Sjogren's syndrome - A plethora of clinical and immunological phenotypes with a complex genetic background
Sjogren's syndrome - A plethora of clinical and immunological phenotypes with a complex genetic background
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DOI：
10.1196/annals.1422.046
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发表时间：
2007-01-01
期刊：
影响因子：
--
通讯作者：
Brun, Johan G.
中科院分区：
文献类型：
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作者：
Jonsson, Roland;Bolstad, Anne Isine;Brun, Johan G.
原发性干燥综合征是一种复杂的自身免疫性疾病，被认为是研究自身免疫机制的理想疾病，因为其表现具有器官特异性和系统性。靶器官的特征性组织学发现是单核淋巴细胞进行性局灶性浸润，取代腺上皮（淋巴上皮病变）。 2002 年修订的欧盟干燥综合征标准再次强调了这种参与。此外，干燥综合征中的异位次级淋巴滤泡包含与驱动抗免疫反应相关的所有元素。许多细胞因子和趋化因子都参与其中，特别是 B 细胞激活因子似乎通过增强浸润 B 细胞的增殖和成熟来指导其寿命。最近发现 B 细胞耗竭后的临床益处也凸显了 B 细胞在干燥综合征中的关键作用。干燥综合征的一个主要挑战是对疾病过程进行分层，包括遗传和环境触发因素。新的遗传和分子标记的鉴定可能会导致针对干燥综合征（包括其全身并发症）开发出更好的诊断和预后工具。这篇小综述将涵盖当前关于分类、发病机制、多重发现、潜在候选基因、基因分析结果和新治疗方法的知识。干燥综合征复杂性背后的新假设预计将会随之而来。
Primary Sjogren's syndrome is a complex autoimmune disorder, considered to represent an ideal disease with which to study the mechanisms underlying autoimmunity because its manifestations are both organ specific and systemic in nature. The characteristic histologic finding in target organs is a progressive focal infiltration of mononuclear lymphoid cells, replacing glandular epithelium (lymphoepithelial lesion). This involvement has been re-emphasized in the 2002 revised EU criteria for Sjogren's syndrome. Moreover, ectopic secondary lymphoid follicles in Sjogren's syndrome contain all elements of relevance for driving an antoimmune response. A number of cytokines and chemokines are involved and particularly B cell activating factor seems to direct the lifespan of infiltrating B cells by enhancing their proliferation and maturation. The recent discovery of clinical benefit after B cell depletion also highlights the pivotal role of B cells in Sjogren's syndrome. A major challenge in Sjogren's syndrome will be to stratify the disease process including genetic and environmental triggers. Identification of novel genetic and molecular markers may lead to the development of better diagnostic and prognostic tools in Sjogren's syndrome including its systemic complications. This minor review will cover the current knowledge on classification, pathogenesis, multiplex findings, potential candidate genes, gene profiling results, and novel therapy approaches. New hypotheses behind the complexity of Sjogren's syndrome are expected to follow.