Response to: 'The level of peripheral regulatory T cells is linked to changes in gut commensal microflora in patients with systemic lupus erythematosus' by Zhang et al and the phylogeny of a candidate pathobiont in lupus nephritis.
Response to: 'The level of peripheral regulatory T cells is linked to changes in gut commensal microflora in patients with systemic lupus erythematosus' by Zhang et al and the phylogeny of a candidate pathobiont in lupus nephritis.
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回应：Zhang 等人的“外周调节性 T 细胞水平与系统性红斑狼疮患者肠道共生微生物群的变化有关”以及狼疮性肾炎候选病原体的系统发育。
DOI：
10.1136/annrheumdis-2019-216523
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发表时间：
2021
影响因子：
27.4
通讯作者：
Azzouz,DouaF
中科院分区：
文献类型：
--
作者：
Silverman,GreggJ;Azzouz,DouaF
我们感谢有机会对Zhang等人的通信作出回应，并完全同意阐明个体分类群在临床狼疮发病机制中的特定作用的重要性。这些作者断言，我们早期论文中的候选致病菌“缺乏与淋巴细胞的精确联系......”。然而，这是完全错误的，因为我们表明，具有Ruminococcus gavus物种扩增的狼疮患者也具有识别这种候选致病菌物种中的菌株限制性脂聚糖抗原的循环抗体。2这些外周免疫反应也显示与IgG抗天然DNA抗体交叉反应，这些抗体在狼疮发病机制中具有良好的记录作用。当然，循环抗体由外周B细胞和终末分化的浆细胞产生。事实上，这种类型的机制联系的重要性也已在用嗜热阿克曼菌属物种定殖的小鼠中得到证实，该物种具有类似于我们的候选致病菌的一些潜在性质，并且还具有可能有助于肠道渗漏的粘蛋白溶解性质，并且可以类似地诱导全身性物种特异性全身性IgG应答。3Zhang等人试图强调他们自己的观察结果，即基于16S rRNA文库分析，血液中携带Treg表型的T细胞水平与瘤胃球菌属的肠道丰度之间存在直接相关性。然而，直接的证据，免疫识别的抗原，从这个类群的外周T细胞是失踪。
We appreciate the opportunity to respond to the correspondence from Zhang et al, 1 and fully agree with the importance of elucidating the specific roles of individual taxa in clinical lupus pathogenesis. These authors assert that the candidate pathobiont in our earlier paper ‘is lacking in a precise link with lymphocytes…’. Yet, this is completely erroneous as we showed that lupus patients with expansions of the Ruminococcus gnavus species also had circulating antibodies that recognised strain-restricted lipoglycan antigens in this candidate pathobiont species. 2 These peripheral immune responses were also shown to be cross-reactive with IgG anti-native DNA antibodies that have well-documented roles in lupus pathogenesis. Of course, circulating antibodies are produced by peripheral B cells and end-differentiated plasma cells. Indeed, the importance of this type of mechanistic link has also been demonstrated in mice colonised with the commensal Akkermansia species, which has some potential properties akin to our candidate pathobiont, and also has mucinolytic properties that may contribute to gut leakiness and can similarly induce systemic species-specific systemic IgG responses. 3Zhang et al seek to highlight their own observations regarding a direct correlation between the level of T cells in the blood, bearing a Treg phenotype, and gut abundance of the Ruminococcus genus, based on 16S rRNA library analysis. Direct evidence, however, of immune recognition of antigens from this taxa by peripheral Tregs is missing.