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Article Dans Une Revue Kidney International Année : 2020

HLA-D and PLA2R1 risk alleles associate with recurrent primary membranous nephropathy in kidney transplant recipients.

1 Des Maladies Rénales Rares aux Maladies Fréquentes, Remodelage et Réparation
2 HUG - Geneva University Hospital
3 CRC (UMR_S_1138 / U1138) - Centre de Recherche des Cordeliers
4 Mayo Clinic [Rochester]
5 INEM - UM 111 (UMR 8253 / U1151) - Institut Necker Enfants-Malades
6 Service Néphrologie et transplantation rénale Adultes [CHU Necker]
7 Radboud University Medical Center [Nijmegen]
8 University of Manchester [Manchester]
9 CHU Dijon - Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand
10 BIOSPECT - Biospectroscopie Translationnelle - EA 7506
11 Hôpital universitaire Robert Debré [Reims]
12 IntegraGen
13 IKEM - Institute for Clinical and Experimental Medicine
14 Hôpital Edouard Herriot [CHU - HCL]
15 EFS - Etablissement français du sang - Auvergne-Rhône-Alpes
16 IDIBELL - Institut d'Investigació Biomèdica de Bellvitge = Bellvitge Biomedical Research Institute
17 University of Barcelona
18 ULL - Universidad de La Laguna [Tenerife - SP]
19 UK - Univerzita Karlova [Praha, Česká republika] = Charles University [Prague, Czech Republic]
20 CHU Nantes - Centre Hospitalier Universitaire de Nantes
21 IRM - Immuno-Rhumatologie Moléculaire
22 FMTS - Fédération de Médecine Translationnelle de Strasbourg
23 MEDyC - Matrice Extracellulaire et Dynamique Cellulaire - UMR CNRS 7369
24 CHU Amiens-Picardie
25 MP3CV - Mécanismes physiopathologiques et conséquences des calcifications vasculaires - UR UPJV 7517
26 Département de Néphrologie [CHU Necker]
27 Fundación Puigvert
28 CHU Tenon [AP-HP]
Eric Letouzé
Sylvain Guibert
  • Fonction : Auteur

Résumé

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 the genetic testing in donor selection.
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Dates et versions

hal-02935575 , version 1 (10-09-2020)

Identifiants

Citer

Lena Berchtold, Eric Letouzé, Mariam Priya Alexander, Guillaume Canaud, Anne-Els van De Logt, et al.. HLA-D and PLA2R1 risk alleles associate with recurrent primary membranous nephropathy in kidney transplant recipients.. Kidney International, 2020, 99 (3), pp.671-685. ⟨10.1016/j.kint.2020.08.007⟩. ⟨hal-02935575⟩
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