Neutrophil extracellular traps (NETs) are macromolecular structures programmed to trap circulating bacteria and viruses. The accumulation of NETs in the circulation correlates with the formation of anti-double-stranded (ds) DNA antibodies and is considered a causative factor for systemic lupus erythematosus (SLE). The digestion of DNA by DNase1 and DNases1L3 is the rate- limiting factor for NET accumulation. Mutations occurring in one of these two DNase genes determine anti-DNA formation and are associated with severe Lupus-like syndromes and lupus nephritis (LN). A second mechanism that may lead to DNase functional impairment is the presence of circulating DNase inhibitors in patients with low DNase activity, or the generation of anti-DNase antibodies. This phenomenon has been described in a relevant number of patients with SLE and may represent an important mechanism determining autoimmunity flares. On the basis of the reviewed studies, it is tempting to suppose that the blockade or selective depletion of anti-DNase autoantibodies could represent a potential novel therapeutic approach to prevent or halt SLE and LN. In general, strategies aimed at reducing NET formation might have a similar impact on the progression of SLE and LN.
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机译：中性粒细胞胞外陷阱 （NET） 是被编程为捕获循环细菌和病毒的大分子结构。NET 在循环中的积累与抗双链 （ds） DNA 抗体的形成相关，被认为是系统性红斑狼疮 （SLE） 的致病因素。DNase1 和 DNases1L3 对 DNA 的消化是 NET 积累的速率限制因素。这两个 DNase 基因之一发生的突变决定了抗 DNA 的形成，并与严重的狼疮样综合征和狼疮性肾炎 （LN） 有关。可能导致 DNase 功能障碍的第二种机制是 DNase 活性低的患者存在循环 DNase 抑制剂，或产生抗 DNase 抗体。这种现象已在相关数量的 SLE 患者中被描述，可能代表了决定自身免疫发作的重要机制。根据所回顾的研究，人们很容易假设抗 DNase 自身抗体的阻断或选择性耗竭可能代表一种潜在的新型治疗方法来预防或阻止 SLE 和 LN。一般来说，旨在减少 NET 形成的策略可能对 SLE 和 LN 的进展产生类似的影响。
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