Allograft rejection (WP2328)
Homo sapiens
This pathway illustrates molecular interactions involved in the fundamental adaptive immune response for allograft destruction. This pathway was adapted in large part from [http://www.genome.jp/kegg/pathway/hsa/hsa05330.html KEGG]. In the initial step of this diagram, antigen presenting cells (APC's), either those from the donor (direct pathway) or from the recipient (indirect pathway) activate naive t cells leading to both CD8+ and CD4+ T cell maturation. CD8+ stimulated T cells lead to apoptosis of the allograft donor cells whereas CD4+ T cells differentiate into TH1, TH2, T17, and Treg cells. Activated TH1 produces TNFA and NO and damages donor graft cells by cytotoxicity. TH2 cell activates B cells. Activated B cells lead to plasma cell formation followed by IgG antibodies and the complement cascade pathway in acute antibody-mediated rejection (AMR) and chronic AMR with C3 being the therapeutic target. Exogenous treatment with YCF inhibits C3, thus preventing AMR. Eculizumab binds to C5 which prevent C5a production and the membrane attack complex. C3a and C35 act as potent chemotactic factors, promoting the infiltration of pro-inflammatory cells. Belatacept inhibits CD80/86 binding to CD28. Corticosteroids inhibit pro-inflammatory cytokines. Corticosteroids contribute to immune suppression such as CTLA4 which inhibits T-cell activation. Proteins on this pathway have targeted assays available via the [https://assays.cancer.gov/available_assays?wp_id=WP2328 CPTAC Assay Portal]
Authors
Nathan Salomonis , Deborah Micael , Daniela Digles , Kristina Hanspers , Martina Summer-Kutmon , Marianthi Kalafati , Alex Pico , Friederike Ehrhart , Denise Slenter , Eric Weitz , and Susan CoortActivity
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Cited In
- Immunomodulation of Pluripotent Stem Cell-Derived Mesenchymal Stem Cells in Rotator Cuff Tears Model (2022).
- An NF-κB- and Therapy-Related Regulatory Network in Glioma: A Potential Mechanism of Action for Natural Antiglioma Agents (2022).
- DNA methylation of ARHGAP30 is negatively associated with ARHGAP30 expression in lung adenocarcinoma, which reduces tumor immunity and is detrimental to patient survival (2021).
- Bioinformatics and system biology approach to identify the influences of SARS-CoV-2 infections to idiopathic pulmonary fibrosis and chronic obstructive pulmonary disease patients (2021).
- LMWF5A suppresses cytokine release by modulating select inflammatory transcription factor activity in stimulated PBMC (2020).
- Hematopoietic stem-cell senescence and myocardial repair - Coronary artery disease genotype/phenotype analysis of post-MI myocardial regeneration response induced by CABG/CD133+ bone marrow hematopoietic stem cell treatment in RCT PERFECT Phase 3 (2020).
- Construction and analysis of protein-protein interaction network of non-alcoholic fatty liver disease.
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Organisms
Homo sapiensCommunities
Annotations
Pathway Ontology
allograft rejection pathway disease pathway adaptive immune response pathway| Label | Type | Compact URI | Comment |
|---|---|---|---|
| Nitric oxide | Metabolite | kegg.compound:C00533 | |
| Belatacept | Metabolite | cas:706808-37-9 | |
| ECULIZUMAB | Metabolite | cas:219685-50-4 | |
| Tacrolimus | Metabolite | cas:104987-11-3 | |
| Ciclosporin | Metabolite | cas:59865-13-3 | |
| Daclizumab | Metabolite | cas:152923-56-3 | |
| Basiliximab | Metabolite | cas:152923-56-3 | |
| Prednisone | Metabolite | cas:53-03-2 | |
| Methylprednisolone | Metabolite | cas:83-43-2 | |
| Sirolimus | Metabolite | cas:53123-88-9 | |
| Fenofibrate | Metabolite | cas:49562-28-9 | |
| GDNF | GeneProduct | ensembl:ENSG00000168621 | |
| C5 | GeneProduct | ensembl:ENSG00000106804 | |
| CCL19 | GeneProduct | ensembl:ENSG00000172724 | |
| VEGFA | GeneProduct | ensembl:ENSG00000112715 | |
| MICA | GeneProduct | ncbigene:100507436 | |
| BHMT2 | GeneProduct | ensembl:ENSG00000132840 | |
| LRRK2 | GeneProduct | ensembl:ENSG00000188906 | |
| PECR | GeneProduct | ensembl:ENSG00000115425 | |
| PDGFRA | GeneProduct | ensembl:ENSG00000134853 | |
| STAT1 | GeneProduct | ensembl:ENSG00000115415 | |
| IL21 | GeneProduct | ensembl:ENSG00000138684 | |
| CXCL11 | GeneProduct | ensembl:ENSG00000169248 | |
| IL2 | GeneProduct | ensembl:ENSG00000109471 | |
| CXCR5 | GeneProduct | ensembl:ENSG00000160683 | |
| GNLY | GeneProduct | ensembl:ENSG00000115523 | |
| HARS | GeneProduct | ensembl:ENSG00000170445 | |
| CXCL9 | GeneProduct | ensembl:ENSG00000138755 | |
| CXCL13 | GeneProduct | ensembl:ENSG00000156234 | |
| CSNK2A2 | GeneProduct | ensembl:ENSG00000070770 | |
| C3 | GeneProduct | ensembl:ENSG00000125730 | |
| TUBA1B | GeneProduct | ensembl:ENSG00000123416 | |
| CXCL12 | GeneProduct | ensembl:ENSG00000107562 | |
| CCL21 | GeneProduct | ensembl:ENSG00000137077 | |
| GABPA | GeneProduct | ensembl:ENSG00000154727 | |
| AGTR1 | GeneProduct | ensembl:ENSG00000144891 | |
| IL1A | GeneProduct | ensembl:ENSG00000115008 | |
| C4A | GeneProduct | ncbigene:720 | |
| COL5 | GeneProduct | ensembl:ENSG00000130635 | |
| IL8 | GeneProduct | ensembl:ENSG00000169429 | |
| IFNG | GeneProduct | ensembl:ENSG00000111537 | |
| VIM | GeneProduct | ensembl:ENSG00000026025 | |
| ABCB1 | GeneProduct | ensembl:ENSG00000085563 | |
| CD28 | GeneProduct | ncbigene:940 | Original kegg element: gene;29;hsa:940 |
| IL13 | GeneProduct | ensembl:ENSG00000169194 | |
| IL4 | GeneProduct | ensembl:ENSG00000113520 | |
| IL12B | GeneProduct | ncbigene:3593 | Original kegg element: gene;41;hsa:3592 hsa:3593 |
| HLA-B | GeneProduct | ncbigene:3106 | Original kegg element: gene;20;hsa:3105 hsa:3106 hsa:3107 hsa:3133 hsa:3134 hsa:3135 hsa:652614 |
| TRBV | GeneProduct | ncbigene:6957 | previously: ko:K10785 ; T-cell receptor beta chain V region |
| IL10 | GeneProduct | ncbigene:3586 | Original kegg element: gene;31;hsa:3586 |
| Cell adhesion molecules (CAMs) | GeneProduct | kegg.genes:path:hsa04514 | Original kegg element: map;7;path:hsa04514 |
| HLA-G | GeneProduct | ncbigene:3135 | Original kegg element: gene;20;hsa:3105 hsa:3106 hsa:3107 hsa:3133 hsa:3134 hsa:3135 hsa:652614 |
| HLA-F | GeneProduct | ncbigene:3134 | Original kegg element: gene;20;hsa:3105 hsa:3106 hsa:3107 hsa:3133 hsa:3134 hsa:3135 hsa:652614 |
| PRF1 | GeneProduct | ncbigene:5551 | Original kegg element: gene;22;hsa:5551 |
| HLA-C | GeneProduct | ncbigene:3107 | Original kegg element: gene;20;hsa:3105 hsa:3106 hsa:3107 hsa:3133 hsa:3134 hsa:3135 hsa:652614 |
| FOXP3 | GeneProduct | ensembl:ENSG00000049768 | |
| IL22 | GeneProduct | ensembl:ENSG00000127318 | |
| HLA-E | GeneProduct | ncbigene:3133 | Original kegg element: gene;20;hsa:3105 hsa:3106 hsa:3107 hsa:3133 hsa:3134 hsa:3135 hsa:652614 |
| GZMB | GeneProduct | ncbigene:3002 | Original kegg element: gene;21;hsa:3002 |
| TGFB1 | GeneProduct | ensembl:ENSG00000105329 | |
| IL10 | GeneProduct | ensembl:ENSG00000136634 | |
| TNF | GeneProduct | ncbigene:7124 | Original kegg element: gene;39;hsa:7124 |
| TRAV | GeneProduct | ncbigene:6955 | Previously: ko:K10784 ; T cell receptor alpha chain V region |
| IL5 | GeneProduct | ncbigene:3567 | Original kegg element: gene;27;hsa:3567 |
| IL17A | GeneProduct | ensembl:ENSG00000112115 | |
| IL4 | GeneProduct | ncbigene:3565 | Original kegg element: gene;26;hsa:3565 |
| IL12A | GeneProduct | ncbigene:3592 | Original kegg element: gene;41;hsa:3592 hsa:3593 |
| IFNG | GeneProduct | ncbigene:3458 | Original kegg element: gene;34;hsa:3458 |
| IL5 | GeneProduct | ensembl:ENSG00000113525 | |
| CD40LG | GeneProduct | ncbigene:959 | Original kegg element: gene;38;hsa:959 |
| CD40 | GeneProduct | ncbigene:958 | Original kegg element: gene;37;hsa:958 |
| FAS | GeneProduct | ncbigene:355 | Original kegg element: gene;17;hsa:355 |
| HLA-A | GeneProduct | ncbigene:3105 | Original kegg element: gene;20;hsa:3105 hsa:3106 hsa:3107 hsa:3133 hsa:3134 hsa:3135 hsa:652614 |
| FASLG | GeneProduct | ncbigene:356 | Original kegg element: gene;18;hsa:356 |
| BOLA class I histocompatibility antigen | GeneProduct | ncbigene:652614 | Original kegg element: gene;20;hsa:3105 hsa:3106 hsa:3107 hsa:3133 hsa:3134 hsa:3135 hsa:652614 |
| immunoglobulin heavy chain | GeneProduct | ncbiprotein:XP_011544500 | Previously: ko:K06856 |
| CTLA4 | GeneProduct | ensembl:ENSG00000163599 | |
| C2 | GeneProduct | ncbigene:717 | |
| C9 | GeneProduct | ncbigene:735 | |
| C8B | GeneProduct | ncbigene:732 | |
| C6 | GeneProduct | ncbigene:729 | |
| CD55 | GeneProduct | ncbigene:1604 | |
| C1QA | GeneProduct | ncbigene:712 | update: C1QA HUMAN |
| C1QB | GeneProduct | ncbigene:713 | |
| C7 | GeneProduct | ncbigene:730 | |
| C8A | GeneProduct | ncbigene:731 | |
| C4B | GeneProduct | ncbigene:721 | |
| C1QC | GeneProduct | ncbigene:714 | update C1QC HUMAN |
| CASP8 | GeneProduct | ensembl:ENSG00000064012 | |
| CASP7 | GeneProduct | ensembl:ENSG00000165806 | |
| CASP3 | GeneProduct | ensembl:ENSG00000164305 | |
| CASP9 | GeneProduct | ensembl:ENSG00000132906 | |
| PRKCZ | GeneProduct | ensembl:ENSG00000067606 | |
| IL2RA | GeneProduct | ensembl:ENSG00000134460 | |
| IL1B | GeneProduct | ensembl:ENSG00000125538 | |
| HLA-DRB3 | GeneProduct | ncbigene:3125 | Original kegg element: gene;10;hsa:100133583 hsa:3108 hsa:3109 hsa:3111 hsa:3112 hsa:3113 hsa:3115 hsa:3117 hsa:3118 hsa:3119 hsa:3122 hsa:3123 hsa:3125 hsa:3126 hsa:3127 |
| HLA-DRA | GeneProduct | ncbigene:3122 | Original kegg element: gene;10;hsa:100133583 hsa:3108 hsa:3109 hsa:3111 hsa:3112 hsa:3113 hsa:3115 hsa:3117 hsa:3118 hsa:3119 hsa:3122 hsa:3123 hsa:3125 hsa:3126 hsa:3127 |
| HLA-DMB | GeneProduct | ncbigene:3109 | Original kegg element: gene;10;hsa:100133583 hsa:3108 hsa:3109 hsa:3111 hsa:3112 hsa:3113 hsa:3115 hsa:3117 hsa:3118 hsa:3119 hsa:3122 hsa:3123 hsa:3125 hsa:3126 hsa:3127 |
| HLA-DRB1 | GeneProduct | ncbigene:3123 | Original kegg element: gene;10;hsa:100133583 hsa:3108 hsa:3109 hsa:3111 hsa:3112 hsa:3113 hsa:3115 hsa:3117 hsa:3118 hsa:3119 hsa:3122 hsa:3123 hsa:3125 hsa:3126 hsa:3127 |
| HLA-DQA2 | GeneProduct | ncbigene:3118 | Original kegg element: gene;10;hsa:100133583 hsa:3108 hsa:3109 hsa:3111 hsa:3112 hsa:3113 hsa:3115 hsa:3117 hsa:3118 hsa:3119 hsa:3122 hsa:3123 hsa:3125 hsa:3126 hsa:3127 |
| HLA-DPA1 | GeneProduct | ncbigene:3113 | Original kegg element: gene;10;hsa:100133583 hsa:3108 hsa:3109 hsa:3111 hsa:3112 hsa:3113 hsa:3115 hsa:3117 hsa:3118 hsa:3119 hsa:3122 hsa:3123 hsa:3125 hsa:3126 hsa:3127 |
| HLA-DOB | GeneProduct | ncbigene:3112 | Original kegg element: gene;10;hsa:100133583 hsa:3108 hsa:3109 hsa:3111 hsa:3112 hsa:3113 hsa:3115 hsa:3117 hsa:3118 hsa:3119 hsa:3122 hsa:3123 hsa:3125 hsa:3126 hsa:3127 |
| HLA-DRB4 | GeneProduct | ncbigene:3126 | Original kegg element: gene;10;hsa:100133583 hsa:3108 hsa:3109 hsa:3111 hsa:3112 hsa:3113 hsa:3115 hsa:3117 hsa:3118 hsa:3119 hsa:3122 hsa:3123 hsa:3125 hsa:3126 hsa:3127 |
| HLA-DOA | GeneProduct | ncbigene:3111 | Original kegg element: gene;10;hsa:100133583 hsa:3108 hsa:3109 hsa:3111 hsa:3112 hsa:3113 hsa:3115 hsa:3117 hsa:3118 hsa:3119 hsa:3122 hsa:3123 hsa:3125 hsa:3126 hsa:3127 |
| HLA-DQA1 | GeneProduct | ncbigene:3117 | Original kegg element: gene;10;hsa:100133583 hsa:3108 hsa:3109 hsa:3111 hsa:3112 hsa:3113 hsa:3115 hsa:3117 hsa:3118 hsa:3119 hsa:3122 hsa:3123 hsa:3125 hsa:3126 hsa:3127 |
| HLA-DQB1 | GeneProduct | ncbigene:3119 | Original kegg element: gene;10;hsa:100133583 hsa:3108 hsa:3109 hsa:3111 hsa:3112 hsa:3113 hsa:3115 hsa:3117 hsa:3118 hsa:3119 hsa:3122 hsa:3123 hsa:3125 hsa:3126 hsa:3127 |
| HLA-DRB5 | GeneProduct | ncbigene:3127 | Original kegg element: gene;10;hsa:100133583 hsa:3108 hsa:3109 hsa:3111 hsa:3112 hsa:3113 hsa:3115 hsa:3117 hsa:3118 hsa:3119 hsa:3122 hsa:3123 hsa:3125 hsa:3126 hsa:3127 |
| CD80 | GeneProduct | ncbigene:941 | Original kegg element: gene;28;hsa:941 hsa:942 |
| HLA-DMA | GeneProduct | ncbigene:3108 | Original kegg element: gene;10;hsa:100133583 hsa:3108 hsa:3109 hsa:3111 hsa:3112 hsa:3113 hsa:3115 hsa:3117 hsa:3118 hsa:3119 hsa:3122 hsa:3123 hsa:3125 hsa:3126 hsa:3127 |
| HLA-DPB1 | GeneProduct | ncbigene:3115 | Original kegg element: gene;10;hsa:100133583 hsa:3108 hsa:3109 hsa:3111 hsa:3112 hsa:3113 hsa:3115 hsa:3117 hsa:3118 hsa:3119 hsa:3122 hsa:3123 hsa:3125 hsa:3126 hsa:3127 |
| CD28 | GeneProduct | ncbigene:940 | Original kegg element: gene;36;hsa:940 |
| CD80 | GeneProduct | ncbigene:941 | Original kegg element: gene;35;hsa:941 hsa:942 |
| HLA-E | GeneProduct | ncbigene:3133 | Original kegg element: gene;32;hsa:3105 hsa:3106 hsa:3107 hsa:3133 hsa:3134 hsa:3135 hsa:652614 |
| HLA-G | GeneProduct | ncbigene:3135 | Original kegg element: gene;32;hsa:3105 hsa:3106 hsa:3107 hsa:3133 hsa:3134 hsa:3135 hsa:652614 |
| HLA-F | GeneProduct | ncbigene:3134 | Original kegg element: gene;32;hsa:3105 hsa:3106 hsa:3107 hsa:3133 hsa:3134 hsa:3135 hsa:652614 |
| HLA-B | GeneProduct | ncbigene:3106 | Original kegg element: gene;32;hsa:3105 hsa:3106 hsa:3107 hsa:3133 hsa:3134 hsa:3135 hsa:652614 |
| HLA-C | GeneProduct | ncbigene:3107 | Original kegg element: gene;32;hsa:3105 hsa:3106 hsa:3107 hsa:3133 hsa:3134 hsa:3135 hsa:652614 |
| HLA-A | GeneProduct | ncbigene:3105 | Original kegg element: gene;32;hsa:3105 hsa:3106 hsa:3107 hsa:3133 hsa:3134 hsa:3135 hsa:652614 |
| CD86 | GeneProduct | ncbigene:942 | Original kegg element: gene;35;hsa:941 hsa:942 |
| GZMB | GeneProduct | ensembl:ENSG00000100453 | |
| PRF1 | GeneProduct | ensembl:ENSG00000180644 |
References
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- Characterization of intra-graft B cells during renal allograft rejection. Zarkhin V, Kambham N, Li L, Kwok S, Hsieh SC, Salvatierra O, et al. Kidney Int. 2008 Sep;74(5):664–73. PubMed Europe PMC Scholia
- Balancing efficacy and toxicity of kidney transplant immunosuppression. Naesens M, Lerut E, Sarwal M, Van Damme B, Vanrenterghem Y, Kuypers DRJ. Transplant Proc. 2009 Oct;41(8):3393–5. PubMed Europe PMC Scholia
- Rejection of the kidney allograft. Nankivell BJ, Alexander SI. N Engl J Med. 2010 Oct 7;363(15):1451–62. PubMed Europe PMC Scholia
- Non-HLA antibodies to immunogenic epitopes predict the evolution of chronic renal allograft injury. Sigdel TK, Li L, Tran TQ, Khatri P, Naesens M, Sansanwal P, et al. J Am Soc Nephrol. 2012 Apr;23(4):750–63. PubMed Europe PMC Scholia
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- Role of non-HLA antibodies in organ transplantation. Dragun D, Philippe A, Catar R. Curr Opin Organ Transplant. 2012 Aug;17(4):440–5. PubMed Europe PMC Scholia
- The role of complement in antibody-mediated rejection in kidney transplantation. Stegall MD, Chedid MF, Cornell LD. Nat Rev Nephrol. 2012 Nov;8(11):670–8. PubMed Europe PMC Scholia
- Significance and suppression of redundant IL17 responses in acute allograft rejection by bioinformatics based drug repositioning of fenofibrate. Roedder S, Kimura N, Okamura H, Hsieh SC, Gong Y, Sarwal MM. PLoS One. 2013;8(2):e56657. PubMed Europe PMC Scholia