Grignaschi Silvia, Sbalchiero Anna, Spinozzi Giuseppe, Palermo Bianca Lucia, Cantarini Claudia, Nardiello Chantal, Cavagna Lorenzo, Olivieri Carla
Department of Internal Medicine and Medical Therapeutics, University of Pavia, Pavia, Italy.
Rheumatology Division, Fondazione Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS) Policlinico San Matteo, Pavia, Italy.
Front Med (Lausanne). 2022 Aug 18;9:964526. doi: 10.3389/fmed.2022.964526. eCollection 2022.
Systemic Sclerosis (SSc) is a rare autoimmune disease whose pathogenesis is still poorly understood. The Transforming Growth Factor β superfamily is considered pivotal and a crucial role has been suggested for the type III receptor, Endoglin (ENG). The aim of this systematic review is to investigate and combine the current clinical and molecular available data, to suggest novel hints for further studies.
We followed PRISMA guidelines; the search was performed on three databases (MEDLINE, Web of Science, Embase) in date November 2nd, 2021. Subsequent to the exclusion of duplicates, we applied as inclusion criteria: 1. focus on the relationship between ENG and SSc; 2. English language. As exclusion criteria: 1. ENG exclusively as a cellular biomarker; 2. no focus on ENG-SSc relationship; 3. review articles and 4. abstracts that did not add novel data. Eligibility was assessed independently by each author to reduce biases. We divided records into clinical and molecular works and subgrouped them by their study features and aim.
We selected 25 original papers and 10 conference abstracts. Molecular studies included 6 articles and 4 abstracts, whereas clinical studies included 17 articles and 6 abstracts; 2 articles presented both characteristics. Molecular studies were focussed on ENG expression in different cell types, showing an altered ENG expression in SSc-affected cells. Clinical studies mainly suggested that different disease phenotypes can be related to peculiar disregulations in soluble ENG concentrations.
Concerning the possible limits of our search, boolean operators in our strings might have been uneffective. However, the use of different strings in different databases should have reduced this issue at a minimum. Another bias can be represented by the selection step, in which we excluded many articles based on the role of Endoglin as a histological vascular marker rather than a signaling receptor. We tried to reduce this risk by performing the selection independently by each author and discussing disagreements. Our systematic review pointed out that ENG has a pivotal role in activating different TGFβ-stimulated pathways that can be crucial in SSc pathogenesis and progression.
系统性硬化症（SSc）是一种罕见的自身免疫性疾病，其发病机制仍未完全明确。转化生长因子β超家族被认为起着关键作用，且有人提出III型受体内皮糖蛋白（ENG）具有重要作用。本系统评价的目的是调查并整合当前可用的临床和分子数据，为进一步研究提供新线索。
我们遵循PRISMA指南；于2021年11月2日在三个数据库（MEDLINE、科学网、Embase）中进行检索。在排除重复项后，我们采用以下纳入标准：1. 关注ENG与SSc之间的关系；2. 英文文献。排除标准为：1. ENG仅作为细胞生物标志物；2. 不关注ENG与SSc的关系；3. 综述文章；4. 未提供新数据的摘要。每位作者独立评估纳入资格以减少偏倚。我们将记录分为临床和分子研究，并根据其研究特征和目的进行亚组划分。
我们筛选出25篇原创论文和10篇会议摘要。分子研究包括6篇文章和4篇摘要，临床研究包括17篇文章和6篇摘要；2篇文章兼具两者特征。分子研究聚焦于ENG在不同细胞类型中的表达，显示在SSc受累细胞中ENG表达发生改变。临床研究主要表明，不同的疾病表型可能与可溶性ENG浓度的特定失调有关。
关于我们检索可能存在的局限性，检索词中的布尔运算符可能效果不佳。然而，在不同数据库中使用不同的检索词应已将此问题降至最低。另一个偏倚可能体现在筛选步骤中，我们基于内皮糖蛋白作为组织学血管标志物而非信号受体的作用排除了许多文章。我们试图通过每位作者独立进行筛选并讨论分歧来降低这种风险。我们的系统评价指出，ENG在激活不同的TGFβ刺激途径中起关键作用，这些途径可能在SSc的发病机制和进展中至关重要。
