Evaluation of M1 and M2 Macrophages in Endometriotic Tissue of Women Affected by Endometriosis at Different Stages.

NCT03136978 | Completed

• 1 other identifier: ENDOMAC
• Study Type: observational
• Target: 45
• Locations: 1 country
• Sites: 1

Brief Summary

Accumulating evidence suggests that the peritoneal microenvironment of women affected by endometriosis undergoes a number of local inflammatory-reparative phenomena, with the involvement of resident macrophages, and the attraction and recruitment of peripheral mononuclear cells (monocytes and lymphocytes) from the blood into the peritoneal cavity: during endometriosis a breakdown occurs in endometrial and peritoneal homeostasis caused by cytokine-addressed cell proliferation and dysregulation of apoptosis. The surrounding microenvironment may address the macrophage plasticity towards a transient and reversible polarization. These polarized phenotypes reflects the proinflammatory or anti-inflammatory status and may change over the time. They could be functionally classified in two main populations: "classically activated" macrophages (M1) and "alternatively activated" macrophages (M2). Considering that published data so far are still not robust enough to drawn firm conclusion, the aim of this research project will be to evaluate M1 and M2 macrophages in endometriotic tissue from women affected by endometriosis at different stages.

Conditions

Endometriosis

Keywords

Macrophages; Macrophages, Peritoneal; Endometriosis

Outcome Measures

Primary Outcomes (1)

• Quantification of M1 and M2 macrophages in endometriotic tissue for each stage of endometriosis.

  To assess surface expression of macrophage markers, endometrial tissue cells will be stained for flow cytometry with fluorochrome-conjugated monoclonal antibodies against CD14, CD68, CCR7 and CD80 to identify M1, whereas fluorochrome-conjugated monoclonal antibodies against CD14, CD68, CD163 and CD206 to identify M2.

  Day 1

Secondary Outcomes (2)

• Correlation of M1 and M2 macrophages quantity in endometriotic tissue to the presence of endometriosis-associated infertility.

  Day 1

• Correlation of M1 and M2 macrophages quantity in endometriotic tissue to the presence of endometriosis-associated chronic pelvic pain.

  Day 1

Study Arms (2)

Endometriosis

Patients affected by endometriosis (histologically confirmed) at different stages, who will undergo laparoscopic surgery.

Diagnostic Test: Evaluation of M1 and M2 macrophages by flow cytometry.

Ovarian functional cysts

Patients affected by ovarian functional cysts, who will undergo laparoscopic surgery.

Diagnostic Test: Evaluation of M1 and M2 macrophages by flow cytometry.

Interventions

Evaluation of M1 and M2 macrophages by flow cytometry. DIAGNOSTIC_TEST

To assess surface expression of macrophage markers, tissue samples will be stained for flow cytometry with fluorochrome-conjugated monoclonal antibodies against CD14, CD68, CCR7 and CD80 to identify M1, whereas fluorochrome-conjugated monoclonal antibodies against CD14, CD68, CD163 and CD206 to identify M2.

Endometriosis; Ovarian functional cysts

Eligibility Criteria

• Age: 18 Years - 35 Years
• Gender Eligibility Details: Female patients.
• Healthy Volunteers: No
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Reproductive-aged patients affected by histologically confirmed endometriosis (cases) and by ovarian functional cysts (controls), who will undergo laparoscopic surgery.

You may qualify if:

• Patients affected by histologically confirmed endometriosis (cases)
• Patients affected by ovarian function cysts (controls)

You may not qualify if:

• Other pelvic disorders (apart ovarian functional cysts)
• Chronic circulatory disorders
• Autoimmune disorders
• Neoplastic disorders
• Patients who were treated with any anti-inflammatory or hormonal or immunomodulatory medication in the preceding 6 months.

Sponsors & Collaborators

• University of Messina: lead
• University of Ljubljana: collaborator
• University of Padova: collaborator

Study Sites (1)

University of Messina

Messina, 98122, Italy

Location

Related Publications (22)

• Kavoussi SK, Lim CS, Skinner BD, Lebovic DI, As-Sanie S. New paradigms in the diagnosis and management of endometriosis. Curr Opin Obstet Gynecol. 2016 Aug;28(4):267-76. doi: 10.1097/GCO.0000000000000288.

  PMID: 27306924 BACKGROUND

• Dunselman GA, Vermeulen N, Becker C, Calhaz-Jorge C, D'Hooghe T, De Bie B, Heikinheimo O, Horne AW, Kiesel L, Nap A, Prentice A, Saridogan E, Soriano D, Nelen W; European Society of Human Reproduction and Embryology. ESHRE guideline: management of women with endometriosis. Hum Reprod. 2014 Mar;29(3):400-12. doi: 10.1093/humrep/det457. Epub 2014 Jan 15.

  PMID: 24435778 BACKGROUND

• Triolo O, Lagana AS, Sturlese E. Chronic pelvic pain in endometriosis: an overview. J Clin Med Res. 2013 Jun;5(3):153-63. doi: 10.4021/jocmr1288w. Epub 2013 Apr 23.

  PMID: 23671540 BACKGROUND

• Buttice S, Lagana AS, Barresi V, Inferrera A, Mucciardi G, Di Benedetto A, D'Amico CE, Magno C. Lumbar Ureteral Stenosis due to Endometriosis: Our Experience and Review of the Literature. Case Rep Urol. 2013;2013:812475. doi: 10.1155/2013/812475. Epub 2013 May 2.

  PMID: 23738189 BACKGROUND

• Lagana AS, Condemi I, Retto G, Muscatello MR, Bruno A, Zoccali RA, Triolo O, Cedro C. Analysis of psychopathological comorbidity behind the common symptoms and signs of endometriosis. Eur J Obstet Gynecol Reprod Biol. 2015 Nov;194:30-3. doi: 10.1016/j.ejogrb.2015.08.015. Epub 2015 Aug 15.

  PMID: 26319653 BACKGROUND

• Rock JA. The revised American Fertility Society classification of endometriosis: reproducibility of scoring. ZOLADEX Endometriosis Study Group. Fertil Steril. 1995 May;63(5):1108-10. doi: 10.1016/s0015-0282(16)57556-6.

  PMID: 7720925 BACKGROUND

• Haas D, Chvatal R, Habelsberger A, Wurm P, Schimetta W, Oppelt P. Comparison of revised American Fertility Society and ENZIAN staging: a critical evaluation of classifications of endometriosis on the basis of our patient population. Fertil Steril. 2011 Apr;95(5):1574-8. doi: 10.1016/j.fertnstert.2011.01.135.

  PMID: 21315335 BACKGROUND

• Adamson GD, Pasta DJ. Endometriosis fertility index: the new, validated endometriosis staging system. Fertil Steril. 2010 Oct;94(5):1609-15. doi: 10.1016/j.fertnstert.2009.09.035.

  PMID: 19931076 BACKGROUND

• Donnez J, Donnez O, Orellana R, Binda MM, Dolmans MM. Endometriosis and infertility. Panminerva Med. 2016 Jun;58(2):143-50. Epub 2016 Feb 2.

  PMID: 26837776 BACKGROUND

• Sofo V, Gotte M, Lagana AS, Salmeri FM, Triolo O, Sturlese E, Retto G, Alfa M, Granese R, Abrao MS. Correlation between dioxin and endometriosis: an epigenetic route to unravel the pathogenesis of the disease. Arch Gynecol Obstet. 2015 Nov;292(5):973-86. doi: 10.1007/s00404-015-3739-5. Epub 2015 Apr 29.

  PMID: 25920525 BACKGROUND

• Maniglio P, Ricciardi E, Lagana AS, Triolo O, Caserta D. Epigenetic modifications of primordial reproductive tract: A common etiologic pathway for Mayer-Rokitansky-Kuster-Hauser Syndrome and endometriosis? Med Hypotheses. 2016 May;90:4-5. doi: 10.1016/j.mehy.2016.02.015. Epub 2016 Feb 27. No abstract available.

  PMID: 27063075 BACKGROUND

• Lagana AS, Sturlese E, Retto G, Sofo V, Triolo O. Interplay between Misplaced Mullerian-Derived Stem Cells and Peritoneal Immune Dysregulation in the Pathogenesis of Endometriosis. Obstet Gynecol Int. 2013;2013:527041. doi: 10.1155/2013/527041. Epub 2013 Jun 13.

  PMID: 23843796 BACKGROUND

• Lagana AS, Triolo O, Salmeri FM, Granese R, Palmara VI, Ban Frangez H, Vrtcnik Bokal E, Sofo V. Natural Killer T cell subsets in eutopic and ectopic endometrium: a fresh look to a busy corner. Arch Gynecol Obstet. 2016 May;293(5):941-9. doi: 10.1007/s00404-015-4004-7. Epub 2016 Jan 6.

  PMID: 26739265 BACKGROUND

• Pizzo A, Salmeri FM, Ardita FV, Sofo V, Tripepi M, Marsico S. Behaviour of cytokine levels in serum and peritoneal fluid of women with endometriosis. Gynecol Obstet Invest. 2002;54(2):82-7. doi: 10.1159/000067717.

  PMID: 12566749 BACKGROUND

• Sturlese E, Salmeri FM, Retto G, Pizzo A, De Dominici R, Ardita FV, Borrielli I, Licata N, Lagana AS, Sofo V. Dysregulation of the Fas/FasL system in mononuclear cells recovered from peritoneal fluid of women with endometriosis. J Reprod Immunol. 2011 Dec;92(1-2):74-81. doi: 10.1016/j.jri.2011.08.005. Epub 2011 Oct 5.

  PMID: 21978769 BACKGROUND

• Salmeri FM, Lagana AS, Sofo V, Triolo O, Sturlese E, Retto G, Pizzo A, D'Ascola A, Campo S. Behavior of tumor necrosis factor-alpha and tumor necrosis factor receptor 1/tumor necrosis factor receptor 2 system in mononuclear cells recovered from peritoneal fluid of women with endometriosis at different stages. Reprod Sci. 2015 Feb;22(2):165-72. doi: 10.1177/1933719114536472. Epub 2014 May 20.

  PMID: 24844917 BACKGROUND

• Elie Metchnikoff (1845-1916), advocate of phagocytosis. JAMA. 1968 Jan 8;203(2):139-41. No abstract available.

  PMID: 4864332 BACKGROUND

• Sica A, Mantovani A. Macrophage plasticity and polarization: in vivo veritas. J Clin Invest. 2012 Mar;122(3):787-95. doi: 10.1172/JCI59643. Epub 2012 Mar 1.

  PMID: 22378047 BACKGROUND

• Liu YC, Zou XB, Chai YF, Yao YM. Macrophage polarization in inflammatory diseases. Int J Biol Sci. 2014 May 1;10(5):520-9. doi: 10.7150/ijbs.8879. eCollection 2014.

  PMID: 24910531 BACKGROUND

• Locati M, Mantovani A, Sica A. Macrophage activation and polarization as an adaptive component of innate immunity. Adv Immunol. 2013;120:163-84. doi: 10.1016/B978-0-12-417028-5.00006-5.

  PMID: 24070384 BACKGROUND

• Mantovani A, Biswas SK, Galdiero MR, Sica A, Locati M. Macrophage plasticity and polarization in tissue repair and remodelling. J Pathol. 2013 Jan;229(2):176-85. doi: 10.1002/path.4133. Epub 2012 Nov 29.

  PMID: 23096265 BACKGROUND

• Capobianco A, Rovere-Querini P. Endometriosis, a disease of the macrophage. Front Immunol. 2013 Jan 28;4:9. doi: 10.3389/fimmu.2013.00009. eCollection 2013.

  PMID: 23372570 BACKGROUND

Biospecimen

Retention: SAMPLES WITHOUT DNA

* Endometriotic tissue (histologically confirmed) from patients affected by endometriosis at different stages (cases). * Tissue samples from ovarian functional cysts (controls).

MeSH Terms

Conditions

Endometriosis

Condition Hierarchy (Ancestors)

Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Study Officials

• Antonio Simone Laganà, M.D.

  University of Messina

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: April 27, 2017
• First Posted: May 2, 2017
• Study Start: December 1, 2016
• Primary Completion: December 1, 2018
• Study Completion: December 1, 2019
• Last Updated: March 24, 2020

Record last verified: 2020-03

Data Sharing

• IPD Sharing: Will share

Locations

IT (1)