Pathogenesis of Sjögren's syndrome.
Pathogenesis of Sjögren's syndrome.
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DOI：
10.1097/bor.0b013e32832eba21
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发表时间：
2009-09
影响因子：
5.1
通讯作者：
Illei GG
中科院分区：
文献类型：
--
作者：
Nikolov NP;Illei GG
总结干燥综合征发病机制的最新进展，重点是炎症和外分泌功能障碍之间的关系。动物模型证实了干燥综合征中免疫和非免疫机制之间的复杂相互作用。先天免疫系统的激活可导致在显著炎症之前或没有显著炎症的情况下的外分泌功能障碍，而在其他模型中，尽管有强烈的炎症浸润，唾液腺功能仍得以保留。水通道中的原发性或炎症相关异常有助于外分泌病。通过外周血和唾液腺中1型干扰素调节基因（干扰素标签）的上调以及B细胞活化因子及其受体的异常表达来证明患者先天免疫的激活。可能导致外分泌功能障碍的非免疫机制包括局部和全身雄激素缺乏和自主神经系统功能障碍。针对毒蕈碱乙酰胆碱受体的自身抗体将提供自身免疫和外分泌功能障碍之间的联系，但这些抗体的存在，频率和生理影响的数据仍然存在争议。最近对干燥综合征患者和动物模型的研究发现，遗传因素、环境和随机事件之间存在复杂的相互作用，涉及先天和适应性免疫、激素机制和自主神经系统。这些发现表明，外分泌腺功能障碍可能先于自身免疫或代表一个独立于炎症的过程中干燥综合征的发病机制。
To summarize recent developments in our understanding of the pathogenesis of Sjögren's syndrome with a focus on the relationship between inflammation and exocrine dysfunction. Animal models demonstrated the complex interactions between immunologic and nonimmunologic mechanisms in Sjögren's syndrome. Activation of the innate immune system can lead to exocrine dysfunction before or without significant inflammation, whereas in other models, salivary gland function is preserved despite intense inflammatory infiltrates. Primary or inflammation-related abnormalities in water channels contribute to the exocrinopathy. Activation of the innate immunity in patients is demonstrated by the upregulation of type-1 interferon-regulated genes (interferon signature) in peripheral blood and salivary glands and abnormal expression of B cell-activating factor and its receptors. Nonimmune mechanisms that may contribute to exocrine dysfunction include local and systemic androgen deficiency and autonomic nervous system dysfunction. Autoantibodies against the muscarinic acetylcholine receptors would provide a link between autoimmunity and exocrine dysfunction, but the data on the presence, frequency and physiologic affect of these antibodies remain controversial. Recent discoveries from studies in patients with Sjögren's syndrome and animal models suggest a complex interplay between genetic factors, environmental and stochastic events that involve innate and adaptive immunity, hormonal mechanisms and the autonomic nervous system. Some of these findings suggest that exocrine gland dysfunction may precede autoimmunity or represent a process independent from inflammation in the pathogenesis of Sjögren's syndrome.