{"paper_id":"45c37791-4268-4e4c-a99e-57510ec2e6d6","body_text":"Abstract\nObjective\nTo identify and characterize endometriosis-associated immune cell infiltrates (EMaICI). Furthermore, to define occurrence and size of EMaICI in various types of endometriosis.\nMethods\nImmune cells were characterized in samples of 60 premenopausal women with histological proven endometriosis. Therefore, immunohistochemical staining with monoclonal antibodies for CD3, CD4, CD8, CD45RO, CD25, CD56, CD68, and CD20 on sections of paraffin-embedded endometriotic tissue was performed.\nResults\nEMaICI were observed in all the types of endometriosis, and characterized as T lymphocytes (CD3+), helper T lymphocytes (CD4+), cytotoxic T lymphocytes (CD8+), antigen-experienced T lymphocytes”memory cells” (CD45RO+), macrophages (CD68+), and B lymphocytes (CD20+). The maximum frequency of EMaICI and their distribution per endometriotic lesion (EML) was observed in peritoneal endometriosis (pEM) and in ovarian endometriosis (Ov. EM). In myometrium from adenomyosis (M/AM), EMaICI occurrence was lower and smaller in size in comparison with EMaICI seen in other forms of endometriosis. EMaICI were negative for regulatory T cells (CD25+ high, FoxP3+) and natural killer cells (NK cells, CD56+).\nConclusion\nNumerous and brisk EMaICI comprising several types of immune cells in all endometriosis forms suggest acute immunological reactions within the microenvironment of endometriosis lesions.\nSimilar content being viewed by others\nAbbreviations\n- AM:\n-\nAdenomyosis\n- CD:\n-\nCluster of differentiation\n- DIE:\n-\nDeep infiltrating rectovaginal endometriosis\n- EDT:\n-\nEndometriosis disease theory\n- EM:\n-\nEndometriosis\n- EMaICI:\n-\nEndometriosis-associated immune cell infiltrates\n- EML:\n-\nEndometriotic lesions\n- EN1/pEM:\n-\nEndometrium from patients with peritoneal EM\n- EN2/AM:\n-\nEndometrium from adenomyosis\n- EN3k/UM:\n-\nEndometrium from uterus myomatosus, used as control\n- ICI:\n-\nImmune cell infiltrates\n- IHC:\n-\nImmunohistochemistry\n- M/AM:\n-\nMyometrium from adenomyosis\n- M/UM:\n-\nMyometrium from myomatosus uterus, used as control\n- NK:\n-\nNatural killer cells\n- NLP:\n-\nNon-lesional peritoneum, used as control\n- NLO:\n-\nNon-lesional ovarium, used as control\n- Ov. EM:\n-\nOvarian endometriosis\n- p EM:\n-\nPeritoneal endometriosis\n- p:\n-\nProliferative phase\n- s:\n-\nSecretory phase\nReferences\nEbert A (2006) Endometriose. Walter de Gruyter, Berlin. In: Update 2006\nMeyer R (1919) Uber den Stand der Frage der Adenomyositis und Adenomyome in allgemeinen und insbesondere über Adenomyositis serosoepithlialis und Adenomyometritis sarcomatosa. ZentralblGynäkol 43:745–750\nSampson JA (1927) Metastatic or embolic endometriosis, due to the menstrual dissemination of endometrial tissue into the venous circulation. Am J Pathol 3(2):93–110, 143\nLeyendecker G, Kunz G, Noe M, Herbertz M, Mall G (1998) Endometriosis: a dysfunction and disease of the archimetra. Hum Reprod Update 4(5):752–762\nLeyendecker G, Wildt L, Mall G (2009) The pathophysiology of endometriosis and adenomyosis: tissue injury and repair. Arch Gynecol Obstet 280(4):529–538\nDmowski WP, Steele RW, Baker GF (1981) Deficient cellular immunity in endometriosis. Am J Obstet Gynecol 141(4):377–383\nMorris H, Edwards J, Tiltman A, Emms M (1985) Endometrial lymphoid tissue: an immunohistological study. J Clin Pathol 38(6):644–652\nKamat BR, Isaacson PG (1987) The immunocytochemical distribution of leukocytic subpopulations in human endometrium. Am J Pathol 127(1):66–73\nMarshall RJ, Jones DB (1988) An immunohistochemical study of lymphoid tissue in human endometrium. Int J Gynecol Pathol 7(3):225–235\nWitz CA, Montoya IA, Dey TD, Schenken RS (1994) Characterization of lymphocyte subpopulations and T cell activation in endometriosis. Am J Reprod Immunol 32(3):173–179\nOosterlynck DJ, Cornillie FJ, Waer M, Koninckx PR (1993) Immunohistochemical characterization of leucocyte subpopulations in endometriotic lesions. Arch Gynecol Obstet 253(4):197–206\nStartseva NV (1980) Clinical immunological aspects of genital endometriosis. Akush Ginekol (Mosk) 3:23–26\nMettler L, Volkov NI, Kulakov VI et al (1996) Lymphocyte Subsets in the Endometrium of patients with Endometriosis throughout the Menstrual Cycle. Am J Reprod Immunol 36:342–348\nRevised American Society for Reproductive Medicine classification of endometriosis: 1996. Fertil Steril 1997, 67(5):817–821\nWang Y, Zhang L, Wang X (2001) Study on the distribution of lymphocyte subsets in the eutopic and ectopic endometrium of women with endometriosis. Zhonghua fu chan ke za zhi 36(2):85–88\nBulun SE (2009) Endometriosis. N Engl J Med 360(3):268–279\nSzyllo K, Tchorzewski H, Banasik M, Glowacka E, Lewkowicz P, Kamer-Bartosinska A (2003) The involvement of T lymphocytes in the pathogenesis of endometriotic tissues overgrowth in women with endometriosis. Mediators Inflamm 12(3):131–138\nAgic A, Xu H, Finas D, Banz C, Diedrich K, Hornung D (2006) Is endometriosis associated with systemic subclinical inflammation? Gynecol Obstet Invest 62(3):139–147\nBraun DP, Muriana A, Gebel H, Rotman C, Rana N, Dmowski WP (1994) Monocyte-mediated enhancement of endometrial cell proliferation in women with endometriosis. Fertil Steril 61(1):78–84\nBerbic M, Hey-Cunningham AJ, Ng C, Tokushige N, Ganewatta S, Markham R, Russell P, Fraser IS. The role of Foxp3+ regulatory T-cells in endometriosis: a potential controlling mechanism for a complex, chronic immunological condition. Hum Reprod 25(4):900–907\nOsuga Y, Koga K, Hirota Y, Hirata T, Yoshino O, Taketani Y. Lymphocytes in endometriosis. Am J Reprod Immunol\nOosterlynck DJ, Cornillie FJ, Waer M, Vandeputte M, Koninckx PR (1991) Women with endometriosis show a defect in natural killer activity resulting in a decreased cytotoxicity to autologous endometrium. Fertil Steril 56(1):45–51\nWilson TJ, Hertzog PJ, Angus D, Munnery L, Wood EC, Kola I (1994) Decreased natural killer cell activity in endometriosis patients: relationship to disease pathogenesis. Fertil Steril 62(5):1086–1088\nAntsiferova YS, Sotnikova NY, Posiseeva LV, Shor AL (2005) Changes in the T-helper cytokine profile and in lymphocyte activation at the systemic and local levels in women with endometriosis. Fertil Steril 84(6):1705–1711\nConfino E, Harlow L, Gleicher N (1990) Peritoneal fluid and serum autoantibody levels in patients with endometriosis. Fertil Steril 53(2):242–245\nJones RK, Bulmer JN, Searle RF (1995) Immunohistochemical characterization of proliferation, oestrogen receptor and progesterone receptor expression in endometriosis: comparison of eutopic and ectopic endometrium with normal cycling endometrium. Hum Reprod (Oxford, England) 10(12):3272–3279\nJones RK, Bulmer JN, Searle RF (1996) Immunohistochemical characterization of stromal leukocytes in ovarian endometriosis: comparison of eutopic and ectopic endometrium with normal endometrium. Fertil Steril 66(1):81–89\nIsaacson KB, Xu Q, Lyttle CR (1991) The effect of estradiol on the production and secretion of complement component 3 by the rat uterus and surgically induced endometriotic tissue. Fertil Steril 55(2):395–402\nAuthor information\nAuthors and Affiliations\nCorresponding author\nEthics declarations\nConflict of interest\nAll authors of this work declare that they have no conflict of interest.\nEthical issues\nAll procedures performed in this study involving human samples were in accordance with the ethical standards of the Charité ethics committee. The study was approved by the IRB of Charité ethics committee (EA) and informed consent was obtained from all patients.\nRights and permissions\nAbout this article\nCite this article\nScheerer, C., Bauer, P., Chiantera, V. et al. Characterization of endometriosis-associated immune cell infiltrates (EMaICI). Arch Gynecol Obstet 294, 657–664 (2016). https://doi.org/10.1007/s00404-016-4142-6\nReceived:\nAccepted:\nPublished:\nIssue date:\nDOI: https://doi.org/10.1007/s00404-016-4142-6","source_license":"CC0","license_restricted":false}