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Case series of anifrolumab for treatment of cutaneous lupus erythematosus and lupus-related mucocutaneous manifestations in patients with SLE 阿尼洛单抗治疗系统性红斑狼疮患者皮肤红斑狼疮和狼疮相关粘膜表现的病例系列
IF 3.9 2区 医学 Q1 RHEUMATOLOGY Pub Date : 2023-12-01 DOI: 10.1136/lupus-2023-001007
Aaron Bao, Michelle A Petri, Andrea Fava, Jun Kang
Objective To assess the efficacy of anifrolumab, a type-1 interferon receptor subunit-1 monoclonal antibody, in treating refractory cutaneous lupus erythematosus (CLE) and lupus non-specific mucocutaneous manifestations in patients with systemic lupus erythematosus (SLE). Methods A case series comprising four SLE patients with refractory CLE received anifrolumab (300mg) as add-on therapy. Medical history, serological markers and images were collected. Cutaneous Lupus Erythematosus Disease Area and Severity Index–Activity (CLASI-A) was assessed at baseline and post-treatment visits. Results Patient 1: Anifrolumab effectively treated refractory chronic cutaneous lupus erythematosus with lupus panniculitis and calcinosis cutis. Patient 2: Anifrolumab demonstrated rapid improvement in generalised discoid lupus, achieving a substantial reduction in CLASI-A from 40 to 8. Patient 3: Switching from belimumab to anifrolumab led to notable improvement in photosensitivity and tumid lupus. Patient 4: Anifrolumab effectively managed refractory subacute cutaneous lupus erythematosus, resulting in remarkable cutaneous improvement and successful tapering of prednisone and mycophenolate mofetil. Conclusion Anifrolumab demonstrates efficacy in treating refractory CLE subtypes and lupus non-specific mucocutaneous manifestations in SLE patients. Further studies are needed to establish response rates, optimal dosing, and long-term outcomes.
目的 评估1型干扰素受体亚单位-1单克隆抗体阿尼夫单抗治疗系统性红斑狼疮(SLE)患者难治性皮肤红斑狼疮(CLE)和狼疮非特异性皮肤黏膜表现的疗效。方法 由四名患有难治性 CLE 的系统性红斑狼疮患者组成的病例系列接受了阿尼单抗(300 毫克)作为附加疗法。收集病史、血清学指标和图像。在基线和治疗后访视时对皮肤红斑狼疮疾病面积和严重程度指数-活动性(CLASI-A)进行评估。结果 患者1:阿尼单抗有效治疗了难治性慢性皮肤红斑狼疮伴狼疮性泛发炎和皮肤钙化症。患者 2:阿尼单抗能迅速改善全身性盘状狼疮,使 CLASI-A 从 40 显著降至 8。患者 3:从贝利姆单抗转用安非鲁单抗后,光敏性狼疮和瘤型狼疮得到明显改善。患者 4:阿尼单抗有效控制了难治性亚急性皮肤红斑狼疮,使皮肤症状显著改善,并成功减少了泼尼松和霉酚酸酯的用量。结论 Anifrolumab 对治疗系统性红斑狼疮患者难治性 CLE 亚型和狼疮非特异性皮肤黏膜表现具有疗效。还需要进一步的研究来确定反应率、最佳剂量和长期疗效。
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引用次数: 0
Clinical significance of exostosin 1 in confirmed and suspected lupus membranous nephropathy 外司素 1 在确诊和疑似狼疮膜性肾病中的临床意义
IF 3.9 2区 医学 Q1 RHEUMATOLOGY Pub Date : 2023-12-01 DOI: 10.1136/lupus-2023-001051
Tian Ye, Mengya Jiang, Xueyan Zeng, Dan Zong, Yuanyuan Du, Xiaohong Li, Biao Huang, Xuanli Tang
Objective This study aimed to investigate the clinical significance of exostosin 1 (EXT1) in confirmed and suspected lupus membranous nephropathy (LMN). Methods EXT1 was detected in 67 renal tissues of M-type phospholipase A2 receptor (PLA2R)-negative and ANA-positive membranous nephropathy by immunohistochemistry, and cases were divided into confirmed LMN and suspected LMN. The clinicopathological data were compared among the above groups, as well as EXT1-positive group and EXT1-negative group. Results Twenty-two cases (73.3%) of confirmed LMN and six cases (16.2%) of suspected LMN exhibited EXT1 expression on the glomerular basement membrane and/or mesangium area, showing a significant difference (p<0.001). Concurrently, lupus nephritis (LN) of pure class V demonstrated a lower frequency of EXT1 positivity compared with mixed class V LN in the confirmed LMN group (31.8% vs 68.2%, p=0.007). EXT1-positive patients in the confirmed and suspected LMN group showed significant differences in some clinicopathological data comparing with EXT1-negative patients (p<0.05). Follow-up data revealed that a greater proportion of patients in the EXT1-positive group achieved complete remission post-treatment (p<0.05). Cox regression analysis showed that EXT1 positivity was significantly correlated with complete remission across the entire study cohort (HR 5.647; 95% CI, 1.323 to 12.048; p=0.019). Kaplan-Meier analysis indicated that the EXT1-positive group had a higher rate of accumulated nephrotic remission compared with the EXT1-negative group in the whole study cohort (p=0.028). Conclusions The EXT1-positive group exhibited a higher active index and a more favourable renal outcome than the EXT1-negative group. It would be better to recognise suspected LMN with EXT1 positivity as a potential autoimmune disease and maintain close follow-up due to its similarities with confirmed LMN. Data are available upon reasonable request.
目的 本研究旨在探讨EXT1在确诊和疑似狼疮膜性肾病(LMN)中的临床意义。方法 采用免疫组化方法在 67 例 M 型磷脂酶 A2 受体(PLA2R)阴性和 ANA 阳性膜性肾病患者的肾组织中检测 EXT1,并将病例分为确诊 LMN 和疑似 LMN。比较上述各组以及 EXT1 阳性组和 EXT1 阴性组的临床病理数据。结果 22 例确诊 LMN(73.3%)和 6 例疑似 LMN(16.2%)的肾小球基底膜和/或系膜区有 EXT1 表达,差异显著(P<0.001)。同时,在确诊的 LMN 组中,纯 V 类狼疮肾炎(LN)的 EXT1 阳性率低于混合 V 类 LN(31.8% 对 68.2%,P=0.007)。确诊组和疑似 LMN 组的 EXT1 阳性患者与 EXT1 阴性患者相比,在一些临床病理数据上存在显著差异(P<0.05)。随访数据显示,EXT1 阳性组患者治疗后完全缓解的比例更高(P<0.05)。Cox回归分析显示,在整个研究队列中,EXT1阳性与完全缓解显著相关(HR 5.647; 95% CI, 1.323 to 12.048; p=0.019)。卡普兰-梅耶尔分析表明,在整个研究队列中,EXT1 阳性组的累积肾病缓解率高于 EXT1 阴性组(P=0.028)。结论 与 EXT1 阴性组相比,EXT1 阳性组表现出更高的活跃指数和更有利的肾脏预后。由于 EXT1 阳性的疑似 LMN 与确诊的 LMN 相似,因此最好将 EXT1 阳性的疑似 LMN 识别为潜在的自身免疫性疾病,并保持密切随访。如有合理要求,可提供相关数据。
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引用次数: 0
Methylprednisolone pulse-enhanced neutrophil extracellular trap formation in mice with imiquimod-induced lupus-like disease, resulting in ischaemia of the femoral head cartilage 甲基强的松龙脉冲增强了咪喹莫特诱发狼疮样疾病小鼠体内中性粒细胞胞外陷阱的形成,导致股骨头软骨缺血
IF 3.9 2区 医学 Q1 RHEUMATOLOGY Pub Date : 2023-12-01 DOI: 10.1136/lupus-2023-001042
Hodaka Ogawa, Shunichi Yokota, Yumeka Hosoi, Ayano Shindo, Naho Ogawa, Ryodai Yamamura, Tomohiro Shimizu, Issei Nakade, Suishin Arai, Mai Taniguchi, Yuka Nishibata, Sakiko Masuda, Daigo Nakazawa, Utano Tomaru, Norimasa Iwasaki, Akihiro Ishizu
Objectives Methylprednisolone (mPSL) pulse therapy is an essential option for patients with active systemic lupus erythematosus, but there is a risk of adverse events related to microcirculation disorders, including idiopathic osteonecrosis of the femoral head (ONFH). Recent studies have revealed that excessive neutrophil extracellular traps (NETs) are involved in microcirculation disorders. This study aimed to demonstrate that mPSL pulse could induce NETs in lupus mice and identify the factors contributing to this induction. Methods Six mice with imiquimod (IMQ)-induced lupus-like disease and six normal mice were intraperitoneally injected with mPSL on days 39 to 41, and five mice with IMQ-induced lupus-like disease and six normal mice were injected with phosphate-buffered saline. Pathological examinations were conducted to evaluate the ischaemic state of the femoral head and tissue infiltration of NET-forming neutrophils. Proteome analysis was performed to extract plasma proteins specifically elevated in mPSL-administered mice with IMQ-induced lupus-like disease, and their effects on NET formation were assessed in vitro. Results Mice with IMQ-induced lupus-like disease that received mPSL pulse demonstrated ischaemia of the femoral head cartilage with tissue infiltration of NET-forming neutrophils. Proteome analysis suggested that prenylcysteine oxidase 1 (PCYOX1) played a role in this phenomenon. The reaction of PCYOX1-containing very low-density lipoproteins (VLDL) with its substrate farnesylcysteine (FC) induced NETs in vitro. The combined addition of IMQ and mPSL synergistically enhanced VLDL-plus-FC-induced NET formation. Conclusion PCYOX1 and related factors are worthy of attention to understand the underlying mechanisms and create novel therapeutic strategies for mPSL-mediated microcirculation disorders, including ONFH. Data are available on reasonable request.
目的 甲基强的松龙(methylprednisolone,mPSL)脉冲疗法是活动性系统性红斑狼疮患者的基本选择,但有可能出现与微循环障碍有关的不良事件,包括特发性股骨头坏死(ONFH)。最近的研究发现,过多的中性粒细胞胞外捕获物(NET)参与了微循环障碍。本研究旨在证明 mPSL 脉冲可诱导狼疮小鼠体内的 NETs,并确定导致这种诱导的因素。方法 在第39至41天,给6只患有咪喹莫特(IMQ)诱导的狼疮样疾病的小鼠和6只正常小鼠腹腔注射mPSL,给5只患有IMQ诱导的狼疮样疾病的小鼠和6只正常小鼠注射磷酸盐缓冲盐水。病理学检查评估了股骨头的缺血状态和NET形成的中性粒细胞的组织浸润情况。进行了蛋白质组分析,以提取在注射 mPSL 的 IMQ 诱导的狼疮样疾病小鼠中特异性升高的血浆蛋白质,并在体外评估它们对 NET 形成的影响。结果 接受 mPSL 脉冲治疗的 IMQ 诱导的狼疮样疾病小鼠表现出股骨头软骨缺血,NET 形成的中性粒细胞浸润组织。蛋白质组分析表明,前酰基半胱氨酸氧化酶 1(PCYOX1)在这一现象中发挥了作用。含有 PCYOX1 的极低密度脂蛋白(VLDL)与其底物法呢酰半胱氨酸(FC)反应在体外诱导 NET。联合添加 IMQ 和 mPSL 可协同增强 VLDL 加 FC 诱导的 NET 的形成。结论 PCYOX1 和相关因子值得关注,以了解其基本机制,并为 mPSL 介导的微循环障碍(包括 ONFH)制定新的治疗策略。如有合理要求,可提供相关数据。
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引用次数: 0
Burden of systemic lupus erythematosus in clinical practice: baseline data from the SLE Prospective Observational Cohort Study (SPOCS) by interferon gene signature 系统性红斑狼疮在临床实践中的负担:系统性红斑狼疮前瞻性观察队列研究(SPOCS)通过干扰素基因特征得出的基线数据
IF 3.9 2区 医学 Q1 RHEUMATOLOGY Pub Date : 2023-12-01 DOI: 10.1136/lupus-2023-001032
Laurent Arnaud, Richard Furie, Eric F Morand, Martin Aringer, Christine Peschken, Barnabas Desta, Eleni Rapsomaniki, Jonatan Hedberg, Jacob Knagenhjelm, Caroline Seo, Tina Grünfeld Eén, Alessandro Sorrentino, Raj Tummala, Heide A Stirnadel-Farrant, Bo Ding
Objective The longitudinal Systemic Lupus Erythematosus Prospective Observational Cohort Study (SPOCS) aims to assess SLE disease course overall and according to type I interferon 4 gene signature (IFNGS). Here, we describe SPOCS patient characteristics by IFNGS and baseline disease activity. Methods SPOCS ([NCT03189875][1]) is an international study of patients with SLE according to Systemic Lupus International Collaborating Clinics (SLICC)/American College of Rheumatology (ACR) criteria. Enrolled patients from 135 centres in 8 countries were followed biannually for ≤3 years from June 2017 to November 2022. Baseline demographics, disease characteristics, organ system involvement/damage and flares were analysed descriptively according to SLE Disease Activity Index-2000 score (SLEDAI-2K <10/≥10) and IFNGS status (high/low). Results The study population (n=823) was 93.2% female, with mean (SD) age 45.3 (13.9) years and 11.1 (9.2) years since diagnosis; 52.4% had baseline SLICC/ACR Damage Index score ≥1. Patients with SLEDAI-2K scores ≥10 (241 of 584, 41.3%) vs <10 were younger (mean 42.8 (13.7) vs 46.6 (14.2) years; nominal p=0.001), had shorter SLE duration (10.4 (8.6) vs 12.4 (9.6) years; nominal p=0.012) and more severe flares (12.9% vs 5.3%; nominal p=0.001). IFNGS-high patients (522 of 739, 70.6%) were younger than IFNGS-low patients at first SLE manifestation (30.0 (12.7) vs 36.8 (14.6) years; nominal p<0.001). Proportions of IFNGS-high patients differed according to race (nominal p<0.001), with higher proportions among Asian (83.3%) and black (86.5%) versus white patients (63.5%). Greater proportions of IFNGS-high versus IFNGS-low patients had haematological (12.6% vs 4.1%), immunological (74.4% vs 45.6%) or dermal (69.7% vs 62.2%) involvement. Conclusions We identified key characteristics of patients with high disease activity and/or elevated type I IFN signalling, populations with SLE with high unmet needs. Baseline SLEDAI-2K ≥10 was associated with shorter disease duration and more severe flares. IFNGS-high patients were younger at diagnosis and had distinct patterns of organ involvement, compared with IFNGS-low patients. Data are available upon reasonable request. Data underlying the findings described in this manuscript may be obtained in accordance with AstraZeneca’s data sharing policy described at [https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure][2]. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT03189875&atom=%2Flupusscimed%2F10%2F2%2Fe001032.atom [2]: https://www.astrazenecaclinicaltrials.com/our-transparency-commitments/
目的 系统性红斑狼疮前瞻性观察队列纵向研究(SPOCS)旨在评估系统性红斑狼疮的总体病程和 I 型干扰素 4 基因特征(IFNGS)。在此,我们按 IFNGS 和基线疾病活动度描述 SPOCS 患者的特征。方法 SPOCS([NCT03189875][1])是一项根据系统性红斑狼疮国际合作诊所(SLICC)/美国风湿病学会(ACR)标准对系统性红斑狼疮患者进行的国际研究。自2017年6月至2022年11月,对来自8个国家135个中心的入组患者进行了为期≤3年的半年随访。根据系统性红斑狼疮疾病活动指数-2000评分(SLEDAI-2K<10/≥10)和IFNGS状态(高/低)对基线人口统计学、疾病特征、器官系统受累/损伤和复发进行了描述性分析。结果 研究对象(n=823)中 93.2% 为女性,平均(标清)年龄为 45.3(13.9)岁,确诊时间为 11.1(9.2)年;52.4% 的基线 SLICC/ACR 损伤指数评分≥1。3%)vs <10分的患者更年轻(平均42.8 (13.7) vs 46.6 (14.2)岁;标称P=0.001),系统性红斑狼疮病程更短(10.4 (8.6) vs 12.4 (9.6)岁;标称P=0.012),病情发作更严重(12.9% vs 5.3%;标称P=0.001)。IFNGS高的患者(739人中有522人,占70.6%)在首次出现系统性红斑狼疮表现时比IFNGS低的患者年轻(30.0 (12.7) vs 36.8 (14.6)岁;标称P<0.001)。IFNGS高的患者比例因种族而异(标称P<0.001),亚洲人(83.3%)和黑人(86.5%)的比例高于白人(63.5%)。IFNGS 高分患者与 IFNGS 低分患者相比,血液(12.6% vs 4.1%)、免疫(74.4% vs 45.6%)或皮肤(69.7% vs 62.2%)受累的比例更高。结论 我们发现了疾病活动度高和/或 I 型 IFN 信号升高的患者的主要特征,这些患者都是系统性红斑狼疮患者,他们的需求尚未得到满足。基线SLEDAI-2K≥10与疾病持续时间较短和复发较严重有关。与 IFNGS 低的患者相比,IFNGS 高的患者确诊时更年轻,器官受累的模式也更独特。如有合理要求,可提供相关数据。根据阿斯利康公司在 [https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure][2] 中描述的数据共享政策,可获取本手稿中描述的研究结果所依据的数据。[1]:/lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT03189875&atom=%2Flupusscimed%2F10%2F2%2Fe001032.atom [2]: https://www.astrazenecaclinicaltrials.com/our-transparency-commitments/
{"title":"Burden of systemic lupus erythematosus in clinical practice: baseline data from the SLE Prospective Observational Cohort Study (SPOCS) by interferon gene signature","authors":"Laurent Arnaud, Richard Furie, Eric F Morand, Martin Aringer, Christine Peschken, Barnabas Desta, Eleni Rapsomaniki, Jonatan Hedberg, Jacob Knagenhjelm, Caroline Seo, Tina Grünfeld Eén, Alessandro Sorrentino, Raj Tummala, Heide A Stirnadel-Farrant, Bo Ding","doi":"10.1136/lupus-2023-001032","DOIUrl":"https://doi.org/10.1136/lupus-2023-001032","url":null,"abstract":"Objective The longitudinal Systemic Lupus Erythematosus Prospective Observational Cohort Study (SPOCS) aims to assess SLE disease course overall and according to type I interferon 4 gene signature (IFNGS). Here, we describe SPOCS patient characteristics by IFNGS and baseline disease activity. Methods SPOCS ([NCT03189875][1]) is an international study of patients with SLE according to Systemic Lupus International Collaborating Clinics (SLICC)/American College of Rheumatology (ACR) criteria. Enrolled patients from 135 centres in 8 countries were followed biannually for ≤3 years from June 2017 to November 2022. Baseline demographics, disease characteristics, organ system involvement/damage and flares were analysed descriptively according to SLE Disease Activity Index-2000 score (SLEDAI-2K <10/≥10) and IFNGS status (high/low). Results The study population (n=823) was 93.2% female, with mean (SD) age 45.3 (13.9) years and 11.1 (9.2) years since diagnosis; 52.4% had baseline SLICC/ACR Damage Index score ≥1. Patients with SLEDAI-2K scores ≥10 (241 of 584, 41.3%) vs <10 were younger (mean 42.8 (13.7) vs 46.6 (14.2) years; nominal p=0.001), had shorter SLE duration (10.4 (8.6) vs 12.4 (9.6) years; nominal p=0.012) and more severe flares (12.9% vs 5.3%; nominal p=0.001). IFNGS-high patients (522 of 739, 70.6%) were younger than IFNGS-low patients at first SLE manifestation (30.0 (12.7) vs 36.8 (14.6) years; nominal p<0.001). Proportions of IFNGS-high patients differed according to race (nominal p<0.001), with higher proportions among Asian (83.3%) and black (86.5%) versus white patients (63.5%). Greater proportions of IFNGS-high versus IFNGS-low patients had haematological (12.6% vs 4.1%), immunological (74.4% vs 45.6%) or dermal (69.7% vs 62.2%) involvement. Conclusions We identified key characteristics of patients with high disease activity and/or elevated type I IFN signalling, populations with SLE with high unmet needs. Baseline SLEDAI-2K ≥10 was associated with shorter disease duration and more severe flares. IFNGS-high patients were younger at diagnosis and had distinct patterns of organ involvement, compared with IFNGS-low patients. Data are available upon reasonable request. Data underlying the findings described in this manuscript may be obtained in accordance with AstraZeneca’s data sharing policy described at [https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure][2]. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT03189875&atom=%2Flupusscimed%2F10%2F2%2Fe001032.atom [2]: https://www.astrazenecaclinicaltrials.com/our-transparency-commitments/","PeriodicalId":18126,"journal":{"name":"Lupus Science & Medicine","volume":"35 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138823491","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Development and psychometric evaluation of a physician global assessment for type 2 systemic lupus erythematosus symptoms 针对 2 型系统性红斑狼疮症状的医生总体评估的开发和心理计量学评估
IF 3.9 2区 医学 Q1 RHEUMATOLOGY Pub Date : 2023-12-01 DOI: 10.1136/lupus-2023-001016
Megan E B Clowse, Jennifer L Rogers, Theresa Coles, David S Pisetsky, Lisa G Criscione-Schreiber, Dana Burshell, Jayanth Doss, Rebecca E Sadun, Kai Sun, Mithu Maheswaranathan, Amanda M Eudy
Objective Manifestations of SLE can be categorised as type 1 (classic signs and symptoms of SLE) or type 2 (fatigue, widespread pain and brain fog with an unclear relationship to inflammation). While measures of type 1 SLE activity exist, most current physician-reported measures do not encompass type 2 SLE manifestations. To better evaluate type 2 SLE symptoms, we developed and psychometrically evaluated a physician-reported measure of type 2 symptoms, the Type 2 Physician Global Assessment (‘Type 2 PGA’). Methods and analysis The Type 2 PGA was developed and evaluated by six rheumatologists practising in the same academic lupus clinic. The study began with a roundtable discussion to establish consensus guidelines for scoring the Type 2 PGA. Following the roundtable, the Type 2 PGA was psychometrically evaluated using data prospectively collected from 263 patients with SLE enrolled in the Duke Lupus Registry. Results There was strong intra-rater and inter-rater reliability (intraclass correlation coefficient=0.83), indicating the Type 2 PGA scores were consistent within a rheumatologist and across rheumatologists. The Type 2 PGA was correlated with patient-reported symptoms of polysymptomatic distress (r=0.76), fatigue (r=0.68), cognitive dysfunction (r=0.63), waking unrefreshed (r=0.62) and forgetfulness (r=0.60), and weakly correlated with the Type 1 PGA and the Systemic Lupus Erythematosus Disease Activity Index. Conclusion The Type 2 PGA performed well as a physician-reported measure of type 2 SLE symptoms. The incorporation of the Type 2 PGA into a routine rheumatology visit may improve patient care by bringing the provider’s attention to certain symptoms not well represented in conventional measures of disease activity. Data are available upon reasonable request.
系统性红斑狼疮的客观表现可分为 1 型(系统性红斑狼疮的典型体征和症状)和 2 型(疲劳、广泛性疼痛和脑雾,与炎症的关系不明确)。虽然目前已有针对 1 型系统性红斑狼疮活动的测量方法,但大多数由医生报告的测量方法并不包括 2 型系统性红斑狼疮的表现。为了更好地评估 2 型系统性红斑狼疮的症状,我们开发了一种由医生报告的 2 型症状测量方法,即 2 型系统性红斑狼疮医生总体评估("Type 2 PGA"),并对其进行了心理计量学评估。方法与分析 2型PGA由在同一狼疮学术诊所执业的六位风湿病学家共同开发和评估。研究以圆桌讨论的形式开始,目的是为 2 型 PGA 的评分建立共识准则。圆桌会议结束后,使用从杜克大学狼疮登记处登记的 263 名系统性红斑狼疮患者中收集的数据,对 2 型 PGA 进行了心理计量学评估。结果 评定者内部和评定者之间具有很高的可靠性(类内相关系数=0.83),表明风湿病学家内部和不同风湿病学家之间的 2 型 PGA 评分是一致的。2 型 PGA 与患者报告的多症状困扰(r=0.76)、疲劳(r=0.68)、认知功能障碍(r=0.63)、醒后无精神(r=0.62)和健忘(r=0.60)等症状相关,与 1 型 PGA 和系统性红斑狼疮疾病活动指数的相关性较弱。结论 2型PGA作为医生报告的2型系统性红斑狼疮症状测量方法表现良好。将 2 型 PGA 纳入常规风湿病就诊中,可使医疗服务提供者注意到某些在传统疾病活动指标中没有得到很好体现的症状,从而改善对患者的护理。如有合理要求,可提供相关数据。
{"title":"Development and psychometric evaluation of a physician global assessment for type 2 systemic lupus erythematosus symptoms","authors":"Megan E B Clowse, Jennifer L Rogers, Theresa Coles, David S Pisetsky, Lisa G Criscione-Schreiber, Dana Burshell, Jayanth Doss, Rebecca E Sadun, Kai Sun, Mithu Maheswaranathan, Amanda M Eudy","doi":"10.1136/lupus-2023-001016","DOIUrl":"https://doi.org/10.1136/lupus-2023-001016","url":null,"abstract":"Objective Manifestations of SLE can be categorised as type 1 (classic signs and symptoms of SLE) or type 2 (fatigue, widespread pain and brain fog with an unclear relationship to inflammation). While measures of type 1 SLE activity exist, most current physician-reported measures do not encompass type 2 SLE manifestations. To better evaluate type 2 SLE symptoms, we developed and psychometrically evaluated a physician-reported measure of type 2 symptoms, the Type 2 Physician Global Assessment (‘Type 2 PGA’). Methods and analysis The Type 2 PGA was developed and evaluated by six rheumatologists practising in the same academic lupus clinic. The study began with a roundtable discussion to establish consensus guidelines for scoring the Type 2 PGA. Following the roundtable, the Type 2 PGA was psychometrically evaluated using data prospectively collected from 263 patients with SLE enrolled in the Duke Lupus Registry. Results There was strong intra-rater and inter-rater reliability (intraclass correlation coefficient=0.83), indicating the Type 2 PGA scores were consistent within a rheumatologist and across rheumatologists. The Type 2 PGA was correlated with patient-reported symptoms of polysymptomatic distress (r=0.76), fatigue (r=0.68), cognitive dysfunction (r=0.63), waking unrefreshed (r=0.62) and forgetfulness (r=0.60), and weakly correlated with the Type 1 PGA and the Systemic Lupus Erythematosus Disease Activity Index. Conclusion The Type 2 PGA performed well as a physician-reported measure of type 2 SLE symptoms. The incorporation of the Type 2 PGA into a routine rheumatology visit may improve patient care by bringing the provider’s attention to certain symptoms not well represented in conventional measures of disease activity. Data are available upon reasonable request.","PeriodicalId":18126,"journal":{"name":"Lupus Science & Medicine","volume":"105 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138716371","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Efficacy and safety of telitacicept in patients with systemic lupus erythematosus: a multicentre, retrospective, real-world study. 泰利他塞普对系统性红斑狼疮患者的疗效和安全性:一项多中心、回顾性、真实世界研究。
IF 3.9 2区 医学 Q1 RHEUMATOLOGY Pub Date : 2023-11-24 DOI: 10.1136/lupus-2023-001074
Hui-Zhi Jin, Yu-Jing Li, Xin Wang, Zhijun Li, Bin Ma, Lin Niu, Peng Wang, Hai-Feng Pan, Si-Dong Li, Wei Bao, Guosheng Wang, Xiao-Mei Li, Zhu Chen

Objective: To examine the efficacy and safety of telitacicept in the treatment of patients with SLE in everyday clinical practice.

Methods: Seventy-two patients with active SLE who received telitacicept for more than 24 weeks at multiple centres in China between 2019 and 2022 were retrospectively identified. Twenty-one of these patients received 52 continuous weeks of treatment with telitacicept. Treatment outcomes were analysed separately according to whether patients had renal or haematological abnormalities. Trajectory analysis was performed to identify patients with a limited response. Factors contributing to a limited response were explored by multivariable logistic regression analysis.

Results: After treatment with telitacicept for 4, 12, 24 and 52 weeks, 22.22%, 54.17%, 72.22% and 80.95% of patients, respectively, achieved an SLE Responder Index 4; 8.33%, 26.39%, 34.72% and 47.62% achieved a Lupus Low Disease Activity State; and 0%, 4.17%, 8.33% and 23.81% achieved remission. Significant decreases in serum IgA, IgG and IgM levels were observed at 4 weeks and showed a downward trend at 12, 24 and 52 weeks. The median 24-hour urinary protein declined from 1323.5 mg to 224.0 mg in patients with lupus nephritis after treatment with telitacicept for 52 weeks. Furthermore, a large proportion of patients (10 of 13) with haematological abnormalities recovered after 52 weeks of treatment with telitacicept. No severe adverse events were reported during the observation period. Age appeared to have a negative impact on treatment efficacy.

Conclusions: Telitacicept demonstrated favourable efficacy and safety in patients with active SLE and improved the renal and haematological manifestations of the disease.

目的:在日常临床实践中探讨替利他赛普治疗SLE的有效性和安全性。方法:回顾性分析2019年至2022年期间在中国多个中心接受telitacicept治疗超过24周的72例活动性SLE患者。其中21例患者连续52周接受telitacicept治疗。根据患者是否有肾脏或血液学异常分别分析治疗结果。进行轨迹分析以确定反应有限的患者。通过多变量logistic回归分析探讨了影响有限反应的因素。结果:替利他赛普治疗4周、12周、24周和52周后,达到SLE应答指数4的患者比例分别为22.22%、54.17%、72.22%和80.95%;达到狼疮低疾病活动度的分别为8.33%、26.39%、34.72%和47.62%;缓解率分别为0%、4.17%、8.33%和23.81%。血清IgA、IgG和IgM水平在第4周显著降低,在第12、24和52周呈下降趋势。狼疮性肾炎患者在接受替利他塞普治疗52周后,24小时尿蛋白中位数从1323.5 mg降至224.0 mg。此外,大部分血液学异常患者(13例中的10例)在使用telitacicept治疗52周后恢复。观察期间无严重不良事件发生。年龄似乎对治疗效果有负面影响。结论:替利他赛在活动性SLE患者中表现出良好的疗效和安全性,并改善了该疾病的肾脏和血液学表现。
{"title":"Efficacy and safety of telitacicept in patients with systemic lupus erythematosus: a multicentre, retrospective, real-world study.","authors":"Hui-Zhi Jin, Yu-Jing Li, Xin Wang, Zhijun Li, Bin Ma, Lin Niu, Peng Wang, Hai-Feng Pan, Si-Dong Li, Wei Bao, Guosheng Wang, Xiao-Mei Li, Zhu Chen","doi":"10.1136/lupus-2023-001074","DOIUrl":"10.1136/lupus-2023-001074","url":null,"abstract":"<p><strong>Objective: </strong>To examine the efficacy and safety of telitacicept in the treatment of patients with SLE in everyday clinical practice.</p><p><strong>Methods: </strong>Seventy-two patients with active SLE who received telitacicept for more than 24 weeks at multiple centres in China between 2019 and 2022 were retrospectively identified. Twenty-one of these patients received 52 continuous weeks of treatment with telitacicept. Treatment outcomes were analysed separately according to whether patients had renal or haematological abnormalities. Trajectory analysis was performed to identify patients with a limited response. Factors contributing to a limited response were explored by multivariable logistic regression analysis.</p><p><strong>Results: </strong>After treatment with telitacicept for 4, 12, 24 and 52 weeks, 22.22%, 54.17%, 72.22% and 80.95% of patients, respectively, achieved an SLE Responder Index 4; 8.33%, 26.39%, 34.72% and 47.62% achieved a Lupus Low Disease Activity State; and 0%, 4.17%, 8.33% and 23.81% achieved remission. Significant decreases in serum IgA, IgG and IgM levels were observed at 4 weeks and showed a downward trend at 12, 24 and 52 weeks. The median 24-hour urinary protein declined from 1323.5 mg to 224.0 mg in patients with lupus nephritis after treatment with telitacicept for 52 weeks. Furthermore, a large proportion of patients (10 of 13) with haematological abnormalities recovered after 52 weeks of treatment with telitacicept. No severe adverse events were reported during the observation period. Age appeared to have a negative impact on treatment efficacy.</p><p><strong>Conclusions: </strong>Telitacicept demonstrated favourable efficacy and safety in patients with active SLE and improved the renal and haematological manifestations of the disease.</p>","PeriodicalId":18126,"journal":{"name":"Lupus Science & Medicine","volume":"10 2","pages":""},"PeriodicalIF":3.9,"publicationDate":"2023-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10679987/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138440865","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Genotype-guided new approach for dose optimisation of hydroxychloroquine administration in Chinese patients with SLE. 基因型导向的中国SLE患者羟氯喹给药剂量优化新方法。
IF 3.9 2区 医学 Q1 RHEUMATOLOGY Pub Date : 2023-11-22 DOI: 10.1136/lupus-2023-000997
Han Xie, Xin Wen, Yuchun Wang, Xuan Huang, Qing Shu, Dandan Wang, Linyu Geng, Ziyi Jin, Wei Shen, Weihong Ge, Yizhun Zhu, Lingyun Sun

Objectives: The study aims to investigate the impact of gene polymorphisms on blood hydroxychloroquine (HCQ) concentrations in patients with SLE and provide guidelines for individualised care.

Methods: 489 Chinese patients with SLE taking HCQ for more than 3 months were collected in this study. The blood HCQ, desethylhydroxychloroquine (DHCQ) and desethylchloroquine concentrations were measured. The optimal blood concentration of HCQ was determined by receiver operating characteristic curve analysis. Single nucleotide polymorphisms of metabolic enzymes involved in HCQ metabolism were genotyped and the associations with treatment effects were investigated.

Results: The cut-off value of HCQ was 559.67 ng/mL, with sensitivity and specificity values of 0.51 and 0.89, respectively. The TC and CC genotypes of CYP2C8 (rs7910936) were significantly related to the increase in blood HCQ concentrations, and the CYP2C8 (rs10882521) TT genotype was associated with lower blood HCQ concentrations. The DHCQ:HCQ ratio was highest in patients with the GG genotype of the CYP2D6*10 (rs1065852) polymorphism and lowest in those with the AA genotype. Patients with the CYP2C8 (rs7910936) CC genotype were more likely to achieve the optimal blood concentration (p=0.030) in HCQ 200 mg/day group and patients with the CYP2D6*10 (rs1065852) GG genotype were more likely to reach the optimal blood concentration (p=0.049) in 400 mg/day group.

Conclusions: Our results suggest that the optimal blood concentration of HCQ measured approximately 12-18 hours after the last dosage may be between 500 and 600 ng/mL in Chinese patients with SLE. The observed variations in HCQ concentrations between individuals can potentially be attributed to genetic polymorphisms in CYP2D6*10 (rs1065852) and CYP2C8 (rs7910936 and rs10882521). Genotypical testing of patients and regular monitoring of blood levels are recommended for optimising HCQ dosage management in Chinese patients with SLE.

Trial registration number: ChiCTR2300070628.

目的:本研究旨在探讨基因多态性对SLE患者血液羟氯喹(HCQ)浓度的影响,并为个性化护理提供指导。方法:收集489例接受HCQ治疗3个月以上的SLE患者。测定血HCQ、去乙基羟氯喹(DHCQ)和去乙基氯喹浓度。通过受试者工作特征曲线分析确定HCQ的最佳血药浓度。对参与HCQ代谢的代谢酶的单核苷酸多态性进行了基因分型,并对其与治疗效果的关系进行了研究。结果:HCQ的临界值为559.67 ng/mL,灵敏度为0.51,特异性为0.89。CYP2C8 (rs7910936) TC和CC基因型与血HCQ浓度升高显著相关,CYP2C8 (rs10882521) TT基因型与血HCQ浓度降低相关。CYP2D6*10 (rs1065852)多态性的GG基因型患者DHCQ:HCQ比值最高,AA基因型患者DHCQ:HCQ比值最低。CYP2C8 (rs7910936) CC基因型患者在HCQ 200 mg/天组更容易达到最佳血药浓度(p=0.030), CYP2D6*10 (rs1065852) GG基因型患者在400 mg/天组更容易达到最佳血药浓度(p=0.049)。结论:我们的研究结果表明,中国SLE患者在最后一次给药后约12-18小时测量的HCQ最佳血药浓度可能在500 - 600 ng/mL之间。观察到的个体间HCQ浓度的差异可能归因于CYP2D6*10 (rs1065852)和CYP2C8 (rs7910936和rs10882521)的遗传多态性。建议对中国SLE患者进行基因型检测和定期监测血液水平,以优化HCQ剂量管理。试验注册号:ChiCTR2300070628。
{"title":"Genotype-guided new approach for dose optimisation of hydroxychloroquine administration in Chinese patients with SLE.","authors":"Han Xie, Xin Wen, Yuchun Wang, Xuan Huang, Qing Shu, Dandan Wang, Linyu Geng, Ziyi Jin, Wei Shen, Weihong Ge, Yizhun Zhu, Lingyun Sun","doi":"10.1136/lupus-2023-000997","DOIUrl":"10.1136/lupus-2023-000997","url":null,"abstract":"<p><strong>Objectives: </strong>The study aims to investigate the impact of gene polymorphisms on blood hydroxychloroquine (HCQ) concentrations in patients with SLE and provide guidelines for individualised care.</p><p><strong>Methods: </strong>489 Chinese patients with SLE taking HCQ for more than 3 months were collected in this study. The blood HCQ, desethylhydroxychloroquine (DHCQ) and desethylchloroquine concentrations were measured. The optimal blood concentration of HCQ was determined by receiver operating characteristic curve analysis. Single nucleotide polymorphisms of metabolic enzymes involved in HCQ metabolism were genotyped and the associations with treatment effects were investigated.</p><p><strong>Results: </strong>The cut-off value of HCQ was 559.67 ng/mL, with sensitivity and specificity values of 0.51 and 0.89, respectively. The TC and CC genotypes of CYP2C8 (rs7910936) were significantly related to the increase in blood HCQ concentrations, and the CYP2C8 (rs10882521) TT genotype was associated with lower blood HCQ concentrations. The DHCQ:HCQ ratio was highest in patients with the GG genotype of the CYP2D6*10 (rs1065852) polymorphism and lowest in those with the AA genotype. Patients with the CYP2C8 (rs7910936) CC genotype were more likely to achieve the optimal blood concentration (p=0.030) in HCQ 200 mg/day group and patients with the CYP2D6*10 (rs1065852) GG genotype were more likely to reach the optimal blood concentration (p=0.049) in 400 mg/day group.</p><p><strong>Conclusions: </strong>Our results suggest that the optimal blood concentration of HCQ measured approximately 12-18 hours after the last dosage may be between 500 and 600 ng/mL in Chinese patients with SLE. The observed variations in HCQ concentrations between individuals can potentially be attributed to genetic polymorphisms in CYP2D6*10 (rs1065852) and CYP2C8 (rs7910936 and rs10882521). Genotypical testing of patients and regular monitoring of blood levels are recommended for optimising HCQ dosage management in Chinese patients with SLE.</p><p><strong>Trial registration number: </strong>ChiCTR2300070628.</p>","PeriodicalId":18126,"journal":{"name":"Lupus Science & Medicine","volume":"10 2","pages":""},"PeriodicalIF":3.9,"publicationDate":"2023-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10668244/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138295477","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Muscle strength, not muscle mass, determines the health-related quality of life in Indonesian women with systemic lupus erythematosus. 决定印尼系统性红斑狼疮患者健康生活质量的是肌肉力量,而不是肌肉质量。
IF 3.9 2区 医学 Q1 RHEUMATOLOGY Pub Date : 2023-11-01 DOI: 10.1136/lupus-2023-001025
Stevent Sumantri, Euphemia Seto, Iris Rengganis

Objective: No study evaluated the impact of low muscle strength and mass on the Sarcopenia-related Quality of Life (SarQoL) in women with SLE.

Methods: This cross-sectional study recruited 145 women with SLE consecutively; muscle strength was measured with a calibrated Jamar handheld dynamometer, muscle mass was measured with appendicular muscle mass index (Tanita MC-780 MAP body impedance analyser) and health-related quality of life with SarQoL Questionnaire. The cut-off points for low muscle strength, low muscle mass and sarcopenia were derived from the Asian Working Group on Sarcopenia 2019. Statistical analysis was conducted with a t-test for mean difference, and logistic regression was used to evaluate for low muscle strength contributing factors.

Results: There was a significant difference in the mean total score of SarQoL in individuals with normal compared with low muscle strength (74.36 vs 64.85; mean difference 9.50; 95% CI 2.10 to 5.33; p<0.001). On the other hand, there was no difference in individuals with normal compared with low muscle mass (71.07 vs 70.79; mean difference 0.28; -5.18 to 5.74; p=0.91). After minimally adjusted with age, we found moderate-severe joint pain (B -9.280; p<0.001) and low muscle strength (B -6.979; p=0.001) to be independently associated with low mean SarQoL total score.

Conclusion: There was a lower total SarQoL score in individuals with low muscle strength but not with low muscle mass.

目的:没有研究评估低肌肉力量和低质量对系统性红斑狼疮(SLE)妇女与肌肉萎缩相关的生活质量(SarQoL)的影响。方法:本横断面研究连续招募了145名SLE患者;用校准的Jamar手持式测功机测量肌肉力量,用阑尾肌肉质量指数(Tanita MC-780 MAP身体阻抗分析仪)测量肌肉质量,用SarQoL问卷测量健康相关的生活质量。低肌肉力量、低肌肉量和少肌症的分界点来自2019年亚洲少肌症工作组。统计分析采用t检验平均差异,逻辑回归用于评估低肌肉力量的影响因素。结果:与低肌肉力量相比,正常个体的SarQoL平均总分有显著差异(74.36 vs 64.85;平均差异9.50;95%CI 2.10至5.33;P结论:低肌肉力量但不低肌肉质量的个体的SarQoL总分较低。
{"title":"Muscle strength, not muscle mass, determines the health-related quality of life in Indonesian women with systemic lupus erythematosus.","authors":"Stevent Sumantri, Euphemia Seto, Iris Rengganis","doi":"10.1136/lupus-2023-001025","DOIUrl":"10.1136/lupus-2023-001025","url":null,"abstract":"<p><strong>Objective: </strong>No study evaluated the impact of low muscle strength and mass on the Sarcopenia-related Quality of Life (SarQoL) in women with SLE.</p><p><strong>Methods: </strong>This cross-sectional study recruited 145 women with SLE consecutively; muscle strength was measured with a calibrated Jamar handheld dynamometer, muscle mass was measured with appendicular muscle mass index (Tanita MC-780 MAP body impedance analyser) and health-related quality of life with SarQoL Questionnaire. The cut-off points for low muscle strength, low muscle mass and sarcopenia were derived from the Asian Working Group on Sarcopenia 2019. Statistical analysis was conducted with a t-test for mean difference, and logistic regression was used to evaluate for low muscle strength contributing factors.</p><p><strong>Results: </strong>There was a significant difference in the mean total score of SarQoL in individuals with normal compared with low muscle strength (74.36 vs 64.85; mean difference 9.50; 95% CI 2.10 to 5.33; p<0.001). On the other hand, there was no difference in individuals with normal compared with low muscle mass (71.07 vs 70.79; mean difference 0.28; -5.18 to 5.74; p=0.91). After minimally adjusted with age, we found moderate-severe joint pain (B -9.280; p<0.001) and low muscle strength (B -6.979; p=0.001) to be independently associated with low mean SarQoL total score.</p><p><strong>Conclusion: </strong>There was a lower total SarQoL score in individuals with low muscle strength but not with low muscle mass.</p>","PeriodicalId":18126,"journal":{"name":"Lupus Science & Medicine","volume":"10 2","pages":""},"PeriodicalIF":3.9,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10626751/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71424850","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Preclinical in vitro model of monocyte influence on microvessel structure in systemic lupus erythematosus. 系统性红斑狼疮单核细胞对微血管结构影响的临床前体外模型。
IF 3.9 2区 医学 Q1 RHEUMATOLOGY Pub Date : 2023-11-01 DOI: 10.1136/lupus-2023-001013
Holly Ryan, Alison Veintimilla, Christine Groso, Erika Moore
{"title":"Preclinical in vitro model of monocyte influence on microvessel structure in systemic lupus erythematosus.","authors":"Holly Ryan, Alison Veintimilla, Christine Groso, Erika Moore","doi":"10.1136/lupus-2023-001013","DOIUrl":"10.1136/lupus-2023-001013","url":null,"abstract":"","PeriodicalId":18126,"journal":{"name":"Lupus Science & Medicine","volume":"10 2","pages":""},"PeriodicalIF":3.9,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10649862/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72209859","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Clinical implications of discordance between anti-dsDNA antibodies by multiplex flow immunoassay and Crithidia luciliae assay in a multiethnic racial cohort of patients with SLE. 多种族SLE患者多种族队列中多重流免疫测定法和透明荷叶测定法抗dsdna抗体不一致的临床意义
IF 3.9 2区 医学 Q1 RHEUMATOLOGY Pub Date : 2023-11-01 DOI: 10.1136/lupus-2023-001012
Devyn Zaminski, Amit Saxena, Peter Izmirly, Jill P Buyon, H Michael Belmont

Objective: Anti-dsDNA antibodies (anti-dsDNA) are a component of all classification schemes in SLE and comprise one of the domains in validated activity indices. Anti-dsDNA is frequently measured commercially by an enzyme immunoassay (EIA) or Crithidia luciliae immunofluorescence test (CLIFT). To address the clinical impact of measuring these antibodies by two different assays, this study leveraged a well-phenotyped multiethnic/racial cohort.

Methods: All patients fulfilled the classification criteria for SLE by at least one of the validated schemes: American College of Rheumatology, Systemic Lupus Erythematosus International Collaborating Clinics and/or American College of Rheumatology/European League Against Rheumatism classification criteria. Patients with one or more simultaneously paired anti-dsDNA by multiplex EIA and CLIFT were identified. Analysis of concordance or discordance, titre comparability of assays and association with hybrid SLE Disease Activity Index score, prevalence of lupus nephritis (LN), ability to predict a flare and classification criteria was performed.

Results: 207 patients were simultaneously tested by EIA and CLIFT at least once for anti-dsDNA, generating 586 paired results. 377 pairs were concordant and 209 were discordant. 41 of 207 patients always had discordant paired results and 39 patients always had results with titre discordance. In 100 patients with LN, 60 were positive by EIA and 72 by CLIFT. Sensitivities and specificities for patients with LN versus patients without LN were EIA 60% and 47%, and CLIFT 72% and 37%, respectively. 42 patients had flare assessment within 90 days of their paired result. Six of seven patients with mild flares and all four patients with severe flares had concordant positive results.

Conclusion: Our data demonstrate that discordance of positivity between both assays for anti-dsDNA is relatively common, occurring in a fifth of patients overall and a third of visits. EIA positivity is associated with LN less often than CLIFT positivity. With the significant discordance of results between anti-dsDNA assays, obtaining both CLIFT and EIA assays may be beneficial for classification and routine monitoring of SLE.

目的:抗dsdna抗体(Anti-dsDNA)是SLE所有分类方案的一个组成部分,并且是已验证的活性指数中的一个结构域。抗dsdna通常通过酶免疫测定法(EIA)或荧光石斛(Crithidia luciliae)免疫荧光试验(CLIFT)进行商业测量。为了解决通过两种不同的检测方法测量这些抗体的临床影响,本研究利用了一个表型良好的多民族/种族队列。方法:所有患者均符合至少一种经过验证的SLE分类标准:美国风湿病学会、系统性红斑狼疮国际合作诊所和/或美国风湿病学会/欧洲抗风湿病联盟分类标准。通过多重EIA和CLIFT鉴定出一个或多个同时配对的抗- dsdna患者。分析一致性或不一致性、试验的三度可比性以及与混合型SLE疾病活动指数评分、狼疮肾炎(LN)患病率、预测急性发作的能力和分类标准的关联。结果:207例患者同时通过EIA和CLIFT检测抗dsdna至少一次,产生586对结果。377对一致,209对不一致。207例患者中有41例配对结果总是不一致,39例结果总是滴度不一致。在100例LN患者中,60例EIA阳性,72例CLIFT阳性。LN患者与非LN患者的敏感性和特异性分别为EIA的60%和47%,CLIFT的72%和37%。42例患者在配对结果后90天内进行了耀斑评估。7例轻度耀斑患者中的6例和4例重度耀斑患者均有一致的阳性结果。结论:我们的数据表明,抗dsdna两种检测方法的阳性不一致是相对常见的,发生在五分之一的患者和三分之一的就诊中。与CLIFT阳性相比,EIA阳性较少与LN相关。由于抗dsdna检测结果存在显著差异,因此同时获得CLIFT和EIA检测结果可能有助于SLE的分类和常规监测。
{"title":"Clinical implications of discordance between anti-dsDNA antibodies by multiplex flow immunoassay and <i>Crithidia luciliae</i> assay in a multiethnic racial cohort of patients with SLE.","authors":"Devyn Zaminski, Amit Saxena, Peter Izmirly, Jill P Buyon, H Michael Belmont","doi":"10.1136/lupus-2023-001012","DOIUrl":"10.1136/lupus-2023-001012","url":null,"abstract":"<p><strong>Objective: </strong>Anti-dsDNA antibodies (anti-dsDNA) are a component of all classification schemes in SLE and comprise one of the domains in validated activity indices. Anti-dsDNA is frequently measured commercially by an enzyme immunoassay (EIA) or <i>Crithidia luciliae</i> immunofluorescence test (CLIFT). To address the clinical impact of measuring these antibodies by two different assays, this study leveraged a well-phenotyped multiethnic/racial cohort.</p><p><strong>Methods: </strong>All patients fulfilled the classification criteria for SLE by at least one of the validated schemes: American College of Rheumatology, Systemic Lupus Erythematosus International Collaborating Clinics and/or American College of Rheumatology/European League Against Rheumatism classification criteria. Patients with one or more simultaneously paired anti-dsDNA by multiplex EIA and CLIFT were identified. Analysis of concordance or discordance, titre comparability of assays and association with hybrid SLE Disease Activity Index score, prevalence of lupus nephritis (LN), ability to predict a flare and classification criteria was performed.</p><p><strong>Results: </strong>207 patients were simultaneously tested by EIA and CLIFT at least once for anti-dsDNA, generating 586 paired results. 377 pairs were concordant and 209 were discordant. 41 of 207 patients always had discordant paired results and 39 patients always had results with titre discordance. In 100 patients with LN, 60 were positive by EIA and 72 by CLIFT. Sensitivities and specificities for patients with LN versus patients without LN were EIA 60% and 47%, and CLIFT 72% and 37%, respectively. 42 patients had flare assessment within 90 days of their paired result. Six of seven patients with mild flares and all four patients with severe flares had concordant positive results.</p><p><strong>Conclusion: </strong>Our data demonstrate that discordance of positivity between both assays for anti-dsDNA is relatively common, occurring in a fifth of patients overall and a third of visits. EIA positivity is associated with LN less often than CLIFT positivity. With the significant discordance of results between anti-dsDNA assays, obtaining both CLIFT and EIA assays may be beneficial for classification and routine monitoring of SLE.</p>","PeriodicalId":18126,"journal":{"name":"Lupus Science & Medicine","volume":"10 2","pages":""},"PeriodicalIF":3.9,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10649789/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"107591630","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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Lupus Science & Medicine
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