Manuela Colucci1, Rita Carsetti2, Simona Cascioli2, Jessica Serafinelli3, Francesco Emma3,4, Marina Vivarelli3,4. 1. Laboratory of Nephrology, Department of Rare Diseases, IRCCS Ospedale Pediatrico Bambino Gesù, Rome, Italy. manuela.colucci@opbg.net. 2. Department of Laboratories, Immunology Research Area - Unit of Diagnostic Immunology, Unit of B-cell Pathophysiology, IRCCS Ospedale Pediatrico Bambino Gesù, Rome, Italy. 3. Laboratory of Nephrology, Department of Rare Diseases, IRCCS Ospedale Pediatrico Bambino Gesù, Rome, Italy. 4. Division of Nephrology, Department of Pediatric Subspecialties, IRCCS Ospedale Pediatrico Bambino Gesù, Rome, Italy.
Abstract
BACKGROUND: A pathogenic role of B cells in non-genetic nephrotic syndrome has been suggested by the efficacy of rituximab, a B cell depleting antibody, in maintaining a prolonged remission. However, little information is available on B cell homeostasis in nephrotic syndrome patients. METHODS: We retrospectively analyzed by flow cytometry the distribution of different B cell subpopulations in 107 steroid-sensitive and in 6 genetic steroid-resistant nephrotic syndrome pediatric patients, compared with age- and sex-matched controls. RESULTS: Fifty-one steroid-sensitive patients at disease onset, before starting immunosuppression, presented significantly increased levels of total, transitional, memory, and switched memory B cells compared to controls. Oral immunosuppression strongly affected transitional and mature B cell levels in 27 patients in relapse and also in 29 patients in remission, whereas memory B cells were significantly higher compared to controls during relapse, despite the immunosuppressive treatment, and were normalized only in patients in remission. Children with genetic forms of steroid-resistant nephrotic syndrome presented no differences in B cell profile from controls. CONCLUSIONS: Our study indicates that memory B cells, more than other B cell subsets, are increased and appear to be pathogenically relevant in steroid-sensitive nephrotic syndrome pediatric patients.
BACKGROUND: A pathogenic role of B cells in non-genetic nephrotic syndrome has been suggested by the efficacy of rituximab, a B cell depleting antibody, in maintaining a prolonged remission. However, little information is available on B cell homeostasis in nephrotic syndromepatients. METHODS: We retrospectively analyzed by flow cytometry the distribution of different B cell subpopulations in 107 steroid-sensitive and in 6 genetic steroid-resistant nephrotic syndrome pediatric patients, compared with age- and sex-matched controls. RESULTS: Fifty-one steroid-sensitive patients at disease onset, before starting immunosuppression, presented significantly increased levels of total, transitional, memory, and switched memory B cells compared to controls. Oral immunosuppression strongly affected transitional and mature B cell levels in 27 patients in relapse and also in 29 patients in remission, whereas memory B cells were significantly higher compared to controls during relapse, despite the immunosuppressive treatment, and were normalized only in patients in remission. Children with genetic forms of steroid-resistant nephrotic syndrome presented no differences in B cell profile from controls. CONCLUSIONS: Our study indicates that memory B cells, more than other B cell subsets, are increased and appear to be pathogenically relevant in steroid-sensitive nephrotic syndrome pediatric patients.
Entities:
Keywords:
B cells; Children; Immunosuppressive treatment; Nephrotic syndrome
Authors: Marina Vivarelli; Manuela Colucci; Antonio Gargiulo; Chiara Bettini; Anna Lo Russo; Francesco Emma Journal: Pediatr Nephrol Date: 2021-08-05 Impact factor: 3.714
Authors: Stefano Turolo; Alberto Edefonti; Alessandra Mazzocchi; Marie Louise Syren; William Morello; Carlo Agostoni; Giovanni Montini Journal: Int J Mol Sci Date: 2021-05-21 Impact factor: 5.923
Authors: Manuela Colucci; Rita Carsetti; Jessica Serafinelli; Salvatore Rocca; Laura Massella; Antonio Gargiulo; Anna Lo Russo; Claudia Capponi; Nicola Cotugno; Ottavia Porzio; Andrea Onetti Muda; Paolo Palma; Francesco Emma; Marina Vivarelli Journal: Front Immunol Date: 2019-07-16 Impact factor: 7.561