A potential role of neutrophil extracellular traps (NETs) in kidney acute antibody mediated rejection

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.