ACPA-negative rheumatoid arthritis: From immune mechanisms to clinical translation

Li, Ketian; Wang, Min; Zhao, Lu; Liu, Yudong; Zhang, Xuan

doi:10.1016/j.ebiom.2022.104233

Cited by 13 publications

(12 citation statements)

References 80 publications

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“…Additionally, local inflammation is a central element in the development of RA. Inflammatory factors and chemokines, including tumor necrosis factor (TNF), interleukin (IL) and matrix metalloproteinase (MMP), are upregulated in the synovial macrophages and dendritic cell subsets of RA patients [ 11 , 46 ]. These inflammatory mediators lead to cartilage degradation, bone erosion, and the acceleration of RA development [ 47 ].…”

Section: Discussionmentioning

confidence: 99%

Causal associations between rheumatoid arthritis, cataract and glaucoma in European and East Asian populations: A bidirectional two-sample mendelian randomization study

Teng,

Wang,

et al. 2024

PLoS ONE

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Background Previous studies have indicated a heightened susceptibility to cataract and glaucoma among rheumatoid arthritis (RA) patients, while it remains uncertain whether RA is causally associated with cataract and glaucoma. A two-sample mendelian randomization (MR) analysis was used to investigate the causal associations between RA, cataract and glaucoma in European and East Asian populations. Methods In the European population, genome-wide association study (GWAS) summary statistics for cataract (372,386 individuals) and glaucoma (377,277 individuals) were obtained from the FinnGen consortium (R9), while RA summary data were derived from a meta-analysis of GWAS encompassing 97173 samples. In the East Asian population, summary data for cataract (212453 individuals), glaucoma (212453 individuals), and RA (22515 individuals) were sourced from the IEU Open GWAS project. Inverse-variance weighted (IVW, random-effects) method served as the primary analysis, complemented by MR‒Egger regression, weighted median, weighted mode and simple mode methods. Additionally, various sensitivity tests, including Cochran’s Q test, MR‒Egger intercept, MR pleiotropy Residual Sum and Outlier test and leave-one-out test were performed to detect the heterogeneity, horizontal pleiotropy and stability of the analysis results. Results Following stringent screening, the number of selected instrumental variables ranged from 8 to 56. The IVW results revealed that RA had an increased risk of cataract (OR = 1.041, 95% CI = 1.019–1.064; P = 2.08×10−4) and glaucoma (OR = 1.029, 95% CI = 1.003–1.057; P = 2.94×10−2) in European populations, and RA displayed a positive association with cataract (OR = 1.021, 95% CI = 1.004–1.039; P = 1.64×10−2) in East Asian populations. Other methods also supported those results by IVW, and sensitivity tests showed that our analysis results were credible and stable. Conclusions This study revealed a positive causality between RA and the increased risk of cataract and glaucoma, which provides guidance for the early prevention of cataracts and glaucoma in patients with RA and furnishes evidence for the impact of RA-induced inflammation on ophthalmic diseases.

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Section: Discussionmentioning

confidence: 99%

Causal associations between rheumatoid arthritis, cataract and glaucoma in European and East Asian populations: A bidirectional two-sample mendelian randomization study

Teng,

Wang,

et al. 2024

PLoS ONE

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“…Полученные результаты детально проанализированы в обзоре K. Li и соавт. [27], поэтому ниже будут представлены только основные материалы этих исследований. В синовиальной ткани при серопозитивном РА по сравнению с серонегативным превалируют CD4 + Т-клетки, экспрессирующие CXCL13 high , а также GPR56 (рецептор для G-белка), которые локализованы вблизи В-клеток и регулируют дифференцировку плазматических клеток и синтез ИЛ-21 [ С использованием протеомного анализа в сыворотках (и синовиальной жидкости) пациентов с РА идентифицированы новые аутоантитела к карбомилированным белкам («карбамилом») [90], среди которых антитела к гемопексину (транспортный белок при переносе гема из циркулирующей крови в паренхиму печени) и α2-макроглобулину выявлены у 60% пациентов.…”

Section: иммунопатологияunclassified

“…На популяционном уровне внедрение современных методов лечения РА, включая генно-инженерные биологические препараты (ГИБП) и таргетные базисные противовоспалительные препараты (тБПВП), в большей степени привело к улучшению прогноза при серопозитивном, чем при серонегативном РА [22]. Проблемы иммунопатогенеза, биомаркеров, клинического спектра, инструментальной диагностики и фармакотерапии серопозитивного РА суммированы в серии обзоров [3,15,[23][24][25], в то время как анализу этих характеристик при серонегативном РА посвящено значительно меньше исследований [26][27][28].…”

Section: Introductionunclassified

Rheumatoid arthritis as a clinical and immunological syndrome: focus on the seronegative subtype of the disease

Насонов

Авдеева²,

Dibrov³

2023

Naučno-praktičeskaâ revmatologiâ

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Rheumatoid arthritis (RA) is the most common immune mediated (autoimmune) rheumatic disease, manifested by chronic erosive arthritis and systemic internal organ damage. Currently, RA is considered as a syndrome characterized by clinical and pathogenetic heterogeneity associated with a variety of mechanisms of pathological activation of innate and acquired immunity, determining the variability of the course and outcome of the inflammatory process and effectiveness of therapy. Based on the detection or absence of rheumatoid factor (RF) IgM and antibodies to cyclic citrullinated peptides (ACCP), RA can be conventionally divided into two subtypes (phenotypes): seropositive RA and seronegative RA, but thanks to improvement of laboratory diagnostic methods the spectrum of autoantibodies detected in RA has increased significantly. Diagnosis of seronegative RA based on classification (rather than diagnostic) criteria can be difficult, especially in the early stages of the disease, and the diagnosis is made only during long-term follow-up of patients. It complicates the timely prescription of adequate anti-inflammatory therapy. This article summarizes the data on genetic predisposition, immunopathogenesis, biomarkers, clinical spectrum, instrumental diagnosis and pharmacotherapy of seronegative RA.

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“…У пациентов с ранним РА, резистентных к монотерапии метотрексатом, эффективность мАТ к ИЛ-17А (СЕК) изучена только в одном исследовании [126]. В дальнейших исследованиях акцент следует сделать на пациентов с серонегативным по РФ и АЦБ вариантом РА, представляющим собой особый субтип РА [163,164], встречающийся у 20-30% всех пациентов с РА [1]. Примечательно, что, по данным эпидемиологических исследований, за период с 2005 по 2014 г. в популяции наблюдается четкая тенденция к нарастанию частоты серонегативного и снижению частоты серопозитивного РА [165].…”

Section: таблица 5 сравнительная эффективность ингибиторовunclassified

The role of interleukin 17 in the pathogenesis of rheumatoid arthritis. Are there any prospects for the use of IL-17 inhibitors?

Насонов

Авдеева²,

Коротаева³

et al. 2023

Naučno-praktičeskaâ revmatologiâ

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Rheumatoid arthritis (RA) is an immunoinflammatory rheumatic disease (IMRI) characterized by chronic erosive arthritis and systemic damage to internal organs, leading to early disability and reduced life expectancy in patients. Thanks to the progress in the study of the mechanisms of the development of the IVRI and industrial biotechnology, new anti-inflammatory drugs have been created, the use of which has significantly increased the effectiveness of the pharmacotherapy of RA. However, the possibilities of pharmacotherapy for RA are limited, since all genetically engineered biological drugs (GEBDs), regardless of the mechanism of action, have approximately the same effectiveness in achieving remission. It is believed that the relatively unsatisfactory results of RA therapy are due to the heterogeneity of the mechanisms of inflammation. and pain. The significance of the Th17 type of immune response in the pathogenesis of RA, the results of controlled studies of IL-17 inhibitors, and the advisability of further studying the effectiveness of these drugs in patients with certain RA phenotypes are discussed.

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ACPA-negative rheumatoid arthritis: From immune mechanisms to clinical translation

Cited by 13 publications

References 80 publications

Causal associations between rheumatoid arthritis, cataract and glaucoma in European and East Asian populations: A bidirectional two-sample mendelian randomization study

Causal associations between rheumatoid arthritis, cataract and glaucoma in European and East Asian populations: A bidirectional two-sample mendelian randomization study

Rheumatoid arthritis as a clinical and immunological syndrome: focus on the seronegative subtype of the disease

The role of interleukin 17 in the pathogenesis of rheumatoid arthritis. Are there any prospects for the use of IL-17 inhibitors?

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