B cells from African American lupus patients exhibit an activated phenotype
B cells from African American lupus patients exhibit an activated phenotype
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DOI：
10.1172/jci.insight.87310
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发表时间：
2016-06-16
期刊：
影响因子：
8
通讯作者：
Suchard, Suzanne J.
中科院分区：
文献类型：
--
作者：
Menard, Laurence C.;Habte, Sium;Suchard, Suzanne J.
系统性红斑狼疮（SLE）是一种复杂的系统性自身免疫性疾病，由先天性和适应性免疫细胞共同驱动。与欧洲血统的患者相比，非洲裔美国人往往在更早的年龄出现更严重的疾病。为了更好地了解非洲裔美国人和欧洲裔美国人患者之间的免疫差异，我们分析了B细胞亚群的频率和B细胞活化标志物的表达，共68例SLE患者和69例正常健康志愿者。我们发现，表达活化标志物CD 86、CD 80、PD 1和CD 40 L的B细胞以及CD 19（+）CD 27（-）IgD（-）双阴性B细胞在非裔美国患者中比在欧洲血统患者中富集。除了CD 40 L的表达增加外，B细胞上的CD 40表面水平较低，表明CD 40通路的参与。体外实验证实，B细胞表达的CD 40 L可导致邻近B细胞的CD 40活化和内化。综上所述，这些结果表明，与欧洲美国患者相比，非洲裔美国SLE患者存在特别活跃的B细胞成分，可能通过激活CD 40/CD 40 L途径。这些数据可能有助于指导新疗法的开发。
Systemic lupus erythematosus (SLE) is a complex systemic autoimmune disease driven by both innate and adaptive immune cells. African Americans tend to present with more severe disease at an earlier age compared with patients of European ancestry. In order to better understand the immunological differences between African American and European American patients, we analyzed the frequencies of B cell subsets and the expression of B cell activation markers from a total of 68 SLE patients and 69 normal healthy volunteers. We found that B cells expressing the activation markers CD86, CD80, PD1, and CD40L, as well as CD19(+)CD27(-)IgD(-) double-negative B cells, were enriched in African American patients vs. patients of European ancestry. In addition to increased expression of CD40L, surface levels of CD40 on B cells were lower, suggesting the engagement of the CD40 pathway. In vitro experiments confirmed that CD40L expressed by B cells could lead to CD40 activation and internalization on adjacent B cells. To conclude, these results indicate that, compared with European American patients, African American SLE patients present with a particularly active B cell component, possibly via the activation of the CD40/CD40L pathway. These data may help guide the development of novel therapies.