Systemic Sclerosis-Specific Antibodies: Novel and Classical Biomarkers.

IF 8.4 2区 医学 Q1 ALLERGY Clinical Reviews in Allergy & Immunology 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
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引用次数: 15

Abstract

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 wider cohorts in order to restrict the gap of so-called seronegative SSc patients.

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系统性硬化症特异性抗体:新的和经典的生物标志物。
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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来源期刊
CiteScore
22.30
自引率
1.10%
发文量
58
审稿时长
6-12 weeks
期刊介绍: Clinical Reviews in Allergy & Immunology is a scholarly journal that focuses on the advancement of clinical management in allergic and immunologic diseases. The journal publishes both scholarly reviews and experimental papers that address the current state of managing these diseases, placing new data into perspective. Each issue of the journal is dedicated to a specific theme of critical importance to allergists and immunologists, aiming to provide a comprehensive understanding of the subject matter for a wide readership. The journal is particularly helpful in explaining how novel data impacts clinical management, along with advancements such as standardized protocols for allergy skin testing and challenge procedures, as well as improved understanding of cell biology. Ultimately, the journal aims to contribute to the improvement of care and management for patients with immune-mediated diseases.
期刊最新文献
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