RITUXIMAB THERAPY MONITORING IN PATIENTS WITH RHEUMATOID ARTHRITIS HROUGH PERIPHERAL BLOOD GENE EXPRESSION ANALYSIS

Objective: to determine the predictors of the efficiency of rituximab (RTM) therapy through analysis of blood gene expressions in patients with rheumatoid arthritis (RA). Subjects and methods. Sixteen patients (mean age 53.4±10.8 years) with RA (mean duration 8.2±7.1 years) who had previ- ously rece...

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Main Authors: E. V. Chetina, A. V. Pivanova, K. Kh. Kuzikyants, A. Yu. Devyataikina, G. V. Lukina, E. Yu. Samarkina, A. P. Aleksankin, E. N. Aleksandrova
Format: Article
Language:Russian
Published: IMA PRESS LLC 2014-06-01
Series:Научно-практическая ревматология
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Online Access:https://rsp.mediar-press.net/rsp/article/view/1937
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author E. V. Chetina
A. V. Pivanova
K. Kh. Kuzikyants
A. Yu. Devyataikina
G. V. Lukina
E. Yu. Samarkina
A. P. Aleksankin
E. N. Aleksandrova
author_facet E. V. Chetina
A. V. Pivanova
K. Kh. Kuzikyants
A. Yu. Devyataikina
G. V. Lukina
E. Yu. Samarkina
A. P. Aleksankin
E. N. Aleksandrova
author_sort E. V. Chetina
collection DOAJ
description Objective: to determine the predictors of the efficiency of rituximab (RTM) therapy through analysis of blood gene expressions in patients with rheumatoid arthritis (RA). Subjects and methods. Sixteen patients (mean age 53.4±10.8 years) with RA (mean duration 8.2±7.1 years) who had previ- ously received disease-modifying antirheumatic drugs and tumor necrosis factor-α (TNF-α) inhibitors without effects were examined. Each patient underwent a treatment cycle with RTM in a dose of 0.5-1 g. A control group included 26 healthy individuals. Clinical response was assessed with DAS28. Erythrocyte sedimentation rate (ESR), serum levels of anti-cyclic citrullinated peptide antibodies, C-reactive protein (CRP), and rheumatoid factor (RF) were estimated. Bone erosions and joint space narrowing were evaluated radiologically. RNA was isolated from blood and used to estimate the expression of the mTOR, ULK1, caspase 3, p21, TNF-α, cathepsin K, matrix metalloproteinase-9 (MMP-9), interleukin-1β (IL-1β), inter- feron-γ (IFN-γ), and cyclooxygenase-2 (COX-2) genes by real-time reverse transcriptase polymerase chain reaction. Results. At the beginning of the investigation, the expression of all the genes under study was increased (p < 0.05) in the patients with RA versus the healthy individuals. RTM therapy resulted in reductions in DAS28, ESR, CRP levels, and CD10+ B lymphocyte depletion (p < 0.05). There were no changes in the number of erosions and the width of the joint space during RTM therapy. The blood expression of the mTOR, p21, caspase 3, ULK1, TNF-α, IL-1β, and cathepsin K genes was suppressed to that of healthy individuals. As compared to the beginning of the investigation, the expression of MMP-9 was also reduced (p < 0.05); however, it remained far higher than that in the controls and no drastic changes occurred in the expression of the IFN-р and COX-2 genes. Conclusion. Blood gene expression analysis may serve as a source of information on the status of patients with RA dur- ing RTM therapy. The higher residual expression of MMP-9, IFN-γ, and COX-2 may be a reason for the preserved activity of RA and its exacerbation.
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spelling doaj-art-e5d29ff063014f69b6366ecd1eb25e482025-08-20T03:21:47ZrusIMA PRESS LLCНаучно-практическая ревматология1995-44841995-44922014-06-0152326326910.14412/1995-4484-2014-263-2691872RITUXIMAB THERAPY MONITORING IN PATIENTS WITH RHEUMATOID ARTHRITIS HROUGH PERIPHERAL BLOOD GENE EXPRESSION ANALYSISE. V. Chetina0A. V. Pivanova1K. Kh. Kuzikyants2A. Yu. Devyataikina3G. V. Lukina4E. Yu. Samarkina5A. P. Aleksankin6E. N. Aleksandrova7Nasonova Research Institute of Rheumatology, Moscow, RussiaNasonova Research Institute of Rheumatology, Moscow, RussiaФГБУ «Научно- исследовательский институт ревматологии им. В.А. Насоновой» РАН, Москва, РоссияNasonova Research Institute of Rheumatology, Moscow, RussiaNasonova Research Institute of Rheumatology, Moscow, RussiaNasonova Research Institute of Rheumatology, Moscow, RussiaNasonova Research Institute of Rheumatology, Moscow, RussiaNasonova Research Institute of Rheumatology, Moscow, RussiaObjective: to determine the predictors of the efficiency of rituximab (RTM) therapy through analysis of blood gene expressions in patients with rheumatoid arthritis (RA). Subjects and methods. Sixteen patients (mean age 53.4±10.8 years) with RA (mean duration 8.2±7.1 years) who had previ- ously received disease-modifying antirheumatic drugs and tumor necrosis factor-α (TNF-α) inhibitors without effects were examined. Each patient underwent a treatment cycle with RTM in a dose of 0.5-1 g. A control group included 26 healthy individuals. Clinical response was assessed with DAS28. Erythrocyte sedimentation rate (ESR), serum levels of anti-cyclic citrullinated peptide antibodies, C-reactive protein (CRP), and rheumatoid factor (RF) were estimated. Bone erosions and joint space narrowing were evaluated radiologically. RNA was isolated from blood and used to estimate the expression of the mTOR, ULK1, caspase 3, p21, TNF-α, cathepsin K, matrix metalloproteinase-9 (MMP-9), interleukin-1β (IL-1β), inter- feron-γ (IFN-γ), and cyclooxygenase-2 (COX-2) genes by real-time reverse transcriptase polymerase chain reaction. Results. At the beginning of the investigation, the expression of all the genes under study was increased (p < 0.05) in the patients with RA versus the healthy individuals. RTM therapy resulted in reductions in DAS28, ESR, CRP levels, and CD10+ B lymphocyte depletion (p < 0.05). There were no changes in the number of erosions and the width of the joint space during RTM therapy. The blood expression of the mTOR, p21, caspase 3, ULK1, TNF-α, IL-1β, and cathepsin K genes was suppressed to that of healthy individuals. As compared to the beginning of the investigation, the expression of MMP-9 was also reduced (p < 0.05); however, it remained far higher than that in the controls and no drastic changes occurred in the expression of the IFN-р and COX-2 genes. Conclusion. Blood gene expression analysis may serve as a source of information on the status of patients with RA dur- ing RTM therapy. The higher residual expression of MMP-9, IFN-γ, and COX-2 may be a reason for the preserved activity of RA and its exacerbation.https://rsp.mediar-press.net/rsp/article/view/1937rheumatoid arthritisgene expressionperipheral bloodinflammationjoint lesionrituximab.
spellingShingle E. V. Chetina
A. V. Pivanova
K. Kh. Kuzikyants
A. Yu. Devyataikina
G. V. Lukina
E. Yu. Samarkina
A. P. Aleksankin
E. N. Aleksandrova
RITUXIMAB THERAPY MONITORING IN PATIENTS WITH RHEUMATOID ARTHRITIS HROUGH PERIPHERAL BLOOD GENE EXPRESSION ANALYSIS
Научно-практическая ревматология
rheumatoid arthritis
gene expression
peripheral blood
inflammation
joint lesion
rituximab.
title RITUXIMAB THERAPY MONITORING IN PATIENTS WITH RHEUMATOID ARTHRITIS HROUGH PERIPHERAL BLOOD GENE EXPRESSION ANALYSIS
title_full RITUXIMAB THERAPY MONITORING IN PATIENTS WITH RHEUMATOID ARTHRITIS HROUGH PERIPHERAL BLOOD GENE EXPRESSION ANALYSIS
title_fullStr RITUXIMAB THERAPY MONITORING IN PATIENTS WITH RHEUMATOID ARTHRITIS HROUGH PERIPHERAL BLOOD GENE EXPRESSION ANALYSIS
title_full_unstemmed RITUXIMAB THERAPY MONITORING IN PATIENTS WITH RHEUMATOID ARTHRITIS HROUGH PERIPHERAL BLOOD GENE EXPRESSION ANALYSIS
title_short RITUXIMAB THERAPY MONITORING IN PATIENTS WITH RHEUMATOID ARTHRITIS HROUGH PERIPHERAL BLOOD GENE EXPRESSION ANALYSIS
title_sort rituximab therapy monitoring in patients with rheumatoid arthritis hrough peripheral blood gene expression analysis
topic rheumatoid arthritis
gene expression
peripheral blood
inflammation
joint lesion
rituximab.
url https://rsp.mediar-press.net/rsp/article/view/1937
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