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Adding low dose cyclophosphamide to rituximab for remission-induction may prolong relapse-free survival in patients with ANCA vasculitis: A retrospective study 在利妥昔单抗中加入低剂量环磷酰胺进行缓解诱导可能延长ANCA血管炎患者的无复发生存期:一项回顾性研究
IF 3.9 Q2 Medicine Pub Date : 2023-01-01 DOI: 10.1016/j.jtauto.2022.100178
Renée Ysermans , Matthias H. Busch , Joop P. Aendekerk , Jan G.M.C. Damoiseaux , Pieter van Paassen

Objective

Rituximab (RTX) and cyclophosphamide (CYC) are effective remission-induction therapies in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). However, combining these therapies may favor prognosis in patients with a major disease presentation. We conducted a retrospective study to compare patients treated with a combination of RTX and low dose CYC (RTX-CYC) or with RTX only, both followed by tailored maintenance with RTX, with regard to long-term outcomes.

Methods

Patients treated in the Maastricht University Medical Center between March 2007 and January 2019, were screened for eligibility. The primary outcome variable was major relapse rate after two and five years. Secondary outcome variables were clinical data and laboratory parameters.

Results

Of the 246 screened patients, 34 received RTX-CYC and 28 RTX only for remission-induction. All patients were followed for at least two years, with a median follow-up of 48 months (IQR 24–60). At baseline, renal involvement was more prevalent in the RTX-CYC patients (85% vs. 61%, P = 0.028). Major relapse rates within two years, but not after five years, were significantly lower in the RTX-CYC group (3% vs. 24%, P = 0.032). The rate of infections, hypogammaglobulinemia, end-stage renal disease, malignancies, and mortality did not differ after two and five years.

Conclusion

Adding low dose CYC to RTX is safe and may prevent major relapses in patients with severe AAV in the first two years after remission-induction. Randomized controlled trials that compare the efficacy and safety between RTX and a combination of RTX with CYC are needed.

目的:利妥昔单抗(RTX)和环磷酰胺(CYC)是抗中性粒细胞胞浆抗体(ANCA)相关血管炎(AAV)的有效缓解诱导疗法。然而,联合这些疗法可能有利于有重大疾病表现的患者的预后。我们进行了一项回顾性研究,比较RTX和低剂量CYC (RTX-CYC)联合治疗或仅RTX治疗的患者,两种治疗均采用RTX进行量身定制的维持,以观察长期结果。方法对2007年3月至2019年1月期间在马斯特里赫特大学医学中心接受治疗的患者进行资格筛选。主要结局变量为2年和5年后的主要复发率。次要结局变量为临床数据和实验室参数。结果在246例筛选的患者中,34例接受RTX- cyc治疗,28例仅用于缓解诱导。所有患者随访至少2年,中位随访48个月(IQR 24-60)。在基线时,肾受累在RTX-CYC患者中更为普遍(85%比61%,P = 0.028)。RTX-CYC组两年内的主要复发率显著低于RTX-CYC组(3% vs. 24%, P = 0.032)。感染率、低丙种球蛋白血症、终末期肾病、恶性肿瘤和死亡率在2年和5年后没有差异。结论在RTX中加入低剂量CYC是安全的,可以预防严重AAV患者在缓解诱导后的头2年内的严重复发。需要进行随机对照试验,比较RTX与RTX联合CYC的疗效和安全性。
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引用次数: 0
Belimumab treatment in autoimmune hepatitis and primary biliary cholangitis – a case series 贝利单抗治疗自身免疫性肝炎和原发性胆管炎-一个病例系列
IF 3.9 Q2 Medicine Pub Date : 2023-01-01 DOI: 10.1016/j.jtauto.2023.100189
Mirjam Kolev , Adela-Cristina Sarbu , Burkhard Möller , Britta Maurer , Florian Kollert , Nasser Semmo

Background

The majority of patients with autoimmune hepatitis (AIH) achieve complete remission with established treatment regiments. In patients with intolerance or insufficient response to these drugs, the remaining options are limited and novel treatment approaches necessary. In primary biliary cholangitis (PBC), ursodeoxycholic acid (UDCA) and fibrates have improved prognosis dramatically, but there remains a proportion of patients with refractory disease.

In patients with refractory AIH and/or PBC, we used a novel treatment strategy with the anti-B cell activating factor, belimumab. The first three patients had concomitant Sjögren's disease. The connecting element between all three diseases is B cell activation, including elevated levels of the B cell activating factor (BAFF). Furthermore, belimumab has been shown to be beneficial in Sjögren's disease.

Aims and methods

To retrospectively investigate treatment response in six patients with AIH or PBC with or without concomitant Sjögren's disease treated with the anti-BAFF therapy belimumab at the University Hospital in Bern, Switzerland.

Results

In all three patients with AIH, belimumab improved disease control and helped by-pass or reduce problematic side effects from corticosteroids and calcineurin inhibitors. In PBC patients (n = 3), there was no clear improvement of liver function tests, despite reduction or normalization of IgM. All patients with concomitant Sjögren's disease (n = 3) had an improvement of sicca symptoms and two out of three patients experienced an initially marked reduction in fatigue, which lessened over time.

Conclusions

Belimumab may be a promising treatment option for patients with AIH and further investigations are needed. In PBC however, response was not convincing. The effects on sicca symptoms and fatigue were encouraging.

背景:大多数自身免疫性肝炎(AIH)患者通过既定的治疗方案获得完全缓解。对于不耐受或对这些药物反应不足的患者,剩余的选择有限,需要新的治疗方法。在原发性胆道胆管炎(PBC)中,熊去氧胆酸(UDCA)和贝特类药物可显著改善预后,但仍有一部分患者难治性疾病。在难治性AIH和/或PBC患者中,我们使用了一种新的治疗策略,即抗b细胞活化因子贝利单抗。前三名患者同时患有Sjögren病。这三种疾病之间的联系因素是B细胞活化,包括B细胞活化因子(BAFF)水平升高。此外,belimumab已被证明对Sjögren的疾病有益。目的和方法回顾性研究在瑞士伯尔尼大学医院接受抗baff治疗的6例伴有或不伴有Sjögren病的AIH或PBC患者的治疗反应。结果在所有3例AIH患者中,贝利单抗改善了疾病控制,并有助于绕过或减少皮质类固醇和钙调磷酸酶抑制剂的问题副作用。在PBC患者(n = 3)中,尽管IgM降低或正常化,但肝功能检查没有明显改善。所有伴有Sjögren's疾病的患者(n = 3)都有sicca症状的改善,三分之二的患者最初的疲劳明显减轻,随着时间的推移逐渐减轻。结论belimumab可能是AIH患者的一种有希望的治疗选择,需要进一步的研究。然而,中国人民银行的回应并不令人信服。对干燥症状和疲劳的效果令人鼓舞。
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引用次数: 1
Risk factors of cardiovascular involvement in patients with Behcet's disease 白塞病患者心血管疾病的危险因素
IF 3.9 Q2 Medicine Pub Date : 2023-01-01 DOI: 10.1016/j.jtauto.2023.100195
Yuqian Wang, Sheng Li, Shunli Tang, Xiaoxuan Cai, Juan Bai, Qingmiao Sun, Jianjun Qiao, Hong Fang

Objectives

Behcet's disease (BD) is a multi-systemic inflammatory vasculitis which may be life-threatening if combined with cardiovascular problems. The aim of the study was to identify potential risk factors associated with cardiovascular involvement in BD.

Methods

We reviewed the medical databases of a single center. All BD patients identified as fulfilling the 1990 International Study Group criteria or the International Criteria for Behcet's Disease criteria. Cardiovascular involvement, clinical manifestations, laboratory features, and treatments were recorded. The relationship between parameters and cardiovascular involvement was analyzed.

Results

111 BD patients were included: 21 (18.9%) had documented cardiovascular involvement (CV BD group) and 99 (81.1%) had no cardiovascular involvement (non-CV BD group). Compared with non-CV BD, the proportion of males and smokers were significantly increased in CV BD (p = 0.024 and p < 0.001, respectively). Levels of activated partial thromboplastin time (APTT), cardiac troponin I and C-reactive protein were significantly higher (p = 0.001, p = 0.031, and p = 0.034, respectively) in the CV BD group. Cardiovascular involvement was associated with smoking state, the presence of papulopustular lesions, and higher APTT in multivariate analyzed (p = 0.029, p = 0.021, and p = 0.006, respectively). The ROC curve showed that APTT predicts the risk of cardiovascular involvement (p < 0.01) at a cut-off value of 33.15 s with a sensitivity of 57.1% and specificity of 82.2%.

Conclusion

Cardiovascular involvement in BD patients was associated with gender, smoking state, the presence of papulopustular lesions, and higher APTT. All patients newly diagnosed with BD should be systematically screened for cardiovascular involvement.

目的白塞氏病(BD)是一种多系统炎症性血管炎,合并心血管疾病可危及生命。本研究的目的是确定与心血管疾病相关的潜在危险因素。方法我们回顾了单一中心的医学数据库。所有双相障碍患者均符合1990年国际研究组标准或白塞病国际标准。记录心血管受累情况、临床表现、实验室特征和治疗情况。分析了参数与心血管受累的关系。结果纳入111例BD患者:21例(18.9%)有心血管受累(CV BD组),99例(81.1%)无心血管受累(非CV BD组)。与非CV型BD患者相比,CV型BD患者中男性和吸烟者的比例显著增加(p = 0.024和p <分别为0.001)。活性部分凝血活素时间(APTT)、心肌肌钙蛋白I和c反应蛋白水平在CV BD组显著升高(p = 0.001、p = 0.031和p = 0.034)。在多变量分析中,心血管疾病与吸烟状态、丘疹病变的存在和较高的APTT相关(p = 0.029, p = 0.021和p = 0.006)。ROC曲线显示APTT可预测心血管受累风险(p <0.01),临界值为33.15 s,敏感性为57.1%,特异性为82.2%。结论BD患者心血管疾病累及与性别、吸烟状况、丘疹病变及APTT升高有关。所有新诊断为双相障碍的患者都应系统地筛查心血管疾病。
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引用次数: 1
Antiphospholipid antibodies induce proinflammatory and procoagulant pathways in endothelial cells 抗磷脂抗体诱导内皮细胞的促炎和促凝途径
IF 3.9 Q2 Medicine Pub Date : 2023-01-01 DOI: 10.1016/j.jtauto.2023.100202
Markos Patsouras , Eirini Alexopoulou , Spyros Foutadakis , Eirini Tsiki , Panagiota Karagianni , Marios Agelopoulos , Panayiotis G. Vlachoyiannopoulos

Antiphospholipid syndrome (APS) is an autoimmune thrombophilia characterized by recurrent thrombotic events and/or pregnancy morbidity in the presence of antiphospholipid antibodies detected either as anti-cardiolipin, anti-β2 Glycoprotein I (anti-β2GPI) or Lupus anticoagulant (LA). Endothelial deregulation characterizes the syndrome. To address gene expression changes accompanying the development of autoimmune phenotype in endothelial cells in the context of APS, we performed transcriptomics analysis in Human Umbilical Vein Endothelial Cells (HUVECs) stimulated with IgG from APS patients and β2GPI, followed by intersection of RNA-seq data with published microarray and ChIP-seq results (Chromatin Immunoprecipitation). Our strategy revealed that during HUVEC activation diverse signaling pathways such as TNF-α, TGF-β, MAPK38, and Hippo are triggered as indicated by Gene Ontology (GO) classification and pathway analysis. Finally, cell biology approaches performed side-by-side in naïve and stimulated cultured HUVECs, as well as, in placenta specimens derived from Healthy donors (HDs) and APS-patients verified the evolution of an APS-characteristic gene expression program in endothelial cells during the initial stages of the disease's development.

抗磷脂综合征(APS)是一种自身免疫性血栓形成倾向性疾病,其特征是在存在抗磷脂抗体(抗心磷脂、抗β2糖蛋白I(抗β2GPI)或狼疮抗凝剂(LA))的情况下反复发生血栓事件和/或妊娠发病率。内皮失调是该综合征的特征。为了解决APS背景下内皮细胞中伴随自身免疫表型发展的基因表达变化,我们对用APS患者IgG和β2GPI刺激的人脐静脉内皮细胞(HUVECs)进行了转录组学分析,然后将RNA-seq数据与已发表的微阵列和ChIP-seq结果进行交叉(染色质免疫沉淀)。我们的策略显示,在HUVEC激活过程中,不同的信号通路,如TNF-α、TGF-β、MAPK38和Hippo,如基因本体论(GO)分类和通路分析所示,会被触发。最后,在幼稚和刺激培养的HUVECs中,以及在来自健康供体(HD)和APS患者的胎盘标本中并行进行的细胞生物学方法验证了在疾病发展的初始阶段内皮细胞中APS特征基因表达程序的进化。
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引用次数: 0
Immunological and translational key challenges in systemic lupus erythematosus: A symposium update 系统性红斑狼疮的免疫学和翻译的关键挑战:研讨会更新
IF 3.9 Q2 Medicine Pub Date : 2023-01-01 DOI: 10.1016/j.jtauto.2023.100199
Yves Renaudineau , Sylviane Muller , Christian M. Hedrich , Dominique Chauveau , Julie Bellière , Sébastien De Almeida , Jan Damoiseaux , Marc Scherlinger , Jean Charles Guery , Laurent Sailler , Chloé Bost

The first LBMR-Tim (Toulouse Referral Medical Laboratory of Immunology) symposium convened on December 16, 2022 in Toulouse, France to address challenging questions in systemic lupus erythematosus (SLE). Special focus was put on (i) the role played by genes, sex, TLR7, and platelets on SLE pathophysiology; (ii) autoantibodies, urinary proteins, and thrombocytopenia contribution at the time of diagnosis and during follow-up; (iii) neuropsychiatric involvement, vaccine response in the COVID-19 era, and lupus nephritis management at the clinical frontline; and (iv) therapeutic perspectives in patients with lupus nephritis and the unexpected adventure of the Lupuzor/P140 peptide. The multidisciplinary panel of experts further supports the concept that a global approach including basic sciences, translational research, clinical expertise, and therapeutic development have to be prioritized in order to better understand and then improve the management of this complex syndrome.

首届LBMR-Tim(图卢兹转诊免疫医学实验室)研讨会于2022年12月16日在法国图卢兹召开,旨在解决系统性红斑狼疮(SLE)的挑战性问题。特别关注(i)基因、性别、TLR7和血小板在SLE病理生理中的作用;(ii)自身抗体、尿蛋白和血小板减少症在诊断和随访期间的贡献;(iii) 2019冠状病毒病(COVID-19)时代的神经精神病学参与、疫苗反应和狼疮性肾炎的临床一线管理;(iv)狼疮性肾炎患者的治疗前景和Lupuzor/P140肽的意外冒险。多学科专家小组进一步支持这一概念,即必须优先考虑包括基础科学、转化研究、临床专业知识和治疗开发在内的全球方法,以便更好地了解并改进这一复杂综合征的管理。
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引用次数: 3
Clinical characteristics and outcome of elderly onset adult-onset Still's disease: A 10-year retrospective study 老年发病成人发病斯蒂尔氏病的临床特点和预后:一项10年回顾性研究
IF 3.9 Q2 Medicine Pub Date : 2023-01-01 DOI: 10.1016/j.jtauto.2023.100196
Sheng Li , Shuni Ying , Juan Bai , Yuqian Wang, Changyi Yang, Qingmiao Sun, Hong Fang, Jianjun Qiao

Objective

Our objective was to retrospectively analyze the clinical characteristics and outcome of adult-onset Still's disease (AOSD) patients with elderly onset.

Methods

Retrospective data of patients diagnosed with AOSD in our institute during 2013–2021 were analyzed. The diagnoses were based on the Yamaguchi criteria for AOSD. All long-term follow-up data were collected from medical records and phone calls.

Results

In total, 281 AOSD patients were enrolled in this study, with the median follow-up interval of 47 months. Thirty-two (11.4%, ≥65 years) AOSD patients were classified into the elderly onset groups. Compared to the younger onset group, the percentage of patients with skin rash (p = 0.047), sore throat (p = 0.001), myalgia (p = 0.001), splenomegaly (p = 0.039), hepatosplenomegaly (p = 0.002) and the Pouchot's score (p = 0.002) were significantly lower in the elderly onset group. The death rate (p = 0.014) of elderly onset group is higher than younger onset group, and the independent risk factors of mortality in all AOSD patients were age at onset (HR: 1.115, p = 0.044), disseminated intravascular coagulation (HR: 391.576, p = 0.001) and pleuritis (HR: 23.162, p = 0.033). The probability of relapse was significantly increased in the patients with macrophage activation syndrome (MAS) compared with the patients without MAS (p < 0.001), though the different age groups of AOSD patients with MAS showed no difference in the probability of relapse (p = 0.737).

Conclusion

Elderly onset AOSD patients were distinguished by several distinct clinical features compared to younger onset AOSD patients. The frequency of relapse and complications were similar to that of AOSD patients with elderly or younger onset. A higher mortality rate was observed in elderly onset AOSD patients, and the mortality of AOSD patients was related to age at onset, DIC and pleuritis.

目的回顾性分析老年起病成人起病斯蒂尔氏病(AOSD)患者的临床特点和转归。方法回顾性分析我院2013-2021年诊断为AOSD的患者资料。诊断依据AOSD的Yamaguchi标准。所有的长期随访数据都是从医疗记录和电话中收集的。结果共纳入281例AOSD患者,中位随访时间为47个月。32例(11.4%,≥65岁)AOSD患者分为老年起病组。与年轻起病组相比,老年起病组出现皮疹(p = 0.047)、喉咙痛(p = 0.001)、肌痛(p = 0.001)、脾肿大(p = 0.039)、肝脾肿大(p = 0.002)和Pouchot评分(p = 0.002)的比例显著降低。老年发病组的死亡率(p = 0.014)高于年轻发病组,且所有AOSD患者死亡的独立危险因素为发病年龄(HR: 1.115, p = 0.044)、弥散性血管内凝血(HR: 391.576, p = 0.001)和胸膜炎(HR: 23.162, p = 0.033)。巨噬细胞活化综合征(MAS)患者的复发概率明显高于无MAS患者(p <0.001),但不同年龄组的AOSD合并MAS患者的复发概率没有差异(p = 0.737)。结论老年AOSD与年轻AOSD有明显的临床特征。复发及并发症发生率与老年或低龄AOSD患者相似。高龄AOSD患者病死率较高,且病死率与发病年龄、DIC、胸膜炎有关。
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引用次数: 1
Development and validation of the AF score for diagnosis of adult-onset Still's disease in fever of unknown origin 发展和验证AF评分诊断成人起病不明原因发热斯蒂尔氏病
IF 3.9 Q2 Medicine Pub Date : 2023-01-01 DOI: 10.1016/j.jtauto.2022.100184
Shuni Ying , Duo Lv , Dingxian Zhu , Sheng Li , Yuwei Ding , Chuanyin Sun , Yu Shi , Hong Fang , Jianjun Qiao

Objective

To develop and validate a diagnostic score to identify adult-onset Still's disease (AOSD) in fever of unknown origin (FUO).

Methods

A single center, retrospective case-control study of inpatients with FUO from January 2018 to December 2021. Using clinical and laboratory data from 178 cases with AOSD and 486 cases with FUO, we developed an AOSD/FUO (AF) score with a Bayesian Model Averaging approach. AF score and Yamaguchi's criteria were evaluated by sensitivity, specificity, accuracy, and positive/negative predictive value for diagnosis of AOSD in developmental and validation samples.

Results

Persistent pruritic eruptions (PPEs) in patients with rashes was higher in AOSD group than FUO group (52.3% vs 7.4%; P < 0.01). PPEs yielded a specificity of 97.5% and a sensitivity of 44.9%. AF score = PPEs × 3.795+Evanescent rash × 2.774+Serum ferritin × 1.678+Myalgia × 0.958+Neutrophil count × 0.185+Platelet count × 0.004. A cut-off value ≥ 5.245 revealed the maximizing sensitivity of 88.7% and specificity of 95.8% in discriminating AOSD from FUO in the validation group. And AF score improved the accuracy from 82.6% to 93.3% compared with Yamaguchi's criteria.

Conclusions

We developed and validated a new score which can identify AOSD in FUO with higher classification accuracy than Yamaguchi's criteria. Future multi-centric prospective studies need to be designed to confirm the diagnosis value of AF score.

目的建立并验证不明原因发热(FUO)成人发病斯蒂尔氏病(AOSD)的诊断评分。方法对2018年1月至2021年12月住院的FUO患者进行单中心、回顾性病例对照研究。利用178例AOSD和486例FUO的临床和实验室数据,我们采用贝叶斯模型平均方法建立了AOSD/FUO (AF)评分。在发展样本和验证样本中,评估AF评分和Yamaguchi标准诊断AOSD的敏感性、特异性、准确性和阳性/阴性预测值。结果AOSD组皮疹患者持续瘙痒性发疹(PPEs)发生率高于FUO组(52.3% vs 7.4%;P & lt;0.01)。PPEs的特异性为97.5%,敏感性为44.9%。AF评分= PPEs × 3.795+消逝性皮疹× 2.774+血清铁蛋白× 1.678+肌痛× 0.958+中性粒细胞计数× 0.185+血小板计数× 0.004。截断值≥5.245时,验证组区分AOSD和FUO的最大灵敏度为88.7%,特异度为95.8%。与山口标准相比,AF评分将准确率从82.6%提高到93.3%。结论建立并验证了一种新的诊断FUO中AOSD的评分方法,其分类准确率高于Yamaguchi标准。未来需要设计多中心前瞻性研究来证实房颤评分的诊断价值。
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引用次数: 0
Mechanism of action and promising clinical application of melatonin from a dermatological perspective 从皮肤病学角度看褪黑素的作用机制及临床应用前景
IF 3.9 Q2 Medicine Pub Date : 2023-01-01 DOI: 10.1016/j.jtauto.2023.100192
Shan Zhang, Xu Yao

Melatonin is the main neuroendocrine product in the pineal gland. Melatonin can regulate circadian rhythm-related physiological processes. Evidence indicates an important role of melatonin in hair follicles, skin, and gut. There appears to be a close association between melatonin and skin disorders. In this review, we focus on the latest research of the biochemical activities of melatonin (especially in the skin) and its promising clinical applications.

褪黑素是松果体中主要的神经内分泌产物。褪黑素可以调节昼夜节律相关的生理过程。有证据表明,褪黑素在毛囊、皮肤和肠道中起着重要作用。褪黑素和皮肤疾病之间似乎有密切的联系。本文就褪黑素(尤其是皮肤中的褪黑素)的生化活性及其临床应用的最新研究进展作一综述。
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引用次数: 1
Polyautoimmunity in systemic lupus erythematosus patients: New insights from a cross-sectional study 系统性红斑狼疮患者的多重自身免疫:来自横断面研究的新见解
IF 3.9 Q2 Medicine Pub Date : 2023-01-01 DOI: 10.1016/j.jtauto.2022.100187
Pedro Santos-Moreno , Julián Arias-Aponte , Gabriel-Santiago Rodríguez-Vargas , Paula Daniela Nieto-Zambrano , Laura Villarreal , Linda Ibatá , Susan Martinez , Jaime-Andrés Rubio-Rubio , Pedro Rodríguez , Adriana Rojas-Villarraga

Objective

To assess the frequency of polyautoimmunity (PolyA) in a cohort of Colombian patients with systemic lupus erythematosus (SLE) and to identify associated factors.

Methods

This is an analytical cross-sectional study in a specialized center., a comprehensive review of the medical records of SLE patients was performed from 2015 to 2020 in order to obtain demographic, clinical data, laboratory, and treatment information. Associations between PolyA, demographic, and characteristics of the disease were explored.

Results

A total of 463 patients were included in the analysis. The average age was 47.3 ± 15 years. Most of this population were female (87.4%), whom were diagnosed with SLE in a long-term SLE (10.6 ± 10.1 years). Out of the total patients, 34.7% were diagnosed with PolyA. Among the most frequent clinical criteria for SLICC, arthritis (65%), kidney impairment (39.5%), and alopecia (34.8%) were found. The most frequent SLE-associated PolyA were antiphospholipid syndrome (APS) and Sjögren's syndrome (SS) (16.63% and 10.58%, respectively). PolyA-associated factors were age, xerophthalmia, central nervous system occlusion, and deep vein thrombosis (DVT). In contrast, renal impairment was significantly less frequent in PolyA patients after multivariate analysis.

Conclusion

The results have showed associated factors with PolyA like age, xerophthalmia, central nervous system occlusion, and deep vein thrombosis in this cohort. On the other hand, lupus nephritis was less frequent in patients with PolyA. This study provides a spotlight of a specific SLE population as real-life evidence for a better characterization of PolyA in the future.

目的评估哥伦比亚系统性红斑狼疮(SLE)患者多重自身免疫(PolyA)的发生率,并确定相关因素。方法:本研究是在某专业中心进行的分析性横断面研究。,对2015年至2020年SLE患者的医疗记录进行了全面回顾,以获得人口统计学、临床数据、实验室和治疗信息。探讨了PolyA、人口统计学和疾病特征之间的关系。结果共纳入463例患者。平均年龄47.3±15岁。其中女性居多(87.4%),诊断为长期SLE(10.6±10.1年)。在所有患者中,34.7%被诊断为PolyA。SLICC最常见的临床诊断标准是关节炎(65%)、肾脏损害(39.5%)和脱发(34.8%)。最常见的与slea相关的PolyA是抗磷脂综合征(APS)和Sjögren综合征(SS)(分别为16.63%和10.58%)。与polya相关的因素有年龄、干眼症、中枢神经系统阻塞和深静脉血栓形成。相比之下,多因素分析后,PolyA患者肾脏损害的发生率明显较低。结论年龄、干眼症、中枢神经系统闭塞、深静脉血栓形成等因素与PolyA的发生有关。另一方面,狼疮肾炎在PolyA患者中较少发生。这项研究提供了一个特定SLE人群的焦点,作为未来更好地表征PolyA的现实证据。
{"title":"Polyautoimmunity in systemic lupus erythematosus patients: New insights from a cross-sectional study","authors":"Pedro Santos-Moreno ,&nbsp;Julián Arias-Aponte ,&nbsp;Gabriel-Santiago Rodríguez-Vargas ,&nbsp;Paula Daniela Nieto-Zambrano ,&nbsp;Laura Villarreal ,&nbsp;Linda Ibatá ,&nbsp;Susan Martinez ,&nbsp;Jaime-Andrés Rubio-Rubio ,&nbsp;Pedro Rodríguez ,&nbsp;Adriana Rojas-Villarraga","doi":"10.1016/j.jtauto.2022.100187","DOIUrl":"10.1016/j.jtauto.2022.100187","url":null,"abstract":"<div><h3>Objective</h3><p>To assess the frequency of polyautoimmunity (PolyA) in a cohort of Colombian patients with systemic lupus erythematosus (SLE) and to identify associated factors.</p></div><div><h3>Methods</h3><p>This is an analytical cross-sectional study in a specialized center., a comprehensive review of the medical records of SLE patients was performed from 2015 to 2020 in order to obtain demographic, clinical data, laboratory, and treatment information. Associations between PolyA, demographic, and characteristics of the disease were explored.</p></div><div><h3>Results</h3><p>A total of 463 patients were included in the analysis. The average age was 47.3 ± 15 years. Most of this population were female (87.4%), whom were diagnosed with SLE in a long-term SLE (10.6 ± 10.1 years). Out of the total patients, 34.7% were diagnosed with PolyA. Among the most frequent clinical criteria for SLICC, arthritis (65%), kidney impairment (39.5%), and alopecia (34.8%) were found. The most frequent SLE-associated PolyA were antiphospholipid syndrome (APS) and Sjögren's syndrome (SS) (16.63% and 10.58%, respectively). PolyA-associated factors were age, xerophthalmia, central nervous system occlusion, and deep vein thrombosis (DVT). In contrast, renal impairment was significantly less frequent in PolyA patients after multivariate analysis.</p></div><div><h3>Conclusion</h3><p>The results have showed associated factors with PolyA like age, xerophthalmia, central nervous system occlusion, and deep vein thrombosis in this cohort. On the other hand, lupus nephritis was less frequent in patients with PolyA. This study provides a spotlight of a specific SLE population as real-life evidence for a better characterization of PolyA in the future.</p></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/39/48/main.PMC9841268.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9100305","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 1
Selective induction of thymic stromal lymphopoietin expression by novel nitrogen-containing steroid compounds in PAM-212 cells 新型含氮类固醇化合物选择性诱导PAM-212细胞胸腺基质淋巴生成素表达
IF 3.9 Q2 Medicine Pub Date : 2023-01-01 DOI: 10.1016/j.jtauto.2022.100186
Yu Wang , Ryosuke Segawa , Yan Weng , Katsuya Nakai , Keiichiro Ohashi , Masahiro Hiratsuka , Mieko Arisawa , Noriyasu Hirasawa

Background

Thymic stromal lymphopoietin (TSLP) has been shown to be able to amplify Tregs. Thus, TSLP induction has the potential to induce endogenous Tregs and control autoimmunity. In the previous research, we found that a new compound named 02F04 can induce TSLP production while simultaneously activating the liver X receptor (LXR). Because LXR activation leads to a decrease in Treg, we attempted to find a 02F04-derivative, druggable lead compound with a basic skeleton that induces TSLP production without activating LXR. As the results, we found HA-7 and HA-19 and, in this study, examined the molecular mechanisms in TSLP production.

Methods

A murine keratinocyte cell line PAM 212 was stimulated with HA-7 and HA-19, and then the expressions of cytokines were examined via ELISA and real-time fluorescence quantitative PCR.

Results

HA-7 and HA-19 induced TSLP production but almost not the expression of TNF-α, IL-13, IL-25, and IL-33 in PAM212 cells. These compounds inhibited LXR activities. The TSLP expression induced by HA-7 and HA-19 was inhibited by the Gq/11 inhibitor YM-254890, ROCK inhibitor Y-27632, and ERK inhibitor U0126. HA-7 and HA-19 also induced the formation of stress fiber and ERK phosphorylation, which were inhibited by YM-254890 and Y-27632.

Conclusions

Our findings indicated that HA-7 and HA-19 selectively induced TSLP production in PAM212 via Gq/11, Rho/ROCK and ERK pathways. Our findings also indicated that TSLP expression was differentially regulated from other cytokines, and the selective expression could be induced with low-molecular-weight compounds such as HA-7 and HA-19.

背景胸腺基质淋巴细胞生成素(TSLP)已被证明能够扩增Tregs。因此,TSLP诱导具有诱导内源性Tregs和控制自身免疫的潜力。在之前的研究中,我们发现一种名为02F04的新化合物可以诱导TSLP的产生,同时激活肝脏X受体(LXR)。由于LXR的激活会导致Treg的降低,我们试图找到一种02F04衍生物、可药用的铅化合物,该化合物具有基本骨架,可以在不激活LXR的情况下诱导TSLP的产生。结果,我们发现了HA-7和HA-19,并在本研究中检测了TSLP产生的分子机制。方法用HA-7和HA-19刺激小鼠角质形成细胞系PAM 212,然后用ELISA和实时荧光定量PCR检测细胞因子的表达。结果HA-7和HA-19诱导PAM212细胞产生TSLP,但几乎不表达TNF-α、IL-13、IL-25和IL-33。这些化合物抑制LXR活性。由HA-7和HA-19诱导的TSLP表达被Gq/11抑制剂YM-254890、ROCK抑制剂Y-27632和ERK抑制剂U0126抑制。HA-7和HA-19还诱导应激纤维的形成和ERK磷酸化,YM-254890和Y-27632抑制了这一过程。结论HA-7和HA-19通过Gq/11、Rho/ROCK和ERK途径选择性诱导PAM212产生TSLP。我们的研究结果还表明,TSLP的表达与其他细胞因子不同,并且低分子量化合物如HA-7和HA-19可以诱导选择性表达。
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引用次数: 0
期刊
Journal of Translational Autoimmunity
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