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Systemic Sclerosis-Specific Antibodies: Novel and Classical Biomarkers. 系统性硬化症特异性抗体:新的和经典的生物标志物。
IF 9.1 2区 医学 Q1 ALLERGY Pub Date : 2023-06-01 DOI: 10.1007/s12016-022-08946-w
Ilaria Cavazzana, Tamara Vojinovic, Paolo Airo', Micaela Fredi, Angela Ceribelli, Eleonora Pedretti, Maria Grazia Lazzaroni, Emirena Garrafa, Franco Franceschini
<p><p>Disease-specific autoantibodies are considered the most important biomarkers for systemic sclerosis (SSc), due to their ability to stratify patients with different severity and prognosis. Anti-nuclear antibodies (ANA), occurring in subjects with isolated Raynuad's phenomenon, are considered the strongest independent predictors of definite SSc and digital microvascular damage, as observed by nailfold videocapillaroscopy. ANA are present in more than 90% of SSc, but ANA negativity does not exclude SSc diagnosis: a little rate of SSc ANA negative exists and shows a distinct subtype of disease, with less vasculopathy, but more frequent lower gastrointestinal involvement and severe disease course. Anti-centromere, anti-Th/To, and anti-Topoisomerase I antibodies could be considered as classical biomarkers, covering about 60% of SSc and defining patients with well-described cardio-pulmonary complications. In particular, anti-Topoisomerase I represent a risk factor for development of diffuse cutaneous involvement and digital ulcers in the first 3 years of disease, as well as severe interstitial lung disease (ILD). Anti-RNA polymerase III is a biomarker with new clinical implications: very rapid skin thickness progression, gastric antral vascular ectasia, the occurrence of synchronous cancers, and possible association with silicone breast implants rupture. Moreover, novel SSc specific autoantibodies have been globally described in about 10% of "seronegative" SSc patients: anti-elF2B, anti-RuvBL1/2 complex, anti-U11/U12 RNP, and anti-BICD2 depict specific SSc subtypes with severe organ complications. Many autoantibodies could be considered markers of overlap syndromes, including SSc. Anti-Ku are found in 2-7% of SSc, strictly defining the PM/SSc overlap. They are associated with synovitis, joint contractures, myositis, and negatively associated with vascular manifestation of disease. Anti-U3RNP are associated with a well-defined clinical phenotype: Afro-Caribbean male patients, younger at diagnosis, and higher risk of pulmonary hypertension and gastrointestinal involvement. Anti-PM/Scl define SSc patients with high frequency of ILD, calcinosis, dermatomyositis skin changes, and severe myositis. The accurate detection of autoantibodies SSc specific and associated with overlap syndromes is crucial for patients' stratification. ANA should be correctly identified using indirect immunofluorescent assay and a standardized way of patterns' interpretation. The gold-standard technique for autoantibodies' identification in SSc is still considered immunoprecipitation, for its high sensitivity and specificity, but other assays have been widely used in routine practice. The identification of SSc autoantibodies with high diagnostic specificity and high predictive value is mandatory for early diagnosis, a specific follow-up and the possible definition of the best therapy for every SSc subsets. In addition, the validation of novel autoantibodies is mandatory in wide
疾病特异性自身抗体被认为是系统性硬化症(SSc)最重要的生物标志物,因为它们能够对不同严重程度和预后的患者进行分层。抗核抗体(ANA)出现在孤立的雷诺氏现象的受试者中,被认为是明确的SSc和数字微血管损伤的最强独立预测因子,这是通过甲襞视频毛细血管镜观察到的。超过90%的SSc中存在ANA,但ANA阴性并不能排除SSc的诊断:少量SSc存在ANA阴性,并表现出明显的疾病亚型,血管病变较少,但更频繁地累及下消化道,病程严重。抗着丝粒、抗th /To和抗拓扑异构酶I抗体可以被认为是经典的生物标志物,覆盖了约60%的SSc,并定义了有明确描述的心肺并发症的患者。特别是,抗拓扑异构酶I是疾病前3年发生弥漫性皮肤受累和手指溃疡以及严重间质性肺疾病(ILD)的危险因素。抗rna聚合酶III是一种具有新的临床意义的生物标志物:非常迅速的皮肤厚度进展,胃胃窦血管扩张,同步癌的发生,并可能与硅胶乳房植入物破裂有关。此外,在全球约10%的血清阴性SSc患者中发现了新的SSc特异性自身抗体:抗elf2b、抗ruvbl1 /2复合物、抗u11 /U12 RNP和抗bicd2描述了具有严重器官并发症的特异性SSc亚型。许多自身抗体可被认为是重叠综合征的标志物,包括SSc。在2-7%的SSc中发现了Anti-Ku,严格定义了PM/SSc重叠。它们与滑膜炎、关节挛缩、肌炎相关,并与疾病的血管表现负相关。抗u3rnp与明确的临床表型相关:非裔加勒比男性患者,诊断时更年轻,肺动脉高压和胃肠道受累的风险更高。抗pm /Scl定义SSc患者有高频率的ILD、钙质沉着、皮肌炎、皮肤改变和严重的肌炎。准确检测SSc特异性和与重叠综合征相关的自身抗体对患者分层至关重要。应使用间接免疫荧光法和标准化的模式解释方法正确识别ANA。自体抗体鉴定的金标准技术仍然被认为是免疫沉淀,因为它具有高灵敏度和特异性,但其他检测方法已广泛应用于常规实践。鉴定具有高诊断特异性和高预测价值的SSc自身抗体对于早期诊断,特定随访和可能定义每个SSc亚群的最佳治疗是必需的。此外,为了限制所谓血清阴性SSc患者的差距,新型自身抗体的验证必须在更广泛的队列中进行。
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引用次数: 15
Reproductive Issues and Pregnancy Implications in Systemic Sclerosis. 系统性硬化症的生殖问题和妊娠影响。
IF 9.1 2区 医学 Q1 ALLERGY Pub Date : 2023-06-01 DOI: 10.1007/s12016-021-08910-0
Maria-Grazia Lazzaroni, Francesca Crisafulli, Liala Moschetti, Paolo Semeraro, Ana-Rita Cunha, Agna Neto, Andrea Lojacono, Francesca Ramazzotto, Cristina Zanardini, Sonia Zatti, Paolo Airò, Angela Tincani, Franco Franceschini, Laura Andreoli

Systemic sclerosis (SSc) is a rare systemic autoimmune disease that can influence reproductive health. SSc has a strong female predominance, and the disease onset can occur during fertility age in almost 50% of patients. Preconception counseling, adjustment of treatment, and close surveillance during pregnancy by a multidisciplinary team, are key points to minimize fetal and maternal risks and favor successful pregnancy outcomes. The rates of spontaneous pregnancy losses are comparable to those of the general obstetric population, except for patients with diffuse cutaneous SSc and severe internal organ involvement who may carry a higher risk of abortion. Preterm birth can frequently occur in women with SSc, as it happens in other rheumatic diseases. Overall disease activity generally remains stable during pregnancy, but particular attention should be paid to women with major organ disease, such as renal and cardiopulmonary involvement. Women with such severe involvement should be thoroughly informed about the risks during pregnancy and possibly discouraged from getting pregnant. A high frequency of sexual dysfunction has been described among SSc patients, both in females and in males, and pathogenic mechanisms of SSc may play a fundamental role in determining this impairment. Fertility is overall normal in SSc women, while no studies in the literature have investigated fertility in SSc male patients. Nevertheless, some considerations regarding the impact of some immunosuppressive drugs should be done with male patients, referring to the knowledge gained in other rheumatic diseases.

系统性硬化症(SSc)是一种罕见的影响生殖健康的系统性自身免疫性疾病。SSc有很强的女性优势,疾病发作可发生在生育年龄的近50%的患者。孕前咨询,调整治疗,密切监测妊娠期间由多学科团队,是关键点,以尽量减少胎儿和产妇的风险,有利于成功的妊娠结局。自发性流产率与一般产科人群相当,除了弥漫性皮肤SSc和严重内脏受损伤的患者可能有更高的流产风险。与其他风湿性疾病一样,患有SSc的妇女经常会出现早产。总体疾病活动在怀孕期间通常保持稳定,但应特别注意患有主要器官疾病的妇女,如肾脏和心肺受累。有这种严重影响的妇女应该被彻底告知怀孕期间的风险,并可能劝阻怀孕。在男性和女性SSc患者中,性功能障碍的频率很高,SSc的致病机制可能在决定这种损害方面起着根本作用。SSc女性的生育能力总体正常,而文献中没有研究调查SSc男性患者的生育能力。然而,一些免疫抑制药物对男性患者的影响应考虑到,参考其他风湿病的知识。
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引用次数: 2
Therapeutic Approaches to Systemic Sclerosis: Recent Approvals and Future Candidate Therapies. 系统性硬化症的治疗方法:最近的批准和未来的候选疗法。
IF 8.4 2区 医学 Q1 ALLERGY Pub Date : 2023-06-01 Epub Date: 2021-09-01 DOI: 10.1007/s12016-021-08891-0
Alain Lescoat, David Roofeh, Masataka Kuwana, Robert Lafyatis, Yannick Allanore, Dinesh Khanna

Systemic sclerosis is the rheumatic disease with the highest individual mortality. The severity of the disease is determined by the extent of fibrotic changes to cutaneous and internal organ tissues, the most life-threatening visceral manifestations being interstitial lung disease, SSc-associated-pulmonary arterial hypertension and myocardial involvement. The heterogeneity of the disease has initially hindered the design of successful clinical trials, but considerations on classification criteria have improved patient selection in trials, allowing the identification of more homogeneous groups of patients based on progressive visceral manifestations or the extent of skin involvement with a focus of patients with early disease. Two major subsets of systemic sclerosis are classically described: limited cutaneous systemic sclerosis characterized by distal skin fibrosis and the diffuse subset with distal and proximal skin thickening. Beyond this dichotomic subgrouping of systemic sclerosis, new phenotypic considerations based on antibody subtypes have provided a better understanding of the heterogeneity of the disease, anti-Scl70 antibodies being associated with progressive interstitial lung disease regardless of cutaneous involvement. Two targeted therapies, tocilizumab (a monoclonal antibody targeting interleukin-6 receptors (IL-6R)) and nintedanib (a tyrosine kinase inhibitor), have recently been approved by the American Food & Drug Administration to limit the decline of lung function in patients with SSc-associated interstitial lung disease, demonstrating that such better understanding of the disease pathogenesis with the identification of key targets can lead to therapeutic advances in the management of some visceral manifestations of the disease. This review will provide a brief overview of the pathogenesis of SSc and will present a selection of therapies recently approved or evaluated in this context. Therapies evaluated and approved in SSc-ILD will be emphasized and a review of recent phase II trials in diffuse cutaneous systemic sclerosis will be proposed. We will also discuss selected therapeutic pathways currently under investigation in systemic sclerosis that still lack clinical data in this context but that may show promising results in the future based on preclinical data.

系统性硬化症是个人死亡率最高的风湿病。疾病的严重程度取决于皮肤和内脏器官组织纤维化的程度,最危及生命的内脏表现是间质性肺病、系统性硬化症相关肺动脉高压和心肌受累。这种疾病的异质性最初阻碍了临床试验的成功设计,但对分类标准的考虑改进了试验中的患者选择,从而可以根据进展性内脏表现或皮肤受累程度确定更多同质的患者组别,并将早期患者作为重点。系统性硬化症有两大亚型:以远端皮肤纤维化为特征的局限性皮肤系统性硬化症和远端及近端皮肤增厚的弥漫性亚型。除了系统性硬化症的这种二分法亚组之外,基于抗体亚型的新表型考虑使人们更好地了解了这种疾病的异质性,抗Scl70抗体与进行性间质性肺病相关,与皮肤受累无关。最近,美国食品和药物管理局批准了两种靶向疗法--托西珠单抗(一种靶向白细胞介素-6受体(IL-6R)的单克隆抗体)和宁替达尼(一种酪氨酸激酶抑制剂),用于限制SSc相关间质性肺疾病患者肺功能的下降。本综述将简要概述 SSc 的发病机理,并介绍最近批准或评估的部分治疗方法。我们将重点介绍在 SSc-ILD 中评估和批准的疗法,并对最近在弥漫性皮肤系统性硬化症中进行的 II 期试验进行回顾。我们还将讨论目前正在研究的某些系统性硬化症治疗途径,这些途径目前仍缺乏临床数据,但根据临床前数据,未来可能会显示出良好的效果。
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引用次数: 0
A Narrative Review of Pathogenetic and Histopathologic Aspects, Epidemiology, Classification Systems, and Disease Outcome Measures in Systemic Sclerosis. 系统性硬化症的病原学和组织病理学方面、流行病学、分类系统和疾病结果测量的叙述性综述。
IF 8.4 2区 医学 Q1 ALLERGY Pub Date : 2023-06-01 Epub Date: 2022-03-07 DOI: 10.1007/s12016-022-08929-x
Maria-Grazia Lazzaroni, Silvia Piantoni, Fabrizio Angeli, Stefania Bertocchi, Franco Franceschini, Paolo Airò

Systemic sclerosis (SSc) is a rare systemic autoimmune disease, characterized by the presence of three main actors: vasculopathy, immune activation, and fibrosis. This pathologic process is then translated in a clinical picture with great variability among different patients in terms of type of organ involvement, disease severity and prognosis. This heterogeneity is a main feature of SSc, which, in addition to the presence of early phases of the disease characterized by mild symptoms, can explain the high difficulty in establishing classification criteria, and in defining patients' subsets and disease outcomes. The definition of disease outcomes is particularly relevant in the setting of clinical trials, where the aim is to provide reliable endpoints, able to measure the magnitude of the efficacy of a certain drug or intervention. For this reason, in the last years, increasing efforts have been done to design measures of disease activity, damage, severity, and response to treatment, often in the context of composite indexes. When considering disease outcomes, the experience of the patient represents a relevant and complementary aspect. The tools able to capture this experience, the patient-reported outcomes, have been increasingly used in the last years in clinical practice and in clinical trials, both as primary and secondary endpoints. This comprehensive narrative review on SSc will therefore cover pathogenetic and histopathologic aspects, epidemiology, classification systems, and disease outcome measures, in order to focus on issues that are relevant for clinical research and design of clinical trials.

系统性硬化症(SSc)是一种罕见的系统性自身免疫性疾病,其特点是存在三个主要角色:血管病变、免疫激活和纤维化。这一病理过程转化为临床表现,不同患者在受累器官类型、疾病严重程度和预后方面存在很大差异。这种异质性是 SSc 的一个主要特征,再加上疾病早期症状轻微,这就解释了为什么在建立分类标准、定义患者亚群和疾病预后方面存在很大困难。在临床试验中,疾病结果的定义尤为重要,因为临床试验的目的是提供可靠的终点,以衡量某种药物或干预措施的疗效大小。因此,在过去的几年里,人们越来越努力地设计疾病活动、损害、严重程度和对治疗的反应的测量方法,通常采用综合指数的形式。在考虑疾病结果时,患者的经历是一个相关的补充方面。在过去几年中,临床实践和临床试验中越来越多地使用能够捕捉这种体验的工具,即患者报告的结果,并将其作为主要和次要终点。因此,这篇关于 SSc 的综合叙述性综述将涵盖病原学和组织病理学方面、流行病学、分类系统和疾病结果测量,以便重点关注与临床研究和临床试验设计相关的问题。
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引用次数: 0
Mesenchymal Stem Cell-Based Therapy as a New Approach for the Treatment of Systemic Sclerosis. 间充质干细胞为基础的治疗系统性硬化症的新途径。
IF 9.1 2区 医学 Q1 ALLERGY Pub Date : 2023-06-01 DOI: 10.1007/s12016-021-08892-z
Xiufen Zhuang, Xiao Hu, Shuren Zhang, Xingmin Li, Xiaoying Yuan, Yanhong Wu

Systemic sclerosis (SSc) is an intractable autoimmune disease with unmet medical needs. Conventional immunosuppressive therapies have modest efficacy and obvious side effects. Targeted therapies with small molecules and antibodies remain under investigation in small pilot studies. The major breakthrough was the development of autologous haematopoietic stem cell transplantation (AHSCT) to treat refractory SSc with rapidly progressive internal organ involvement. However, AHSCT is contraindicated in patients with advanced visceral involvement. Mesenchymal stem cells (MSCs) which are characterized by immunosuppressive, antifibrotic and proangiogenic capabilities may be a promising alternative option for the treatment of SSc. Multiple preclinical and clinical studies on the use of MSCs to treat SSc are underway. However, there are several unresolved limitations and safety concerns of MSC transplantation, such as immune rejections and risks of tumour formation, respectively. Since the major therapeutic potential of MSCs has been ascribed to their paracrine signalling, the use of MSC-derived extracellular vesicles (EVs)/secretomes/exosomes as a "cell-free" therapy might be an alternative option to circumvent the limitations of MSC-based therapies. In the present review, we overview the current knowledge regarding the therapeutic efficacy of MSCs in SSc, focusing on progresses reported in preclinical and clinical studies using MSCs, as well as challenges and future directions of MSC transplantation as a treatment option for patients with SSc.

系统性硬化症(SSc)是一种难以满足医疗需求的自身免疫性疾病。常规免疫抑制疗法疗效一般,副作用明显。小分子和抗体靶向治疗仍在小规模试点研究中进行研究。主要的突破是自体造血干细胞移植(AHSCT)的发展,以治疗难治性SSc并迅速进展的内部器官受累。然而,AHSCT是晚期内脏受累患者的禁忌症。间充质干细胞(MSCs)具有免疫抑制、抗纤维化和促血管生成能力,可能是治疗SSc的一个有希望的替代选择。使用MSCs治疗SSc的多项临床前和临床研究正在进行中。然而,MSC移植存在一些未解决的限制和安全性问题,例如免疫排斥和肿瘤形成的风险。由于间充质干细胞的主要治疗潜力归因于其旁分泌信号,因此使用间充质干细胞衍生的细胞外囊泡(ev)/分泌组/外泌体作为“无细胞”治疗可能是规避基于间充质干细胞的治疗局限性的另一种选择。在本综述中,我们概述了目前关于MSCs在SSc中的治疗效果的知识,重点介绍了MSCs在临床前和临床研究中的进展,以及MSC移植作为SSc患者治疗选择的挑战和未来方向。
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引用次数: 13
Renal Disease and Systemic Sclerosis: an Update on Scleroderma Renal Crisis. 肾脏疾病和系统性硬化症:硬皮病肾危机的最新进展。
IF 9.1 2区 医学 Q1 ALLERGY Pub Date : 2023-06-01 DOI: 10.1007/s12016-022-08945-x
Alice Cole, Voon H Ong, Christopher P Denton

Scleroderma renal crisis (SRC) is a life-threatening complication of systemic sclerosis (SSc) with a mortality of 20% at 6 months. Once the leading cause of mortality in scleroderma (SSc), it remains a serious complication, often necessitating level three care for patients affected. Whilst renal outcomes have significantly improved following the advent of angiotensin-converting enzyme inhibitor (ACEi) therapy, SRC remains a precarious challenge for clinicians, due to lack of preventative measures and the fact that patients can rapidly decline despite best medical management. Large cohort studies spanning decades have allowed clear identification of phenotypes particularly at risk of developing SRC thus allowing enhanced monitoring and early identification in those individuals. Novel urinary biomarkers for renal disease in SSc may offer a new window for early identification of SRC patients and response to treatment. Multiple studies have demonstrated increased activity of complement pathways in SRC with some anecdotal cases exhibiting serological response to treatment with eculizumab where ACEi and therapeutic plasma exchange (TPE) were not successful. Endothelin-1 blockade, a therapeutic strategy in other SSc vasculopathies, has shown potential as a target but clinical trials are yet to show a clear treatment benefit. Clear guidelines for the management of SRC are in place to standardise care and facilitate early collaboration between rheumatology and renal physicians. Outcomes following renal transplant have improved but the mortality of SRC remains high, indicating the need for continued exploration of the mechanisms precipitating and exacerbating SRC in order to develop novel therapies.

硬皮病肾危象(SRC)是系统性硬化症(SSc)的一种危及生命的并发症,6个月死亡率为20%。曾经是硬皮病(SSc)死亡的主要原因,它仍然是一个严重的并发症,通常需要对受影响的患者进行三级护理。随着血管紧张素转换酶抑制剂(ACEi)治疗的出现,肾脏预后有了显著改善,但由于缺乏预防措施,以及尽管有最好的医疗管理,患者仍可能迅速恶化,SRC对临床医生来说仍然是一个不稳定的挑战。跨越数十年的大型队列研究已经能够清楚地识别表型,特别是在发生SRC的风险中,从而可以加强对这些个体的监测和早期识别。新的尿液生物标志物可能为SRC患者的早期识别和治疗反应提供新的窗口。多项研究表明,补体通路在SRC中的活性增加,一些轶事病例在ACEi和治疗性血浆交换(TPE)不成功的情况下,对eculizumab治疗表现出血清学反应。内皮素-1阻断是其他SSc血管病变的一种治疗策略,已显示出作为靶点的潜力,但临床试验尚未显示出明确的治疗益处。对于SRC的管理有明确的指导方针,以规范治疗并促进风湿病医生和肾脏医生之间的早期合作。肾移植后的预后有所改善,但SRC的死亡率仍然很高,这表明需要继续探索诱发和加重SRC的机制,以开发新的治疗方法。
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引用次数: 15
A Summary on the Genetics of Systemic Lupus Erythematosus, Rheumatoid Arthritis, Systemic Sclerosis, and Sjögren's Syndrome. 系统性红斑狼疮、类风湿性关节炎、系统性硬化症和Sjögren综合征的遗传学综述。
IF 9.1 2区 医学 Q1 ALLERGY Pub Date : 2023-06-01 DOI: 10.1007/s12016-022-08951-z
Lourdes Ortíz-Fernández, Javier Martín, Marta E Alarcón-Riquelme

Systemic lupus erythematosus, systemic sclerosis, rheumatoid arthritis, and Sjögren's syndrome are four major autoimmune rheumatic diseases characterized by the presence of autoantibodies, caused by a dysregulation of the immune system that leads to a wide variety of clinical manifestations. These conditions present complex etiologies strongly influenced by multiple environmental and genetic factors. The human leukocyte antigen (HLA) region was the first locus identified to be associated and still represents the strongest susceptibility factor for each of these conditions, particularly the HLA class II genes, including DQA1, DQB1, and DRB1, but class I genes have also been associated. Over the last two decades, the genetic component of these disorders has been extensively investigated and hundreds of non-HLA risk genetic variants have been uncovered. Furthermore, it is widely accepted that autoimmune rheumatic diseases share molecular disease pathways, such as the interferon (IFN) type I pathways, which are reflected in a common genetic background. Some examples of well-known pleiotropic loci for autoimmune rheumatic diseases are the HLA region, DNASEL13, TNIP1, and IRF5, among others. The identification of the causal molecular mechanisms behind the genetic associations is still a challenge. However, recent advances have been achieved through mouse models and functional studies of the loci. Here, we provide an updated overview of the genetic architecture underlying these four autoimmune rheumatic diseases, with a special focus on the HLA region.

系统性红斑狼疮、系统性硬化症、类风湿关节炎和Sjögren综合征是四种主要的自身免疫性风湿病,其特征是存在自身抗体,由免疫系统失调引起,导致各种临床表现。这些疾病的病因复杂,受多种环境和遗传因素的强烈影响。人类白细胞抗原(HLA)区域是第一个被确定为相关的位点,并且仍然是这些疾病的最强易感因素,特别是HLA II类基因,包括DQA1、DQB1和DRB1,但I类基因也有相关。在过去的二十年中,对这些疾病的遗传成分进行了广泛的研究,并发现了数百种非hla风险遗传变异。此外,人们普遍认为,自身免疫性风湿性疾病具有共同的分子疾病途径,如干扰素(IFN) I型途径,这反映在共同的遗传背景中。一些众所周知的自身免疫性风湿性疾病的多效性位点的例子是HLA区域,DNASEL13, TNIP1和IRF5等。确定遗传关联背后的因果分子机制仍然是一个挑战。然而,最近通过小鼠模型和基因座的功能研究取得了进展。在这里,我们提供了这四种自身免疫性风湿性疾病的遗传结构的最新概述,特别关注HLA区域。
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引用次数: 10
Real-Life Effectiveness of Benralizumab, Mepolizumab and Omalizumab in Severe Allergic Asthma Associated with Nasal Polyps. Benralizumab, Mepolizumab和Omalizumab在鼻息肉相关的严重过敏性哮喘中的实际有效性
IF 9.1 2区 医学 Q1 ALLERGY Pub Date : 2023-04-01 DOI: 10.1007/s12016-022-08938-w
Angelica Tiotiu, Paula Mendez-Brea, Iulia Ioan, Rodrigo Romero-Fernandez, Jean Philippe Oster, Thi-Cam-Tu Hoang, Pauline Roux, Diana Carolina Ochoa-Gutierrez, Philippe Bonniaud, Frederic de Blay, Francisco-Javier Gonzalez-Barcala

Biological therapies are available for the treatment of the severe allergic asthma (SAA) with blood eosinophil count ≥ 0.3 × 109/L. Several of them also showed benefits on nasal polyps (NP), one of the most frequent comorbidities of the severe asthma, but comparative studies on their effectiveness in the association SAA-NP are currently lacking. The aim of this study is to compare the effectiveness of benralizumab, mepolizumab and omalizumab in patients with SAA-NP in real-life settings. A retrospective, observational, multicenter real-life study was realized including patients with SAA-NP treated by benralizumab, mepolizumab or omalizumab for 6 months. We analysed the nasal and respiratory symptoms, the number of asthma attacks and salbutamol use/week, acute sinusitis and severe exacerbation rates, the asthma control score, the lung function parameters, the NP endoscopic score, the sinus imaging and the blood eosinophil count 6 months before and after treatment. Seventy-two patients with SAA-NP were included: 16 treated by benralizumab, 21 by mepolizumab and 35 by omalizumab. After 6 months of treatment, almost all studied parameters were improved (except sinus imaging) with a greater effect of omalizumab on the nasal pruritus (p = 0.001) and more benefits of benralizumab on exacerbations rate, asthma attacks per week and lung function (all p < 0.05). Benralizumab and mepolizumab were more effective to improve the NP endoscopic score and the blood eosinophil count (both p < 0.001). All three biological therapies showed effectiveness by improving asthma and nasal outcomes in patients with SAA-NP. Several differences have been found that should be confirmed by larger comparative studies.

血液嗜酸性粒细胞≥0.3 × 109/L的严重变应性哮喘(SAA)可采用生物疗法治疗。其中一些药物也显示出对鼻息肉(NP)的疗效,鼻息肉是严重哮喘最常见的合共病之一,但目前缺乏对它们与SAA-NP相关的有效性的比较研究。本研究的目的是比较benralizumab, mepolizumab和omalizumab在现实生活中SAA-NP患者中的有效性。一项回顾性、观察性、多中心现实研究纳入了接受benralizumab、mepolizumab或omalizumab治疗6个月的SAA-NP患者。我们分析了治疗前后6个月的鼻部和呼吸道症状、哮喘发作次数和沙丁胺醇使用次数/周、急性鼻窦炎和严重加重率、哮喘控制评分、肺功能参数、NP内窥镜评分、鼻窦成像和血嗜酸性粒细胞计数。纳入72例SAA-NP患者:16例使用benralizumab, 21例使用mepolizumab, 35例使用omalizumab。治疗6个月后,几乎所有研究参数都得到改善(鼻窦成像除外),奥玛珠单抗对鼻瘙痒的影响更大(p = 0.001),贝纳利珠单抗对加重率、每周哮喘发作和肺功能的益处更大(p = 0.001)
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引用次数: 9
Inflammaging and Frailty in Immune-Mediated Rheumatic Diseases: How to Address and Score the Issue. 免疫介导的风湿病的炎症和虚弱:如何解决和评分问题。
IF 9.1 2区 医学 Q1 ALLERGY Pub Date : 2023-04-01 DOI: 10.1007/s12016-022-08943-z
Fausto Salaffi, Andrea Di Matteo, Sonia Farah, Marco Di Carlo

Frailty is a new concept in rheumatology that can help identify people more likely to have less favorable outcomes. Sarcopenia and inflammaging can be regarded as the biological foundations of physical frailty. Frailty is becoming more widely accepted as an indicator of ageing and is linked to an increased risk of negative outcomes such as falls, injuries, and mortality. Frailty identifies a group of older adults that seem poorer and more fragile than their age-matched counterparts, despite sharing similar comorbidities, demography, sex, and age. Several studies suggest that inflammation affects immune-mediated pathways, multimorbidity, and frailty by inhibiting growth factors, increasing catabolism, and by disrupting homeostatic signaling. Frailty is more common in the community-dwelling population as people get older, ranging from 7 to 10% in those over 65 years up to 40% in those who are octogenarians. Different parameters have been validated to identify frailty. These primarily relate to two conceptual models: Fried's physical frailty phenotype and Rockwood's cumulative deficit method. Immune-mediated rheumatic diseases (IMRDs), such as rheumatoid arthritis, spondyloarthritis, systemic lupus erythematosus, systemic sclerosis, and vasculitis, are leading causes of frailty in developing countries. The aim of this review was to quantitatively synthesize published literature on the prevalence of frailty in IMRDs and to summarize current evidence on the relevance and applicability of the most widely used frailty screening tools.

虚弱是风湿病学中的一个新概念,可以帮助识别更有可能出现不良结果的人。骨骼肌减少症和炎症可被视为身体虚弱的生物学基础。虚弱正越来越被广泛接受为衰老的一项指标,并与跌倒、受伤和死亡等负面后果的风险增加有关。“虚弱”指的是一群老年人,尽管他们的合并症、人口结构、性别和年龄相似,但他们似乎比同龄的老年人更贫穷、更脆弱。一些研究表明,炎症通过抑制生长因子、增加分解代谢和破坏体内平衡信号来影响免疫介导的途径、多发病和虚弱。随着年龄的增长,虚弱在社区居民中更为常见,65岁以上的老年人中虚弱的比例为7%至10%,而80多岁的老年人中虚弱的比例为40%。已经验证了不同的参数来识别脆弱性。这些主要涉及两个概念模型:弗里德的身体脆弱表型和洛克伍德的累积缺陷方法。免疫介导的风湿性疾病(imrd),如类风湿关节炎、脊椎关节炎、系统性红斑狼疮、系统性硬化症和血管炎,是发展中国家虚弱的主要原因。本综述的目的是定量综合已发表的关于imrd中虚弱患病率的文献,并总结目前最广泛使用的虚弱筛查工具的相关性和适用性的证据。
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引用次数: 13
Immunology of Aging: the Birth of Inflammaging. 衰老免疫学:炎症的诞生。
IF 9.1 2区 医学 Q1 ALLERGY Pub Date : 2023-04-01 DOI: 10.1007/s12016-021-08899-6
T Fulop, A Larbi, G Pawelec, A Khalil, A A Cohen, K Hirokawa, J M Witkowski, C Franceschi

The inflammaging concept was introduced in 2000 by Prof. Franceschi. This was an evolutionary or rather a revolutionary conceptualization of the immune changes in response to a lifelong stress. This conceptualization permitted to consider the lifelong proinflammatory process as an adaptation which could eventually lead to either beneficial or detrimental consequences. This dichotomy is influenced by both the genetics and the environment. Depending on which way prevails in an individual, the outcome may be healthy longevity or pathological aging burdened with aging-related diseases. The concept of inflammaging has also revealed the complex, systemic nature of aging. Thus, this conceptualization opens the way to consider age-related processes in their complexity, meaning that not only the process but also all counter-processes should be considered. It has also opened the way to add new concepts to the original one, leading to better understanding of the nature of inflammaging and of aging itself. Finally, it showed the way towards potential multimodal interventions involving a holistic approach to optimize the aging process towards a healthy longevity.

炎症的概念是由Franceschi教授在2000年提出的。这是一个进化的,或者说是革命性的概念,免疫变化是对终身压力的反应。这一概念允许将终身促炎过程视为一种适应,最终可能导致有益或有害的后果。这种二分法受到遗传和环境的双重影响。取决于个体中哪种方式盛行,结果可能是健康长寿,也可能是与衰老相关的疾病带来的病理性衰老。炎症的概念也揭示了衰老的复杂性和系统性。因此,这种概念化为考虑与年龄相关的过程的复杂性开辟了道路,这意味着不仅要考虑过程,还要考虑所有反过程。它还开辟了在原有的基础上增加新概念的道路,从而更好地理解炎症和衰老本身的本质。最后,它显示了实现潜在的多模式干预的方式,包括采用整体方法来优化衰老过程,以实现健康长寿。
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引用次数: 92
期刊
Clinical Reviews in Allergy & Immunology
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