Preclinical stage abundance and nuclear antigen reactivity of faecal Immunoglobulin A vary among males and females of lupus-prone mouse models.
Preclinical stage abundance and nuclear antigen reactivity of faecal Immunoglobulin A vary among males and females of lupus-prone mouse models.
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系统性红斑狼疮（SLE）的特征是产生具有核抗原（nAg）特异性的致病性自身抗体。使用（SWR×NZB）F1（SNF 1）小鼠，我们发现在狼疮易感性下，肠道中伊加的产生水平较高，粪便伊加的nAg反应性也较高。在此，我们确定了粪便伊加丰度和nAg反应性是否在各种狼疮易感临床前模型（MRL/lpr、NZB×NZW-F1、SNF 1、NZM 2410和NZM 2328）中较高（在不同模型中）。我们还确定了在血清阳性前年龄的粪便伊加nAg反应性是否与这些小鼠模型的雄性和雌性中的最终血清自身抗体水平相关。我们发现，年龄依赖性增加粪便伊加的丰度和nAg反应性可以在不同的狼疮易感小鼠模型之间变化。重要的是，这些小鼠中的粪便伊加显示出显著水平的nAg反应性，早在幼年时就开始了。此外，在大多数狼疮易感菌株中，粪便伊加的血清阳性阶段前nAg反应性与最终的血清阳性阶段全身性自身抗体水平相关性良好。血清自身抗体水平的性别差异之前，粪便伊加丰度和nAg反应性的类似差异。这些观察结果表明，粪便伊加特征，特别是nAg反应性，可以作为早期预测狼疮易感受试者最终全身性自身免疫的生物标志物。
Systemic lupus erythematosus (SLE) is characterized by the production of pathogenic autoantibodies with nuclear antigen (nAg) specificity. Using (SWR×NZB)F1 (SNF1) mice, we showed higher levels of IgA production in the intestine and the nAg reactivity of fecal IgA under lupus susceptibility. Here, we determined if the fecal IgA abundance and nAg reactivity are higher in, different among, various lupus-prone preclinical models (MRL/lpr, NZB×NZW-F1, SNF1, NZM2410 and NZM2328). We also determined if the fecal IgA nAg reactivity at pre-seropositive ages correlates with the eventual serum autoantibody levels in males and females of these mouse models. We show that age dependent increase in the abundance and nAg reactivity of fecal IgA can vary among different lupus-prone mouse models. Importantly, fecal IgA in these mice show significant levels of nAg reactivity, starting as early as at juvenile age. Furthermore, the pre-seropositive stage nAg reactivity of fecal IgA in most lupus-prone strains correlates well with that of eventual, seropositive stage systemic autoantibody levels. Gender differences in serum autoantibody levels were preceded by similar differences in the fecal IgA abundance and nAg reactivity. These observations suggest that fecal IgA features, nAg reactivity particularly, could serve as a biomarker for early prediction of the eventual systemic autoimmunity in lupus-prone subjects.
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