Novel insights into non-HLA alloimmunity in kidney transplantation.
Roman Reindl-SchwaighoferAndreas HeinzlGuido A GualdoniLaurent MesnardFrans H J ClaasRainer OberbauerPublished in: Transplant international : official journal of the European Society for Organ Transplantation (2019)
Recognition of non-self structures on donor cells represents the main immunological barrier in solid organ transplantation. The human leukocyte antigens (HLA) are considered the most important non-self (allo)antigens in transplantation. Long-term graft attrition is mainly caused by the formation of alloreactive antibodies that are directed against non-self structures (i.e., epitopes) on cell surface proteins. Recently published data provided evidence for a similar importance of non-HLA mismatches between donors and recipients in acute rejection as well as long-term kidney allograft survival. These data suggest a broader concept of immunological non-self that goes beyond HLA incompatibility and expands the current concept of polymorphic non-self epitopes on cell surface molecules from HLA to non-HLA targets. Amino acid substitutions caused by single nucleotide variants in protein-coding genes or complete loss of gene expression represent the basis for polymorphic residues in both HLA and non-HLA molecules. To better understand these novel insights in non-HLA alloimmunity, we will first review basic principles of the alloimmune response with a focus on the HLA epitope concept in donor-specific antibody formation before discussing key publications on non-HLA antibodies.
Keyphrases
- kidney transplantation
- gene expression
- cell surface
- amino acid
- stem cells
- endothelial cells
- dna methylation
- randomized controlled trial
- big data
- induced apoptosis
- high resolution
- oxidative stress
- cell death
- cell proliferation
- bone marrow
- cell therapy
- deep learning
- peripheral blood
- electronic health record
- data analysis
- drug induced