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

• Published in: Transplant immunology 2020-06, Vol.60, p.101286, Article 101286
• Main Authors: Torres-Ruiz, Jiram, Villca-Gonzales, Roxana, Gómez-Martín, Diana, Zentella-Dehesa, Alejandro, Tapia-Rodríguez, Miguel, Uribe-Uribe, Norma O., Morales-Buenrostro, Luis E., Alberú, Josefina
• Format: Article
• Language: English
• Subjects: Acute Disease; Acute rejection; Adult; Apoptosis; Extracellular Traps - physiology; Female; Graft Rejection - immunology; Humans; Isoantibodies - metabolism; Kidney - pathology; Kidney Transplantation; Male; Middle Aged; NETs; Neutrophil Activation; Neutrophils; Neutrophils - immunology; Young Adult
• ISSN: 0966-3274; 1878-5492
• DOI: 10.1016/j.trim.2020.101286

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). 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. 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. 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. •Neutrophils have been suggested as pivotal elements in the development of AAMR.•Kidney transplant recipients show enhanced NETosis.•NETosis may indicate a permanent activation of neutrophils in KTR.•NETs and netting neutrophils in biopsies suggest a role of NETosis in AAMR.