Division of Nephrology, Dialysis and Transplantation, IRCCS Istituto Giannina Gaslini, GenoaLargo Gaslini, 16148 Genoa, Italy.
Laboratory of Molecular Nephrology, IRCCS Istituto Giannina Gaslini, GenoaLargo Gaslini, 16148 Genoa, Italy.
Cells. 2021 Oct 5;10(10):2667. doi: 10.3390/cells10102667.
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.
中性粒细胞胞外诱捕网（NETs）是一种被编程用来捕获循环中的细菌和病毒的大分子结构。循环中 NETs 的积累与抗双链（ds）DNA 抗体的形成相关，并被认为是系统性红斑狼疮（SLE）的一个致病因素。DNase1 和 DNases1L3 对 DNA 的消化是 NET 积累的限速因素。这两种 DNase 基因之一的突变决定了抗 DNA 的形成，并与严重的狼疮样综合征和狼疮性肾炎（LN）相关。另一种可能导致 DNase 功能障碍的机制是在 DNase 活性低的患者中存在循环 DNase 抑制剂，或产生抗 DNase 抗体。这种现象在大量 SLE 患者中已有描述，可能是决定自身免疫发作的一个重要机制。基于已审查的研究，人们不禁假设，阻断或选择性耗尽抗 DNase 自身抗体可能是预防或阻止 SLE 和 LN 的一种潜在新的治疗方法。一般来说，旨在减少 NET 形成的策略可能对 SLE 和 LN 的进展有类似的影响。
