J Immunol：葡萄球菌可能是红斑狼疮的致病因素

近日，梅奥诊所的一项最新研究表明即使慢性暴露于少量的金黄色葡萄球菌环境下也可能是慢性炎症性疾病狼疮的致病危险因素。在梅奥诊所的研究中，老鼠被暴露在金黄色葡萄球菌中发现的一种低剂量的蛋白质下，老鼠发展罹患了狼疮样疾病伴随有肾脏疾病。

研究结果发表在本月初的Journal of Immunology杂志上。研究人员下一步是研究狼疮患者，探究是否金黄色葡萄球菌蛋白在人患该类疾病中也起着类似的作用。

Chowdhary博士说：我们认为，这种蛋白质可能导致或加剧狼疮易感基因的产生。另一个关键问题是，是否对于高危人群进行消除金黄色葡萄球菌治疗可以防止狼疮的发病。

狼疮发生时，免疫系统攻击组织和关节。这可能会影响身体的任何部分，这一点事很难诊断，因为它常常会被误诊为其他疾病。

Chowdhary博士说：医生目前还不知道是什么原因导致狼疮，但该研究发现金黄色葡萄球菌蛋白可能在疾病发病过程中发挥作用这一点是非常令人振奋。在小鼠模型研究中，金黄色葡萄球菌中发现的一种蛋白质称为金黄色葡萄球菌肠毒素B或SEB，能激活状态的自身反应性T/B淋巴细胞导致炎症性疾病如狼疮的发生。

编译自：Chronic exposure to staph bacteria may be risk factor for lupus, study finds

doi:10.4049/jimmunol.1201097
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Chronic Exposure to Staphylococcal Superantigen Elicits a Systemic Inflammatory Disease Mimicking Lupus

Vaidehi R. Chowdhary*, Ashenafi Y. Tilahun, Chad R. Clark, Joseph P. Grande and Govindarajan Rajagopalan

Chronic nasal and skin colonization with superantigen (SAg)-producing Staphylococcus aureus is well documented in humans. Given that trans-mucosal and trans-cutaneous absorption of SAgs can occur, we determined whether chronic exposure to small amounts of SAg per se could activate autoreactive CD4⁺ and CD8⁺ T cells and precipitate any autoimmune disease without further external autoantigenic stimulation. Because HLA class II molecules present SAg more efficiently than do mouse MHC class II molecules, HLA-DQ8 transgenic mice were implanted s.c. with mini-osmotic pumps capable of continuously delivering the SAg, staphylococcal enterotoxin B (total of 10 μg/mouse), or PBS over 4 wk. Chronic exposure to staphylococcal enterotoxin B resulted in a multisystem autoimmune inflammatory disease with features similar to systemic lupus erythematosus. The disease was characterized by mononuclear cell infiltration of lungs, liver, and kidneys, accompanied by the production of anti-nuclear Abs and deposition of immune complexes in the renal glomeruli. The inflammatory infiltrates in various organs predominantly consisted of CD4⁺ T cells bearing TCR Vβ8. The extent of immunopathology was markedly reduced in mice lacking CD4⁺ T cells and CD28, indicating that the disease is CD4⁺ T cell mediated and CD28 dependent. The absence of disease in STAT4-deficient, as well as IFN-γ–deficient, HLA-DQ8 mice suggested the pathogenic role of Th1-type cytokines, IL-12 and IFN-γ. In conclusion, our study suggests that chronic exposure to extremely small amounts of bacterial SAg could be an etiological factor for systemic lupus erythematosus.