HLA-D and PLA2R1 risk alleles associate with recurrent primary membranous nephropathy in kidney transplant recipients
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00023001%3A_____%2F21%3A00080802" target="_blank" >RIV/00023001:_____/21:00080802 - isvavai.cz</a>
Alternative codes found
RIV/00216208:11110/21:10430104 RIV/00064165:_____/21:10430104
Result on the web
<a href="https://reader.elsevier.com/reader/sd/pii/S0085253820309674?token=37CC762621B3F3FCC40B52DFC914921CCB7CF4CDCBEFA32DD1860CCDB83A78E0F0337810E28A8F71293F8FE5C8C35387" target="_blank" >https://reader.elsevier.com/reader/sd/pii/S0085253820309674?token=37CC762621B3F3FCC40B52DFC914921CCB7CF4CDCBEFA32DD1860CCDB83A78E0F0337810E28A8F71293F8FE5C8C35387</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.kint.2020.08.007" target="_blank" >10.1016/j.kint.2020.08.007</a>
Alternative languages
Result language
angličtina
Original language name
HLA-D and PLA2R1 risk alleles associate with recurrent primary membranous nephropathy in kidney transplant recipients
Original language description
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. © 2020
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30213 - Transplantation
Result continuities
Project
—
Continuities
N - Vyzkumna aktivita podporovana z neverejnych zdroju
Others
Publication year
2021
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Kidney international
ISSN
0085-2538
e-ISSN
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Volume of the periodical
99
Issue of the periodical within the volume
3
Country of publishing house
US - UNITED STATES
Number of pages
15
Pages from-to
671-685
UT code for WoS article
000680828500024
EID of the result in the Scopus database
2-s2.0-85100007627