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HLA-D and PLA2R1 risk alleles associate with recurrent primary membranous nephropathy in kidney transplant recipients
L. Berchtold, E. Letouzé, MP. Alexander, G. Canaud, AV. Logt, P. Hamilton, C. Mousson, V. Vuiblet, AM. Moyer, S. Guibert, P. Mrázová, C. Levi, V. Dubois, JM. Cruzado, A. Torres, MJ. Gandhi, N. Yousfi, V. Tesar, . OndrejViklický, M. Hourmant, B....
Jazyk angličtina Země Spojené státy americké
Typ dokumentu časopisecké články, práce podpořená grantem
Grantová podpora
MR/J010847/1
Medical Research Council - United Kingdom
NLK
Freely Accessible Science Journals
od 1972
Open Access Digital Library
od 1972-01-01
- MeSH
- alely MeSH
- jednonukleotidový polymorfismus MeSH
- lidé MeSH
- membranózní glomerulonefritida * diagnóza genetika MeSH
- receptory pro fosfolipasy A2 genetika MeSH
- retrospektivní studie MeSH
- transplantace ledvin * škodlivé účinky MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Recurrence of primary membranous nephropathy after transplantation occurs in up to 44% of patients and is driven by PLA2R antibody. Here, we asked whether genetic determinants could improve risk prediction. First, we sequenced PLA2R1 and HLA-D loci in 248 patients with primary membranous nephropathy and identified two independent single nucleotide polymorphisms (SNPs) at risk for primary membranous nephropathy at each locus. These were rs9271188 (intergenic between HLA-DRB1 and HLA-DQA1,) and rs9275086 (intergenic between HLA-DQB1 and HLA-DQA2) at the HLA-D locus along with rs6726925 and rs13018963 at the PLA2R1 locus. Then we investigated whether primary membranous nephropathy at-risk variants were associated with recurrence in a retrospective cohort of 105 donor-recipient pairs and a replication cohort of 40 pairs. Seven SNPs located between HLA-DRB1 and HLA-DQA1 in linkage disequilibrium with rs9271188, and three SNPs in the PLA2R1 region predicted recurrence when presented by the donor, but not when presented by the recipient. The two SNPs in the HLA-D region most strongly associated with recurrence (rs9271705 and rs9271550) were confirmed in the replication cohort. A genetic risk score based on the two best predictors at each locus (rs9271705, rs9271550, rs17830558, and rs3828323) identified a group of patients with high risk of recurrence. Thus, our results suggest that the graft contributes to recurrence of primary membranous nephropathy through the disease susceptibility HLA-D and PLA2R1 SNPs in an autoimmune milieu. Further studies are needed before implementation of genetic testing for these in donor selection.
BioSpec T Laboratory EA 7506 URCA Reims France
Centre de Recherche des Cordeliers Sorbonne Université INSERM France
Department of Adult Nephrology and Transplantation Necker Enfants Malades Hospital Paris France
Department of Laboratory Medicine and Pathology Mayo Clinic Rochester Minnesota USA
Department of Nephrology and Transplantation University Hospital Dijon France
Department of Nephrology AP HP Tenon Hospital Paris France
Department of Nephrology Fundación Puigvert Barcelona Spain
Department of Nephrology Strasbourg University Hospital Strasbourg France
Department of Nephrology University Hospital Amiens France
Department of Nephrology University Hospital Nantes France
Division of Nephrology Reims University Hospital Reims France
Division of Transfusion Medicine Mayo Clinic Rochester Minnesota USA
Fédération de Médecine Translationnelle de Strasbourg Strasbourg France
Inserm U1151 Necker Enfants Malades Hospital Paris France
Laboratoire HLA Etablissement Français du Sang Auvergne Rhone Alpes Lyon France
Nephrology Department Hospital Universitari Bellvitge Bellvitge Research Institute Barcelona Spain
Nephropathology Department of Biopathology Laboratory Reims University Hospital Reims France
RedInRen RD16 0009 0031 University of Barcelona L'Hospitalet de Llobregat Barcelona Spain
Sorbonne Université Université Pierre et Marie Curie Paris 06 Paris France
Transplant Laboratory Institute for Clinical and Experimental Medicine Prague Czech Republic
Université de Reims Champagne Ardenne CNRS UMR 7369 Reims France
Citace poskytuje Crossref.org
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- $a Berchtold, Lena $u Sorbonne Université, Université Pierre et Marie Curie Paris 06, Paris, France; Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche S1155, Paris, France; Division of Nephrology, Department of Internal Medicine Specialties, University Hospital of Geneva, Geneva, Switzerland
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- $a HLA-D and PLA2R1 risk alleles associate with recurrent primary membranous nephropathy in kidney transplant recipients / $c L. Berchtold, E. Letouzé, MP. Alexander, G. Canaud, AV. Logt, P. Hamilton, C. Mousson, V. Vuiblet, AM. Moyer, S. Guibert, P. Mrázová, C. Levi, V. Dubois, JM. Cruzado, A. Torres, MJ. Gandhi, N. Yousfi, V. Tesar, . OndrejViklický, M. Hourmant, B. Moulin, P. Rieu, G. Choukroun, C. Legendre, J. Wetzels, P. Brenchley, JA. Ballarín Castan, H. Debiec, P. Ronco
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- $a Recurrence of primary membranous nephropathy after transplantation occurs in up to 44% of patients and is driven by PLA2R antibody. Here, we asked whether genetic determinants could improve risk prediction. First, we sequenced PLA2R1 and HLA-D loci in 248 patients with primary membranous nephropathy and identified two independent single nucleotide polymorphisms (SNPs) at risk for primary membranous nephropathy at each locus. These were rs9271188 (intergenic between HLA-DRB1 and HLA-DQA1,) and rs9275086 (intergenic between HLA-DQB1 and HLA-DQA2) at the HLA-D locus along with rs6726925 and rs13018963 at the PLA2R1 locus. Then we investigated whether primary membranous nephropathy at-risk variants were associated with recurrence in a retrospective cohort of 105 donor-recipient pairs and a replication cohort of 40 pairs. Seven SNPs located between HLA-DRB1 and HLA-DQA1 in linkage disequilibrium with rs9271188, and three SNPs in the PLA2R1 region predicted recurrence when presented by the donor, but not when presented by the recipient. The two SNPs in the HLA-D region most strongly associated with recurrence (rs9271705 and rs9271550) were confirmed in the replication cohort. A genetic risk score based on the two best predictors at each locus (rs9271705, rs9271550, rs17830558, and rs3828323) identified a group of patients with high risk of recurrence. Thus, our results suggest that the graft contributes to recurrence of primary membranous nephropathy through the disease susceptibility HLA-D and PLA2R1 SNPs in an autoimmune milieu. Further studies are needed before implementation of genetic testing for these in donor selection.
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