Background

The aim of this study was to evaluate neutrophil extracellular traps (NETs) in kidney transplant recipients (KTR) and their potential involvement in acute antibody-mediated rejection (AAMR).

Methods

We studied 3 groups: KTR with AAMR (KTR-Cases, n = 14); KTR without any immunologic event (KTR-Controls, n = 14) and donors (n = 12). Spontaneous and lipopolysaccharide-induced NETosis were evaluated by immunofluorescence indirect (IFI) (NET/cells ratio). Plasmatic cH3-DNA complexes were evaluated by ELISA, (Optic Density Index - ODI). The expression of MPO and citrullinated histone 4 (cH4) was evaluated in renal biopsies.

Results

We found an enhanced spontaneous NETosis in KTR regardless of whether they had rejection. The Nets/cells ratio in spontaneous NETosis was 0.203 (IQR 0.12–0.34) in Total-KTR and 0.094 (IQR 0.01–0.17) in donors, p = .011. Likewise, the ODI of cH3-DNA was 1.41 (IQR 0.94–1.72) in Total-KTR, and 0.95 (IQR 0.83–1.27) in donors, p = .019. KTR-Cases had the higher amount of NETs 1.70 (IQR 1.19–1.91). In two KTR-Cases, expression of MPO and cH4 was found in biopsies.

Conclusions

KTR show enhanced NETosis. This may indicate a permanent activation of neutrophils. Although more studies are needed, the higher amount of NETs and netting neutrophils in biopsies of KTR-Cases suggest a role of NETosis in AAMR.

中文翻译：

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中性粒细胞胞外陷阱（NETs）在肾急性抗体介导的排斥反应中的潜在作用。

背景

这项研究的目的是评估肾移植受体（KTR）中的中性粒细胞胞外陷阱（NETs）及其在急性抗体介导的排斥反应（AAMR）中的潜在作用。

方法

我们研究了3组：KT与AMR（KTR-Cases，n  = 14）；没有任何免疫事件的KTR（KTR-Controls，n = 14）和供体（n  = 12）。通过免疫荧光间接（IFI）（NET /细胞比）评估自发性和脂多糖诱导的NETosis。通过ELISA评估血浆cH3-DNA复合物（光学密度指数-ODI）。在肾活检中评估了MPO和瓜氨酸化组蛋白4（cH4）的表达。

结果

我们发现KTR的自发性netosis增强，无论他们是否有排斥反应。自发性netosis的净/细胞比在总KTR中为0.203（IQR 0.12-0.34），在供体中为0.094（IQR 0.01-0.17），p  = .011。同样，cH3-DNA的ODI在总KTR中为1.41（IQR 0.94–1.72），在供体中为0.95（IQR 0.83–1.27），p  = .019。KTR-Cases的NETs数量较高，为1.70（IQR 1.19–1.91）。在两个KTR病例中，在活组织检查中发现了MPO和cH4的表达。

结论

KTR显示出增强的NETosis。这可能表明嗜中性粒细胞永久活化。尽管还需要进行更多的研究，但在KTR-Cases活检中，NETs和中性粒细胞的净含量较高表明NETosis在AMR中的作用。