The Westmead Institute for Medical Research, University of Sydney, Westmead Hospital, NSW Health Pathology, Westmead, New South Wales, Australia.
SA Pathology and Flinders University, Bedford Park, South Australia, Australia.
Arthritis Care Res (Hoboken). 2023 Jul;75(7):1580-1587. doi: 10.1002/acr.25011. Epub 2023 Jan 5.
Sjögren's disease (SjD) is an archetypal and heterogenous autoimmune disorder that is characterized by exocrine glandular dysfunction. A proportion of patients develop severe extraglandular manifestations, such as cryoglobulinemia, and have an increased risk of lymphoma, both of which can adversely affect quality of life and occasionally mortality. As with most autoimmune disorders, the pathogenesis is poorly understood and difficult to predict, and, frustratingly, there is a lack of targeted therapies to cure this disease. We review the disease manifestations of SjD and propose a staged model for understanding the evolution of pathology. In longitudinal studies, most patients remain relatively stable in terms of their laboratory and clinical parameters. However, in the setting of various risk factors, a proportion of patients develop severe symptoms and/or lymphoma. We discuss potential underlying mechanisms for disease progression and the strengths and limitations of using a staged model to correlate the pathogenesis and spectrum of manifestations in SjD. Ultimately, understanding how and why some patients remain relatively stable, whereas others progress and develop florid systemic disease and a fraction develop lymphoma, is key to developing preventative and therapeutic treatments.
干燥综合征（SjD）是一种典型的异质性自身免疫性疾病，其特征为外分泌腺功能障碍。一部分患者会出现严重的腺外表现，如冷球蛋白血症，并且淋巴瘤风险增加，这两者都会对生活质量产生不良影响，有时甚至会导致死亡。与大多数自身免疫性疾病一样，其发病机制尚不清楚，难以预测，令人沮丧的是，目前缺乏能够治愈这种疾病的靶向治疗方法。我们回顾了 SjD 的疾病表现，并提出了一个理解病理演变的分期模型。在纵向研究中，大多数患者在实验室和临床参数方面相对稳定。然而，在各种风险因素的作用下，一部分患者会出现严重的症状和/或淋巴瘤。我们讨论了疾病进展的潜在机制，以及使用分期模型来关联 SjD 发病机制和表现谱的优缺点。最终，了解为什么有些患者相对稳定，而有些患者会进展并出现明显的全身疾病，还有一部分患者会发展为淋巴瘤，这对于开发预防和治疗性治疗方法至关重要。
