Divya Bhatia1, Aditi Sinha1, Pankaj Hari1, Shailaja Sopory2, Savita Saini1, Mamta Puraswani1, Himanshi Saini1, Dipendra K Mitra3, Arvind Bagga4. 1. Division of Nephrology, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India. 2. Pediatric Biology Center, Translational Health Science & Technology Institute, Faridabad, India. 3. Department of Transplant Immunology & Immunogenetics, All India Institute of Medical Sciences, New Delhi, India. 4. Division of Nephrology, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India. arvindbagga@hotmail.com.
Abstract
BACKGROUND: Rituximab, a monoclonal antibody targeting B lymphocytes, effectively sustains remission in steroid-dependent nephrotic syndrome (SDNS). We studied its effects on lymphocyte subsets and urinary CD80 excretion (uCD80) in patients with SDNS. METHODS: Blood and urine samples were collected from 18 SDNS patients before rituximab, and after 1 month and 1 year or at first relapse. T and B lymphocytes and uCD80 were determined by flow cytometry and ELISA, respectively. RESULTS: Treatment was associated with reduction in counts of Th17, Th2, and memory T cells, and increased T-regulatory (Treg) cells. The Th17/Treg ratio declined from baseline (median 0.6) to 1 month (0.2, P = 0.006) and increased during relapse (0.3, P = 0.016). Ratios of Th1/Th2 cells at baseline, 1 month after rituximab, and during relapse were 7.7, 14.0 (P = 0.0102), and 8.7, respectively. uCD80 decreased 1 month following rituximab (45.5 vs. 23.0 ng/g creatinine; P = 0.0039). B lymphocytes recovered earlier in relapsers (60.0 vs.183.0 days; P < 0.001). Memory B cells were higher during relapse than remission (29.7 vs.18.0 cells/µL; P = 0.029). CONCLUSION: Rituximab-induced sustained remission and B-cell depletion was associated with reduced numbers of Th17 and Th2 lymphocytes, and increased Treg cells; these changes reversed during relapses. Recovery of B cells and memory B cells predicted the occurrence of a relapse.
BACKGROUND:Rituximab, a monoclonal antibody targeting B lymphocytes, effectively sustains remission in steroid-dependent nephrotic syndrome (SDNS). We studied its effects on lymphocyte subsets and urinary CD80 excretion (uCD80) in patients with SDNS. METHODS: Blood and urine samples were collected from 18 SDNSpatients before rituximab, and after 1 month and 1 year or at first relapse. T and B lymphocytes and uCD80 were determined by flow cytometry and ELISA, respectively. RESULTS: Treatment was associated with reduction in counts of Th17, Th2, and memory T cells, and increased T-regulatory (Treg) cells. The Th17/Treg ratio declined from baseline (median 0.6) to 1 month (0.2, P = 0.006) and increased during relapse (0.3, P = 0.016). Ratios of Th1/Th2 cells at baseline, 1 month after rituximab, and during relapse were 7.7, 14.0 (P = 0.0102), and 8.7, respectively. uCD80 decreased 1 month following rituximab (45.5 vs. 23.0 ng/g creatinine; P = 0.0039). B lymphocytes recovered earlier in relapsers (60.0 vs.183.0 days; P < 0.001). Memory B cells were higher during relapse than remission (29.7 vs.18.0 cells/µL; P = 0.029). CONCLUSION:Rituximab-induced sustained remission and B-cell depletion was associated with reduced numbers of Th17 and Th2 lymphocytes, and increased Treg cells; these changes reversed during relapses. Recovery of B cells and memory B cells predicted the occurrence of a relapse.
Authors: Pietro Ravani; Manuela Colucci; Maurizio Bruschi; Marina Vivarelli; Michela Cioni; Armando DiDonato; Paolo Cravedi; Francesca Lugani; Francesca Antonini; Marco Prunotto; Francesco Emma; Andrea Angeletti; Gian Marco Ghiggeri Journal: J Am Soc Nephrol Date: 2021-09-20 Impact factor: 14.978
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: Kenna R Degner; Nancy A Wilson; Shannon R Reese; Sandesh Parajuli; Fahad Aziz; Neetika Garg; Maha Mohamed; Tripti Singh; Didier A Mandelbrot; Sarah E Panzer; Robert R Redfield; Kristin Van Hyfte; Weixiong Zhong; Luis G Hidalgo; Arjang Djamali Journal: Kidney360 Date: 2020-05-28
Authors: Divya Bhatia; Kuei-Pin Chung; Kiichi Nakahira; Edwin Patino; Michelle C Rice; Lisa K Torres; Thangamani Muthukumar; Augustine Mk Choi; Oleh M Akchurin; Mary E Choi Journal: JCI Insight Date: 2019-12-05