S Boyer-Suavet1, M Cremoni2, T Dupeyrat2, K Zorzi3, V Brglez3, S Benzaken4, V Esnault2, B Seitz-Polski5. 1. Service de Néphrologie-Dialyse-Transplantation, Hôpital Pasteur, Université Nice-Sophia Antipolis, France; Centre de Référence Maladies Rares, Syndrome Néphrotique Idiopathique, CHU de Nice, Université Nice-Sophia Antipolis, France. 2. Service de Néphrologie-Dialyse-Transplantation, Hôpital Pasteur, Université Nice-Sophia Antipolis, France. 3. Centre de Référence Maladies Rares, Syndrome Néphrotique Idiopathique, CHU de Nice, Université Nice-Sophia Antipolis, France. 4. Laboratoire d'Immunologie, Hôpital l'Archet, Université de Nice-Sophia Antipolis, France. 5. Service de Néphrologie-Dialyse-Transplantation, Hôpital Pasteur, Université Nice-Sophia Antipolis, France; Laboratoire d'Immunologie, Hôpital l'Archet, Université de Nice-Sophia Antipolis, France; Centre de Référence Maladies Rares, Syndrome Néphrotique Idiopathique, CHU de Nice, Université Nice-Sophia Antipolis, France. Electronic address: seitz-polski.b@chu-nice.fr.
Abstract
BACKGROUND: Infections remain the second most common cause of death in patients with end-stage kidney disease (ESKD). We aimed to evaluate non-specific cell-mediated immunity in an ESKD cohort using a functional assay applicable to routine use, QuantiFERON-Monitor (Qiagen), and assess whether it can predict infectious events. METHODS: In this prospective study, we performed the QuantiFERON-Monitor test in 80 subjects including 54 patients with ESKD. QuantiFERON-Monitor is based on the measurement of plasma interferon-gamma (IFN-γ) after stimulation of NK-cells with a TLR-7 agonist, and T-cells with a TCR agonist. Patients were subsequently followed for 6 to 12 months. RESULTS: QuantiFERON-Monitor showed lower stimulated IFN-γ production in ESKD patients (n = 54) compared to healthy donors (n = 19) (p < 0.0001) and to chronic kidney disease stage 3-4 patients (n = 7) (hemodialysis (n = 30): p < 0.01; peritoneal dialysis (n = 13): p = 0.03 and ESKD on conservative management (n = 11): p < 0.001). No significant difference in stimulated IFN-γ production was observed between ESKD patients with renal replacement therapies or conservative management. Stimulated IFN-γ production was significantly lower in patients later developing infections (13.9 [5.5-48.3] IU/mL vs 85.8 [35.5-236] IU/mL, p = 0.007). Using ROC analysis, we identified a cutoff value of 63.55 IU/mL (sensitivity = 80.95%, specificity = 79.17%, AUC = 0.78, p = 0.008) to discriminate patients at higher risk of infections. Patients with stimulated IFN-γ levels measured by QuantiFERON Monitor below 63.55 IU/mL (n = 21) had a hazard ratio of 10.71 ([3.68-31.13], p < 0.0001) for the development of subsequent infections. CONCLUSION: Monitoring of IFN-γ production after stimulation of innate and adaptive immunity may identify ESKD patients with high risk of infection. This allows for therapeutic interventions to restore cellular immunity, thereby minimizing both infections and rejections after kidney-transplantation.
BACKGROUND:Infections remain the second most common cause of death in patients with end-stage kidney disease (ESKD). We aimed to evaluate non-specific cell-mediated immunity in an ESKD cohort using a functional assay applicable to routine use, QuantiFERON-Monitor (Qiagen), and assess whether it can predict infectious events. METHODS: In this prospective study, we performed the QuantiFERON-Monitor test in 80 subjects including 54 patients with ESKD. QuantiFERON-Monitor is based on the measurement of plasma interferon-gamma (IFN-γ) after stimulation of NK-cells with a TLR-7 agonist, and T-cells with a TCR agonist. Patients were subsequently followed for 6 to 12 months. RESULTS: QuantiFERON-Monitor showed lower stimulated IFN-γ production in ESKDpatients (n = 54) compared to healthy donors (n = 19) (p < 0.0001) and to chronic kidney disease stage 3-4 patients (n = 7) (hemodialysis (n = 30): p < 0.01; peritoneal dialysis (n = 13): p = 0.03 and ESKD on conservative management (n = 11): p < 0.001). No significant difference in stimulated IFN-γ production was observed between ESKDpatients with renal replacement therapies or conservative management. Stimulated IFN-γ production was significantly lower in patients later developing infections (13.9 [5.5-48.3] IU/mL vs 85.8 [35.5-236] IU/mL, p = 0.007). Using ROC analysis, we identified a cutoff value of 63.55 IU/mL (sensitivity = 80.95%, specificity = 79.17%, AUC = 0.78, p = 0.008) to discriminate patients at higher risk of infections. Patients with stimulated IFN-γ levels measured by QuantiFERON Monitor below 63.55 IU/mL (n = 21) had a hazard ratio of 10.71 ([3.68-31.13], p < 0.0001) for the development of subsequent infections. CONCLUSION: Monitoring of IFN-γ production after stimulation of innate and adaptive immunity may identify ESKDpatients with high risk of infection. This allows for therapeutic interventions to restore cellular immunity, thereby minimizing both infections and rejections after kidney-transplantation.
Authors: David Tougeron; Barbara Seitz-Polski; Maxime Hentzien; Firouze Bani-Sadr; Jean Bourhis; Michel Ducreux; Sébastien Gaujoux; Philippe Gorphe; Boris Guiu; Anne Claire Hardy-Bessard; Khê Hoang Xuan; Florence Huguet; Thierry Lecomte; Astrid Lièvre; Christophe Louvet; Léon Maggiori; Pascale Mariani; Pierre Michel; Amélie Servettaz; Juliette Thariat; Virginie Westeel; Thomas Aparicio; Jean Yves Blay; Olivier Bouché Journal: Bull Cancer Date: 2021-04-12 Impact factor: 1.276
Authors: Alexandre Gérard; Jerome Doyen; Henri Montaudié; Barbara Seitz-Polski; Marion Cremoni; Laurent Bailly; Kevin Zorzi; Caroline Ruetsch-Chelli; Vesna Brglez; Alexandra Picard-Gauci; Laura Troin; Vincent L M Esnault; Thierry Passeron Journal: J Immunother Cancer Date: 2021-06 Impact factor: 13.751
Authors: Marion Cremoni; Jonathan Allouche; Daisy Graça; Kevin Zorzi; Céline Fernandez; Maxime Teisseyre; Sylvia Benzaken; Caroline Ruetsch-Chelli; Vincent L M Esnault; Jean Dellamonica; Michel Carles; Jérôme Barrière; Michel Ticchioni; Vesna Brglez; Barbara Seitz-Polski Journal: Front Immunol Date: 2022-09-26 Impact factor: 8.786