Arthritis Research and Therapy

Although the relationship between obesity and incident gout has been clarified, the influence of weight changes during the transition from early adulthood to midlife and the different weight change patterns in specific age ranges on the incidence of gout in later life remain unknown. Therefore, we aimed to investigate the association between weight change patterns across adulthood and incident gout.Using data from the National Health and Nutrition Examination Survey (NHANES), we categorized individuals into four weight change patterns: those who remained obese (stable obese), those who moved from a non-obese body mass index (BMI) to an obese BMI (gaining), those who moved from an obese BMI to a non-obese BMI (losing), and those who remained non-obese (stable non-obese). Incident gout reflected its occurrence over the 10-year follow-up from the recalled midlife weight measure to the time of this survey. Hazard ratios (HRs) and 95% confidence intervals relating weight change patterns to incident gout over the 10-year follow-up period were calculated using Cox models adjusted for covariates. The hypothetical population attributable fraction (PAF) for the weight change patterns was calculated.Among our sample of adults aged 40-74 years at their midlife weight measure (n = 11,079), 320 developed gout. The highest risk of incident gout was found for participants with the stable obese pattern (HR 1.84; 1.08-3.14) and not for participants who remained stable non-obese during adulthood. Moreover, gaining weight was a significant risk factor for incident gout (HR 1.65; 1.19-2.29). No significant associations were found between losing weight change patterns and the risk of gout during the study period. If participants who gained weight had become non-obese during the 10-year follow-up, an estimated 3.2% (95% CI 0-6.3) of observed gout cases could have been averted. In addition, if the population had maintained a normal BMI, 32.9% (95% CI 18.2-44.9) cases could have been prevented during the 10 years.Gaining weight over adulthood was associated with an increased risk of gout. These findings have highlighted that maintaining non-obese weight and weight loss across adulthood is essential for the prevention and treatment of gout in adult life.

Lu Bai

Jian-Bo Zhou

Tao Zhou

Roger B. Newson

Marly Augusto Cardoso

Arthritis Research & Therapy

Arthritis Res Ther

Incident gout and weight change patterns: a retrospective cohort study of US adults

Ferritin positively associates with serum urate and an interventional study suggests that iron has a role in triggering gout flares. The objective of this study was to further explore the relationship between iron/ferritin and urate/gout. European (100 cases, 60 controls) and Polynesian (100 cases, 60 controls) New Zealand (NZ) males and 189 US male cases and 60 male controls participated. The 10,727 participants without gout were from the Jackson Heart (JHS; African American = 1260) and NHANES III (European = 5112; African American = 4355) studies. Regression analyses were adjusted for age, sex, body mass index and C-reactive protein. To test for a causal relationship between ferritin and urate, bidirectional two-sample Mendelian randomization analysis was performed. Serum ferritin positively associated with gout in NZ Polynesian (OR (per 10 ng ml− 1 increase) = 1.03, p = 1.8E–03) and US (OR = 1.11, p = 7.4E–06) data sets but not in NZ European (OR = 1.00, p = 0.84) data sets. Ferritin positively associated with urate in NZ Polynesian (β (mg dl− 1) = 0.014, p = 2.5E–04), JHS (β = 0.009, p = 3.2E–05) and NHANES III (European β = 0.007, p = 5.1E–11; African American β = 0.011, p = 2.1E–16) data sets but not in NZ European (β = 0.009, p = 0.31) or US (β = 0.041, p = 0.15) gout data sets. Ferritin positively associated with the frequency of gout flares in two of the gout data sets. By Mendelian randomization analysis a one standard deviation unit increase in iron and ferritin was, respectively, associated with 0.11 (p = 8E–04) and 0.19 mg dl− 1 (p = 2E–04) increases in serum urate. There was no evidence for a causal effect of urate on iron/ferritin. These data replicate the association of ferritin with serum urate. Increased ferritin levels associated with gout and flare frequency. There was evidence of a causal effect of iron and ferritin on urate.

Tahzeeb Fatima

Cushla McKinney

Tanya J. Major

Lisa K. Stamp

Nicola Dalbeth

Cory Iverson

Tony R. Merriman

Jeffrey N. Miner

The relationship between ferritin and urate levels and risk of gout

铁蛋白与尿酸水平及痛风风险的关系

Plasmablasts and plasma cells play a key role in many autoimmune diseases, such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). This study was undertaken to evaluate the potential of targeting CD38 as a plasma cell/plasmablast depletion mechanism by daratumumab in the treatment of patients with RA and SLE.RNA-sequencing analysis of synovial biopsies from various stages of RA disease progression, flow cytometry analysis of peripheral blood mononuclear cells (PBMC) from patients with RA or SLE and healthy donors, immunohistochemistry assessment (IHC) of synovial biopsies from patients with early RA, and ex vivo immune cell depletion assays using daratumumab (an anti-CD38 monoclonal antibody) were used to assess CD38 as a therapeutic target.We demonstrated that the plasma cell/plasmablast-related genes CD38, XBP1, IRF4, PRDM1, IGJ and TNFSF13B are significantly up-regulated in synovial biopsies from patients with arthralgia, undifferentiated arthritis (UA), early RA and established RA as compared to healthy controls and control patients with osteoarthritis. In addition, the highest CD38 expression was observed on plasma cells and plasmablasts compared to natural killer (NK) cells, classical dendritic cells (DCs), plasmacytoid DCs (pDCs) and T cells, in blood from healthy controls and patients with SLE and RA. Furthermore, IHC showed CD38 staining in the same region as CD3 and CD138 staining in synovial tissue biopsies from patients with early RA. Most importantly, our data show for the first time that daratumumab effectively depletes plasma cells/plasmablasts in PBMC from patients with SLE and RA in a dose-dependent manner ex vivo.These results indicate that CD38 may be a potential target for RA disease interception and daratumumab should be evaluated clinically for the treatment of both RA and SLE.

Suzanne Cole

Alice Walsh

Xuefeng Yin

Mihir D. Wechalekar

Malcolm D. Smith

Susanna M. Proudman

Douglas J. Veale

Ursula Fearon

Costantino Pitzalis

Frances Humby

Michele Bombardieri

Amy Axel

Homer Adams

Christopher Chiu

Michael Sharp

John Alvarez

Ian Anderson

Loui Madakamutil

Sunil Nagpal

Yanxia Guo

Integrative analysis reveals CD38 as a therapeutic target for plasma cell-rich pre-disease and established rheumatoid arthritis and systemic lupus erythematosus

综合分析揭示CD38作为浆细胞增多前期疾病和已建立的类风湿性关节炎及系统性红斑狼疮的治疗靶点

Abstract Background Osteoarthritis (OA) and Kashin-Beck disease (KBD) both are two severe osteochondral disorders. In this study, we aimed to compare the gut microbiota structure between OA and KBD patients. Methods Fecal samples collected from OA and KBD patients were used to characterize the gut microbiota using 16S rDNA gene sequencing. To identify whether gut microbial changes at the species level are associated with the genes or functions of the gut bacteria between OA and KBD groups, metagenomic sequencing of fecal samples from OA and KBD subjects was performed. Results The OA group was characterized by elevated Epsilonbacteraeota and Firmicutes levels. A total of 52 genera were identified to be significantly differentially abundant between the two groups. The genera Raoultella , Citrobacter , Flavonifractor , g__Lachnospiraceae_UCG-004 , and Burkholderia-Caballeronia-Paraburkholderia were more abundant in the OA group. The KBD group was characterized by higher Prevotella_9 , Lactobacillus , Coprococcus_2 , Senegalimassilia , and Holdemanella . The metagenomic sequencing showed that the Subdoligranulum_sp._APC924/74 , Streptococcus_parasanguinis , and Streptococcus_salivarius were significantly increased in abundance in the OA group compared to those in the KBD group, and the species Prevotella_copri , Prevotella_sp._CAG:386 , and Prevotella_stercorea were significantly decreased in abundance in the OA group compared to those in the KBD group by using metagenomic sequencing. Conclusion Our study provides a comprehensive landscape of the gut microbiota between OA and KBD patients and provides clues for better understanding the mechanisms underlying the pathogenesis of OA and KBD.

Yujie Ning

Minhan Hu

Yi Gong

Ruitian Huang

Ke Xu

Sijie Chen

Feiyu Zhang

Yanli Liu

Feihong Chen

Yanhai Chang

Guanghui Zhao

Cheng Li

Rong Zhou

Mikko J. Lammi

Xiong Guo

Xi Wang

Comparative analysis of the gut microbiota composition between knee osteoarthritis and Kashin-Beck disease in Northwest China

中国西北地区膝骨关节炎与大骨节病肠道菌群组成的比较分析

Abstract Background While it is known that klotho has negative regulatory effects in a variety of diseases such as metabolic disorders and kidney disease, the specific role of klotho in rheumatoid arthritis (RA) and its effect on mortality are unclear. This study investigated the association between serum klotho levels and mortality in patients with RA. Methods This study included 841 adults with RA from the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2016 to extract the concentrations of serum klotho. The association between klotho and RA was determined using Cox regression, Kaplan–Meier (KM) curves, and restricted cubic spline (RCS) models. Results A total of 841 patients with RA were included in this study, who were divided into four groups based on the quartiles of serum klotho levels (Q1, Q2, Q3, and Q4). Cox regression analysis with adjustment for covariates revealed that high levels of klotho lowered the risk of both all-cause and cardiovascular mortality compared to the Q1 group. The KM curve analysis suggested that this effect was more pronounced for all-cause mortality. The RCS-fitted Cox regression model indicated a U-shaped correlation between serum klotho levels and RA mortality. The risk of all-cause mortality increased with decreasing serum klotho levels below a threshold of 838.81 pg/mL. Subgroup analysis revealed that the protective effect of klotho was more pronounced in patients with the following characteristics: male, white ethnicity, age ≥ 60 years, body mass index &lt; 25 kg/m 2 , estimated glomerular filtration rate ≥ 60 mL/ (min × 1.73 m 2 ), and 25-hydroxyvitamin D level ≥ 50 nmol/L. Conclusion Serum klotho levels had a U-shaped correlation with all-cause mortality in patients with RA, indicating that maintain a certain level of serum klotho could prevent premature death.

Qin-cheng Che

Qian Jia

Xiao-yu Zhang

Shu-ning Sun

Xiao-jie Zhang

Qiang Shu

A prospective study of the association between serum klotho and mortality among adults with rheumatoid arthritis in the USA

美国类风湿性关节炎成人血清klotho与死亡率关联的前瞻性研究

Abstract Objective The high potential of CD19.CAR-T cells to treat autoimmune diseases such as Systemic Sclerosis (SSc) supposedly relies on the disappearance of autoantibodies. Here we investigated effects of CAR-T cells on the innate immune system which is an important contributor to pathology in SSc. Methods Longitudinal analysis of peripheral blood mononuclear cells from an Scl70 + SSc patient treated with CAR-T cells sampled over 18 months by 29-color spectral flow cytometry, in vitro experiments using sera from patient cohorts. Results In the patient treated with CAR-T cells, the substantial clinical improvement was paralleled by dynamic changes in innate lymphoid cells, namely Fcγ-receptor IIIA-expressing natural killer (NK) cells. NK cells adopted a more juvenile, less activated, and less differentiated phenotype. In parallel, the potency of serum to form Scl70-containing immune complexes that activate Fcγ-receptor IIIA decreased over time. These observations suggested a mechanistic link between reversal of adaptive autoimmunity and recovering Fcγ-receptor IIIA-expressing innate immune cells after CAR-T cell therapy via regressing immune complex activity. Experiments with sera from the non-CAR-T-treated SSc cohort confirmed that Scl70-containing immune complexes activate Fcγ-receptor IIIA-expressing NK cells in a dose-dependent manner, substantiating the relevance of this link between adaptive and innate immunity in SSc. Conclusion This report describes for the first time the phenotypic recovery of innate Fcγ-receptor-expressing cells in an SSc patient treated with CAR-T cells. Decreasing autoantibody levels associated with a reduced ability to form functional immune complexes, the latter appearing to contribute to pathology in SSc via activation of Fcγ receptor IIIA + cells such as NK cells. Graphical Abstract Proposed mechanism of involvement of NK cells and soluble Immune Complexes (sICs) in disease progression during active autoimmunity in SSc (left) and resolution of fibrosis after deep B cell depletion by CD19.CAR-T cells and disappearance of autoantibodies (right).

Maren Claus

Merle Freitag

Meike Ewald

Lea Rodon

Franca Deicher

Carsten Watzl

Philipp Kolb

Hanns-Martin Lorenz

Michael Schmitt

Wolfgang Merkt

Immunological effects of CD19.CAR-T cell therapy in systemic sclerosis: an extended case study

CD19.CAR-T细胞疗法在系统性硬化症中的免疫学效应：一项扩展病例研究

Clonal T cell populations are frequently detected in patients with rheumatic diseases. The relevance of this finding is often uncertain, as the clinical spectrum can range from being asymptomatic to T cell leukemia. Former studies suggested that certain anti-rheumatic drugs might influence the course of the clonal T cell populations.

Michael Gernert

Tobias Müller

Lukas Schweiker

Marc Schmalzing

Matthias Fröhlich

Lea-Kristin Nagler

Patrick-Pascal Strunz

Hannah Labinsky

Eva Christina Schwaneck

Clonal T cell populations scarcely impair patients with rheumatic diseases: a prospective long-term follow up study

克隆性T细胞群体对风湿性疾病患者影响甚微：一项前瞻性长期随访研究

Abstract Background To investigate the association between the development of incident interstitial lung disease (ILD) in patients with rheumatoid arthritis (RA) and the disease activity of RA with its various components, especially C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). Methods We analysed data from RA patients, observed in the German biologics register RABBIT between 2001 and 2021. In a nested case-control study, patients with a reported incident ILD diagnosis during follow-up were matched 1:5 to patients without ILD. Matching criteria were sex, age, RA duration, date of enrolment and observation time. Defined by a directed acyclic graph (DAG), we adjusted the conditional logistic regression models for rheumatoid factor, smoking, chronic obstructive pulmonary disease and tuberculosis/chronic viral infections to investigate the impact of disease activity/systemic inflammation. Mean and categorized values were analysed within 12 months prior to ILD and during the entire observation time. Additionally, two sensitivity analyses were performed, using validated ILD cases only and considering ILD cases with an observation time of more than 12 months. Results We identified 139 RA patients with incident ILD and matched them to 686 controls. In 94 cases the diagnosis could be validated, and 98 cases had a follow-up of &gt; 12 months. The averaged DAS28 composite score (including ESR or CRP) was not associated with developing RA-ILD (odds ratios 1.16 [95% confidence interval: 0.97–1.40] and 1.06 [0.86–1.29], respectively). However, single measures of inflammation, log ESR (1.86 [1.35–2.57]) and log CRP (1.55 [1.21–1.97]), were significantly associated with an increased RA-ILD risk. A higher risk for ILD was also revealed for persistently high inflammation. Other DAS28 components showed no significant associations with RA-ILD. These results were consistent for values over the entire observation time of a patient and within 12 months prior to the ILD. Sensitivity analyses confirmed these findings. Conclusion Higher levels of systemic inflammation, as indicated by ESR and CRP, but not joint counts or patient’s global assessment, were significantly associated with the occurrence of incident ILD in patients with RA. As possible predictor for the development of RA-ILD, systemic inflammation should be monitored closely and independently of joint count results.

Ronja Ramien

Tatjana Rudi

Rieke Alten

Andreas Krause

Matthias Schneider

Martin Schaefer

Anja Strangfeld

Yvette Meissner

Impact of systemic inflammation and disease activity on the incidence of interstitial lung disease in patients with rheumatoid arthritis – a nested case-control study within the German biologics register RABBIT

系统性炎症和疾病活动对类风湿性关节炎患者间质性肺疾病发病率的影响——基于德国生物制剂注册登记RABBIT的嵌套病例对照研究

Abstract Background Spondyloarthritides (SpAs) are a group of common rheumatic diseases that often cause limited mobility and lower back pain. Physiotherapy is an integral part of treatment, but access to physiotherapy limits treatment success. Digital health applications (DHAs) enable home-based physiotherapy and could significantly improve access for SpAs patients. The aim is to investigate the clinical effects of the DHA ViViRA compared with those of standard physiotherapy. Methods SpAs patients with chronic back pain were enrolled in a randomized controlled trial. The intervention group received ViViRA DHA, whereas the control group received standard physiotherapy. Pain (verbal rating scale, PAIN-Detect), quality of life (SF-36) and mobility (BASMI) were assessed at baseline and after 12 weeks as the primary outcomes. Results Data from 59 participants (71.2% female, mean age 45.2 years) were analyzed. The intervention group showed a significant improvement in mobility (average BASMI score: baseline: 1.1 [range 0.7–1.5]; follow-up: 1.0 [range 0.5–1.4]; p = 0.05), whereas the control group showed a significant decrease in mobility (baseline: 1.5 [range 1.1–1.9]; follow-up: 1.8 [range 1.4–2.2]; p = 0.00). The intervention group demonstrated lower pain intensity (VRS pain level at week 3.5 ± 2.8) than did the control group (VRS pain level at week 4.5 ± 2) after 12 weeks. Conclusion Our results highlight the efficacy of DHAs such as ViViRA in the treatment of lower back pain in SpAs patients. Compared with the current gold standard, physiotherapy, DHA use results in superior outcomes. However, further larger studies are needed to confirm these promising results. Trial registration The study is registered in the German clinical trial registry (DRKS) under the following ID: DRKS00031254.

Paloma Palm von Alten Blaskowitz

Anna-Maria Liphardt

Claudia Bouzas

Birte Coppers

Pascal Petit

Nicolas Vuillerme

Vanessa Bundle

Sebastian Rudolf

Johannes Knitza

Maria Gabriella Raimondo

Lukas Hatscher

Andreas Wirsching

Daniela Bohr

Elizabeth Araujo

Andreas Ramming

Alina Ramming

Georg Schett

Harriet Morf

Impact of the digital health application ViViRA on spinal mobility, physical function, quality of life and pain perception in spondyloarthritides patients: a randomized controlled trial

数字健康应用ViViRA对脊柱关节炎患者脊柱活动度、身体功能、生活质量和疼痛感知的影:一项随机对照试验

This study investigates the causal role of metabolites mediating immune cells in rheumatoid arthritis (RA) and ankylosing spondylitis (AS) through a Mendelian randomization (MR) study. The two-sample and two-step MR methods were used for the current analysis: (1) causal effects of immune cells on RA and AS; (2) mediation effects of metabolites. Inverse variance weighted (IVW) is the main method to analyze causality, and MR results are verified by several sensitive analyses. This study first identified the immune cells and metabolites that are causally associated with RA and AS, respectively. Subsequent mediation analyses revealed that of the 61 metabolic factors that were causally associated with RA, 6 were identified as mediators of the relationship between immune cells and RA, including 4-cholesten-3-one levels (mediation ratio: 8.91%), N-lactoyl isoleucine levels (13%), 3- phosphoglycerate to glycerate ratio (12.9%, 2.31%, respectively), Gamma-glutamyl histidine levels (9.54%), and Citrulline to phosphate ratio (15.6%). Among the 52 metabolic factors that were causally associated with AS, 2 were identified as mediators of the relationship between immune cells and AS, including salicylate levels (10.4%) and Glucose to N-palmitoyl-sphingosine (d18:1 to 16:0) ratio (8.72%). These results performed well in sensitivity analysis. Genetic predictions show causal relationships between immune cells and autoimmune diseases, and that these causal relationships can be mediated by certain metabolites as mediators.

Jinpeng Wei

Jian Li

Tianyang Li

Tao Xu

Yingchi Zhang

Shuhan Yang

Hua Wu

Haihu Hao

Genetically predicted metabolite mediates the causal relationship between immune cells and autoimmune diseases

遗传预测的代谢物介导免疫细胞与自身免疫病之间的因果关系

Abbreviation	Arthritis Res Ther
Journal Impact	4.57
Quartiles(Global)	RHEUMATOLOGY(Q1)

ISSN	1478-6354, 1478-6362
h-index	177
Top Journals	Yes

Publication Information	Publisher: BioMed Central Ltd，Publishing cycle: ，Journal Type: journal，Open Access Journals: Yes
Basic data	Year of publication: 2003，Proportion of original research papers: 93.92%，Self Citation Rate:2.30%， Gold OA Rate: 100.00%
Journal Fees	$3390Details
Average review cycle	网友分享经验：平均2.3月
Average recruitment ratio	网友分享经验：约41.66%

Arthritis Research and Therapy

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