The miR-338-3p expression level in pemphigus diagnosis

Cover Page

Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription Access

Abstract

BACKGROUND: Pemphigus is a group of potentially fatal chronic cutaneous diseases in which blisters appear on the skin and mucous membranes as a result of IgG autoantibodies binding to desmosomes in the epidermis, leading to keratinocytes acantholysis. Currently, methods to monitor disease activity and therapy efficiency using various biomarkers are being investigated. MicroRNA expression, in particular miR-338-3p, has been one of these biomarkers, as changes in miR-338-3p expression may trigger the Th1/Th2 cell imbalance and possibly be involved in the pathogenesis of the disease.

AIM: This study aimed to design a protocol to evaluate the level of miR-338-3p expression in peripheral blood mononuclear cells and verify the diagnostic value of miR-338-3p expression in pemphigus.

MATERIALS AND METHODS: Experimental prospective comparative study was conducted from February 2023 to February 2024 at the Dermatology Department of Sechenov University. The study included 10 patients with pemphigus in the active stage of the disease, 3 patients in remission, and 9 participants of the control group. The expression of miRNA-338-3p was analyzed by real-time polymerase chain reaction, cDNA was obtained using StemLoop method. The evaluation of miRNA-338-3p expression level was based on its comparison with the expression of U6 gene using 2-ΔΔСt method.

RESULTS: The expression level of miR-338-3p was analyzed in 10 patients in the active stage of the disease (5 men, 50%; 5 women, 50%; mean age 46±10.7 years), 3 patients in remission (2 women, 66.7%; 1 man, 33.3%; mean age 57±8 years), 9 control group (8 women, 88.9%; 1 man, 11.1%; mean age 36±16.8 years). The mean expression level of miR-338-3p was 8.64 (SD±5.72) in patients with active disease, 3.38 (SD±1.44) in patients in remission, and 1.48 (SD±1.12) in controls. A statistically significant increase in the expression level of miR-338-3p was found in patients in the active disease stage compared to the control group (p=0.002). A statistically significant correlation was found between the level of miR-338-3p expression and the PDAI index score (p <0.001).

CONCLUSION: Based on the data obtained in this study, it can be assumed that microRNAs are important in pemphigus, and miR-338-3p expression in particular may serve as a key element in pemphigus pathogenesis. More detailed study of microRNAs and analysis of expression variability according to clinical data may provide the basis for developing new diagnostic methods and severity scoring, allowing more accurate and less invasive diagnostic methods, as well as monitoring and predicting disease progression.

About the authors

Natalia P. Teplyuk

I.M. Sechenov First Moscow State Medical University (Sechenov University)

Email: teplyukn@gmail.com
ORCID iD: 0000-0002-5800-4800
SPIN-code: 8013-3256

MD, Dr. Sci. (Medicine), Professor

Russian Federation, 8-2 Trubetskaya street, 119991 Moscow

Daria V. Mak

I.M. Sechenov First Moscow State Medical University (Sechenov University)

Author for correspondence.
Email: dariamak25@gmail.com
ORCID iD: 0000-0002-7020-0572
SPIN-code: 8204-4555
Russian Federation, 8-2 Trubetskaya street, 119991 Moscow

Yuliya V. Kolesova

I.M. Sechenov First Moscow State Medical University (Sechenov University)

Email: kolesovamsmu@gmail.com
ORCID iD: 0000-0002-3617-2555
SPIN-code: 1441-8730
Russian Federation, 8-2 Trubetskaya street, 119991 Moscow

Anfisa A. Lepekhova

I.M. Sechenov First Moscow State Medical University (Sechenov University)

Email: anfisa.lepehova@yandex.ru
ORCID iD: 0000-0002-4365-3090
SPIN-code: 3261-3520

MD, Cand. Sci. (Medicine), Associate Professor

Russian Federation, 8-2 Trubetskaya street, 119991 Moscow

Tatiana A. Fedotcheva

The Russian National Research Medical University named after N.I. Pirogov

Email: tfedotcheva@mail.ru
ORCID iD: 0000-0003-4998-9991
SPIN-code: 1261-5650

MD, Dr. Sci. (Medicine), Professor

Russian Federation, Moscow

Darya N. Ulchenko

The Russian National Research Medical University named after N.I. Pirogov

Email: motci@list.ru
ORCID iD: 0009-0008-1894-5746
SPIN-code: 9735-2364
Russian Federation, Moscow

References

  1. Olisova OY, Teplyuk NP. Illustrated guide to dermatology for preparation of doctors for accreditation. Moscow: GEOTAR-Media; 2023. 376 р. (In Russ).
  2. Makhneva VM, Teplyuk NP, Beletskaya LV. Autoimmune vesicle: From the origins of development to our days. Moscow: Resheniya; 2016. 308 р. (In Russ).
  3. Joly P, Litrowski N. Pemphigus group (vulgaris, vegetans, foliaceus, herpetiformis, brasiliensis). Clin Dermatol. 2011;29(4):432–436. doi: 10.1016/j.clindermatol.2011.01.013
  4. Amagai M, Tanikawa A, Shimizu T, et al. Committee for Guidelines for the Management of Pemphigus Disease. Japanese guidelines for the management of pemphigus. J Dermatol. 2014;41(6):471–486. doi: 10.1111/1346-8138.12486
  5. Kridin K. Pemphigus group: Overview, epidemiology, mortality, and comorbidities. Immunol Res. 2018;66(2):255–270. EDN: MOQLDI doi: 10.1007/s12026-018-8986-7
  6. Shamim T, Varghese VI, Shameena PM, Sudha S. Pemphigus vulgaris in oral cavity: Clinical analysis of 71 cases. Med Oral Patol Oral Cir Bucal. 2008;13(10):E622–E626.
  7. Pollmann R, Schmidt T, Eming R, Hertl M. Pemphigus: A comprehensive review on pathogenesis, clinical presentation and novel therapeutic approaches. Clin Rev Allergy Immunol. 2018;54(1):1–25. EDN: YEXVDV doi: 10.1007/s12016-017-8662-z
  8. Gonçalves GA, Brito MM, Salathiel AM, et al. Incidence of pemphigus vulgaris exceeds that of pemphigus foliaceus in a region where pemphigus foliaceus is endemic: Analysis of a 21-year historical series. An Bras Dermatol. 2011;86(6):1109–1112. doi: 10.1590/s0365-05962011000600007
  9. Harel-Raviv M, Srolovitz H, Gornitsky M. Pemphigus vulgaris: The potential for error. A case report. Spec Care Dentist. 1995;15(2):61–64. doi: 10.1111/j.1754-4505.1995.tb00478.x 20
  10. Morishima-Koyano M, Nobeyama Y, Fukasawa-Momose M, et al. Case of pemphigus foliaceus misdiagnosed as a single condition of erythrodermic psoriasis and modified by brodalumab. J Dermatol. 2020;47(5):e201–e202. doi: 10.1111/1346-8138.15295
  11. Daltaban Ö, Özçentik A, Karakaş A, et al. Clinical presentation and diagnostic delay in pemphigus vulgaris: A prospective study from Turkey. J Oral Pathol Med. 2020;49(7):681–686. doi: 10.1111/jop.13052
  12. Khamaganova IV, Malyarenko EN, Denisova EV, et al. Mistakes of diagnostics in pemphigus vulgaris: Case report. Russ J Skin Venereal Dis. 2017; 20(1):30–33. EDN: YGTAJL doi: 10.18821/1560-9588-2017-20-1-30-33
  13. Petrova SY, Berzhets VM, Radikova OV. Difficulties of differential diagnosis of blistering dermatoses. pemphigus erythematosus: A case from clinical practice. Immunopatol allergol infectol. 2017;(4):31–36. EDN: YWEQBI doi: 10.14427/jipai.2017.4.31
  14. Petruzzi M, Vella F, Squicciarini N, et al. Diagnostic delay in autoimmune oral diseases. Oral Dis. 2023;29(7):2614–2623. EDN: ZIUCAV doi: 10.1111/odi.14480
  15. Teplyuk NP, Kolesova YV, Mak DV, et al. Pemphigus: New approaches to diagnosis and disease severity assessment. Russ J Skin Venereal Dis. 2023;26(5):515–526. EDN: MSAHYT doi: 10.17816/dv492306
  16. Saha M, Bhogal B, Black MM, et al. Prognostic factors in pemphigus vulgaris and pemphigus foliaceus. Br J Dermatol. 2014;170(1):116–122. doi: 10.1111/bjd.12630
  17. Delavarian Z, Layegh P, Pakfetrat A, et al. Evaluation of desmoglein 1 and 3 autoantibodies in pemphigus vulgaris: Correlation with disease severity. J Clin Exp Dentistry. 2020;12(5):e440–e445. doi: 10.4317/jced.56289
  18. Russo I, De Siena FP, Saponeri A, Alaibac M. Evaluation of anti-desmoglein-1 and anti-desmoglein-3 autoantibody titers in pemphigus patients at the time of the initial diagnosis and after clinical remission. Medicine. 2017;96(46):e8801. doi: 10.1097/MD.0000000000008801
  19. Condrat CE, Thompson DC, Barbu MG, et al. MiRNAs as biomarkers in disease: Latest findings regarding their role in diagnosis and prognosis. Cells. 2020;9(2):276. EDN: OAGKOW doi: 10.3390/cells9020276
  20. O’Brien J, Hayder H, Zayed Y, Peng C. Overview of microRNA biogenesis, mechanisms of actions, and circulation. Front Endocrinol. 2018;9:402. EDN: HCLKYH doi: 10.3389/fendo.2018.00402
  21. Shu J, Silva BV, Gao T, et al. Dynamic and modularized microRNA regulation and its implication in human cancers. Sci Rep. 2017;7(1):13356. EDN: YKCIGN doi: 10.1038/s41598-017-13470-5
  22. Kozomara A, Griffiths-Jones S. MiRBase: Annotating high confidence microRNAs using deep sequencing data. Nucleic Acids Res. 2014;42:D68–73.
  23. Treiber T, Treiber N, Meister G. Regulation of microRNA biogenesis and its crosstalk with other cellular pathways: Nature reviews. Mol Cell Biol. 2019;20(1):5–20. doi: 10.1038/s41580-018-0059-1
  24. Long H, Wang X, Chen Y, et al. Dysregulation of microRNAs in autoimmune diseases: Pathogenesis, biomarkers and potential therapeutic targets. Cancer Letters. 2018;428:90–103. EDN: YGWIVF doi: 10.1016/j.canlet.2018.04.016
  25. Dai R, Ahmed SA. MicroRNA, a new paradigm for understanding immunoregulation, inflammation, and autoimmune diseases. Translational research. J Lab Clin Med. 2011;157(4):163–179. doi: 10.1016/j.trsl.2011.01.007
  26. Wang Z, Lu Q, Wang Z. Epigenetic alterations in cellular immunity: New insights into autoimmune diseases. Cell Physiol Biochem. 2017;41(2):645–660. EDN: YFIBLS doi: 10.1159/000457944
  27. Weiland M, Gao XH, Zhou L, Mi QS. Small RNAs have a large impact: Circulating microRNAs as biomarkers for human diseases. RNA Biol. 2012;9(6):850–859. doi: 10.4161/rna.20378
  28. Valentino A, Leuci S, Galderisi U, et al. Plasma exosomal microRNA profile reveals miRNA 148a-3p downregulation in the mucosal-dominant variant of pemphigus vulgaris. Int J Mol Sci. 2023;24(14):11493. EDN: FABUJS doi: 10.3390/ijms241411493
  29. Khabou B, Fakhfakh R, Tahri S, et al. MiRNA implication in the pathogenesis and the outcome of Tunisian endemic pemphigus foliaceus. Exp Dermatol. 2023;32(7):1132–1142. doi: 10.1111/exd.14821
  30. He W, Xing Y, Li C, et al. Identification of six microRNAs as potential biomarkers for pemphigus vulgaris: From diagnosis to pathogenesis. Diagnostics (Basel, Switzerland). 2022;12(12):3058. EDN: ZZLOOJ doi: 10.3390/diagnostics12123058
  31. Xu M, Liu Q, Li S, et al. Increased expression of miR-338-3p impairs Treg-mediated immunosuppression in pemphigus vulgaris by targeting RUNX1. Exp Dermatol. 2020;29(7):623–629. doi: 10.1111/exd.14111
  32. Lin N, Liu Q, Wang M, et al. Usefulness of miRNA-338-3p in the diagnosis of pemphigus and its correlation with disease severity. Peer J. 2018;6:e5388. doi: 10.7717/peerj.5388
  33. Liu Q, Cui F, Wang M, et al. Increased expression of microRNA-338-3p contributes to production of Dsg3 antibody in pemphigus vulgaris patients. Mol Med Rep. 2018;18(1):550–556. EDN: VFMILM doi: 10.3892/mmr.2018.8934
  34. Wang M, Liang L, Li L, et al. Increased miR-424-5p expression in peripheral blood mononuclear cells from patients with pemphigus. Mol Med Rep. 2017;15(6):3479–3484. doi: 10.3892/mmr.2017.6422
  35. Satyam A, Khandpur S, Sharma VK, Sharma A. Involvement of T(h)1/T(h)2 cytokines in the pathogenesis of autoimmune skin disease: Pemphigus vulgaris. Immunol Invest. 2009;38(6):498–509. doi: 10.1080/08820130902943097
  36. Lee SH, Hong WJ, Kim SC. Analysis of serum cytokine profile in pemphigus. Ann Dermatol. 2017;29(4):438–445. doi: 10.5021/ad.2017.29.4.438
  37. Rizzo C, Fotino M, Zhang Y, et al. Direct characterization of human T cells in pemphigus vulgaris reveals elevated autoantigen-specific Th2 activity in association with active disease. Clin Experimental Dermatol. 2005;30(5):535–540. doi: 10.1111/j.1365-2230.2005.01836.x
  38. Pritchard CC, Cheng HH, Tewari M. MicroRNA profiling: Approaches and considerations. Nature Rev Genetics. 2012;13(5):358–369. doi: 10.1038/nrg3198
  39. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 2001;25(4):402–408. doi: 10.1006/meth.2001.1262
  40. Buch AC, Kuma H, Panicker N, et al. A cross-sectional study of direct immunofluorescence in the diagnosis of immunobullous dermatoses. Indian J Dermatol. 2014;59(4):364–368. doi: 10.4103/0019-5154.135488
  41. Belloni-Fortina A, Faggion D, Pigozzi B, et al. Detection of autoantibodies against recombinant desmoglein 1 and 3 molecules in patients with pemphigus vulgaris: Correlation with disease extent at the time of diagnosis and during follow-up. Clin Dev Immunol. 2009;2009:187864. doi: 10.1155/2009/187864
  42. Giurdanella F, Nijenhuis AM, Diercks GF, et al. Keratinocyte binding assay identifies anti-desmosomal pemphigus antibodies where other tests are negative. Front Immunol. 2018;9:839. doi: 10.3389/fimmu.2018.00839
  43. Saleh MA, El-Bahy MM. Do normal Egyptians possess anti-desmoglein 3 antibodies? Int J Dermatol. 2015;54(10):1145–1149. doi: 10.1111/ijd.12662
  44. Xuan RR, Yang A, Murrell DF. New biochip immunofluorescence test for the serological diagnosis of pemphigus vulgaris and foliaceus: A review of the literature. Int J Women’s Dermatol. 2018;4(2):102–108. doi: 10.1016/j.ijwd.2017.10.001
  45. Yang A, Xuan R, Melbourne W, et al. Validation of the BIOCHIP test for the diagnosis of bullous pemphigoid, pemphigus vulgaris and pemphigus foliaceus. J Eur Acad Dermatol Venereol. 2020;34(1):153–160. doi: 10.1111/jdv.15770
  46. Sanz-Rubio D, Martin-Burriel I, Gil A, et al. Stability of circulating exosomal miRNAs in healthy subjects. Sci Rep. 2018;8(1):10306. EDN: VHZDCQ doi: 10.1038/s41598-018-28748-5
  47. Matias-Garcia PR, Wilson R, Mussack V, et al. Impact of long-term storage and freeze-thawing on eight circulating microRNAs in plasma samples. PLoS One. 2020;15(1):e0227648. doi: 10.1371/journal.pone.0227648
  48. Ward Gahlawat A, Lenhardt J, Witte T, et al. Evaluation of storage tubes for combined analysis of circulating nucleic acids in liquid biopsies. Int J Mol Sci. 2019;20(3):704. doi: 10.3390/ijms20030704
  49. Papara C, Zillikens D, Sadik CD, Baican A. MicroRNAs in pemphigus and pemphigoid diseases. Autoimmunity Rev. 2021;20(7):102852. EDN: BWVCMC doi: 10.1016/j.autrev.2021.102852
  50. Ramani P, Ravikumar R, Pandiar D, et al. Apoptolysis: A less understood concept in the pathogenesis of pemphigus vulgaris. Apoptosis. 2022;27(5-6):322–328. EDN: FRNMYI doi: 10.1007/s10495-022-01726-z
  51. Lee AY, Kim T, Kim JH. Understanding CD4+ T cells in autoimmune bullous diseases. Front Immunol. 2023;14():1161927. EDN: XEJLJM doi: 10.3389/fimmu.2023.1161927
  52. Araghi F, Dadkhahfar S, Robati RM, et al. The emerging role of T cells in pemphigus vulgaris: A systematic review. Clin Exp Med. 2023;23(4):1045–1054. EDN: AXVIWX doi: 10.1007/s10238-022-00855-8
  53. Rodriguez MS, Egaña I, Lopitz-Otsoa F, et al. The RING ubiquitin E3 RNF114 interacts with A20 and modulates NF-κB activity and T-cell activation. Cell Death Dis. 2014;5(8):e1399. doi: 10.1038/cddis.2014.366
  54. Yang P, Lu Y, Li M, et al. Identification of RNF114 as a novel positive regulatory protein for T cell activation. Immunobiol. 2014;219(6):432–439. EDN: SQZAYB doi: 10.1016/j.imbio.2014.02.002

Supplementary files

Supplementary Files
Action
1. JATS XML
2. Fig. 1. Mean expression level of miR-338-3p. Groups: 1 ― patients with active stage of the disease; 2 ― patients in remission; 3 ― control group of healthy volunteers.

Download (243KB)
3. Fig. 2. Correlation between miR-338-3p expression level and PDAI index score.

Download (280KB)

Copyright (c) 2024 Eco-Vector


 


Согласие на обработку персональных данных с помощью сервиса «Яндекс.Метрика»

1. Я (далее – «Пользователь» или «Субъект персональных данных»), осуществляя использование сайта https://journals.rcsi.science/ (далее – «Сайт»), подтверждая свою полную дееспособность даю согласие на обработку персональных данных с использованием средств автоматизации Оператору - федеральному государственному бюджетному учреждению «Российский центр научной информации» (РЦНИ), далее – «Оператор», расположенному по адресу: 119991, г. Москва, Ленинский просп., д.32А, со следующими условиями.

2. Категории обрабатываемых данных: файлы «cookies» (куки-файлы). Файлы «cookie» – это небольшой текстовый файл, который веб-сервер может хранить в браузере Пользователя. Данные файлы веб-сервер загружает на устройство Пользователя при посещении им Сайта. При каждом следующем посещении Пользователем Сайта «cookie» файлы отправляются на Сайт Оператора. Данные файлы позволяют Сайту распознавать устройство Пользователя. Содержимое такого файла может как относиться, так и не относиться к персональным данным, в зависимости от того, содержит ли такой файл персональные данные или содержит обезличенные технические данные.

3. Цель обработки персональных данных: анализ пользовательской активности с помощью сервиса «Яндекс.Метрика».

4. Категории субъектов персональных данных: все Пользователи Сайта, которые дали согласие на обработку файлов «cookie».

5. Способы обработки: сбор, запись, систематизация, накопление, хранение, уточнение (обновление, изменение), извлечение, использование, передача (доступ, предоставление), блокирование, удаление, уничтожение персональных данных.

6. Срок обработки и хранения: до получения от Субъекта персональных данных требования о прекращении обработки/отзыва согласия.

7. Способ отзыва: заявление об отзыве в письменном виде путём его направления на адрес электронной почты Оператора: info@rcsi.science или путем письменного обращения по юридическому адресу: 119991, г. Москва, Ленинский просп., д.32А

8. Субъект персональных данных вправе запретить своему оборудованию прием этих данных или ограничить прием этих данных. При отказе от получения таких данных или при ограничении приема данных некоторые функции Сайта могут работать некорректно. Субъект персональных данных обязуется сам настроить свое оборудование таким способом, чтобы оно обеспечивало адекватный его желаниям режим работы и уровень защиты данных файлов «cookie», Оператор не предоставляет технологических и правовых консультаций на темы подобного характера.

9. Порядок уничтожения персональных данных при достижении цели их обработки или при наступлении иных законных оснований определяется Оператором в соответствии с законодательством Российской Федерации.

10. Я согласен/согласна квалифицировать в качестве своей простой электронной подписи под настоящим Согласием и под Политикой обработки персональных данных выполнение мною следующего действия на сайте: https://journals.rcsi.science/ нажатие мною на интерфейсе с текстом: «Сайт использует сервис «Яндекс.Метрика» (который использует файлы «cookie») на элемент с текстом «Принять и продолжить».