{"doi":"10.1016/j.kint.2023.11.012","title":"Transcriptomic signatures of chronic active antibody-mediated rejection deciphered by RNA sequencing of human kidney allografts","abstract":"Natural killer (NK) cells mediate spontaneous cell-mediated cytotoxicity and antibody-dependent cell-mediated cytotoxicity. This dual functionality could enable their participation in chronic active antibody-mediated rejection (CA-ABMR). Earlier microarray profiling studies have not subcategorized antibody-mediated rejection into CA-ABMR and active-ABMR, and the gene expression pattern of CA-ABMR has not been compared with that of T cell-mediated rejection (TCMR). To fill these gaps, we RNA sequenced human kidney allograft biopsies categorized as CA-ABMR, active-ABMR, TCMR, or No Rejection (NR). Among the 15,910 genes identified in the biopsies, 60, 114, and 231 genes were uniquely overexpressed in CA-ABMR, TCMR, and active-ABMR, respectively, compared to NR, 50 genes were shared between CA-ABMR and active-ABMR, and 164 genes between CA-ABMR and TCMR. The overexpressed genes were annotated to NK cells and T cells in CA-ABMR and TCMR, and to neutrophils and monocytes in active-ABMR. The NK cell cytotoxicity and allograft rejection pathways were enriched in CA-ABMR. Genes encoding perforin, granzymes, and death receptor, were overexpressed in CA-ABMR versus ABMR but not compared to TCMR. NK cell cytotoxicity pathway gene set variation analysis score was higher in CA-ABMR compared to active-ABMR but not in TCMR. Principal component analysis of the deconvolved immune cellular transcriptomes separated CA-ABMR and TCMR from active-ABMR and NR. Immunohistochemistry of kidney allograft biopsies validated a higher proportion of CD56+ NK cells in CA-ABMR than in active-ABMR. Thus, CA-ABMR was exemplified by the overexpression of the NK cell cytotoxicity pathway gene set and, surprisingly, molecularly more like TCMR than active-ABMR.","journal":"Kidney International","year":2023,"id":325603,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":31,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9539,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":333460,"name":"Hua Yang","orcid":"0000-0003-4993-7796","position":1,"is_corresponding":false},{"id":333466,"name":"Franco B. Mueller","orcid":"0000-0002-0304-1268","position":2,"is_corresponding":false},{"id":560127,"name":"Carol Li","orcid":"0000-0002-0576-2181","position":3,"is_corresponding":false},{"id":1044537,"name":"Shab E. Gul Rahim","orcid":null,"position":4,"is_corresponding":false},{"id":1044538,"name":"Elly Varma","orcid":null,"position":5,"is_corresponding":false},{"id":791917,"name":"Thalia Salinas","orcid":"0000-0003-1909-4011","position":6,"is_corresponding":false},{"id":271000,"name":"Darshana M. Dadhania","orcid":"0000-0002-7973-1521","position":7,"is_corresponding":false},{"id":105524,"name":"Steven Salvatore","orcid":"0000-0001-7237-2696","position":8,"is_corresponding":false},{"id":288740,"name":"Surya V. Seshan","orcid":"0000-0003-4384-0694","position":9,"is_corresponding":false},{"id":333465,"name":"Vijay K. Sharma","orcid":"0000-0002-8976-5696","position":10,"is_corresponding":false},{"id":41043,"name":"Olivier Elemento","orcid":"0000-0002-8061-9617","position":11,"is_corresponding":false},{"id":333467,"name":"Manikkam Suthanthiran","orcid":"0000-0001-6894-0486","position":12,"is_corresponding":false},{"id":333459,"name":"Thangamani Muthukumar","orcid":"0000-0002-0294-6209","position":13,"is_corresponding":false},{"id":328463,"name":"Yajas Shah","orcid":"0000-0002-9692-4878","position":0,"is_corresponding":true}],"reference_count":54,"raw_metadata":null,"created_at":"2026-07-19T01:08:28.266998Z","pmid":"38040290","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}