Fertil Steril. 2002;78(4):733–739.

40.

Somigliana

Vigano

Tirelli

. 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.

41.

Bilibio

Souza

Rodini

. Serum prolactin and CA-125 levels as biomarkers of peritoneal endometriosis. Gynecol Obstet Invest. 2014;78(1):45–52.

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

Abstract

Keywords

Get full access to this article

References