Effectiveness of treatment of patients with systemic autoimmune diseases on the background of reactivation of persistent Epstein-Barr virus infection
DOI:
https://doi.org/10.26641/2307-0404.2021.3.241936Ключевые слова:
systemic autoimmune diseases, Epstein-Barr virus, antiviral therapyАннотация
The article presents the study of effectiveness of inosine pranobex (IP) in patients with systemic autoimmune diseases (SAD) on the background of reactivation of persistent Epstein-Barr (EBV) infection. Among 380 patients with SAD (systemic lupus erythematosus, systemic vasculitides, rheumatoid arthritis, psoriasis), in 144 patients (37.9%) the reactivation of persistent EBV infection was detected through virus DNA identification using polymerase chain reaction (PCR) in three biological matrices (blood, saliva, scraping from the lesion site). 48 patients were receiving inosine pranobex at a dose of 50 mg/kg per day for three months. Treatment efficacy was controlled by studying the levels of expression of miR-146а, miR-155, miR EBV (BART-13 and BART-15), TLR9, the quantity of lymphocytes populations and subpopulations. After treatment, PCR results showed a decrease in viral replication in 66.7% of cases. The use of IP contributed to a significant decrease in the level of IgM, IgG specific antibodies, an increase in the level of expression of anti-inflammatory miR-146a, a decrease in the level of expression of pro-inflammatory miR-155 which may signify the strengthening of antiviral control. The study data demonstrated the decrease in the expression of miR EBV (BART-13 and BART-15) and TLR9 on the immunocompetent cells that can also be attributed to the criteria for IP effectiveness. The effectiveness of IP was also proved by the stabilization of cell mechanisms, namely the tendency to normalizing T and B cell populations, decrease in the number of natural killer cells and activated cells (CD25+, CD3+ HLA DR+). On the other hand, the number of lymphocytes with suppressor activity (CD4+25+) remained significantly high mitigating autoimmune aggression. The results of the study show that the use of IP for treating the acute phase of EBV infection contributed to the decrease of repliсative activity of the virus; suppressing the aggressiveness of autoimmune reactions. The decrease in the expression of miR EBV (BART-13 and BART-15) can be recommended as a criterion for the IP effectiveness; the decrease in the expression of TLR9 on immunocompetent cells –as a criterion for suppressing autoimmune reactions.
Библиографические ссылки
Svendsen AJ, Westergaard MCW, Draborg AH, Holst R, Kyvik KO, Jakobsen MA, Junker P, Houen G. Altered Antibody Response to Epstein-Barr Virus in Patients With Rheumatoid Arthritis and Healthy Subjects Predisposed to the Disease. A Twin Study. Front Immunol. 2021;12:650-713. doi: https://doi.org/10.3389/fimmu.2021.650713
Chougule D, Nadkar M, Rajadhyaksha A, Pandit-Shende P, Surve P, Dawkar N, Khadilkar P, Patward¬han M, Kaveri S, Ghosh K, Pradhan V. Association of clinical and serological parameters of systemic lupus erythematosus patients with Epstein-Barr virus antibody profile. J Med Virol. 2018;90(3):559-563. doi: https://doi.org/10.1002/jmv.24904
Cohen JI. Herpesviruses in the Activated Phosphatidylinositol-3-Kinase-δ Syndrome. Front. Immunol. 2018;9:237. doi: https://doi.org/10.3389/fimmu.2018.00237
Draborg AH, Trier NH, Sternbæk L, Troelsen L, Larsen JL, Jacobsen S, Houen G. EBNA1 IgM-Based Discrimination Between Rheumatoid Arthritis Patients, Systemic Lupus Erythematosus Patients and Healthy Controls. Antibodies. 2019;8(2):35. doi: https://doi.org/10.3390/antib8020035
Coleman CB, Wohlford EM, Smith NA, King CA, Ritchie JA, Baresel PC, et al. Epstein-Barr virus type 2 latently infects T cells, inducing an atypical activation characterized by expression of lymphocytic cytokines. J Virol. 2015;89(4):2301-12. doi: https://doi.org/10.1128/JVI.03001-14
Faraldi M, Gomarasca M, Banfi G, Lombardi G. Free Circulating miRNAs Measurement in Clinical Settings: The Still Unsolved Issue of the Normalization. Adv Clin Chem. 2018;87:113-39. doi: https://doi.org/10.1016/bs.acc.2018.07.003
Ikeda T, Gion Y, Yoshino T, Sato Y. A review of EBV-positive mucocutaneous ulcers focusing on clinical and pathological aspects. J Clin Exp Hematop. 2019;59(2):64-71. doi: https://doi.org/10.3960/jslrt.18039
Zhang X, Ye Y, Fu M, Zheng B, Qiu Q, Huang Z. Implication of viral microRNAs in the genesis and diag¬nosis of Epstein Barr virus associated tumors (Review). Oncol Lett. 2019;18:3433-3442. doi: https://doi.org/10.3892/ol.2019.10713
Kaur P, Stoltzfus J, Yellapu V. Descriptive statistics. Int J Acad Med 2018;4:60-3. doi: https://doi.org/10.4103/IJAM.IJAM_7_18
Zubchenko S, Potemkina G, Chopyak V, Lishchuk-Yakymovych K. Correlation between miR-146a and miR-155 levels and concentration of cytokines in patients with allergopathy in chronic persistence of Epstein-Barr virus infection. Journal of Education, Health and Sport. 2019;9(10):230-245. doi: https://doi.org/10.5281/zenodo.3520935
Friedrich SK, Lang PA, Friebus-Kardash J, Duhan V, Bezgovsek J, Lang KS. Mechanisms of lymphatic system-specific viral replication and its potential role in autoimmune disease. Clin Exp Immunol. 2019;195(1):64-73. doi: https://doi.org/10.1111/cei.13241
Pender MP. Hypothesis: bipolar disorder is an Epstein–Barr virus‐driven chronic autoimmune disease – implications for immunotherapy. Clin Transl Immunol; 2020;9:e1116. doi: https://doi.org/10.1002/cti2.1116
Lyadova T, Ognivenko O, Rzhevska O, Zago¬rod¬neva O, Volobueva O. Prevalence of polymorphism of the TLR 9 type gene in patients with chronic forms of Eps¬tein-Barr virus infection. Georgian Med News. 2018;(276):112-117. doi: https://doi.org/10.26565/2313-6693-2018-35-06
Ball RJ, Avenell A, Aucott L, Hanlon P, Vickers MA. Systematic review and meta-analysis of the sero-epidemiological association between Epstein-Barr virus and rheumatoid arthritis. Arthritis Res Ther. 2015;17:274. doi: https://doi.org/10.1186/s13075-015-0755-6
Zhang SX, Ma XW, Li YF, Lai NL, Huang ZH, Fan K, Wang CH, Li XF. The Proportion of Regulatory T Cells in Patients with Systemic Lupus Erythematosus: A Meta-Analysis. J Immunol Res. 2018;2018:7103219. doi: https://doi.org/10.1155/2018/7103219
Sepulveda-Toepfer JA, Pichler J, Fink K, Sevo M, Wildburger S, Mudde-Boer LC, Taus C, Mudde GC. TLR9-mediated activation of dendritic cells by CD32 targeting for the generation of highly immunostimulatory vaccines. Human Vaccines & Immunotherapeutics. 2019;15:1: 179-188. doi: https://doi.org/10.1080/21645515.2018.1514223
Yukawa M, Barski A, Salomonis N, Kaufman KM, Kottyan LC, Weirauch MT. Transcription factors operate across disease loci, with EBNA2 implicated in autoimmunity. Nat Genet. 2018 May;50(5):699-707. doi: https://doi.org/10.1038/s41588-018-0102-3
Загрузки
Опубликован
Как цитировать
Выпуск
Раздел
Лицензия
Copyright (c) 2021 Medicni perspektivi (Medical perspectives)
Это произведение доступно по лицензии Creative Commons «Attribution» («Атрибуция») 4.0 Всемирная.
Submitting manuscript to the journal "Medicni perspektivi" the author(s) agree with transferring copyright from the author(s) to publisher (including photos, figures, tables, etc.) editor, reproducing materials of the manuscript in the journal, Internet, translation into other languages, export and import of the issue with the author’s article, spreading without limitation of their period of validity both on the territory of Ukraine and other countries. This and other mutual duties of the author and all co-authors separately and editorial board are secured by written agreement by special form to use the article, the sample of which is presented on the site.
Author signs a written agreement and sends it to Editorial Board simultaneously with submission of the manuscript.