中性粒细胞胞外陷阱 (NETs) 在肾脏急性抗体介导排斥反应中的潜在作用。
A potential role of neutrophil extracellular traps (NETs) in kidney acute antibody mediated rejection.
机构信息
Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico; Emergency Medicine Department, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.
Department of Nephrology, Hospital Regional Lic Adolfo Lopez Mateos, ISSSTE, Mexico City, Mexico.
出版信息
Transpl Immunol. 2020 Jun;60:101286. doi: 10.1016/j.trim.2020.101286. Epub 2020 Mar 7.
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.
背景
本研究旨在评估肾移植受者（KTR）中的中性粒细胞胞外诱捕网（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 组人群：发生 AAMR 的 KTR（KTR-Cases，n=14）；无任何免疫事件的 KTR（KTR-Controls，n=14）和供者（n=12）。通过免疫荧光间接法（IFI）（NET/细胞比值）评估自发性和脂多糖诱导的 NETosis。通过 ELISA（光密度指数 - ODI）评估血浆 cH3-DNA 复合物。通过免疫组化评估肾活检组织中髓过氧化物酶（MPO）和瓜氨酸化组蛋白 4（cH4）的表达。
结果
我们发现，无论是否发生排斥反应，KTR 均存在增强的自发性 NETosis。总 KTR 中的自发性 NETosis 中 Nets/cells 比值为 0.203（IQR 0.12-0.34），而供者中的比值为 0.094（IQR 0.01-0.17），p=0.011。同样，总 KTR 中的 cH3-DNA 的 ODI 为 1.41（IQR 0.94-1.72），而供者中的 ODI 为 0.95（IQR 0.83-1.27），p=0.019。KTR-Cases 中的 NETs 数量最多，为 1.70（IQR 1.19-1.91）。在 2 例 KTR-Cases 的活检中发现 MPO 和 cH4 的表达。
结论
KTR 存在增强的 NETosis。这可能表明中性粒细胞的持续激活。尽管还需要更多的研究，但 KTR-Cases 活检中更多的 NETs 和有 NET 形成的中性粒细胞提示 NETosis 在 AAMR 中的作用。
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