Molecular patterns discriminate accommodation and subclinical antibody-mediated rejection in kidney transplantation
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00023001%3A_____%2F19%3A00077814" target="_blank" >RIV/00023001:_____/19:00077814 - isvavai.cz</a>
Alternative codes found
RIV/00216208:11110/19:10400348 RIV/00023736:_____/19:00012720 RIV/00064165:_____/19:10400348
Result on the web
<a href="https://insights.ovid.com/pubmed?pmid=30801516" target="_blank" >https://insights.ovid.com/pubmed?pmid=30801516</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1097/TP.0000000000002604" target="_blank" >10.1097/TP.0000000000002604</a>
Alternative languages
Result language
angličtina
Original language name
Molecular patterns discriminate accommodation and subclinical antibody-mediated rejection in kidney transplantation
Original language description
BACKGROUND: Accommodation in ABO-incompatible (ABOi) transplantation and subclinical antibody-mediated rejection in HLA-incompatible (HLAi) transplantation share several morphological similarities. Because the clinical long-term outcomes differ, we hypothesized different molecular processes involved in ABOi transplantation and subclinical antibody-mediated rejection. METHODS: Using Illumina Human HT-12 v4 Expression BeadChips, the whole transcriptome was evaluated based on 3-month protocol C4d+ biopsies in otherwise stable ABOi and HLAi kidney grafts, as well as in C4d-negative HLA-compatible grafts exhibiting normal histological findings. Top differently regulated genes were further validated using real-time quantitative polymerase chain reaction in another patient cohort and complement regulatory proteins by immunohistochemistry. RESULTS: In the case of genes involved in immune response-related biological processes, ABOi and HLAi cohorts had similar transcriptomic profiles to C4d-negative controls. The majority of deregulated genes in the ABOi and HLAi groups consisted of metallothioneins and epithelial transporter genes. Increased expression of epithelial transporters (SLC4A1, SLC4A9, SLC17A3, SLC12A3, and SLC30A2) and class 1 metallothioneins (MT1F, MT1G, and MT1X) in HLAi transplantation was validated by real-time quantitative polymerase chain reaction. In comparison to controls, both incompatible cohorts were characterized by the upregulation of intrarenal complement regulatory genes. CD46 and CD59 transcripts were increased in the ABOi cohort, whereas CD46 solely in HLAi group, and CD59 protein expression was similar in both incompatible groups. CONCLUSIONS: Several epithelial transporters and metallothioneins discriminate subclinical antibody-mediated rejection in HLAi transplantation from accommodation in ABOi transplantation, which suggest different involved downstream mechanisms and increased risk of injury in HLAi settings. Metallothioneins with their antioxidative properties may help to attenuate the inflammation response induced by donor-specific anti-HLA antibody binding.
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
<a href="/en/project/NV15-26865A" target="_blank" >NV15-26865A: Alloreactivity in living donor kidney transplantation</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2019
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Transplantation
ISSN
0041-1337
e-ISSN
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Volume of the periodical
103
Issue of the periodical within the volume
5
Country of publishing house
US - UNITED STATES
Number of pages
9
Pages from-to
909-917
UT code for WoS article
000480680900018
EID of the result in the Scopus database
2-s2.0-85065409657