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Role of cytokines in pathogenesis, diagnosis and efficiency evaluation of immunotherapy in various variants of sclerotic lichen in women

https://doi.org/10.15789/1563-0625-ROC-2085

Abstract

Our aim was to evaluate diagnostic and pathogenetic significance of plasma cytokines (IL-20, IL-23, IL-10, TNFα, IFNγ) in the patients with various clinical and histological variants of sclerotic lichen and to assess opportunity for their use as effectiveness criteria of immunotherapy for this disease using a drug based on eukaryotic deoxyribonucleic acid (Derinat). The prospective cohort study included assessment of the clinical manifestations (itching and dyspareunia) and measurement of blood cytokine contents (IL-20, IL-23, IL-10, TNFα, IFNγ) in women (n = 114) with various clinical variants of sclerotic lichen (atrophic, sclerotic and sclerotic-atrophic) before and after immunotherapy with a nucleic acid-based drug (Derinat). Derinat was chosen due to the fact of being an agonist of Toll-like receptors, and a number of immunoregulatory effects, including the ability to modulate cytokine production and to exert a positive influence upon regeneration processes. In addition, based on visual inspection, vulvoscopy and morphohistochemical examination results (evaluation criteria: skin thickness, number of collagen fibers, severity of fibrosis and sclerosis, etc.), the corresponding subgroups were classified within the II group, i.e., 2.1 (minimal sclerotic signs, n = 14), and 2.2 (pronounced sclerotic signs, n = 20). The control group consisted of conditionally healthy women, without history or presence of vulvar pathology (n = 30), with an age ranging from 20 to 50 years. Along with cytokine assessment by enzyme immunoassay, the study used the data of clinical examination (anamnesis collection, examination, palpation, vulvoscopy), as well as complex morphohistochemical evaluation of vulvar tissues. In atrophic variant, we have observed an increase in plasma IL-23 content, along with decreased TNFα; in lichen sclerosis, a maximal increase in IL-20, IL-23, and IFNγ was revealed; in sclerotic form of sclerotic lichen variant with severe sclerotic features, maximally enhanced IL-20, IL-23, TNFα, IFNγ, along with minimal levels of IL-10 was registered, as compared with other groups. Immunotherapy using Derinate resulted into significant reduction in the clinical manifestations in sclerotic lichen, i.e., itching of the vulva and dyspareunia, as well as normalization of cytokine indexes. Our studies have demonstrated an opportunity of using plasma concentrations of IL-20, IL-23, IL-10, TNFα, IFNγ as biomarkers of sclerotic lichen variants, and as laboratory criteria for efficiency of immunotherapy.

About the Authors

E. V. Kolesnikova
Kuban State Medical University
Russian Federation
Kolesnikova Ekaterina V., PhD (Medicine), Associate Professor, Department of Obstetrics, Gynecology and Perinatology of the FPC and PPP

350065, Krasnodar, Snesarev str., 8, apt 280



A. V. Zharov
Kuban State Medical University
Russian Federation

PhD, MD (Medicine), Professor, Department of Obstetrics, Gynecology and Perinatology of the FPC and PPP

Krasnodar



G. A. Penzhoyan
Kuban State Medical University

PhD, MD (Medicine), Professor, Head, Department of Obstetrics, Gynecology and Perinatology of the FPC and PPP

Krasnodar



References

1. Batyrshina S.V., Galikanova E.E. On improving the diagnosis of vulvovaginal candidiasis in patients with dystrophic diseases of the vulva and vagina. Vestnik poslediplomnogo meditsinskogo obrazovaniya = Journal of Postgraduate Medical Education, 2014, no. 4, рр. 24-28. (In Russ.)

2. Gallyamova Yu.A. Focal scleroderma. Lechashchiy vrach = Attending Physician, 2008, no. 5, pp. 46-48. (In Russ.)

3. Kolesnikova E. V., Penzhoyan G. A., Zharov A.V. Clinical-morphological and immunological aspects of background vulva diseases. Akusherstvo i ginekologiya: novosti mneniya, obuchenie = Obstetrics and Gynecology: News Opinions, Training, 2019, Vol. 7, no. 2, pp. 38-41. (In Russ.)

4. Kubanova A.A., Kubanov A.A., Volnukhin V.A. Localized scleroderma: federal clinical guidelines. Dermatovenerology. Moscow: Business Express, 2015, pp. 260-274.

5. Kuzmenko-Moskvina Yu.A., Beach T.A. Lychen lichen sclerosis: current issues of terminology and morphological verification. Dermatovenerologiya. Kosmetologiya = Dermatovenerology. Cosmetology, 2017, no. 3, pp. 334-337. (In Russ.)

6. Makarov I.O., Chulkova E.A., Sheshukova N.A., Makarova I.I. Non-neoplastic diseases of the vulva. Akusherstvo, ginekologiya i reproduktsiya = Obstetrics, Gynecology and Reproduction, 2012, Vol. 6, no. 2, pp. 14-17. (In Russ.)

7. Molochkov V.A., Snarskaya E.S., Romashkina A.S. Focal scleroderma associated with other autoimmune diseases and the spectrum of various autoantibodies. Rossiyskiy zhurnal kozhnykh i venericheskikh bolezney = Russian Journal of Skin and Venereal Diseases, 2011, no. 4, pp. 33-36. (In Russ.)

8. Pankratov V.G., Rakovskaya E.I., Khartonik A.A., Rabchinskaya O.M., Gumbar S.A., Potapyuk V.A. Lychen lichen sclerosis: clinical features, diagnosis, treatment. Meditsinskiy zhurnal = Medical Journal, 2014, no. 3, pp. 36-41. (In Russ.)

9. Porsokhonova D.F., Medzhitov A.M. Main directions in the treatment of degenerative diseases of the vulva. Klinicheskaya dermatologiya i venerologiya = Clinical Dermatology and Venereology, 2015, Vol. 14, no. 5, pp. 11-16. (In Russ.)

10. Reutskaya M.A., Kulinich S.I. New in the diagnosis and treatment of vulva diseases. Sibirskiy meditsinskiy zhurnal = Siberian Medical Journal, 2011, no. 6, pp. 277-279. (In Russ.)

11. Rusinova T.V., Chudilova G.A., Kolesnikova N.V. Comparative assessment of in vitro immunotropic effects of derinate and synthetic TLR9 agonist on the receptor function of neutrophil granulocytes and monocytes in normal and infectious processes. Kubanskiy nauchnyy meditsinskiy vestnik = Kuban Scientific Medical Bulletin, 2016, Vol. 5, no. 160, pp. 94-97. (In Russ.)

12. Serebryanaya N.B. Nucleotides as regulators of the immune response. Immunologiya = Immunology, 2010, no. 5, pp. 273-281. (In Russ.)

13. Simbirtsev A.S. Cytokines in the pathogenesis of infectious and non-infectious human diseases. Meditsinskiy akademicheskiy zhurnal = Medical Academic Journal, 2013, Vol. 1, no. 3, pp. 18-41. (In Russ.)

14. Snarskaya E.S., Semenchuk Yu.A. Lychen lichen sclerosis anogenital localization: morphological, differential-diagnostic features and comprehensive method of treatment of breast cancer. RMZh “Meditsinskoe obozrenie” = Russian Medical Journal “Medical Review”, 2019, no. 12, pp. 9-13. (In Russ.)

15. Stambolieva A.V., Manukhin I.B., Bogatyrev V.N. Evaluation of the clinical effectiveness of laser therapy for chronic dystrophic diseases of the vulva. Rossiyskiy onkologicheskiy zhurnal = Russian Journal of Oncology, 2014, Vol. 19, no. 1, pp. 32-36. (In Russ.)

16. Stepanova E.F., Akopova V.V. The prospects of Derinat use in medical and pharmaceutical practice. Sovremennye naukoemkie tekhnologii = Modern High-Tech Technologies, 2008, no. 8, p. 108. (In Russ.)

17. Fedorenko T.V., Kolesnikova N.V., Pashkova I.A. Early cytokine predictors of acute kidney transplant rejection. Rossiyskiy immunologicheskiy zhurnal = Russian Journal of Immunology, 2019, Vol. 13 (22), no. 2, pp. 590-592. (In Russ.)

18. Filonenko E.V., Serova L.G. Photodynamic therapy in clinical practice. Biomedical Photonic, 2016, Vol. 5, no. 2, pp. 26-37. (In Russ.)

19. Chuprova T.V., Antsiferova L.N., Sannikova T.G., Emelyanchik E.Yu., Kirillova E.P., Krasovskaya N.V., Anikina E.A. Features of the course of scleroatrophic vulvar lichen in children. Lechashchiy vrach = Attending Physician, 2012, no. 1, pp. 13-15. (In Russ.)

20. Bleeker M.C., Visser P.J., Overbeek L.I., van Beurden M., Berkhof J. Lichen sclerosus: incidence and risk of vulvar squamous cell carcinoma. Cancer Epidemiol. Biomarkers Prev., 2016, Vol. 25, no. 8, pp. 1224-1230.

21. Christodoulou C., Choy E.H. Joint inflammation and cytokine inhibition in rheumatoid arthritis. Clin. Exp. Med., 2006, Vol. 6, pp. 13-19.

22. Fröhlich E., Wahl R. Thyroid autoimmunity: role of anti-thyroid antibodies in thyroid and extra-thyroidal diseases. Front. Immunol., 2017, Vol. 8, 521. doi: 10.3389/fimmu.2017.00521.

23. Ghoneum M., Gollapudi S. Neoplasma. Synergistic apoptotic effect of arabinoxylan rice bran (MGN-3/Biobran) and curcumin (turmeric) on human multiple myeloma cell line U266 in vitro. Neoplasma, 2011, Vol. 58, no. 2, рр. 118-123.

24. Hoang M.P., Reuter J., Papalas J.A., Edwards L., Selim M.A. Vulvar inflammatory dermatoses: an update and review. Am. J. Dermatopathol., 2014, Vol. 36, no. 9, рр. 689-704.

25. Mashayekhi S., Flohr C., Lewis F.M. The treatment of vulval lichen sclerosus in prepubertal girls: a critically appraised topic. Br. J. Dermatol., 2017, Vol. 176, no. 2, рр. 307-316.

26. McKay M., Frankman O., Horowitz B.J., Lecart C., Micheletti L., Ridley C.M., Turner M.L., Woodruff J.D. Vulvar vestibulitis and vestibular papillomatosis. Report of the ISSVD committee on vulvodynia. J. Reprod. Med., 1991, Vol. 36, no. 6, pp. 413-415.

27. Rutz S., Wang X., Ouyang W. The IL-20 subfamily of cytokines--from host defence to tissue homeostasis. Nat. Rev. Immunol., 2014, Vol. 14, pp. 783-795.

28. Vieira-Baptista P., Lima-Silva J., Pérez-López F.R., Preti M., Bornstein J. Vulvodynia: a disease commonly hidden in plain sight. Case Rep. Womens Health, 2018, Vol. 20, e00079. doi: 10.1016/j.crwh.2018.e00079.

29. Yoon J., Leyva-Castillo M.G., Wang G.,Galand C., Oyoshi M.K., Kumar L., Hoff S., He R., Chervonsky A., Oppenheim G., Kuchroo V.K., van den Brink M.R., Malefyt Rde W., Tessier P.A., Fuhlbrigge R., Rosenstiel P., Terhorst C., Murphy G., Geha R.S. IL-23 induced in keratinocytes by endogenous TLR4 ligands polarizes dendritic cells to drive IL-22 responses to skin immunization. J. Exp. Med., 2016, Vol. 213, no. 10, pp. 2147-2166.


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For citations:


Kolesnikova E.V., Zharov A.V., Penzhoyan G.A. Role of cytokines in pathogenesis, diagnosis and efficiency evaluation of immunotherapy in various variants of sclerotic lichen in women. Medical Immunology (Russia). 2021;23(1):63-72. (In Russ.) https://doi.org/10.15789/1563-0625-ROC-2085

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