Systemic autoimmune rheumatic diseases (SARDs) exhibit extensive heterogeneity in clinical presentation, disease course, and treatment response. Therefore, precision medicine — whereby treatment is tailored according to the underlying pathogenic mechanisms of an individual patient at a specific time — represents the ‘holy grail’ in SARD clinical care. Current strategies include treat-to-target therapies and autoantibody testing for patient stratification; however, these are far from optimal. Recent innovations in high-throughput ‘omic’ technologies are now enabling comprehensive profiling at multiple levels, helping to identify subgroups of patients who may taper off potentially toxic medications or better respond to current molecular targeted therapies. Such advances may help to optimize outcomes and identify new pathways for treatment, but there are many challenges along the path towards clinical translation. In this Review, we discuss recent efforts to dissect cellular and molecular heterogeneity across multiple SARDs and future directions for implementing stratification approaches for SARD treatment in the clinic.

系统性自身免疫性风湿病 (SARD) 在临床表现、病程和治疗反应方面表现出广泛的异质性。因此，精准医学——根据个体患者在特定时间的潜在致病机制量身定制治疗——代表了 SARD 临床护理中的“圣杯”。目前的策略包括靶向治疗和患者分层的自身抗体检测；然而，这些远非最佳。高通量“组学”技术的最新创新现在可以在多个层面进行全面分析，帮助确定可能逐渐减少潜在毒性药物或更好地响应当前分子靶向治疗的患者亚组。这些进步可能有助于优化结果并确定新的治疗途径，但在临床转化的道路上存在许多挑战。在这篇综述中，我们讨论了最近为剖析多个 SARD 的细胞和分子异质性所做的努力，以及在临床上实施 SARD 治疗分层方法的未来方向。