Department of Internal Medicine 3-Rheumatology and Immunology, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen, 91054 Erlangen, Germany.
Deutsches Zentrum für Immuntherapie (DZI), Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen, 91054 Erlangen, Germany.
Cells. 2022 Aug 23;11(17):2619. doi: 10.3390/cells11172619.
The severity of the coronavirus disease in 2019 (COVID-19) is strongly linked to a dysregulated immune response. This fuels the fear of severe disease in patients with autoimmune disorders continuously using immunosuppressive/immunomodulating medications. One complication of COVID-19 is thromboembolism caused by intravascular aggregates of neutrophil extracellular traps (NETs) occluding the affected vessels. Like COVID-19, systemic lupus erythematosus (SLE) is characterized by, amongst others, an increased risk of thromboembolism. An imbalance between NET formation and clearance is suggested to play a prominent role in exacerbating autoimmunity and disease severity. Serologic evidence of exposure to SARS-CoV-2 has a minor impact on the SLE course in a Swedish cohort reportedly. Herein, we assessed NET formation in patients from this cohort by neutrophil elastase (NE) activity and the presence of cell-free DNA, MPO-DNA, and NE-DNA complexes and correlated the findings to the clinical parameters. The presence of NE-DNA complexes and NE activity differed significantly in pre-pandemic versus pandemic serum samples. The latter correlated significantly with the hemoglobin concentration, blood cell counts, and complement protein 3 and 4 levels in the pre-pandemic but only with the leukocyte count and neutrophil levels in the pandemic serum samples. Taken together, our data suggest a change, especially in the NE activity independent of exposure to SARS-CoV-2.
2019 年冠状病毒病（COVID-19）的严重程度与免疫反应失调密切相关。这使得人们担心自身免疫性疾病患者持续使用免疫抑制/免疫调节药物会出现严重疾病。COVID-19 的一种并发症是由中性粒细胞细胞外陷阱（NETs）形成的血管内聚集物引起的血栓栓塞，这些聚集物阻塞受影响的血管。与 COVID-19 一样，系统性红斑狼疮（SLE）的特征还包括血栓栓塞风险增加。NET 形成和清除之间的失衡被认为在加重自身免疫和疾病严重程度方面起着重要作用。据报道，在瑞典的一个队列中，SLE 患者对 SARS-CoV-2 的血清学证据暴露对 SLE 病程的影响较小。在此，我们通过中性粒细胞弹性蛋白酶（NE）活性和无细胞游离 DNA、MPO-DNA 和 NE-DNA 复合物的存在评估了来自该队列的患者的 NET 形成情况，并将这些发现与临床参数相关联。与大流行前相比，大流行前和大流行期间血清样本中 NE-DNA 复合物和 NE 活性的存在存在显著差异。后者与大流行前的血红蛋白浓度、血细胞计数和补体蛋白 3 和 4 水平显著相关，但仅与大流行期间的白细胞计数和中性粒细胞水平相关。综上所述，我们的数据表明，尤其是在 SARS-CoV-2 暴露之外，NE 活性发生了变化。
