DNA double-strand breaks in immunoinflammatory rheumatic diseases

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. The analysis included 40...

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Main Authors: A. S. Avdeeva, A. P. Aleksankin, Zh. G. Verizhnikova, V. V. Rybakova, M. E. Diatroptov, Yu. N. Gorbunova, A. A. Mesnyankina, D. A. Paranich, A. M. Lila, E. L. Nasonov
Format: Article
Language:Russian
Published: IMA-PRESS LLC 2023-08-01
Series:Современная ревматология
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Online Access:https://mrj.ima-press.net/mrj/article/view/1451
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author A. S. Avdeeva
A. P. Aleksankin
Zh. G. Verizhnikova
V. V. Rybakova
M. E. Diatroptov
Yu. N. Gorbunova
A. A. Mesnyankina
D. A. Paranich
A. M. Lila
E. L. Nasonov
author_facet A. S. Avdeeva
A. P. Aleksankin
Zh. G. Verizhnikova
V. V. Rybakova
M. E. Diatroptov
Yu. N. Gorbunova
A. A. Mesnyankina
D. A. Paranich
A. M. Lila
E. L. Nasonov
author_sort A. S. Avdeeva
collection DOAJ
description 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. 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. 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. 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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spelling doaj-art-bbc5ebb2f0504a76a9c547ed2dc38b832025-08-20T03:59:54ZrusIMA-PRESS LLCСовременная ревматология1996-70122310-158X2023-08-01174131810.14412/1996-7012-2023-4-13-182598DNA double-strand breaks in immunoinflammatory rheumatic diseasesA. S. Avdeeva0A. P. Aleksankin1Zh. G. Verizhnikova2V. V. Rybakova3M. E. Diatroptov4Yu. N. Gorbunova5A. A. Mesnyankina6D. A. Paranich7A. M. Lila8E. L. Nasonov9V.A. Nasonova Research Institute of RheumatologyV.A. Nasonova Research Institute of RheumatologyV.A. Nasonova Research Institute of RheumatologyV.A. Nasonova Research Institute of RheumatologyV.A. Nasonova Research Institute of RheumatologyV.A. Nasonova Research Institute of RheumatologyV.A. Nasonova Research Institute of RheumatologyV.A. Nasonova Research Institute of RheumatologyV.A. Nasonova Research Institute of Rheumatology; Russian Medical Academy of Continuing Professional Education, Ministry of Health of RussiaV.A. Nasonova Research Institute of Rheumatology; I.M. Sechenov First Moscow State Medical University, Ministry of Health of Russia (Sechenov University)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. 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. 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. 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.https://mrj.ima-press.net/mrj/article/view/1451immunoinflammatory rheumatic diseasesdna double strand breaksphosphorylation of histone h2axp53 binding protein i
spellingShingle A. S. Avdeeva
A. P. Aleksankin
Zh. G. Verizhnikova
V. V. Rybakova
M. E. Diatroptov
Yu. N. Gorbunova
A. A. Mesnyankina
D. A. Paranich
A. M. Lila
E. L. Nasonov
DNA double-strand breaks in immunoinflammatory rheumatic diseases
Современная ревматология
immunoinflammatory rheumatic diseases
dna double strand breaks
phosphorylation of histone h2ax
p53 binding protein i
title DNA double-strand breaks in immunoinflammatory rheumatic diseases
title_full DNA double-strand breaks in immunoinflammatory rheumatic diseases
title_fullStr DNA double-strand breaks in immunoinflammatory rheumatic diseases
title_full_unstemmed DNA double-strand breaks in immunoinflammatory rheumatic diseases
title_short DNA double-strand breaks in immunoinflammatory rheumatic diseases
title_sort dna double strand breaks in immunoinflammatory rheumatic diseases
topic immunoinflammatory rheumatic diseases
dna double strand breaks
phosphorylation of histone h2ax
p53 binding protein i
url https://mrj.ima-press.net/mrj/article/view/1451
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