References

rsp

Научно-практическая ревматология

Rheumatology Science and Practice

1995-44841995-4492

IMA-PRESS, LLC

10.14412/1995-4484-2014-263-269

rsp-1937

Research Article

ОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯ

ORIGINAL RESEARCH

Мониторинг терапии ритуксимабом больных ревматоидным артритом посредством анализа экспрессии генов в периферической крови

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

Четина

Е. В.

Chetina

E. V.

etchetina@mail.ru

Пиванова

А. В.

Pivanova

A. V.

Кузикянц

К. Х.

Kuzikyants

K. Kh.

Девятайкина

А. Ю.

Devyataikina

A. Yu.

Лукина

Г. В.

Lukina

G. V.

Самаркина

Е. Ю.

Samarkina

E. Yu.

Алексанкин

А. П.

Aleksankin

A. P.

Александрова

Е. Н.

Aleksandrova

E. N.

ФГБУ «Научно- исследовательский институт ревматологии им. В.А. Насоновой» РАН, Москва, РоссияРоссияNasonova Research Institute of Rheumatology, Moscow, RussiaRussian Federation

ФГБУ «Научно- исследовательский институт ревматологии им. В.А. Насоновой» РАН, Москва, РоссияRussian Federation

2014

20062014

523

№3 (2014)

263269

2014

Четина Е.В., Пиванова А.В., Кузикянц К.Х., Девятайкина А.Ю., Лукина Г.В., Самаркина Е.Ю., Алексанкин А.П., Александрова Е.Н.

Chetina E.V., Pivanova A.V., Kuzikyants K.K., Devyataikina A.Y., Lukina G.V., Samarkina E.Y., Aleksankin A.P., Aleksandrova E.N.

Данная работа распространяется под лицензией Creative Commons Attribution 4.0.

This work is licensed under a Creative Commons Attribution 4.0 License.

https://rsp.mediar-press.net/rsp/article/view/1937

Цель – посредством анализа экспрессии генов в крови больных ревматоидным артритом (РА) определить предикторы эффективности терапии ритуксимабом (РТМ). Материал и методы. Обследованы 16 больных РА (средний возраст 53,4±10,8 года, средняя длительность за- болевания 8,2±7,1 года), получавших ранее без эффекта базисные противовоспалительные препраты и инги- биторы фактора некроза опухоли α (ФНОα). Каждому пациенту проводился один курс лечения РТМ в дозе 0,5–1 г. В контрольную группу вошли 26 здоровых лиц. Клинический ответ оценивали по индексу активно- сти заболевания DAS28, определяли также скорость оседания эритроцитов (СОЭ), сывороточные уровни ан- тител к циклическому цитруллинированному пептиду, С-реактивного белка (СРБ) и ревматоидного факто- ра. Эрозии костей и сужение суставных щелей оценивали рентгенологически. Общую РНК выделяли из кро- ви и использовали для оценки экспрессии генов mTOR, ULK1, каспазы 3, p21, ФНОα, катепсина К, металло- протеиназы (ММП) 9, интерлейкина (ИЛ) 1β, интерферона (ИФН) γ и циклооксигеназы (ЦОГ) 2 посредством обратно-транскриптазной полимеразной цепной реакции в режиме реального времени. Результаты. Экспрессия всех исследованных генов была повышена (p<0,05) у больных РА по сравнению со здоровыми лицами в начале исследования. Терапия РТМ приводила к снижению (p<0,05) DAS28, СОЭ, уровня СРБ и деплеции CD19+ В-лимфоцитов. На фоне лечения РТМ не изменялись число эрозий и вели- чина суставной щели. Отмечалось подавление экспрессии генов mTOR, p21, каспазы 3, ULK1, ФНОα, ИЛ1β и катепсина K в крови до уровня здоровых лиц. Экспрессия ММП9 также снижалась (p<0,05) по сравнению с началом исследования, однако оставалась значительно выше, чем в контроле, а значительных изменений в экспрессии ИФНγ и ЦОГ2 не происходило. Заключение. Анализ экспрессии генов в крови может служить источником информации о состоянии боль- ных РА в ходе терапии РТМ. Остаточная повышенная экспрессия ММП9, ИФНγ и ЦОГ2 после терапии мо- жет быть причиной сохранения активности РА и повторного обострения заболевания.

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.

ревматоидный артритэкспрессия геновпериферическая кровьвоспалениепоражение суставовритуксимаб.

rheumatoid arthritisgene expressionperipheral bloodinflammationjoint lesionrituximab.

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