In anti-neutrophilic cytoplasmic antibody (ANCA)-associated vasculitis (AAV) genetic predisposition, ANCA autoantibodies, neutrophil extracellular traps (NETs), complement activation, and toll-like receptor signaling are implicated in AAV pathogenesis. Heat shock proteins (HSPs), a highly conserved group of small-sized molecular chaperones, take part in protein folding during cellular stress. Although HSPs were initially observed intracellularly, it has been shown that they can be secreted in the extracellular space and modulate the immune response in various autoimmune diseases including AAV. The scope of the present study is to investigate the role of heat shock protein 60 (HSP60) and 70 (HSP70) in the long renal effects in an ANCA vasculitis cohort. In this cohort of ANCA-associated vasculitis, 29 patients were followed up over 20 years. At diagnosis, immunohistochemistry was performed for HSP60 and HSP70 within the various nephron compartments. Higher renal HSP60 expression was associated with increased interstitial inflammatory infiltrates at diagnosis, while HSP70 expression was associated with a greater extent of interstitial fibrosis at diagnosis. Notably, intense tissue expression of HSP70 at the time of biopsy was associated with a worsened kidney survival. Renal HSP70 expression was associated with poor renal outcomes during long-term follow-up. This finding may indicate a role of HSPs in renal disease progression in ANCA vasculitis. Further validating studies are needed to verify a causative association between HSP70 expression and renal outcomes in ANCA-associated vasculitis.

在抗中性粒细胞胞浆抗体 (ANCA) 相关性血管炎 (AAV) 遗传易感性中，ANCA 自身抗体、中性粒细胞胞外陷阱 (NET)、补体激活和 Toll 样受体信号传导与 AAV 发病机制有关。热休克蛋白 (HSP) 是一组高度保守的小分子伴侣，在细胞应激期间参与蛋白质折叠。尽管 HSP 最初是在细胞内观察到的，但研究表明它们可以分泌到细胞外空间并调节包括 AAV 在内的各种自身免疫性疾病的免疫反应。本研究的范围是调查热休克蛋白 60 (HSP60) 和 70 (HSP70) 在 ANCA 血管炎队列的长期肾脏影响中的作用。在这个 ANCA 相关血管炎队列中，29 名患者接受了 20 多年的随访。诊断时，对各个肾单位内的 HSP60 和 HSP70 进行免疫组织化学检查。较高的肾脏 HSP60 表达与诊断时间质炎症浸润增加相关，而 HSP70 表达与诊断时更大程度的间质纤维化相关。值得注意的是，活检时 HSP70 的强烈组织表达与肾脏存活率恶化相关。长期随访期间，肾脏 HSP70 表达与肾脏预后不良相关。这一发现可能表明 HSP 在 ANCA 血管炎的肾脏疾病进展中发挥作用。需要进一步验证研究来验证 HSP70 表达与 ANCA 相关血管炎的肾脏结局之间的因果关系。