Johnsen S J, Gudlaugsson E, Skaland I, Janssen E A M, Jonsson M V, Helgeland L, Berget E, Jonsson R, Omdal R
Clinical Immunology Unit, Department of Internal Medicine, Stavanger University Hospital, Stavanger, Norway.
Department of Pathology, Stavanger University Hospital, Stavanger, Norway.
Scand J Immunol. 2016 Mar;83(3):181-7. doi: 10.1111/sji.12405.
Patients with primary Sjögren's syndrome (pSS) have an increased risk of developing lymphomas, particularly the subtype mucosa-associated lymphoid tissue (MALT) lymphoma. Chronic antigen stimulation and increased activation of nuclear factor-κB (NF-κB) are important factors for the pathogenesis of MALT lymphomas. Protein A20 is an inhibitor of NF-κB. A recent study of pSS-associated MALT lymphomas identified potential functional abnormalities in the TNFAIP3 gene, which encodes protein A20. The present study aimed to assess protein A20 by immunohistochemistry (IHC) in minor salivary glands (MSGs) and lymphoma tissue sections of patients with pSS and investigate a potential association with lymphoma development. Protein A20 staining in lymphocytes was scored in four categories (0 = negative, 1 = weak, 2 = moderate and 3 = strong). For statistical purposes, these scores were simplified into negative (scores 0-1) and positive (scores 2-3). We investigated associations between protein A20-staining, focus scores, germinal centre (GC)-like structures and monoclonal B-cell infiltration in MSGs. MSG protein A20 staining was weaker in pSS patients with lymphomas than in those without lymphomas (P = 0.01). Weak protein A20 staining was also highly associated with a lack of GC formation (P < 0.01). Finally, weaker A20 staining was observed in the majority of pSS-associated MALT lymphoma tissues. In conclusion, we found absent or weak protein A20 immunoreactivity in MSGs of patients with pSS with lymphomas. This finding indicates that protein A20 downregulation in lymphocytes might be a mechanism underlying lymphoma genesis in patients with pSS.
原发性干燥综合征（pSS）患者发生淋巴瘤的风险增加，尤其是黏膜相关淋巴组织（MALT）淋巴瘤亚型。慢性抗原刺激和核因子-κB（NF-κB）激活增加是MALT淋巴瘤发病机制的重要因素。蛋白A20是NF-κB的抑制剂。最近一项关于pSS相关MALT淋巴瘤的研究发现，编码蛋白A20的TNFAIP3基因存在潜在功能异常。本研究旨在通过免疫组织化学（IHC）评估pSS患者小唾液腺（MSG）和淋巴瘤组织切片中的蛋白A20，并研究其与淋巴瘤发生的潜在关联。淋巴细胞中的蛋白A20染色分为四类（0 =阴性，1 =弱阳性，2 =中等阳性，3 =强阳性）。为了统计目的，这些评分被简化为阴性（评分0-1）和阳性（评分2-3）。我们研究了MSG中蛋白A20染色、灶性评分、生发中心（GC）样结构和单克隆B细胞浸润之间的关联。有淋巴瘤的pSS患者的MSG蛋白A20染色比无淋巴瘤的患者弱（P = 0.01）。蛋白A20弱阳性染色也与缺乏GC形成高度相关（P < 0.01）。最后，在大多数pSS相关MALT淋巴瘤组织中观察到A20染色较弱。总之，我们发现在有淋巴瘤的pSS患者的MSG中存在蛋白A20免疫反应性缺失或减弱。这一发现表明，淋巴细胞中蛋白A20的下调可能是pSS患者淋巴瘤发生的潜在机制。
