Nocturne Gaetane, Pontarini Elena, Bombardieri Michele, Mariette Xavier
Department of Rheumatology, Université Paris-Sud, AP-HP, Hôpitaux Universitaires Paris-Sud, Centre for Immunology of Viral Infections and Autoimmune Diseases, INSERM UMR1184, Le Kremlin Bicêtre, France.
Centre for Experimental Medicine and Rheumatology, William Harvey Research Institute, Queen Mary University of London, London, UK.
Rheumatology (Oxford). 2021 Aug 2;60(8):3513-3521. doi: 10.1093/rheumatology/kez052.
Lymphoma development is the most serious complication of SS and the main factor impacting on mortality rate in patients with this condition. Lymphomas in SS are most commonly extranodal non-Hodgkin B-cell lymphomas of the mucosa-associated lymphoid tissue and frequently arise in salivary glands that are the target of a chronic inflammatory autoimmune process. Extensive work on lymphomagenesis in SS has established that the progression towards B-cell lymphoma is a multistep process related to local chronic antigenic stimulation of B cells. These neoplastic B cells in SS frequently derived from autoreactive clones, most commonly RF-producing B cells, which undergo uncontrolled proliferation and malignant escape. In this review, we highlight the most important recent findings that have enhanced our understanding of lymphoma development in SS, with particular reference to the close link between autoimmunity and lymphomagenesis. We also discuss how the identification of key factors involved in B-cell malignancies may impact on our ability to identify at early stages patients at increased risk of lymphoma with potential significant repercussions for the clinical management of SS patients. Finally, we identified the most promising areas of current and further research with the potential to provide novel basic and translational discoveries in the field. The questions of finding new biomarkers, developing a validated score for predicting lymphoma occurrence and assessing if a better control of disease activity will decrease the risk of lymphoma in primary SS will be the enthralling questions of the next few years.
淋巴瘤的发生是干燥综合征最严重的并发症，也是影响该疾病患者死亡率的主要因素。干燥综合征中的淋巴瘤最常见的是黏膜相关淋巴组织的结外非霍奇金B细胞淋巴瘤，且常发生于作为慢性炎症性自身免疫过程靶器官的唾液腺。关于干燥综合征淋巴瘤发生的大量研究已证实，向B细胞淋巴瘤的进展是一个与B细胞局部慢性抗原刺激相关的多步骤过程。干燥综合征中的这些肿瘤性B细胞通常源自自身反应性克隆，最常见的是产生类风湿因子的B细胞，它们会发生不受控制的增殖和恶性逃逸。在本综述中，我们重点介绍了最近最重要的发现，这些发现加深了我们对干燥综合征淋巴瘤发生的理解，特别提到了自身免疫与淋巴瘤发生之间的紧密联系。我们还讨论了B细胞恶性肿瘤相关关键因素的识别如何影响我们在早期识别淋巴瘤风险增加患者的能力，这可能对干燥综合征患者的临床管理产生重大影响。最后，我们确定了当前及进一步研究中最有前景的领域，这些领域有可能在该领域提供新的基础和转化研究发现。寻找新的生物标志物、开发用于预测淋巴瘤发生的有效评分以及评估更好地控制疾病活动是否会降低原发性干燥综合征患者淋巴瘤风险等问题，将是未来几年引人入胜的问题。
