Recurrence of Anti-Semaphorin 3B-Mediated Membranous Nephropathy after Kidney Transplantation.
antibodies
glomerulopathy
immunology and pathology
kidney transplantation
membranous nephropathy
pediatric
recurrence
semaphorin 3B
Journal
Journal of the American Society of Nephrology : JASN
ISSN: 1533-3450
Titre abrégé: J Am Soc Nephrol
Pays: United States
ID NLM: 9013836
Informations de publication
Date de publication:
03 2022
03 2022
Historique:
received:
10
10
2021
accepted:
21
12
2021
pubmed:
13
1
2022
medline:
23
4
2022
entrez:
12
1
2022
Statut:
ppublish
Résumé
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. 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. 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. This case provides evidence that anti-semaphorin 3B antibodies are pathogenic and should be monitored in patients with MN.
Sections du résumé
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.
Identifiants
pubmed: 35017170
pii: 00001751-202203000-00008
doi: 10.1681/ASN.2021101323
pmc: PMC8975066
doi:
Substances chimiques
Receptors, Phospholipase A2
0
Semaphorins
0
Rituximab
4F4X42SYQ6
Types de publication
Case Reports
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
503-509Informations de copyright
Copyright © 2022 by the American Society of Nephrology.
Références
Debiec H, Guigonis V, Mougenot B, Decobert F, Haymann JP, Bensman A, et al.: Antenatal membranous glomerulonephritis due to anti-neutral endopeptidase antibodies. N Engl J Med 346: 2053–2060, 2002
Beck LH, Bonegio RG, Lambeau G, Beck DM, Powell DW, Cummins TD, et al.: M-type phospholipase A2 receptor as target antigen in idiopathic membranous nephropathy. N Engl J Med 361: 11–21, 2009
Tomas NM, Beck LHJ, Meyer-Schwesinger C, Seitz-Polski B, Ma H, Zahner G, et al.: Thrombospondin type-1 domain-containing 7A in idiopathic membranous nephropathy. N Engl J Med 371: 2277–2287, 2014
Kidney Disease: Improving Global Outcomes (KDIGO) Glomerular Diseases Work Group: KDIGO 2021 clinical practice guideline for the management of glomerular diseases. Kidney Int 100: S1–S276, 2021. Available at: https://kdigo.org
Sethi S: New “antigens” in membranous nephropathy. J Am Soc Nephrol 32: 268–278, 2021
Ronco P, Debiec H: Membranous nephropathy: Current understanding of various causes in light of new target antigens. Curr Opin Nephrol Hypertens 30: 287–293, 2021
Sethi S, Debiec H, Madden B, Vivarelli M, Charlesworth MC, Ravindran A, et al.: Semaphorin 3B-associated membranous nephropathy is a distinct type of disease predominantly present in pediatric patients. Kidney Int 98: 1253–1264, 2020
Sethi S, Madden BJ, Debiec H, Charlesworth MC, Gross L, Ravindran A, et al.: Exostosin 1/exostosin 2-associated membranous nephropathy. J Am Soc Nephrol 30: 1123–1136, 2019
Sethi S, Debiec H, Madden B, Charlesworth MC, Morelle J, Gross LA, et al.: Neural epidermal growth factor-like 1 protein (NELL-1) associated membranous nephropathy. Kidney Int 97: 163–174, 2020
Sethi S, Madden BJ, Debiec H, Morelle J, Charlesworth MC, Gross LA, et al.: Protocadherin 7-associated membranous nephropathy. J Am Soc Nephrol 32: 1249–1261, 2021
Al-Rabadi LF, Caza T, Trivin-Avillach C, Rodan AR, Andeen N, Hayashi N, et al.: Serine protease HTRA1 as a novel target antigen in primary membranous nephropathy. J Am Soc Nephrol 32: 1666–1681, 2021
Caza T, Hassen SI, Kuperman M, Sharma SG, Dvanajscak Z, Arthur J, et al.: Neural cell adhesion molecule 1 is a novel autoantigen in membranous lupus nephritis. Kidney Int 100: 171–181, 2021
Stahl R, Hoxha E, Fechner K: PLA2R autoantibodies and recurrent membranous nephropathy after transplantation. N Engl J Med 363: 496–498, 2010
Blosser CD, Ayalon R, Nair R, Thomas C, Beck LH Jr. Very early recurrence of anti-phospholipase A2 receptor-positive membranous nephropathy after transplantation. Am J Transplant 12: 1637–1642, 2012
Tomas NM, Hoxha E, Reinicke AT, Fester L, Helmchen U, Gerth J, et al.: Autoantibodies against thrombospondin type 1 domain-containing 7A induce membranous nephropathy. J Clin Invest 126: 2519–2532, 2016
Meyer-Schwesinger C, Tomas NM, Dehde S, Seifert L, Hermans-Borgmeyer I, Wiech T, et al.: A novel mouse model of phospholipase A2 receptor 1 associated membranous nephropathy mimics podocyte injury in patients. Kidney Int 97: 913–919, 2020