Arthritis & Rheumatology, an official journal of the American College of Rheumatology, is a peer-reviewed publication for scientists and clinicians interested in the natural history, pathophysiology, treatment, and outcome of the rheumatic diseases. Arthritis & Rheumatology publishes the highest quality basic and clinical research related to the rheumatic diseases, encompassing a wide range of areas of investigative activity. In addition, the journal publishes review articles, editorials, and other educational material intended for both researchers and clinicians. Serving the worldwide community of rheumatology investigators and clinicians, Arthritis & Rheumatology is known internationally as a top rheumatology research journal.

Arthritis and Rheumatology is the official journal of the American College of Rheumatology, focusing on the natural history, pathophysiology, treatment, and outcomes of rheumatic diseases. This peer-reviewed publication provides high-quality basic and clinical research for scientists and clinicians, covering a wide range of investigative areas. Additionally, the journal publishes review articles, editorials, and other educational materials aimed at both researchers and clinicians. Serving the global community of rheumatology investigators and clinicians, Arthritis and Rheumatology is recognized internationally as a leading journal in rheumatology research.

《Arthritis and Rheumatology》是美国风湿病学会的官方期刊，专注于风湿病的自然历史、病理生理、治疗及其结果。该期刊为科学家和临床医生提供同行评审的高质量基础和临床研究，涵盖广泛的研究领域。此外，期刊还发表综述文章、社论及其他旨在为研究人员和临床医生提供教育材料的内容。《Arthritis and Rheumatology》服务于全球风湿病研究者和临床医生社区，国际上被公认为顶尖的风湿病研究期刊。

Arthritis and Rheumatology

There is accumulating evidence that complement activation is important in antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis (AAV) pathogenesis. This study was undertaken to investigate complement activation in AAV with myeloperoxidase (MPO) positivity and AAV with proteinase 3 (PR3) positivity after determining optimal methods for measuring activated complement factors in circulation.
Participants included 98 patients with AAV (45 MPO‐ANCA positive, 53 PR3‐ANCA positive) and 35 healthy controls. Plasma was obtained from blood collected using EDTA tubes, with or without 100 μg/ml Futhan. Levels of Bb, C3a, C5a, soluble C5b–9 (sC5b–9), properdin, and C4d were measured by enzyme‐linked immunosorbent assay. Group comparisons were made using Wilcoxon's 2‐sample test. Paired data were analyzed using a matched pairs signed rank test.
Compared to healthy controls, certain complement analyte levels were high in patients with active AAV with MPO positivity, including C3a (P< 0.0001), C5a (P= 0.0004), and sC5b–9 (P= 0.0007). During remission, levels of Bb (P= 0.001), C3a (P< 0.0001), and sC5b–9 (P= 0.003) were higher. Compared to healthy controls, C3a (P< 0.0001), C5a (P= 0.002), sC5b–9 (P= 0.0001), and C4d (P= 0.005) levels were higher in patients with active AAV with PR3 positivity; levels of C3a (P< 0.0001) and C4d (P= 0.007) were also higher duriing remission. There were no significant differences in any complement analyte for either ANCA serotype between patients with active disease and those with disease in remission. Among patients with paired samples, sC5‐9 levels were significantly lower during disease remission compared to active disease. C5a was significantly lower among patients with disease in long‐term remission who were not receiving therapy. For Bb, C5a, and sC5b–9, median levels and individual values were considerably higher in control and patient samples processed without Futhan compared to those processed with Futhan.
Complement activation occurs in both MPO‐positive AAV and PR3‐positive AAV. The complement activation profile differs according to disease activity and possibly ANCA serotype. Futhan reduces in vitro complement activation and provides a more accurate measurement.

Eveline Y. Wu

Elizabeth A. McInnis

Sonia Boyer‐Suavet

Carmen E. Mendoza

Lydia T. Aybar

Kristin B. Kennedy

Caroline J. Poulton

Candace D. Henderson

Yichun Hu

Susan L. Hogan

Peiqi Hu

Hong Xiao

Patrick H. Nachman

J. Charles Jennette

Ronald J. Falk

Donna O. Bunch

Arthritis &amp; Rheumatology

Measuring Circulating Complement Activation Products in Myeloperoxidase– and Proteinase 3–Antineutrophil Cytoplasmic Antibody–Associated Vasculitis

Objective A major signaling pathway that regulates cellular aging is the insulin/insulin‐like growth factor 1 (IGF‐1)/phosphatidylinositol 3‐kinase (PI3K)/Akt/FoxO transcription factor axis. We previously observed that FoxO transcription factors are dysregulated in aged and OA cartilage. The objective of this study was to investigate the impact of down‐regulated FoxO transcription factors on chondrocytes. Methods Small interfering RNAs (siRNAs) targeting FOXO1 (siFOXO1) and FOXO3 (siFOXO3) were transfected into human articular chondrocytes. Cell viability following treatment with the oxidant tert ‐butyl‐hydroperoxide (tBHP) was measured by MTT assay. Caspase 3/7 activation and apoptotic cells were examined. Gene and protein expression of antioxidant proteins and autophagy‐related proteins and changes in inflammatory mediators following treatment with interleukin‐1β were assessed. Cells transfected with FOXO plasmids were also analyzed. Results Cell viability was significantly reduced by siFOXO after treatment with tBHP. Apoptosis accompanied by caspase activation was significantly increased in siFOXO‐transfected chondrocytes. Knockdown of FOXO1 and FOXO1+3 resulted in significant reductions in levels of glutathione peroxidase 1 (GPX‐1), catalase, light chain 3 (LC3), Beclin1, and sirtuin 1 (SIRT‐1) proteins following treatment with tBHP. In contrast, the constitutive active form of FOXO3 increased cell viability while inducing GPX‐1, Beclin1, and LC3 in response to tBHP. Expression and production of ADAMTS‐4 and chemerin were significantly increased in siFOXO‐transfected chondrocytes. Conclusion Reduced expression of FoxO transcription factors in chondrocytes increased susceptibility to cell death induced by oxidative stress. This was associated with reduced levels of antioxidant proteins and autophagy‐related proteins. Our data provide evidence for a key role of FoxO transcription factors as regulators of chondrocyte oxidative stress resistance and tissue homeostasis.

Yukio Akasaki

Oscar Alvarez‐Garcia

Masahiko Saito

Beatriz Caramés

Yukihide Iwamoto

Martin K. Lotz

Arthritis & Rheumatology

FoxO Transcription Factors Support Oxidative Stress Resistance in Human Chondrocytes

FoxO转录因子支持人类软骨细胞的氧化应激抵抗

To estimate the current prevalence rates and decadal trends of gout and hyperuricemia in the US, as well as the prevalence of urate‐lowering therapy (ULT) among gout patients, using 2007–2016 data from a nationally representative survey of American men and women (the National Health and Nutrition Examination Survey [NHANES]).

Michael Chen‐Xu

Chio Yokose

Sharan K. Rai

Michael H. Pillinger

Hyon K. Choi

Arthritis Rheumatol

Contemporary Prevalence of Gout and Hyperuricemia in the United States and Decadal Trends: The National Health and Nutrition Examination Survey, 2007–2016

美国痛风和高尿酸血症的当代流行率及十年趋势：全国健康与营养调查，2007-2016

Objective To investigate the role of the interleukin‐25 ( IL ‐25)/ IL ‐17 receptor B ( IL ‐17 RB ) axis in experimental Sjögren's syndrome ( SS ) and in patients with primary SS and primary SS –associated lymphoma. Methods Expression of IL ‐25, IL ‐17 RB , IL ‐17B, and tumor necrosis factor receptor–associated factor 6 ( TRAF 6) was analyzed on minor salivary gland ( SG ) samples from patients with primary SS and on parotid gland samples from patients with primary SS –associated B cell non‐Hodgkin's lymphoma ( NHL ). IL ‐17 RB expression and the frequencies of natural group 2 innate lymphoid cells ( ILC 2s), inflammatory ILC 2s, and M2‐polarized macrophages were assessed by flow cytometry in SG mononuclear cells and peripheral blood mononuclear cells ( PBMC s). Tissue distribution of ILC 2s was studied by confocal microscopy. The role of recombinant IL ‐25 and of rituximab in modulating IL ‐25 expression was investigated in in vitro studies. IL ‐25/ IL ‐17 RB and TRAF 6 expression and the role of IL ‐25 inhibition were also studied in the experimental murine model of SS . Results Activation of the IL ‐25/ IL ‐17 RB / TRAF 6 axis correlated with the focus score and was observed in patients with primary SS and in patients with primary SS –associated NHL . A significant increase in the frequency of inflammatory ILC 2s was observed both in SG mononuclear cells and in PBMC s. IL ‐25 stimulation of isolated SG mononuclear cells and PBMC s from patients and controls resulted both in inflammatory ILC 2 expansion and in increased autoantibody production. Rituximab modulated expression of inflammatory ILC 2s and IL ‐25 in primary SS . SG protein–immunized mice developed overt SS symptoms with increased IL ‐25 expression and increased frequency of CD 4+ IL ‐17 RB + TRAF 6+ cells. IL ‐25 neutralization attenuated disease progression and tissue pathology in mice with experimental SS . Conclusion IL ‐25 may promote the inflammatory state in primary SS and may be a potential target for novel disease‐modifying therapeutic strategies in patients with primary SS .

Giuliana Guggino

Xiang Lin

Aroldo Rizzo

Fan Xiao

Laura Saieva

Stefania Raimondo

Diana Di Liberto

Giuseppina Candore

Piero Ruscitti

Paola Cipriani

Roberto Giacomelli

Francesco Dieli

Riccardo Alessandro

Giovanni Triolo

Liwei Lu

Francesco Ciccia

Interleukin‐25 Axis Is Involved in the Pathogenesis of Human Primary and Experimental Murine Sjögren's Syndrome

白细胞介素-25轴参与人类原发性及实验性小鼠舍格伦综合征的发病机制

This study was undertaken to identify key disease pathways driving conventional dendritic cell (cDC) alterations in systemic sclerosis (SSc).Transcriptomic profiling was performed on peripheral blood CD1c+ cDCs (cDC2s) isolated from 12 healthy donors and 48 patients with SSc, including all major disease subtypes. We performed differential expression analysis for the different SSc subtypes and healthy donors to uncover genes dysregulated in SSc. To identify biologically relevant pathways, we built a gene coexpression network using weighted gene correlation network analysis. We validated the role of key transcriptional regulators using chromatin immunoprecipitation (ChIP) sequencing and in vitro functional assays.We identified 17 modules of coexpressed genes in cDCs that correlated with SSc subtypes and key clinical traits, including autoantibodies, skin score, and occurrence of interstitial lung disease. A module of immunoregulatory genes was markedly down-regulated in patients with the diffuse SSc subtype characterized by severe fibrosis. Transcriptional regulatory network analysis performed on this module predicted nuclear receptor 4A (NR4A) subfamily genes (NR4A1, NR4A2, NR4A3) as the key transcriptional regulators of inflammation. Indeed, ChIP-sequencing analysis indicated that these NR4A members target numerous differentially expressed genes in SSc cDC2s. Inclusion of NR4A receptor agonists in culture-based experiments provided functional proof that dysregulation of NR4As affects cytokine production by cDC2s and modulates downstream T cell activation.NR4A1, NR4A2, and NR4A3 are important regulators of immunosuppressive and fibrosis-associated pathways in SSc cDCs. Thus, the NR4A family represents novel potential targets to restore cDC homeostasis in SSc.

Nila H. Servaas

Sanne Hiddingh

Eleni Chouri

Catharina G. K. Wichers

Alsya J. Affandi

Andrea Ottria

Cornelis P. J. Bekker

Marta Cossu

Sandra C. Silva‐Cardoso

Maarten van der Kroef

Anneline C. Hinrichs

Tiago Carvalheiro

Nadia Vazirpanah

Lorenzo Beretta

Marzia Rossato

Femke Bonte‐Mineur

Timothy R. D. J. Radstake

Jonas J. W. Kuiper

Marianne Boes

Aridaman Pandit

Nuclear Receptor Subfamily <scp>4A</scp> Signaling as a Key Disease Pathway of <scp>CD1c</scp>+ Dendritic Cell Dysregulation in Systemic Sclerosis

核受体亚家族4A信号作为系统性硬化症中CD1c+树突状细胞功能障碍的关键疾病通路

Wayne YW Lee

Rongliang Wong

Author Reply to Letter to the Editor

作者对读者来信的回复

Objective Systemic sclerosis (SSc) is a rare but severe autoimmune disease characterized by immune dysregulation, fibrosis, and vasculopathy. While previous studies have highlighted the presence of functional autoantibodies targeting the angiotensin II type 1 receptor (AT 1 R) and endothelin‐1 type A receptor (ET A R), leading to autoantibody‐mediated receptor stimulation and subsequent activation of endothelial cells (ECs), a comprehensive understanding of the direct interaction between these autoantibodies and their receptors is currently lacking. Moreover, existing data confirming the presence of these autoantibodies in SSc often rely on similar methodologies and assays. Our aim was to replicate previous findings and to investigate the functional effects of SSc patient‐derived IgG (SSc IgG) on AT 1 R‐ and ET A R signaling, the downstream EC response, as well as presence of AT 1 R‐binding autoantibodies in circulation. Methods Quantitative PCR (qPCR) and cytokine ELISA, alongside a real‐time cell analyzer, were utilized to assess receptor‐specific functional characteristics of purified IgG from SSc patients (n=18). Additionally, a novel protein capture assay using solubilized epitope‐tagged AT 1 R was developed to detect AT 1 R‐binding autoantibodies in plasma samples from SSc patients (n=28) and healthy donors (n=14). Results No evidence for EC activation in an AT 1 R‐ or ET A R‐dependent manner was revealed. Furthermore, stimulation with SSc IgG did not induce receptor activation nor alter GPCR signaling upon agonist stimulation in a model with receptor overexpression. Lastly, no AT 1 R‐binding autoantibodies were detected in plasma from SSc patients when using epitope‐tagged solubilized AT 1 R. Conclusion Overall, our study did not provide evidence to support the presence of AT 1 R‐ or ET A R‐activating autoantibodies in purified SSc IgG, nor AT 1 R‐binding autoantibodies in circulation of SSc patients.

Wieke M. van Oostveen

Eva M. Hoekstra

E.W. Nivine Levarht

Ilana B. Kotliar

Thomas P. Sakmar

René E.M. Toes

Jeska K. de Vries‐Bouwstra

Laura H. Heitman

Cynthia M. Fehres

Absence of Functional Autoantibodies Targeting Angiotensin <scp>II</scp> Type 1 Receptor (<scp>AT1R</scp>) and Endothelin‐1 Type A Receptor (<scp>ETAR</scp>) in Circulation and Purified <scp>IgG</scp> from Patients with Systemic Sclerosis

系统性硬化症患者循环和纯化IgG中靶向血管紧张素II 1型受体（AT1R）和内皮素-1 A型受体（ETAR）的功能性自身抗体的缺失

Objective Cardiovascular disease is a leading cause of mortality in Systemic Lupus Erythematosus (SLE). We assessed atherosclerotic plaque progression and incident cardiovascular events in SLE patients over a 10‐year follow‐up. Methods We prospectively analyzed 738 carotid ultrasound measurements (413 in SLE patients and 325 in age/sex‐matched healthy controls [HC]) to assess new plaque development from baseline to 3‐, 7‐, and 10‐year follow‐up. Multivariate mixed Poisson regression models examined potential predictors of plaque progression, including patient characteristics, Systemic Coronary Risk Evaluation (SCORE), traditional cardiovascular risk factor (CVRF) target attainment, Definition of Remission in SLE (DORIS), medications, and persistent triple antiphospholipid antibody (aPL) positivity during follow‐up. Ten‐year incident cardiovascular events were recorded, and univariate Cox regression analysis assessed potential associations. Results SLE patients had a 2.3‐fold higher risk of carotid plaque progression than HC (Incidence Rate Ratio [IRR]: 2.26; p=0.002). Plaque progression risk in SLE was reduced by 32% (IRR: 0.68, p=0.004) per each sustainedly attained CVRF target during follow‐up, including blood pressure, lipids, smoking, body weight, and physical activity. DORIS achievement ≥75% of follow‐up was associated with a 43% decrease in atherosclerosis progression risk (IRR: 0.57; p=0.033). Ten‐year risk of incident cardiovascular events was higher in SLE than HC individuals (eight versus one event, permutation‐based log‐rank p=0.036) and was associated with persistent triple aPL positivity. Conclusion Patients with SLE experience a 2.3‐fold higher 10‐year atherosclerosis progression risk than HC, mitigated by sustained CVRF control and prolonged clinical remission. Persistent triple aPL positivity is associated with increased incidence of CVD events.

Nikolaos Papazoglou

Petros P. Sfikakis

Maria G. Tektonidou

Atherosclerotic plaque progression and incident cardiovascular events in a 10‐year prospective study of patients with Systemic Lupus Erythematosus: the impact of persistent cardiovascular risk factor target attainment and sustained <scp>DORIS</scp> remission

系统性红斑狼疮患者10年前瞻性研究中的动脉粥样硬化斑块进展与心血管事件发生：持续心血管危险因素目标达成与持续DORIS缓解的影响

Disclosure Form Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

An‐Fang Huang

Wang‐Dong Xu

Comment on: Targeting long non‐coding RNA H19 in Subchondral Bone Osteocytes Alleviates Cartilage Degradation in Osteoarthritis

评述：靶向软骨下骨骨细胞中的长链非编码RNA H19可缓解骨关节炎中的软骨退化

Giant cell arteritis (GCA) is a relapsing large‐vessel vasculitis with risk of serious ischemic manifestations including vision loss and vascular damage in the form of large‐artery stenosis, aneurysms and dissections. Approximately 50% of patients treated with glucocorticoid (GC) monotherapy and 30% of patients receiving adjunctive therapy with tocilizumab experience disease relapses, often during the first 2 years after diagnosis. Although most relapses in GCA do not involve life‐ or organ‐threatening presentations and can be controlled successfully, frequent relapses may lead to increased use of GC and consequent treatment‐related morbidity, in addition to risk of further vascular damage. Emerging data suggests that persistent disease activity may lead to increased vascular morbidity. Additionally, while tocilizumab decreases the frequency of relapses, more than 50% of patients relapse after discontinuation of therapy. Therefore, while interleukin‐6 blockade suppresses disease activity, it does not restore tolerance. In this article, we discuss the practical diagnosis and management of GCA relapses from an expert perspective. Current treatment options for GCA relapses, including those recommended by international guidelines, and novel potential therapies are reviewed.

Abbreviation	Arthritis Rheumatol
Journal Impact	11.37
Quartiles(Global)	RHEUMATOLOGY(Q1)

ISSN	2326-5191, 2326-5205
h-index	353
Top Journals	Yes

Publication Information	Publisher: John Wiley and Sons Ltd，Publishing cycle: ，Journal Type: journal，Open Access Journals: No
Basic data	Year of publication: 2014，Proportion of original research papers: 96.14%，Self Citation Rate:1.80%， Gold OA Rate: 31.48%

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Measuring Circulating Complement Activation Products in Myeloperoxidase– and Proteinase 3–Antineutrophil Cytoplasmic Antibody–Associated Vasculitis

FoxO Transcription Factors Support Oxidative Stress Resistance in Human Chondrocytes

Contemporary Prevalence of Gout and Hyperuricemia in the United States and Decadal Trends: The National Health and Nutrition Examination Survey, 2007–2016

Interleukin‐25 Axis Is Involved in the Pathogenesis of Human Primary and Experimental Murine Sjögren's Syndrome

Nuclear Receptor Subfamily 4A Signaling as a Key Disease Pathway of CD1c+ Dendritic Cell Dysregulation in Systemic Sclerosis

Author Reply to Letter to the Editor

Absence of Functional Autoantibodies Targeting Angiotensin II Type 1 Receptor (AT₁R) and Endothelin‐1 Type A Receptor (ET_AR) in Circulation and Purified IgG from Patients with Systemic Sclerosis

Atherosclerotic plaque progression and incident cardiovascular events in a 10‐year prospective study of patients with Systemic Lupus Erythematosus: the impact of persistent cardiovascular risk factor target attainment and sustained DORIS remission

Comment on: Targeting long non‐coding RNA H19 in Subchondral Bone Osteocytes Alleviates Cartilage Degradation in Osteoarthritis

Expert Perspective: Management of Relapses in Giant Cell Arteritis

Arthritis and Rheumatology

Journal Citation Format

A journal article with 1 author

A journal article with 2 authors

A journal article with 3 authors

A journal article with 5 or more authors

Books Citation Format

Thesis Citation Format

Web sites Citation Format

Patent Citation Format

Staying up late manually editing references? ivySCI automatically matches journals and helps you generate references with a single click.

Share Submission Experience

Measuring Circulating Complement Activation Products in Myeloperoxidase– and Proteinase 3–Antineutrophil Cytoplasmic Antibody–Associated Vasculitis

FoxO Transcription Factors Support Oxidative Stress Resistance in Human Chondrocytes

Contemporary Prevalence of Gout and Hyperuricemia in the United States and Decadal Trends: The National Health and Nutrition Examination Survey, 2007–2016

Interleukin‐25 Axis Is Involved in the Pathogenesis of Human Primary and Experimental Murine Sjögren's Syndrome

Nuclear Receptor Subfamily 4A Signaling as a Key Disease Pathway of CD1c+ Dendritic Cell Dysregulation in Systemic Sclerosis

Author Reply to Letter to the Editor

Absence of Functional Autoantibodies Targeting Angiotensin II Type 1 Receptor (AT1R) and Endothelin‐1 Type A Receptor (ETAR) in Circulation and Purified IgG from Patients with Systemic Sclerosis

Atherosclerotic plaque progression and incident cardiovascular events in a 10‐year prospective study of patients with Systemic Lupus Erythematosus: the impact of persistent cardiovascular risk factor target attainment and sustained DORIS remission

Comment on: Targeting long non‐coding RNA H19 in Subchondral Bone Osteocytes Alleviates Cartilage Degradation in Osteoarthritis

Expert Perspective: Management of Relapses in Giant Cell Arteritis

Absence of Functional Autoantibodies Targeting Angiotensin II Type 1 Receptor (AT₁R) and Endothelin‐1 Type A Receptor (ET_AR) in Circulation and Purified IgG from Patients with Systemic Sclerosis