Jiram Torres-Ruiz1, Roxana Villca-Gonzales2, Diana Gómez-Martín3, Alejandro Zentella-Dehesa4, Miguel Tapia-Rodríguez5, Norma O Uribe-Uribe6, Luis E Morales-Buenrostro7, Josefina Alberú8. 1. 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. 2. Department of Nephrology, Hospital Regional Lic Adolfo Lopez Mateos, ISSSTE, Mexico City, Mexico. 3. Tecnologico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Ave. Morones Prieto 3000, Monterrey 64710, N.L., Mexico. 4. Department of Genomic Medicine and Environmental Toxicology, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Mexico City, Mexico. 5. Microscopy Unit, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Mexico City, Mexico. 6. Department of Pathology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico. 7. Department of Nephrology and Mineral Metabolism, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico. Electronic address: luis_buenrostro@yahoo.com. 8. Tecnologico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Ave. Morones Prieto 3000, Monterrey 64710, N.L., Mexico; Department of Transplantation, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico. Electronic address: josefinaalberu@hotmail.com.
Abstract
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.
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.
Authors: Jeroen G H P Verhoeven; Carla C Baan; Annemiek M A Peeters; Marian C Clahsen-van Groningen; Daan Nieboer; Mariëlle Herzog; Marc Eccleston; Dennis A Hesselink; Karin Boer Journal: Clin Epigenetics Date: 2021-02-11 Impact factor: 6.551
Authors: Simon J Cleary; Nicholas Kwaan; Jennifer J Tian; Daniel R Calabrese; Beñat Mallavia; Mélia Magnen; John R Greenland; Anatoly Urisman; Jonathan P Singer; Steven R Hays; Jasleen Kukreja; Ariel M Hay; Heather L Howie; Pearl Toy; Clifford A Lowell; Craig N Morrell; James C Zimring; Mark R Looney Journal: J Clin Invest Date: 2020-11-02 Impact factor: 14.808