Noviani Maria, Chellamuthu Vasuki Ranjani, Albani Salvatore, Low Andrea Hsiu Ling
Department of Rheumatology and Immunology, Singapore General Hospital, Singapore, Singapore.
Duke-National University of Singapore Medical School, Singapore, Singapore.
Front Med (Lausanne). 2022 Jun 30;9:911977. doi: 10.3389/fmed.2022.911977. eCollection 2022.
Systemic sclerosis (SSc), a complex multi-systemic disease characterized by immune dysregulation, vasculopathy and fibrosis, is associated with high mortality. Its pathogenesis is only partially understood. The heterogenous pathological processes that define SSc and its stages present a challenge to targeting appropriate treatment, with differing treatment outcomes of SSc patients despite similar initial clinical presentations. Timing of the appropriate treatments targeted at the underlying disease process is critical. For example, immunomodulatory treatments may be used for patients in a predominantly inflammatory phase, anti-fibrotic treatments for those in the fibrotic phase, or combination therapies for those in the fibro-inflammatory phase. In advancing personalized care through precision medicine, groups of patients with similar disease characteristics and shared pathological processes may be identified through molecular stratification. This would improve current clinical sub-setting systems and guide personalization of therapies. In this review, we will provide updates in SSc clinical and molecular stratification in relation to patient outcomes and treatment responses. Promises of molecular stratification through advances in high-dimensional tools, including omic-based stratification (transcriptomics, genomics, epigenomics, proteomics, cytomics, microbiomics) and machine learning will be discussed. Innovative and more granular stratification systems that integrate molecular characteristics to clinical phenotypes would potentially improve therapeutic approaches through personalized medicine and lead to better patient outcomes.
系统性硬化症（SSc）是一种复杂的多系统疾病，其特征为免疫失调、血管病变和纤维化，与高死亡率相关。其发病机制仅部分为人所知。定义SSc及其阶段的异质性病理过程对靶向合适的治疗构成挑战，尽管初始临床表现相似，但SSc患者的治疗结果却各不相同。针对潜在疾病过程的适当治疗时机至关重要。例如，免疫调节治疗可用于主要处于炎症阶段的患者，抗纤维化治疗用于纤维化阶段的患者，或联合治疗用于纤维炎症阶段的患者。通过精准医学推进个性化医疗时，可通过分子分层识别具有相似疾病特征和共同病理过程的患者群体。这将改进当前的临床亚组分类系统并指导治疗的个性化。在本综述中，我们将提供与患者预后和治疗反应相关的SSc临床和分子分层的最新情况。将讨论通过高维工具的进展进行分子分层的前景，包括基于组学的分层（转录组学、基因组学、表观基因组学、蛋白质组学、细胞组学、微生物组学）和机器学习。整合分子特征与临床表型的创新且更精细的分层系统可能通过个性化医疗改善治疗方法并带来更好的患者预后。
