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Mitophagy drives maldifferentiation of tissue-resident memory T cells in patients with rheumatoid arthritis. 有丝分裂促使类风湿性关节炎患者的组织驻留记忆 T 细胞发生低分化。
IF 2.2 4区 医学 Q3 RHEUMATOLOGY Pub Date : 2025-03-01 Epub Date: 2024-11-15 DOI: 10.1080/03009742.2024.2420432
T Liu, M Wang, L Li, T Wu, H Ji, M Zheng, L Tang, W Gan, Z Wen, F Yuan

Objective: To investigate the function of mitophagy in instructing T-cell differentiation of patients with rheumatoid arthritis (RA).

Method: The mRNA and protein levels of optic atrophy protein-1 were detected in T cells from 94 RA patients and 37 age- and sex-matched healthy individuals by quantitative polymerase chain reaction and Western blotting. The impact of mitophagy on the differentiation of T cells was determined by flow cytometry. The therapeutic effect of targeting mitophagy was explored in humanized RA chimeras.

Results: Our study showed that T cells exerted high levels of mitophagy in RA patients. Since multiple T-cell subtypes play crucial roles in RA, we determined that mitophagy had a significant impact on the differentiation of tissue-resident memory T (Trm) cells, but not Th1 or Th17 cells. Importantly, we demonstrated that inhibiting mitophagy significantly reduced the number of Trm cells and downregulated inflammatory responses, as evidenced by diminished levels of T cell receptor β, interferon-γ, and interleukin-17A, in the humanized RA chimeras.

Conclusions: Mitophagy is elevated in RA T cells, leading to maldifferentiation of Trm cells in RA patients. Since these findings were obtained from clinical patients, mitophagy may be a potential therapeutic target for RA treatment.

目的研究类风湿性关节炎(RA)患者有丝分裂在指导T细胞分化中的功能:方法:通过定量聚合酶链式反应和 Western 印迹法检测 94 名 RA 患者和 37 名年龄与性别匹配的健康人 T 细胞中视神经萎缩蛋白-1 的 mRNA 和蛋白水平。流式细胞仪测定了有丝分裂对T细胞分化的影响。在人源化 RA 嵌合体中探讨了靶向有丝分裂的治疗效果:我们的研究表明,RA 患者的 T 细胞具有高水平的有丝分裂作用。由于多种T细胞亚型在RA中发挥关键作用,我们确定有丝分裂对组织驻留记忆T细胞(Trm)的分化有显著影响,但对Th1或Th17细胞没有影响。重要的是,我们证实抑制有丝分裂可显著减少Trm细胞的数量,并下调炎症反应,这体现在人源化RA嵌合体中T细胞受体β、干扰素-γ和白细胞介素-17A水平的降低:结论:RA T细胞的有丝分裂率升高,导致RA患者的Trm细胞分化不良。结论:RA T细胞的有丝分裂率升高,导致RA患者的Trm细胞分化不良。由于这些发现来自临床患者,有丝分裂可能是RA治疗的潜在治疗靶点。
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引用次数: 0
Lower limb pain as the initial manifestation of primary Sjögren's syndrome with diffuse large B-cell lymphoma: a case report. 下肢疼痛作为原发性Sjögren综合征伴弥漫性大b细胞淋巴瘤的初始表现:1例报告。
IF 2.1 4区 医学 Q3 RHEUMATOLOGY Pub Date : 2025-03-01 Epub Date: 2025-02-10 DOI: 10.1080/03009742.2025.2451449
J Gan, S Wang
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引用次数: 0
Agreement between child- and parent-reported orofacial symptoms in patients with juvenile idiopathic arthritis. 幼年特发性关节炎患者口面部症状的儿童和家长报告之间的一致性。
IF 2.2 4区 医学 Q3 RHEUMATOLOGY Pub Date : 2025-03-01 Epub Date: 2024-10-30 DOI: 10.1080/03009742.2024.2412459
J M Halbig, T K Pedersen, E B Nordal, M Twilt, P Stoustrup

Objective: To assess the agreement between child- and parent-reported orofacial symptoms in the Danish version of the patient questionnaire Assessment of Orofacial Symptoms in Juvenile Idiopathic Arthritis.

Method: This cross-sectional study was conducted at Aarhus University in March 2023. Eligible candidates were consecutive subjects with juvenile idiopathic arthritis (JIA) and temporomandibular joint involvement accompanied by a parental proxy for examination in the Craniofacial Clinic. After obtaining written informed consent, the questionnaire was completed individually and separately by the child and the parent without any communication between them. The level of agreement was analysed using Cohen's (weighted) kappa for nominal and ordinal outcome variables (orofacial pain frequency, pain location, jaw function, orofacial symptoms, and changes since last visit) and the intraclass correlation coefficient for linear outcome variables (orofacial pain intensity and functional disability of the jaw).

Results: The 34 included dyads had an overall 'poor' to 'moderate' child-proxy reporting agreement on the questionnaire for the assessment of JIA-related orofacial symptoms. After dividing the children into two age groups, < 13 and ≥ 13 years old, we found substantial agreement on pain frequency and moderate to excellent agreement on pain intensity for the older group. The child-proxy agreement for children aged < 13 years was slight on pain frequency and poor to moderate on pain intensity.

Conclusion: The child-proxy reporting agreement on JIA-related orofacial symptoms is inconsistent. We suggest collecting information from both children and parents, especially when assessing orofacial pain and symptoms in children < 13 years of age.

目的评估丹麦语版 "青少年特发性关节炎口面部症状评估 "患者问卷中儿童和家长报告的口面部症状之间的一致性:这项横断面研究于 2023 年 3 月在奥胡斯大学进行。符合条件的受试者均为患有幼年特发性关节炎(JIA)和颞下颌关节受累的连续受试者,并由家长陪同到颅颌面诊所接受检查。在获得书面知情同意后,儿童和家长分别单独填写问卷,彼此之间不进行任何交流。采用科恩(加权)卡帕对名义和顺序结果变量(口面部疼痛频率、疼痛部位、颌骨功能、口面部症状和上次就诊后的变化)的一致性水平进行了分析,并对线性结果变量(口面部疼痛强度和颌骨功能障碍)的类内相关系数进行了分析:结果:所纳入的 34 个二人组在评估 JIA 相关口面部症状的问卷中,儿童与代理报告的总体一致性为 "较差 "至 "中等"。在将儿童分为两个年龄组后,结论得出:儿童和代理人对 JIA 相关口面部症状报告的一致性并不一致。我们建议同时收集儿童和家长的信息,尤其是在评估儿童口面部疼痛和症状时。
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引用次数: 0
Elevated neutrophil-to-lymphocyte and monocyte-to-lymphocyte ratios are associated with increased flares and elevated cardiovascular disease risk in gout. 中性粒细胞与淋巴细胞比率和单核细胞与淋巴细胞比率升高与痛风中耀斑增加和心血管疾病风险升高有关。
IF 2.2 4区 医学 Q3 RHEUMATOLOGY Pub Date : 2025-03-01 Epub Date: 2025-01-17 DOI: 10.1080/03009742.2024.2421622
R D Stultz, L Dai, E van Geel, M Gerritsen, M T Nurmohamed, C Lood

Objective: Although gout is the most common inflammatory arthritis, there are few tools to monitor disease activity and predict complications in gout patients. The neutrophil-to-lymphocyte ratio (NLR) and monocyte-to-lymphocyte ratio (MLR) are associated with disease activity in various diseases and the NLR has been shown to predict coronary artery disease severity, a common comorbid condition with gout. Thus, we evaluated the use of NLR and MLR as novel biomarkers to measure disease activity and predict cardiovascular disease (CVD) risk in gout patients.

Method: Data were collected from 38 gout patients. Disease activity, including total number of acute gout attacks, and 10 year risk of cardiovascular morbidity, were assessed at the patient's visit. Calprotectin, cell counts, and uric acid levels were measured from patients' blood.

Results: Levels of the neutrophil activation marker calprotectin correlated with NLR (r = 0.56, p = 0.0004). MLR correlated with total number of gout attacks as well (r = 0.39, p = 0.02). NLR and MLR, but not absolute monocyte or neutrophil counts, were significantly correlated with body mass index and significantly increased in gout patients with high CVD risk (p < 0.05). Using logistic regression analysis, patients with high NLR or MLR (defined as the upper quartile of patients) had increased odds of developing high CVD risk (odds ratio 7.5, 95% confidence interval 1.7-33.0).

Conclusion: NLR and MLR are potential biomarkers to predict gout flare risk. An increase in either may indicate an increased risk of CVD morbidity.

目的:虽然痛风是最常见的炎症性关节炎,但很少有工具来监测疾病活动和预测痛风患者的并发症。中性粒细胞与淋巴细胞比率(NLR)和单核细胞与淋巴细胞比率(MLR)与各种疾病的疾病活动性有关,NLR已被证明可预测冠状动脉疾病的严重程度,这是痛风的常见合并症。因此,我们评估了NLR和MLR作为测量疾病活动性和预测痛风患者心血管疾病(CVD)风险的新型生物标志物的使用。方法:收集38例痛风患者的资料。在患者就诊时评估疾病活动性,包括急性痛风发作的总次数和10年心血管发病率的风险。从患者的血液中测量钙保护蛋白、细胞计数和尿酸水平。结果:中性粒细胞活化标志物钙保护蛋白水平与NLR相关(r = 0.56, p = 0.0004)。MLR与痛风总发作次数相关(r = 0.39, p = 0.02)。NLR和MLR与体重指数显著相关,而单核细胞和中性粒细胞的绝对计数与体重指数无显著相关性,且痛风高危患者的NLR和MLR显著升高(p < 0.05)。通过logistic回归分析,NLR或MLR高的患者(定义为患者的上四分位数)发生心血管疾病高风险的几率增加(优势比为7.5,95%置信区间为1.7-33.0)。结论:NLR和MLR是预测痛风耀斑风险的潜在生物标志物。两者中任何一项的增加都可能表明心血管疾病发病率的增加。
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引用次数: 0
Macrophage colony-stimulating factor receptor/CD115+ non-classical monocytes are expanded in systemic lupus erythematosus and associated with lupus nephritis. 巨噬细胞集落刺激因子受体/CD115+非典型单核细胞在系统性红斑狼疮中扩增并与狼疮肾炎相关。
IF 2.2 4区 医学 Q3 RHEUMATOLOGY Pub Date : 2025-03-01 Epub Date: 2024-08-22 DOI: 10.1080/03009742.2024.2387483
M Zeisbrich, R Rzepka, S Finzel, N Venhoff, R E Voll

Objective: In systemic lupus erythematosus (SLE), the non-classical monocyte compartment is expanded, but its phenotype and association with clinical disease manifestations have not been explored.

Method: Monocyte subsets from 39 SLE patients, 32 healthy age-matched controls, and 16 patients from a disease control (autoimmune connective tissue disease other than SLE) were determined based on CD14 and CD16 surface expression. Cell surface expression of the receptors for macrophage colony-stimulating factor (M-CSF) (CD115) and granulocyte-macrophage colony-stimulating factor (GM-CSF) (CD116), as well as 6-Sulpho LacNAc (slan), were analysed by flow cytometry. The association of monocyte populations with disease manifestations, disease activity markers, and current medication of each patient was analysed by chart review.

Results: Non-classical monocytes displayed a cell-type specific signature of high M-CSF receptor CD115 and low GM-CSF receptor CD116 expression that separated them from the other two monocyte subsets. In healthy individuals, the M-CSF receptor on non-classical monocytes was an age-dependent surface marker, with lower expression in young adults. However, SLE monocytes were characterized by a marked expansion of M-CSF receptor/CD115+ non-classical monocytes in patients of all ages. The expanded population of M-CSF receptor/CD115+ non-classical monocytes was associated with lupus nephritis but not with disease activity, and coexpressed slan.

Conclusion: The non-classical monocyte subset in SLE is characterized by an expansion of M-CSF receptor/CD115+ cells that are associated with lupus nephritis and coexpress slan.

目的:在系统性红斑狼疮(SLE)患者中,非典型单核细胞增多,但其表型及其与临床疾病表现的关系尚未得到研究:在系统性红斑狼疮(SLE)中,非典型单核细胞区系扩大,但其表型及其与临床疾病表现的关系尚未得到探讨:根据 CD14 和 CD16 的表面表达确定了 39 名系统性红斑狼疮患者、32 名年龄匹配的健康对照者和 16 名疾病对照者(系统性红斑狼疮以外的自身免疫性结缔组织疾病)的单核细胞亚群。流式细胞术分析了巨噬细胞集落刺激因子(M-CSF)(CD115)和粒细胞-巨噬细胞集落刺激因子(GM-CSF)(CD116)受体以及 6-Sulpho LacNAc(slan)的细胞表面表达。通过病历审查分析了单核细胞群与每位患者的疾病表现、疾病活动指标和当前用药的关联:结果:非典型单核细胞显示出细胞类型特异性特征,即高M-CSF受体CD115和低GM-CSF受体CD116表达,这将它们与其他两个单核细胞亚群区分开来。在健康人中,非典型单核细胞上的 M-CSF 受体是一个与年龄相关的表面标志物,年轻成人的表达量较低。然而,系统性红斑狼疮单核细胞的特点是,在所有年龄段的患者中,M-CSF 受体/CD115+ 非典型单核细胞明显增多。M-CSF受体/CD115+非典型单核细胞群的扩大与狼疮肾炎有关,但与疾病活动无关,并且共同表达slan:结论:系统性红斑狼疮的非典型单核细胞亚群的特点是 M-CSF 受体/CD115+细胞扩增,这与狼疮肾炎有关,并共同表达 slan。
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引用次数: 0
'Pencil-in-cup' deformity in systemic sclerosis-rheumatoid arthritis overlap syndrome. 系统性硬化症-类风湿关节炎重叠综合征的“铅笔杯”畸形。
IF 2.2 4区 医学 Q3 RHEUMATOLOGY Pub Date : 2025-03-01 Epub Date: 2025-02-11 DOI: 10.1080/03009742.2025.2456323
E A Acar, S Uslu, O Soysal Gündüz, T Pirildar
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引用次数: 0
Reviewer acknowledgement December 2023 - November 2024. 评审确认2023年12月- 2024年11月。
IF 2.2 4区 医学 Q3 RHEUMATOLOGY Pub Date : 2025-01-01 Epub Date: 2025-01-22 DOI: 10.1080/03009742.2025.2434411
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引用次数: 0
Ultrasonographic findings in diabetic cheiroarthropathy: a pilot study. 糖尿病螯状关节病的超声波检查结果:一项试验性研究。
IF 2.2 4区 医学 Q3 RHEUMATOLOGY Pub Date : 2025-01-01 Epub Date: 2024-07-12 DOI: 10.1080/03009742.2024.2374106
C Löffler, J Leipe, B Hellmich

Objective: Diabetic cheiroarthropathy (DCA) is one of the musculoskeletal manifestations of diabetes mellitus. It is clinically diagnosed using the prayer and tabletop signs. The clinical appearance, however, mimics autoimmune-mediated polyarthritis of the hands and fingers. It is therefore crucial to positively identify DCA patients.

Method: We used high-frequency B-mode ultrasound to investigate 14 patients with DCA and seven non-DCA diabetics with anti-cyclic citrullinated peptide antibody-positive rheumatoid arthritis (RA). We recorded the frequency of synovitis in radiocarpal, metacarpophalangeal, and proximal interphalangeal joints, the presence of tenosynovitis of the finger flexor tendons, echogenicity of the synovia and the flexor tendon sheaths, and soft tissue alterations in the digits. We compared our findings between groups to determine sonographic characteristics of DCA.

Results: A low rate of small finger joint involvement in the presence of a high rate of finger flexor tendinopathy showed a high association with DCA in correlation (p = 0.002) and regression analysis (p < 0.001). Tendon sheaths were significantly more often hyperechoic and proliferative in DCA compared to RA (p = 0.008), and hypoechoic soft tissue alterations were almost exclusively seen in DCA patients (p = 0.003). Radiocarpal joint involvement and its echogenicity did not differ between groups.

Conclusion: Ultrasonography shows typical features in DCA, and is capable of discriminating DCA from non-DCA patients with RA and diabetes.

目的:糖尿病螯状关节病(DCA)是糖尿病的肌肉骨骼表现之一。临床上可通过祈祷征和桌面征诊断该病。但其临床表现类似于自身免疫介导的手和手指多关节炎。因此,积极识别 DCA 患者至关重要:方法:我们使用高频 B 型超声波检查了 14 名 DCA 患者和 7 名抗环瓜氨酸肽抗体阳性的非 DCA 糖尿病患者的类风湿性关节炎(RA)。我们记录了放射性指关节、掌指关节和近端指间关节滑膜炎的频率、手指屈肌腱腱鞘炎的存在情况、滑膜和屈肌腱鞘的回声以及手指软组织的改变。我们比较了各组之间的研究结果,以确定 DCA 的声像图特征:结果:在相关分析(P = 0.002)和回归分析(P)中,小指关节受累率低而屈指肌腱病变率高与 DCA 关系密切:超声波检查显示了DCA的典型特征,能够区分DCA与非DCA的RA和糖尿病患者。
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引用次数: 0
Long-term association between physical activity and global functioning in patients with axial spondyloarthritis: results of a two-year prospective study. 轴性脊柱关节炎患者体育锻炼与整体功能之间的长期关系:一项为期两年的前瞻性研究结果。
IF 2.2 4区 医学 Q3 RHEUMATOLOGY Pub Date : 2025-01-01 Epub Date: 2024-07-24 DOI: 10.1080/03009742.2024.2376810
K Y Kang, S Y Park, T H Chung

Objectives: To assess the longitudinal association between physical activity and global functioning in patients with axial spondyloarthritis (axSpA), and to identify the subtype of physical activity that is longitudinally related to global functioning.

Method: Physical activity was measured using Global Physical Activity Questionnaire. Global functioning was assessed using the Assessment of SpondyloArthritis international Society Health Index (ASAS HI). The amount and subtype (work, transport, and recreation) of physical activity, disease activity, and ASAS HI were assessed at baseline, and at 1 and 2 year follow-up. Physical activity levels were categorized as low, moderate, or high. The longitudinal association between physical activity and ASAS HI scores was analysed using a generalized estimating equation.

Results: The study evaluated 160 patients. Univariate analysis identified physical activity at moderate level and higher, Ankylosing Spondylitis Disease Activity Score (ASDAS), and syndesmophyte number as being longitudinally associated with ASAS HI over 2 years. Multivariate analysis identified physical activity at moderate level and higher as being longitudinally associated with ASAS HI. Physical activity above moderate levels was associated independently with good global functioning. In the analysis stratified by radiographic axSpA and non-radiographic axSpA, a positive association between physical activity and global functioning was observed in both groups. Only recreational activity, but not work- and transport-related activity, showed an independent longitudinal relationship with the ASAS HI score.

Conclusions: Physical activity at moderate level and higher was associated independently with global functioning in axSpA. Therefore, patients should maintain physical activity above moderate levels to preserve global function.

目的评估轴性脊柱关节炎(axSpA)患者的体力活动与整体功能之间的纵向关系,并确定与整体功能有纵向关系的体力活动亚型:方法:使用全球体力活动调查问卷测量体力活动。采用脊柱关节炎国际协会健康指数评估(ASAS HI)对整体功能进行评估。在基线以及 1 年和 2 年的随访中,对体力活动量和亚类型(工作、交通和娱乐)、疾病活动和 ASAS HI 进行了评估。体力活动水平分为低、中、高三个等级。采用广义估计方程分析了体力活动与 ASAS HI 分数之间的纵向联系:研究对 160 名患者进行了评估。单变量分析表明,中度及以上体力活动、强直性脊柱炎疾病活动评分(ASDAS)和联合骨质数量与两年内的 ASAS HI 有纵向关联。多变量分析表明,中等水平及以上的体力活动与 ASAS HI 纵向相关。中等水平以上的体力活动与良好的整体功能独立相关。在按放射性轴性SpA和非放射性轴性SpA进行的分层分析中,两组患者的体力活动与整体功能均呈正相关。只有娱乐活动与ASAS HI评分有独立的纵向关系,而与工作和交通相关的活动则没有:结论:中等水平及以上的体力活动与 axSpA 患者的整体功能有独立的关系。因此,患者应保持中等水平以上的体力活动,以保护全身功能。
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引用次数: 0
Methotrexate prolonged the shedding of replicable SARS-CoV-2 with re-increased antigens in a rheumatoid arthritis patient. 甲氨蝶呤延长了一名类风湿性关节炎患者体内可复制的 SARS-CoV-2 的脱落时间,并重新增加了抗原。
IF 2.2 4区 医学 Q3 RHEUMATOLOGY Pub Date : 2025-01-01 Epub Date: 2024-09-04 DOI: 10.1080/03009742.2024.2361994
A Takatani, T Kobayashi, N Iwamoto, T Aramaki, K Terada, K Izumikawa, M M Ngwe Tun, K Morita, Y Ueki, A Kawakami, K Eguchi
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引用次数: 0
期刊
Scandinavian Journal of Rheumatology
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