mrjСовременная ревматологияModern Rheumatology Journal1996-70122310-158XIMA-PRESS, LLC10.14412/1996-7012-2023-4-13-18mrj-1451Research ArticleОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯORIGINAL INVESTIGATIONSДвунитевые разрывы ДНК при иммуновоспалительных ревматических заболеванияхDNA double-strand breaks in immunoinflammatory rheumatic diseaseshttps://orcid.org/0000-0003-3057-9175АвдееваА. С.AvdeevaA. S.

Авдеева Анастасия Сергеевна.

115522, Москва, Каширское шоссе, 34А

Anastasia S. Avdeeva.

34A, Kashirskoe Shosse, Moscow 115522

9056249400@mail.ruhttps://orcid.org/0000-0001-6686-0896АлексанкинА. П.AleksankinA. P.

115522, Москва, Каширское шоссе, 34А

34A, Kashirskoe Shosse, Moscow 115522

https://orcid.org/0000-0002-4829-5210ВерижниковаЖ. Г.VerizhnikovaZh. G.

115522, Москва, Каширское шоссе, 34А

34A, Kashirskoe Shosse, Moscow 115522

https://orcid.org/0000-0003-1404-4963РыбаковаВ. В.RybakovaV. V.

115522, Москва, Каширское шоссе, 34А

34A, Kashirskoe Shosse, Moscow 115522

https://orcid.org/0000-0001-6404-0042ДиатроптовМ. Е.DiatroptovM. E.

115522, Москва, Каширское шоссе, 34А

34A, Kashirskoe Shosse, Moscow 115522

https://orcid.org/0000-0002-2024-6927ГорбуноваЮ. Н.GorbunovaYu. N.

115522, Москва, Каширское шоссе, 34А

34A, Kashirskoe Shosse, Moscow 115522

https://orcid.org/0000-0001-5411-7317МеснянкинаА. А.MesnyankinaA. A.

115522, Москва, Каширское шоссе, 34А

34A, Kashirskoe Shosse, Moscow 115522

https://orcid.org/0009-0004-3338-8256ПараничД. А.ParanichD. A.

115522, Москва, Каширское шоссе, 34А

34A, Kashirskoe Shosse, Moscow 115522

https://orcid.org/0000-0002-6068-3080ЛилаА. М.LilaA. M.

Кафедра ревматологии ФГБОУ ДПО «РМАНПО» Минздрава России.

115522, Москва, Каширское шоссе, 34А; 125993, Москва, ул. Баррикадная, 2/1, стр.1

Department of Rheumatology Russian Medical Academy of Continuing Professional Education, Ministry of Health of Russia.

34A, Kashirskoe Shosse, Moscow 115522; 2/1, Barrikadnaya Street, Build. 1, Moscow 125993

https://orcid.org/0000-0002-1598-8360НасоновЕ. Л.NasonovE. L.

115522, Москва, Каширское шоссе, 34А; 119991, Москва, ул. Трубецкая, 8, стр. 2

34A, Kashirskoe Shosse, Moscow 115522; 8, Trubetskaya Street, Build. 2, Moscow 119991

ФГБНУ «Научно-исследовательский институт ревматологии им. В.А. Насоновой»РоссияV.A. Nasonova Research Institute of RheumatologyRussian FederationФГБНУ «Научно-исследовательский институт ревматологии им. В.А. Насоновой»; ФГБОУ ДПО «Российская медицинская академия непрерывного профессионального образования» Минздрава России,РоссияV.A. Nasonova Research Institute of Rheumatology; Russian Medical Academy of Continuing Professional Education, Ministry of Health of RussiaRussian FederationФГБНУ «Научно-исследовательский институт ревматологии им. В.А. Насоновой»; ФГАОУ ВО «Первый Московский государственный медицинский университет им. И.М. Сеченова» Минздрава России (Сеченовский университет)РоссияV.A. Nasonova Research Institute of Rheumatology; I.M. Sechenov First Moscow State Medical University, Ministry of Health of Russia (Sechenov University)Russian Federation2023200820231741318Copyright © Авдеева А.С., Алексанкин А.П., Верижникова Ж.Г., Рыбакова В.В., Диатроптов М.Е., Горбунова Ю.Н., Меснянкина А.А., Паранич Д.А., Лила А.М., Насонов Е.Л., 20232023Авдеева А.С., Алексанкин А.П., Верижникова Ж.Г., Рыбакова В.В., Диатроптов М.Е., Горбунова Ю.Н., Меснянкина А.А., Паранич Д.А., Лила А.М., Насонов Е.Л.Avdeeva A.S., Aleksankin A.P., Verizhnikova Z.G., Rybakova V.V., Diatroptov M.E., Gorbunova Y.N., Mesnyankina A.A., Paranich D.A., Lila A.M., Nasonov E.L.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://mrj.ima-press.net/mrj/article/view/1451

Цель исследования — изучить у пациентов с иммуновоспалительными ревматическими заболеваниями (ИВРЗ) частоту спонтанных фокусов двунитевых разрывов (ДР) ДНК, их взаимосвязь с активностью заболевания, уровнем маркеров воспаления и содержанием аутоантител.

Материал и методы

Материал и методы. В анализ включено 40 пациентов с ИВРЗ, среди которых было 19 больных ревматоидным артритом (РА, в том числе 16 женщин, медиана длительности заболевания — 60 [20; 103] мес, DAS28 — 5,05 [4,06; 5,9]) и 21 больной системной красной волчанкой (СКВ, 19 женщин, медиана длительности заболевания — 96,0 [40,0; 158,0] мес, SLEDAI-2K — 8,0 [4,0; 12,0]). Контрольную группу составили 17 здоровых доноров, сопоставимых с больными по полу и возрасту.

ДР ДНК определялись как дискретные фокусы при иммунофлюоресцентном окрашивании культуры лимфоцитов антителами к γH2AXи 53BP1 с последующим анализом на автоматизированной платформе AKLIDES (Medipan).

Результаты и обсуждение

Результаты и обсуждение. Значимых различий числа спонтанных ДР ДНК у пациентов с РА и здоровых доноров не наблюдалось (p>0,05), у пациентов с СКВ выявлены меньшее число клеток с фокусом 53BP1 и меньший процент поврежденных клеток по данному фокусу, чем в контроле. Наблюдалась позитивная корреляция числа поврежденных по γH2AX клеток с CDAI (r=0,45, p=0,035), числа клеток с разрывами по 53BP1 с уровнем IgM ревматоидного фактора (r=0,63, p=0,005) и СОЭ (r=0,53, p=0,02). В группе пациентов с СКВ была позитивная корреляция числа клеток с разрывами по фокусу γH2AX с уровнем антител к двуспиральной ДНК (анти-дсДНК; r=0,56, p=0,007), среднего числа разрывов в клетке по фокусу γH2AXс уровнем анти-дсДНК (r=0,57, p=0,004).

Заключение

Заключение. Число ДР ДНК может быть дополнительным показателем активности ИВРЗ. У пациентов с СКВ, видимо, имеет место нарушение процессов репарации ДНК, ассоциирующееся с высокой активностью заболевания.

Objective

Objective: To study the frequency of spontaneous foci of DNA double-strand breaks (DSBs) in patients with immune-inflammatory rheumatic diseases (IIRD), their relationship to disease activity, levels of inflammatory markers, and levels of autoantibodies.

Material and methods

Material and methods. The analysis included 40 patients with IIRD, including 19 patients with rheumatoid arthritis (RA, including 16 women, median disease duration 60 [20; 103] months, DAS28 was 5.05 [4.06; 5.9]) and 21 patients with systemic lupus erythematosus (SLE, 19 women, median disease duration 96.0 [40.0; 158.0] months, SLEDAI-2K 8.0 [4.0; 12.0]). The control group consisted of 17 healthy donors matched for sex and age.

DNA DSBs were identified as discrete foci by immunofluorescence staining of lymphocyte cultures with antibodies against γH2AX and 53BP1 and subsequently analysed using the automated AKLIDES automated platform (Medipan).

Results and discussion

Results and discussion. There were no significant differences in the number of spontaneous DNA DSBs in patients with RA and healthy donors (p>0.05), a lower number of cells with the 53BP1 focus and a lower percentage of cells damaged in this focus were found in patients with SLE than in controls. There was a positive correlation between the number of γH2AXdamaged cells and CDAI(r=0.45, p=0.035), the number of cells with 53BP1 ruptures and the level of rheumatoid factor IgM (r=0.63, p=0.005) and ESR (r=0.53, p=0.02). In the group of SLE patients, a positive correlation was observed between the number of cells with breaks in the γH2AX focus and the level of antibodies against double-stranded DNA (anti-dsDNA; r=0.56, p=0.007), the average number of breaks in the cell in the γH2AX focus with the level of anti-dsDNA (r=0.57, p=0.004).

Conclusion

Conclusion. The number of DNA DSBs may be an additional indicator of IIRD activity. In patients with SLE, DNA repair processes appear to be impaired, which is associated with the high activity of the disease.

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The authors declare that there are no conflicts of interest present.