{"paper_id":"35d10314-8852-4fb3-a6d0-ee0d94d39c91","body_text":"Abstract\nBackground\nAdenomyosis (ADE) is an enigmatic uterine disorder. Several types have been previously described: diffuse adenomyosis (DIF-ADE), focal adenomyosis (FOC-ADE), and association of focal and diffuse lesions (FOC/DIF-ADE). Abnormal immune phenomena have been described that may provide an understanding of the pathophysiology of adenomyosis. However, the immune imbalance in adenomyosis is however still poorly understood.\nObjective\nTo compare serum cytokine profiles for the various adenomyosis phenotypes in adenomyosis versus disease-free women.\nMaterials and Methods\nThis cohort study included 80 women. Based on the magnetic resonance imaging (MRI) findings, the women were allocated to the ADE group (n = 60) and the control group (n = 20). The ADE group was further subdivided according to the phenotype: DIF-ADE, FOC-ADE, and FOC/DIF-ADE. For all of the women, serum cytokine levels were assayed by multiplex immunoassay.\nResults\nSerum levels of interleukin (IL) 23 (237.77 pg/mL ± 70.97 in the ADE-group versus 1855.04 ± 1411.33 in the control group, P =.019), IL25 (31.98 ± 8.54 vs 222.08 ± 170.90, respectively, P =.006), IL31 (10.13 ± 3.83 vs 91.51 ± 71.21, respectively, P =.034), IL33 (3.77 ± 1.23 vs 17.86 ± 11.49, respectively, P =.016), and IL17F (16.29 ± 2.35 vs 30.12 ± 8.29, respectively, P =.042) were significantly lower in the women with adenomyosis when compared to the controls In the FOC/DIF-ADE group, the serum levels of IL23, IL31, IL25, and IL33 were significantly lower when compared to the control group.\nConclusion\nSerum levels of IL23, IL31, IL25, and IL33 were lower in women exhibiting adenomyosis forms with associated diffuse and focal lesions when compared with controls. The pathogenesis of adenomyosis may be associated with an immunotolerant process that is more pronounced in associated FOC/DIF-ADE.\nSimilar content being viewed by others\nReferences\nBenagiano G, Habiba M, Brosens I. The pathophysiology of uterine adenomyosis: an update. Fertil Steril. 2012;98(3):572–579.\nBergeron C, Amant F, Ferenczy A. Pathology and physiopathology of adenomyosis. Best Pract Res Clin Obstet Gynaecol. 2006;20(4):511–521.\nStreuli I, Dubuisson J, Santulli P, de Ziegler D, Batteux F, Chapron C. An update on the pharmacological management of adenomyosis. Expert Opin Pharmacother. 2014;15(16):2347–2360.\nGordts S, Brosens JJ, Fusi L, Benagiano G, Brosens I. Uterine adenomyosis: a need for uniform terminology and consensus classification. Reprod Biomed Online. 2008;17(2):244–248.\nChapron C. Relationship between the magnetic resonance imaging appearance of adenomyosis and endometriosis phenotypes. Hum Reprod. 2017;32(7):1393–1401.\nBazot M, Cortez A, Darai E, et al. Ultrasonography compared with magnetic resonance imaging for the diagnosis of adenomyosis: correlation with histopathology. Hum Reprod Oxf Engl. 2001;16(11):2427–2433.\nDueholm M. Transvaginal ultrasound for diagnosis of adenomyosis: a review. Best Pract Res Clin Obstet Gynaecol. 2006;20(4):569–582.\nExacoustos C, Brienza L, Di Giovanni A, et al. Adenomyosis: three-dimensional sonographic findings of the junctional zone and correlation with histology. Ultrasound Obstet Gynecol. 2011;37(4):471–479.\nOta H, Igarashi S, Hatazawa J, Tanaka T. Is adenomyosis an immune disease? Hum Reprod Update. 1998;4(4):360–367.\nUlukus EC, Ulukus M, Seval Y, Zheng W, Arici A. Expression of interleukin-8 and monocyte chemotactic protein-1 in adenomyosis. Hum Reprod Oxf Engl. 2005;20(10):2958–2963.\nWang F, Li H, Yang Z, Du X, Cui M, Wen Z. Expression of interleukin-10 in patients with adenomyosis. Fertil Steril. 2009;91(5):1681–1685.\nTremellen KP, Russell P. The distribution of immune cells and macrophages in the endometrium of women with recurrent reproductive failure. II: adenomyosis and macrophages. J Reprod Immunol. 2012;93(1):58–63.\nGui T, Chen C, Zhang Z, et al. The disturbance of TH17-Treg cell balance in adenomyosis. Fertil Steril. 2014;101(2):506–514.\nStreuli I, Santulli P, Chouzenoux S, Chapron C, Batteux F. Serum osteopontin levels are decreased in focal adenomyosis. Reprod Sci Thousand Oaks Calif. 2017;24(5):773–782.\nMillischer A-E, Salomon L, Santulli P, Borghese B, Dousset B, Chapron C. Fusion imaging for evaluation of deep infiltrating endometriosis: feasibility and preliminary results: Fusion imaging of endometriosis. Ultrasound Obstet Gynecol. 2015;46(1):109–117.\nChapron C, Souza C, de Ziegler D, et al. Smoking habits of 411 women with histologically proven endometriosis and 567 unaffected women. Fertil Steril. 2010;94(6):2353–2355.\nMillischer AE, Salomon LJ, Santulli P, Borghese B, Dousset B, Chapron C. Fusion imaging for evaluation of deep infiltrating endometriosis: feasibility and preliminary results: Fusion imaging of endometriosis. Ultrasound Obstet Gynecol. 2015;46(1):109–117.\nNovellas S, Chassang M, Delotte J, et al. MRI characteristics of the uterine junctional zone: from normal to the diagnosis of adenomyosis. AJR Am J Roentgenol. 2011;196(5):1206–1213.\nArnold LL, Ascher SM, Schruefer JJ, Simon JA. The nonsurgical diagnosis of adenomyosis. Obstet Gynecol. 1995;86(3):461–465.\nSantulli P, Borghese B, Chouzenoux S, et al. Serum and peritoneal interleukin-33 levels are elevated in deeply infiltrating endometriosis. Hum Reprod Oxf Engl. 2012;27(7):2001–2009.\nSantulli P, Borghese B, Chouzenoux S, et al. Interleukin-19 and interleukin-22 serum levels are decreased in patients with ovarian endometrioma. Fertil Steril. 2013;99(1):219–226.e2.\nReinhold C, McCarthy S, Bret PM, et al. Diffuse adenomyosis: comparison of endovaginal US and MR imaging with histopathologic correlation. Radiology. 1996;199(1):151–158.\nKunz G, Beil D, Huppert P, Noe M, Kissler S, Leyendecker G. Adenomyosis in endometriosis—prevalence and impact on fertility. Evidence from magnetic resonance imaging. Hum Reprod Oxf Engl. 2005;20(8):2309–2316.\nStamatopoulos CP, Mikos T, Grimbizis GF, et al. Value of magnetic resonance imaging in diagnosis of adenomyosis and myomas of the uterus. J Minim Invasive Gynecol. 2012;19(5):620–626.\nSpits H, Artis D, Colonna M, et al. Innate lymphoid cells—a proposal for uniform nomenclature. Nat Rev Immunol. 2013;13(2):145–149.\nSpits H, Di Santo JP. The expanding family of innate lymphoid cells: regulators and effectors of immunity and tissue remodeling. Nat Immunol. 2011;12(1):21–27.\nEberl G, Colonna M, Di Santo JP, McKenzie AN. Innate lymphoid cells. Innate lymphoid cells: a new paradigm in immunology. Science. 2015;348(6237):aaa6566.\nKlose CSN, Artis D. Innate lymphoid cells as regulators of immunity, inflammation and tissue homeostasis. Nat Immunol. 2016;17(7):765–774.\nArtis D, Spits H. The biology of innate lymphoid cells. Nature. 2015;517(7534):293–301.\nKim CH, Hashimoto-Hill S, Kim M. Migration and tissue tropism of innate lymphoid cells. Trends Immunol. 2016;37(1):68–79.\nChang SH, Dong C. IL-17F: regulation, signaling and function in inflammation. Cytokine. 2009;46(1):7–11.\nLiu L, Shan B, Feng Y. Antitumor effects and immunoregulation mechanisms of IL-23 gene in mouse mammary cancer mediated by retrovirus. Cell Immunol. 2009;258(2):181–187.\nD’Elios MM, Del Prete G, Amedei A. Targeting IL-23 in human diseases. Expert Opin Ther Targets. 2010;14(7):759–774.\nGaffen SL, Jain R, Garg AV, Cua DJ. The IL-23–IL-17 immune axis: from mechanisms to therapeutic testing. Nat Rev Immunol. 2014;14(9):585–600.\nDavidi S, Fremder E, Kan T, et al. The antiangiogenic role of the pro-inflammatory cytokine interleukin-31. Oncotarget. 2017;8(10):16430–16444.\nFan Y, Liu Y, Chen H, Chen W, Wang L. Serum level concentrations of pro-inflammatory cytokines in patients with adenomyosis. Biomedical Research. 2017;28(4):1809–1813.\nÖzçelik K, Çapar M, Gazi Uçar M, Çakιr T, Özçelik F, Tuyan Ilhan T. Are cytokine levels in serum, endometrial tissue, and peritoneal fluid a promising predictor to diagnosis of endometriosis-adenomyosis? Clin Exp Obstet Gynecol. 2016;43(4):569–572.\nSotnikova N, Antsiferova I, Malyshkina A. Cytokine network of eutopic and ectopic endometrium in women with adenomyosis. Am J Reprod Immunol N Y N 1989. 2002;47(4):251–255.\nJiang JF, Xiao SS, Xue M. Decreased expression of interleukin-37 in the ectopic and eutopic endometria of patients with adenomyosis. Gynecol Endocrinol. 2018;34(1):83–86.\nKishi Y, Shimada K, Fujii T, et al. Phenotypic characterization of adenomyosis occurring at the inner and outer myometrium. PloS One. 2017;12(12):e0189522.\nDi Donato N, Montanari G, Benfenati A, et al. Prevalence of adenomyosis in women undergoing surgery for endometriosis. Eur J Obstet Gynecol Reprod Biol. 2014;181:289–293.\nAuthor information\nAuthors and Affiliations\nCorresponding author\nAdditional information\nAuthors’ Note\nFréderic Batteux and Charles Chapron authors contributed equally to this work.\nRights and permissions\nAbout this article\nCite this article\nBourdon, M., Santulli, P., Chouzenoux, S. et al. The Disease Phenotype of Adenomyosis-Affected Women Correlates With Specific Serum Cytokine Profiles. Reprod. Sci. 26, 198–206 (2019). https://doi.org/10.1177/1933719118816852\nPublished:\nVersion of record:\nIssue date:\nDOI: https://doi.org/10.1177/1933719118816852","source_license":"CC0","license_restricted":false}