Апоптоз как фактор организации аутоиммунного воспаления при ревматоидном артрите

The paper summarizes the data available in the literature and those from the authors' studies on the molecular and cellular mechanisms of apoptosis and their state in rheumatoid arthritis (RA). Impaired apoptotic processes in RA are one of the causes of synovial cell hyperactivation that leads to the increased inflammatory process, synovial hyperplasia, and progression of the disease as a whole. The most important feature of a cellular continuum in the affected synovial fluid is the coexistence of just two mechanisms that control apoptosis: 1) a traditional activation mechanism leading to progressive joint inflammation and destruction and 2) an inhibitory mechanism implemented through the expression of proapoptotic molecules. The apoptotic factors are a useful tool for assessing the prognosis of RA and a promising target for pharmacotherapy.В статье суммированы данные литературы и собственных исследований авторов о молекулярно-клеточных механизмах апоптоза и их состоянии при ревматоидном артрите (РА). Нарушения процессов апоптоза при РА являются одной из причин гиперактивации синовиальных клеток, ведущей к усилению воспалительного процесса, гиперплазии синовиальной оболочки и прогрессированию заболевания в целом. Важнейшая особенность клеточного континуума пораженной синовии — сосуществование сразу двух механизмов контроля апоптоза: традиционного активационного, приводящего к прогрессированию воспаления и деструкции сустава, и ингибиторного, реализуемого через экспрессию проапоптотических молекул. Факторы апоптоза являются полезным инструментом для оценки прогноза РА и перспективной мишенью для фармакотерапии

ON THE TERMINOLOGY OF SPONDYLOARTHRITIS

By the end of the first decade of the 21st century, spondyloarthritis studies have accumulated a certain number of terms that are obsolete, but used by physicians in their everyday speech, on the one hand, and a great variety of different definitions, on the other hand. In January 2014, the first organizational meeting of the Expert Group on Spondyloarthritis, Association of Rheumatologists of Russia, decided that its primary task should be to order the terminology used in this area. The authors primarily collected the terms, which had been already used in medical vocabulary, and then divided them into two categories: obsolete definitions and terms to be finalized and unified. This publication gives guidelines for using the medical terms relevant to spondyloarthritis and separately discusses how to correctly write the term sacroiliitis

Ревматоидный артрит в реальной клинической практике. Результаты проекта «Компьютерные терминалы самооценки для пациентов с ревматическими заболеваниями» («ТЕРМИНАЛ-I»)

Objective: to describe the portrait of a patient with rheumatoid arthritis (RA) in real clinical practice, to assess disease activity from the point of view of a physician and a patient, functional status, quality of life (QOL), and the efficiency of the therapy performed.Patients and methods. The investigation enrolled 976 RA patients from a cohort of patients in the TERMINAL-I multicenter study, who, when visiting a rheumatologist, independently assessed the disease activity and QOL using a computer system (the «Computer Terminals of SelfAssessment for Patients with Rheumatic Diseases» project). The mean age of the patients was 52.30±13.3 years; women accounted for 85%; the median disease duration 8.0 [4.0; 14.0] years. Baseline clinical parameters and pharmacotherapy were evaluated for 6 months. The disease activity was determined by the DAS28 and RAPID-3 indices; functional status and quality of life were evaluated by the HAQ and the EQ-5D, respectively.Results. 83% of the RA patients were positive for rheumatoid factor and 60% were for anti-cyclic citrullinated peptide antibodies. There was a preponderance of patients with high (40.5%) and moderate (46.8%) RA activity; 6.9% were observed to have a low activity; 5.8% had clinical remission. The mean values of DAS28 and RAPID-3 were 4.7±1.3 and 13.7±3.6, respectively. Only 14.3% of patients had a good functional status that was comparable with the population-based control (HAQ≤0.5). The remaining patients were found to have a substantial decrease in joint functional parameters (median HAQ 1.88 [1.0; 2.5]) and EQ-5D QOL (0.60 [0.60; 0.74). Prosthetic joints were present in 7.4% of patients. At visit 1 to a rheumatologist, the therapy was changed in 15% of patients. During 6-month follow-up, conventional disease-modifying anti-rheumatic drugs were taken by almost all (91.2%) patients. Of them, 70.9% of the patients were treated with methotrexate (MTX): 77.0% received the latter at a dose of 15 mg/week and 23.0% had it at a dose of >15 mg (17.5 to 40 mg/week). Glucocorticoids could be stopped in 20.5% of the patients within six months. Tumor necrosis factor-α inhibitors and anti-B-cell therapy were used in 6.6 and 16.2% of patients, respectively. At 6-month follow-up (Visit 2), 54% of patients achieved a 20% clinical improvement in the ACR criteria. At the same time, the DAS28 scores decreased substantially from 4.5±1.2 to 3.8±1.1 (p = 0.0001). There was a minimal functional improvement in the HAQ index in 64% of patients and a better EQ-D QOL scores in 16%.Conclusion. The majority of RA patients who came to the rheumatologists showed high to moderate disease activity. This was due to long disease duration, inadequate MTX dose, and insufficient patient monitoring in real clinical practice. Introduction of a computer system for selfassessment of their health status by RA patients in an outpatient setting could improve the interaction of physicians, nurses, and patients, better monitor disease activity, and enhance therapeutic efficiency. Цель исследования – описание «портрета» пациента с ревматоидным артритом (РА) в реальной клинической практике, оценка активности заболевания с точки зрения врача и пациента, функционального состояния, качества жизни (КЖ) и эффективности проводимой терапии.Пациенты и методы. В исследование включено 976 пациентов с РА из когорты больных, входящих в многоцентровое исследование «ТЕРМИНАЛ-I», которые при обращении к ревматологу самостоятельно оценивали активность заболевания и КЖ с помощью компьютерной системы (проект «Компьютерные терминалы самооценки для пациентов с ревматическими заболеваниями»). Средний возраст пациентов составил 52,30±13,3 года, 85% – женщины, медиана длительности заболевания – 8,0 [4,0; 14,0] лет. Проводилась оценка базовых клинических параметров и фармакотерапии в течение 6 мес. Активность заболевания определялась по индексам DAS28 и RAPID-3, функциональный статус – по индексу HAQ, качество жизни – по EQ-5D.Результаты. 83% больных РА были позитивными по ревматоидному фактору и 60% – по антителам к циклическому цитруллинированному пептиду. Преобладали пациенты с высокой (40,5%) и умеренной (46,8%) активностью РА, у 6,9% отмечалась низкая активность, у 5,8% –клиническая ремиссия. Среднее значение индекса DAS28 составило 4,7±1,3, RAPID-3 – 13,7±3,6. Только 14,3% пациентов имели хорошее функциональное состояние, сравнимое с популяционным контролем (HAQ ≤0,5). У остальных больных отмечалось значительное снижение показателей функции суставов (медиана HAQ 1,88 [1,0; 2,5]) и КЖ по индексу EQ-5D (0,60 [0,60; 0,74]). Протезированные суставы имели 7,4% больных. При 1-м визите к ревматологу терапия была изменена у 15% пациентов. В течение 6 мес наблюдения практически все пациенты (91,2%) получали стандартные базисные противовоспалительные препараты. Из них 70,9% пациентов находились на терапии метотрексатом (МТ): 77,0% получали его в дозе 15 мг/нед и 23,0% – >15 мг (от 17,5 до 40 мг/нед). 20,5% пациентам в течение полугода удалось отменить глюкокортикоиды. Ингибиторы фактора некроза опухоли α использовали 6,6% больных, анти-В-клеточную терапию – 16,2%. После 6 мес наблюдения (2-й визит к врачу) 20% клиническое улучшение по критериям ACR достигнуто у 54% больных. При этом отмечалось значительное снижение индекса DAS28 (с 4,5±1,2 до 3,8±1,1 балла; p=0,0001). Минимальное функциональное улучшение по индексу HAQ зафиксировано у 64% пациентов, улучшение КЖ по EQ-5D – у 16%.Выводы. Высокая и умеренная активность заболевания, снижение показателей КЖ были характерны для большинства пациентов с РА, обратившихся к ревматологу. Это было связано с большой длительностью заболевания, неадекватной дозой МТ и недостаточным мониторингом пациентов в реальной клинической практике. Введение компьютерной системы самооценки состояния здоровья пациентов с РА на поликлиническом уровне позволило улучшить взаимодействие врачей, медицинских сестер и пациентов, более качественно контролировать активность заболевания и повысить эффективность терапии.

The comparative responsiveness of Hospital Universitario Princesa Index and other composite indices for assessing rheumatoid arthritis activity

Objective To evaluate the responsiveness in terms of correlation of the Hospital Universitario La Princesa Index (HUPI) comparatively to the traditional composite indices used to assess disease activity in rheumatoid arthritis (RA), and to compare the performance of HUPI-based response criteria with that of the EULAR response criteria. Methods Secondary data analysis from the following studies: ACT-RAY (clinical trial), PROAR (early RA cohort) and EMECAR (pre-biologic era long term RA cohort). Responsiveness was evaluated by: 1) comparing change from baseline (Delta) of HUPI with Delta in other scores by calculating correlation coefficients; 2) calculating standardised effect sizes. The accuracy of response by HUPI and by EULAR criteria was analyzed using linear regressions in which the dependent variable was change in global assessment by physician (Delta GDA-Phy). Results Delta HUPI correlation with change in all other indices ranged from 0.387 to 0.791); HUPI's standardized effect size was larger than those from the other indices in each database used. In ACT-RAY, depending on visit, between 65 and 80% of patients were equally classified by HUPI and EULAR response criteria. However, HUPI criteria were slightly more stringent, with higher percentage of patients classified as non-responder, especially at early visits. HUPI response criteria showed a slightly higher accuracy than EULAR response criteria when using Delta GDA-Phy as gold standard. Conclusion HUPI shows good responsiveness in terms of correlation in each studied scenario (clinical trial, early RA cohort, and established RA cohort). Response criteria by HUPI seem more stringent than EULAR''s

MAST CELLS ARE KEY PARTICIPANTS IN THE PATHOGENESIS OF IMMUNOINFLAMMATORY DISEASES

Mast cells are an integral component of the pathogenetic  chain of immune inflammation in the body's tissues in different diseases. The mechanisms  underlying the proinflammatory effects of mast cells remain inadequately investigated. Their study may contribute to the optimization of therapy for different diseases, including chronic arthritis

P53 pathway changes and their influence on chronic lymphoproliferative diseases pathogenesis

The role of p53 family proteins, both in the pathogenesis of chronic lymphoproliferative disorders, and in aspects of the growi ng interest in thetherapeutic potential of so-called small molecules capable of influencing the regulatory "relationship" of p53, MDM2, p21 and P UMA is currently actively debated. The article is an attempt to summarize the data on experimental tumor and mouse models and availablen ithe l iterature results of studies using human lymphoid tumors. Prognostic significance of p53 family proteins expression in lymphoproliferativ e diseases and possible therapeutic approaches using the features of the p53 relationship with regulators and effectors genes are considered.</p