PDF(Pubmed)
Abstract：
Primary Sjögren\'s disease is primarily driven by B-cell activation and is associated with a high risk of developing non-Hodgkin\'s lymphoma (NHL). Over the last few decades, microRNA-155 (miR-155) has arisen as a key regulator of B-cells. Nevertheless, its role in primary Sjögren\'s disease remains elusive. Thus, the purpose of this study was (i) to explore miR-155, B-cell activating factor (BAFF)-receptor (BAFF-R), and Interleukin 6 receptor (IL-6R) expression in the labial salivary glands (LSG) of patients with primary Sjögren\'s disease, aiming to identify potential B-cell activation biomarkers related to NHL development. Twenty-four patients with primary Sjögren\'s disease, and with available tissue blocks from a LSG biopsy performed at diagnosis, were enrolled. Among them, five patients developed B-cell NHL during follow-up (7.3 ± 3.1 years). A comparison group of 20 individuals with sicca disease was included. Clinical and laboratory parameters were recorded and the LSG biopsies were evaluated to assess local inflammation in terms of miR-155/BAFF-R and IL-6R expression. Stratifying the primary Sjögren\'s disease cohort according to lymphomagenesis, miR-155 was upregulated in primary Sjögren\'s disease patients who experienced NHL, more so than those who did not experience NHL. Moreover, miR-155 expression correlated with the focus score (FS), as well as BAFF-R and IL-6R expression, which were increased in primary Sjögren\'s disease patients and in turn related to neoplastic evolution. In conclusion, epigenetic modulation may play a crucial role in the aberrant activation of B-cells in primary Sjögren\'s disease, profoundly impacting the risk of NHL development.
摘要：
原发性Sjögren病主要由B细胞活化驱动，并且与非霍奇金淋巴瘤（NHL）的高风险相关。在过去的几十年里，microRNA-155(miR-155)已经成为B细胞的关键调节因子。然而，它在原发性干燥病的作用仍然难以捉摸。因此，本研究的目的是（i）探索miR-155，B细胞活化因子（BAFF）-受体（BAFF-R），和白细胞介素6受体（IL-6R）在唇腺（LSG）的表达与原发性干燥病，旨在鉴定与NHL发展相关的潜在B细胞活化生物标志物。24例原发性干燥病患者,并利用诊断时进行的LSG活检的可用组织块，已注册。其中,5例患者在随访期间（7.3±3.1年）发生B细胞NHL。包括20个患有干燥病的个体的比较组。记录临床和实验室参数,并评估LSG活检以评估miR-155/BAFF-R和IL-6R表达方面的局部炎症。根据淋巴瘤形成对原发性干燥综合征的疾病队列进行分层，miR-155在经历NHL的原发性干燥病患者中上调，比那些没有经历NHL的人更多。此外，miR-155表达与焦点评分（FS）相关，以及BAFF-R和IL-6R的表达，在原发性Sjögren病患者中增加，反过来与肿瘤的演变有关。总之,表观遗传调节可能在原发性干燥病的B细胞异常激活中起关键作用，深刻影响NHL发展的风险。
