Arthritis & Rheumatology最新文献_第3页

A randomized, placebo-controlled trial of hydroxychloroquine in incomplete lupus. 羟氯喹治疗不完全性狼疮的随机、安慰剂对照试验。

IF 13.3 1区医学

Arthritis & Rheumatology Pub Date : 2025-09-16 DOI: 10.1002/art.43391

Nancy J Olsen,Duanping Liao,Judith A James,Joel M Guthridge,Cristina Arriens,Diane Kamen,Mariko Ishimori,Daniel J Wallace,Christopher Striebich,Sonali Narain,Benjamin F Chong,Fan He,Eric W Schaefer,Vernon M Chinchilli,David R Karp

{"title":"A randomized, placebo-controlled trial of hydroxychloroquine in incomplete lupus.","authors":"Nancy J Olsen,Duanping Liao,Judith A James,Joel M Guthridge,Cristina Arriens,Diane Kamen,Mariko Ishimori,Daniel J Wallace,Christopher Striebich,Sonali Narain,Benjamin F Chong,Fan He,Eric W Schaefer,Vernon M Chinchilli,David R Karp","doi":"10.1002/art.43391","DOIUrl":"https://doi.org/10.1002/art.43391","url":null,"abstract":"OBJECTIVESPatients with features of systemic lupus erythematosus (SLE) who do not fulfill classification criteria can be designated as incomplete lupus (ILE). This condition includes individuals with a high risk of progression to SLE. Treatment of ILE may reduce symptoms, severity and incidence of SLE.METHODSHydroxychloroquine (HCQ) was chosen as an ILE intervention for a randomized, double-blind trial to determine whether rate of accumulation of SLE features defined by the 2012 SLICC criteria could be reduced. ILE was defined as ANA positivity with 1-2 additional criteria. Patients 15-49 years old were eligible. Randomization was 1:1 HCQ to placebo. Evaluations were at 3-month intervals over 24 months. Meeting SLICC classification sooner required exit.RESULTSParticipants (n=187) were randomized at 7 sites. After excluding 7 patients who met SLE classification at baseline when screening laboratory data were completed, 180 patients were analyzed: 92 on HCQ and 88 on placebo. The mean age was 33 years, 91.1% were female and 74.4% were white. SLE classification developed in 24 (13.3%); another 24 developed additional criteria but did not meet classification. The rates of acquisition of SLICC criteria and progression to SLE were similar in the two groups (P=0.72 and P=0.98, respectively). Development of SLE was associated with new malar rash, oral ulcers, joint tenderness or pleurisy (P<0.04).CONCLUSIONWhile SMILE did not show effects of HCQ on ILE progression, the results offer insights into SLE risk in the ILE population. With development of biomarkers, designing targeted prevention strategies should be feasible.","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"83 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145068243","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Mesenchymal Stromal Cell Therapy Alleviates Lupus Nephritis Through Inhibiting Caspase-4/5/11-mediated Noncanonical Pyroptosis in Macrophages. 间充质间质细胞治疗通过抑制caspase -4/5/11介导的巨噬细胞非典型焦亡来缓解狼疮性肾炎。

IF 13.3 1区医学

Arthritis & Rheumatology Pub Date : 2025-09-16 DOI: 10.1002/art.43380

Sha Liu,Zhikang Wang,Yue Zhang,Panpan Zhou,Huimin Zhu,Yang Hang,Xue Xu,Xiaojun Tang,Genhong Yao,Dandan Wang,Linyu Geng,Weiwei Chen,Lingyun Sun

{"title":"Mesenchymal Stromal Cell Therapy Alleviates Lupus Nephritis Through Inhibiting Caspase-4/5/11-mediated Noncanonical Pyroptosis in Macrophages.","authors":"Sha Liu,Zhikang Wang,Yue Zhang,Panpan Zhou,Huimin Zhu,Yang Hang,Xue Xu,Xiaojun Tang,Genhong Yao,Dandan Wang,Linyu Geng,Weiwei Chen,Lingyun Sun","doi":"10.1002/art.43380","DOIUrl":"https://doi.org/10.1002/art.43380","url":null,"abstract":"BACKGROUNDCaspase-4/5/11 mediated noncanonical pyroptosis emerges as a contributing factor in immune responses under pathological conditions. However, its precise role in the development of lupus nephritis (LN) remains largely unknown. Although mesenchymal stromal cells (MSCs) have demonstrated promising therapeutic effects on LN, whether MSCs influence pyroptosis in macrophages remains unknown. This study aimed to elucidate the role of caspase-4/5/11-mediated noncanonical pyroptosis in macrophages during the pathogenesis of LN and explore the impact of MSCs on macrophages.METHODSThe expression level of noncanonical pyroptosis in macrophages was assessed in patients and mice with LN. Blood samples from 19 refractory SLE patients receiving MSCs transplantation (MSCT) were collected. Caspase-11 inhibitor wedelolactone and MSCs were administered to MRL/lpr mice to examine the therapeutic efficacy. MSCs were co-cultured with macrophages from MRL/lpr mice to explore effects and related mechanisms.RESULTSNoncanonical pyroptosis signaling was activated in macrophages and kidney tissues from humans and mice with LN. The expression level of caspase-4 was increased and positively correlated with the active index and chronic index in the kidneys of LN patients. The end products of pyroptosis directly induced cell death and reduced functional markers expression in murine podocytes. The caspase-11 inhibitor effectively alleviated renal damage in lupus mice. MSCT significantly deactivated pyroptosis signaling both in patients and lupus-prone mice. Mechanically, galectin-3 and interleukin-10 (IL-10) are essential for MSCs to inhibit noncanonical pyroptosis of LN macrophages.CONCLUSIONSOur findings showed that MSCT ameliorates LN by inhibiting the caspase-4/5/11-mediated pyroptosis in macrophages, possibly via secreting galectin-3 and IL-10.","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"35 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145068244","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Interleukin-23 receptor deficiency in podocytes averts the development of lupus nephritis. 足细胞中白细胞介素-23受体缺乏可避免狼疮肾炎的发展。

IF 13.3 1区医学

Arthritis & Rheumatology Pub Date : 2025-09-15 DOI: 10.1002/art.43395

Rong Fu,Afroditi Boulougoura,Shuilian Yu,Hao Li,Wenliang Pan,Yushiro Endo,Rhea Bhargava,Abhiyan Satyam,Vivek Kasinath,Jarrat Jordan,Nandan Padmanabha,Maria G Tsokos,Reza Abdi,George C Tsokos

{"title":"Interleukin-23 receptor deficiency in podocytes averts the development of lupus nephritis.","authors":"Rong Fu,Afroditi Boulougoura,Shuilian Yu,Hao Li,Wenliang Pan,Yushiro Endo,Rhea Bhargava,Abhiyan Satyam,Vivek Kasinath,Jarrat Jordan,Nandan Padmanabha,Maria G Tsokos,Reza Abdi,George C Tsokos","doi":"10.1002/art.43395","DOIUrl":"https://doi.org/10.1002/art.43395","url":null,"abstract":"OBJECTIVEUpregulation of Interleukin 23 (IL-23) in the serum and kidneys of patients with lupus nephritis (LN) has been demonstrated, but its effect on podocytes remains unknown. We hypothesized that IL-23 contributes to podocyte injury and that targeted deletion of IL-23R in podocytes of lupus-prone mice can prevent the development of glomerulonephritis.METHODSKidney biopsies were immunostained for IL-23R. In vitro experiments were conducted using a human podocyte cell line and primary murine podocytes. Human podocytes stimulated with IL-23 underwent bulk-RNA sequencing. The expression of IL-23R, structure and motility of podocytes were assessed. Podocytes isolated from B6 wild type mice injected with a minicircle (MC) encoding IL-23 were studied. To assess the role of IL-23R in the development of nephritis, we generated podocyte-specific Il23r deficient MRL/lpr lupus-prone mice.RESULTSIL-23R was highly expressed in the glomeruli of patients with LN. IL-23R expression was also upregulated in human podocytes and primary podocytes isolated from B6 mice after IL-23 stimulation. Human podocytes stimulated with IL-23 showed decreased expression of synaptopodin and remodeling of the actin cytoskeleton. IL-23 MC-administered mice exhibited a significant increase in the expression of IL-23R and phosphorylated STAT3 (pSTAT3) in podocytes. Finally, MRL/lpr.Podo-Cre+ Il23rfl/fl mice showed decreased clinical and histologic features of LN.CONCLUSIONIL-23R expression is increased in podocytes from mice and humans with systemic lupus erythematosus. IL-23 signaling disrupts the cytoskeleton in podocytes and increases their mobility leading to the development of glomerulonephritis. Podocyte-specific deletion of Il23r in lupus-prone mice abrogates the development of LN.","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"76 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145058888","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

ZBTB20 Regulating Postnatal Articular Cartilage Development and Homeostasis: Implications for Early-Onset Osteoarthritis. ZBTB20调节出生后关节软骨发育和体内平衡：对早发性骨关节炎的影响。

IF 13.3 1区医学

Arthritis & Rheumatology Pub Date : 2025-09-15 DOI: 10.1002/art.43393

Xianhua Ma,Fei Jiang,Zhenbang Qin,Yuqing Zhang,Chunchun Wei,Shuang Han,Yuxia Chen,Hai Zhang,Jiang Tao,Zhifang Xie,Weiping J Zhang

{"title":"ZBTB20 Regulating Postnatal Articular Cartilage Development and Homeostasis: Implications for Early-Onset Osteoarthritis.","authors":"Xianhua Ma,Fei Jiang,Zhenbang Qin,Yuqing Zhang,Chunchun Wei,Shuang Han,Yuxia Chen,Hai Zhang,Jiang Tao,Zhifang Xie,Weiping J Zhang","doi":"10.1002/art.43393","DOIUrl":"https://doi.org/10.1002/art.43393","url":null,"abstract":"OBJECTIVEMutations in ZBTB20, a transcription factor, are linked to epiphyseal dysplasia and articular degeneration in humans. This study investigates the role of ZBTB20 in regulating articular cartilage growth and integrity during postnatal development and its implications for early-onset osteoarthritis (OA) in mice.METHODSWe assessed the spatiotemporal expression of ZBTB20 in articular cartilage using immunostaining and generated an inducible cartilage-specific Zbtb20 knockout mouse model. The impacts of Zbtb20 deletion on cartilage thickness, zonal organization, cellular proliferation, and apoptosis were analyzed. We employed histology, Micro-CT, in situ hybridization, RNA-sequencing, and CUT&Tag to evaluate structural and molecular changes in knees from six to eight male mice per group. ZBTB20 expression in human OA cartilage was analyzed using publicly available datasets.RESULTSZBTB20 was expressed in postnatal developing and adult articular chondrocytes. Postnatal Zbtb20 deletion resulted in progressive thickening of articular cartilage in knees, with a 1.9-fold increase at 2 months of age, particularly in the deep and calcified zones. This was accompanied by chondrocyte overproliferation and differentiation defects, leading to early-onset cartilage degeneration by 6 months. RNA-sequencing and CUT&Tag analyses revealed that ZBTB20 directly regulates a broad set of genes essential for cartilage growth, chondrocyte differentiation, and extracellular matrix organization. Moreover, ZBTB20 expression was significantly reduced in aging-related OA cartilage in both mice and humans, and inducible deletion of Zbtb20 in adult cartilage resulted in severe spontaneous OA-like changes in mice.CONCLUSIONZBTB20 is essential for postnatal articular cartilage development and homeostasis, with a protective role in aging-related OA progression.","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"52 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145058887","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Comparative Real-World Effectiveness of Immunomodulatory Therapies for Prevention of Uveitis Relapse in Behçet's Disease. 免疫调节疗法预防beharret病葡萄膜炎复发的比较实际效果。

IF 13.3 1区医学

Arthritis & Rheumatology Pub Date : 2025-09-15 DOI: 10.1002/art.43382

Zhenyu Zhong,Jiayi Wang,Lan Xia,Shixiang Jing,Yujie Lai,Tao Cai,Peizeng Yang

{"title":"Comparative Real-World Effectiveness of Immunomodulatory Therapies for Prevention of Uveitis Relapse in Behçet's Disease.","authors":"Zhenyu Zhong,Jiayi Wang,Lan Xia,Shixiang Jing,Yujie Lai,Tao Cai,Peizeng Yang","doi":"10.1002/art.43382","DOIUrl":"https://doi.org/10.1002/art.43382","url":null,"abstract":"PURPOSETo evaluate comparative effectiveness of cyclosporine, interferon alfa-2a, and adalimumab for the prevention of uveitis relapse in Behçet's disease in real-world settings.METHODSWe emulated a target trial involving adult patients with Behçet's disease uveitis who initiated cyclosporine, interferon alfa-2a, or adalimumab between April 10, 2008, and August 1, 2024, and were followed up until September 10, 2024. We applied overlap weighting to balance patient characteristics across treatment groups and emulate randomization at baseline. The primary outcome was the annualized relapse rate of uveitis during treatment with study therapy.RESULTSThe cohort comprised 716 cyclosporine users, 193 interferon alfa-2a users, and 103 adalimumab users. The estimated mean annualized relapse rate of uveitis was 0.95 (95%, 0.82 to 1.10) with cyclosporine, 0.52 (95%, 0.40 to 0.69) with interferon alfa-2a, and 0.28 (95%, 0.19 to 0.43) with adalimumab. Patients treated with cyclosporine experienced more relapses than those treated with adalimumab (incidence rate ratio [IRR], 3.36 [95% CI, 2.23 to 5.05]; mean difference, 0.66 [95% CI, 0.48 to 0.85]; P<0.001) or interferon alfa-2a (IRR, 1.81 [95% CI, 1.37 to 2.40]; mean difference, 0.42 [95% CI, 0.22 to 0.62]; P<0.001). The relapse rate was higher with interferon alfa-2a than with adalimumab (IRR, 1.86 [95% CI, 1.16 to 2.97]; mean difference, 0.24 [95% CI, 0.05 to 0.43]; P=0.011).CONCLUSIONIn Behçet's disease, interferon alfa-2a was associated with a reduction in uveitis relapse compared with cyclosporine, while adalimumab demonstrated a stronger association with reduced relapse than interferon alfa-2a.","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"36 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145058953","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Response to: "Gut Microbiota Typing and Donor Factors Shape Fecal Microbiota Transplantation Response in Psoriatic Arthritis". 对“银屑病关节炎患者肠道菌群分型和供体因素影响粪便菌群移植反应”的回应。

IF 13.3 1区医学

Arthritis & Rheumatology Pub Date : 2025-09-15 DOI: 10.1002/art.43394

Maja S Kragsnaes,Panpan Qin,Jens Kjeldsen,Karsten Kristiansen,Torkell Ellingsen

引用次数: 0

Less Is More: Hematologic Safety and Sustained Efficacy of a Modified Low-dose Etoposide Regimen in MAS. 少即是多：改良的低剂量依托泊苷治疗MAS的血液学安全性和持续疗效。

IF 13.3 1区医学

Arthritis & Rheumatology Pub Date : 2025-09-15 DOI: 10.1002/art.43390

Zijun Ma,Xiaoquan Rao,Yingying Wei,Wei Tu,Jixin Zhong

引用次数: 0

Gut Microbiota Typing and Donor Factors Shape Fecal Microbiota Transplantation Response in Psoriatic Arthritis. 肠道菌群分型和供体因子影响银屑病关节炎患者粪便菌群移植反应。