Marc Fila1, Hanna Debiec2, Hélène Perrochia3, Nabila Djouadi1, Marie-Christine Verpont2, David Buob2,4, Pierre Ronco5,6. 1. Department of Pediatric Nephrology, Centre Hospitalier Universitaire de Montpellier, Montpellier, France. 2. Sorbonne Université, and Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche S1155, Paris, France. 3. Department of Pathology, Hôpital Gui de Chauliac, Montpellier, France. 4. Department of Pathology, Hôpital Tenon, Assistance Publique des Hôpitaux de Paris, Paris, France. 5. Sorbonne Université, and Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche S1155, Paris, France pierreronco@yahoo.fr. 6. Department of Nephrology, Centre Hospitalier du Mans, Le Mans, France.
Abstract
BACKGROUND: Membranous nephropathy (MN) is rare in pediatric patients, although its diagnosis may be underestimated in children who are responsive to corticosteroid therapy prescribed for a suspicion of minimal change disease. It is most often associated with an autoimmune disease, predominantly lupus. We previously reported the occurrence of early-onset MN associated with semaphorin 3B in nine children and two adults. METHODS: Biopsies were performed on native kidney and at 1 and 5 months after transplantation. Semaphorin 3B antigen was detected in immune deposits by immunohistochemistry and confocal microscopy on paraffin-embedded biopsies. Anti-semaphorin antibodies were detected by Western blot and analyzed sequentially. RESULTS: We report the first case of early recurrence after transplantation in a 7-year-old boy who presented with severe nephrotic syndrome and advanced kidney failure. There was no evidence of hereditary or associated autoimmune disease. Abundant, almost coalescent deposits were seen by electron microscopy and bright granular, subepithelial staining was observed for semaphorin 3B antigen. Western blot analysis of serum revealed anti-semaphorin 3B antibodies. Recurrence of MN occurred 25 days after transplantation and manifested as nephrotic range proteinuria despite conventional immunosuppressive therapy. Kidney biopsies confirmed histologic MN recurrence with colocalization of semaphorin 3B antigen and IgG. The patient was treated with rituximab. Anti-semaphorin 3B antibodies, which were detected at transplantation, were not detected 40 days after rituximab. CONCLUSION: This case provides evidence that anti-semaphorin 3B antibodies are pathogenic and should be monitored in patients with MN.
BACKGROUND: Membranous nephropathy (MN) is rare in pediatric patients, although its diagnosis may be underestimated in children who are responsive to corticosteroid therapy prescribed for a suspicion of minimal change disease. It is most often associated with an autoimmune disease, predominantly lupus. We previously reported the occurrence of early-onset MN associated with semaphorin 3B in nine children and two adults. METHODS: Biopsies were performed on native kidney and at 1 and 5 months after transplantation. Semaphorin 3B antigen was detected in immune deposits by immunohistochemistry and confocal microscopy on paraffin-embedded biopsies. Anti-semaphorin antibodies were detected by Western blot and analyzed sequentially. RESULTS: We report the first case of early recurrence after transplantation in a 7-year-old boy who presented with severe nephrotic syndrome and advanced kidney failure. There was no evidence of hereditary or associated autoimmune disease. Abundant, almost coalescent deposits were seen by electron microscopy and bright granular, subepithelial staining was observed for semaphorin 3B antigen. Western blot analysis of serum revealed anti-semaphorin 3B antibodies. Recurrence of MN occurred 25 days after transplantation and manifested as nephrotic range proteinuria despite conventional immunosuppressive therapy. Kidney biopsies confirmed histologic MN recurrence with colocalization of semaphorin 3B antigen and IgG. The patient was treated with rituximab. Anti-semaphorin 3B antibodies, which were detected at transplantation, were not detected 40 days after rituximab. CONCLUSION: This case provides evidence that anti-semaphorin 3B antibodies are pathogenic and should be monitored in patients with MN.
Authors: Hanna Debiec; Vincent Guigonis; Béatrice Mougenot; Fabrice Decobert; Jean-Philippe Haymann; Albert Bensman; Georges Deschênes; Pierre M Ronco Journal: N Engl J Med Date: 2002-06-27 Impact factor: 91.245
Authors: Sanjeev Sethi; Benjamin J Madden; Hanna Debiec; M Cristine Charlesworth; LouAnn Gross; Aishwarya Ravindran; Amber M Hummel; Ulrich Specks; Fernando C Fervenza; Pierre Ronco Journal: J Am Soc Nephrol Date: 2019-05-06 Impact factor: 10.121
Authors: Sanjeev Sethi; Benjamin Madden; Hanna Debiec; Johann Morelle; M Cristine Charlesworth; LouAnn Gross; Vivian Negron; David Buob; Sidharth Chaudhry; Michel Jadoul; Fernando C Fervenza; Pierre Ronco Journal: J Am Soc Nephrol Date: 2021-04-08 Impact factor: 10.121
Authors: Sanjeev Sethi; Hanna Debiec; Benjamin Madden; Marina Vivarelli; M Cristine Charlesworth; Aishwarya Ravindran; LouAnn Gross; Tim Ulinski; David Buob; Cheryl L Tran; Francesco Emma; Francesca Diomedi-Camassei; Fernando C Fervenza; Pierre Ronco Journal: Kidney Int Date: 2020-06-11 Impact factor: 10.612
Authors: Tiffany N Caza; Samar I Hassen; Michael Kuperman; Shree G Sharma; Zeljko Dvanajscak; John Arthur; Rick Edmondson; Aaron Storey; Christian Herzog; Daniel J Kenan; Christopher P Larsen Journal: Kidney Int Date: 2020-10-09 Impact factor: 18.998