Molecular Patterns Discriminate Accommodation and Subclinical Antibody-mediated Rejection in Kidney Transplantation
Jazyk angličtina Země Spojené státy americké Médium print
Typ dokumentu časopisecké články, multicentrická studie, pozorovací studie, práce podpořená grantem
- MeSH
- ABO systém krevních skupin imunologie MeSH
- alografty imunologie metabolismus patologie MeSH
- biologické markery metabolismus MeSH
- biopsie MeSH
- dospělí MeSH
- HLA antigeny imunologie MeSH
- isoprotilátky imunologie MeSH
- ledviny imunologie metabolismus patologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- membránové transportní proteiny metabolismus MeSH
- metalothionein metabolismus MeSH
- mladý dospělý MeSH
- následné studie MeSH
- nekompatibilita krevních skupin diagnóza imunologie patologie MeSH
- přežívání štěpu imunologie MeSH
- rejekce štěpu diagnóza imunologie patologie MeSH
- retrospektivní studie MeSH
- senioři MeSH
- stanovení celkové genové exprese MeSH
- transplantace ledvin škodlivé účinky MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- pozorovací studie MeSH
- práce podpořená grantem MeSH
- Názvy látek
- ABO systém krevních skupin MeSH
- biologické markery MeSH
- HLA antigeny MeSH
- isoprotilátky MeSH
- membránové transportní proteiny MeSH
- metalothionein MeSH
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.
Department of Genomics Institute of Hematology and Blood Transfusion Prague Czech Republic
Department of Nephrology Hannover Medical School Hannover Germany
Department of Nephrology Institute for Clinical and Experimental Medicine Prague Czech Republic
Department of Pathology Hannover Medical School Hannover Germany
Transplant Laboratory Institute for Clinical and Experimental Medicine Prague Czech Republic
Transplant Surgery Department Institute for Clinical and Experimental Medicine Prague Czech Republic
Citace poskytuje Crossref.org
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