Institute of Child Health, Alder Hey Children's NHS Foundation Trust, Liverpool University, Liverpool, UK.
Lupus. 2011 May;20(6):641-6. doi: 10.1177/0961203310392421. Epub 2011 Mar 1.
Juvenile-onset systemic lupus erythematosus (JSLE) is a multisystem autoimmune disease characterized by hyperactive B-cells producing auto-antibodies directed against nuclear antigens. A potential source of these antigenic components is apoptotic cells. We have previously demonstrated increased dysregulated neutrophil apoptosis in JSLE patients. Here we investigate autoantigen expression on JSLE neutrophils during apoptosis. Neutrophils from non-inflammatory controls and JSLE patients were incubated with JSLE and control serum. Apoptosis and dsDNA expression was measured using flow cytometry and confocal microscopy. Increased neutrophil apoptosis and dsDNA expression was observed in JSLE and control neutrophils incubated with JSLE serum. During neutrophil apoptosis nuclear material was exposed on the cell surface rather than within the cell as seen with viable neutrophils. The increased neutrophil apoptosis induced by JSLE compared with control serum resulted in increased surface expression of nuclear antigens. This may provide an additional mechanism leading to the generation of autoantibodies in JSLE.
幼年特发性系统性红斑狼疮 (JSLE) 是一种多系统自身免疫性疾病，其特征是产生针对核抗原的自身抗体的活性 B 细胞。这些抗原成分的一个潜在来源是凋亡细胞。我们之前已经证明，JSLE 患者的中性粒细胞凋亡失调增加。在这里，我们研究了 JSLE 中性粒细胞凋亡过程中的自身抗原表达。用 JSLE 和对照血清孵育非炎症对照和 JSLE 患者的中性粒细胞。使用流式细胞术和共聚焦显微镜测量凋亡和 dsDNA 表达。在与 JSLE 血清孵育的 JSLE 和对照中性粒细胞中观察到中性粒细胞凋亡和 dsDNA 表达增加。在凋亡的中性粒细胞中，核物质暴露在细胞表面，而不是活中性粒细胞中可见的细胞内。与对照血清相比，JSLE 诱导的中性粒细胞凋亡增加导致核抗原的表面表达增加。这可能为 JSLE 中产生自身抗体提供了另一种机制。
