{"doi":"10.1172/jci168575","title":"Validated graft-specific biomarkers identify patients at risk for chronic graft-versus-host disease and death","abstract":"BACKGROUNDChronic graft-versus-host disease (cGVHD) is a serious complication of allogeneic hematopoietic cell transplantation (HCT). More accurate information regarding the risk of developing cGVHD is required. Bone marrow (BM) grafts contribute to lower cGVHD, which creates a dispute over whether risk biomarker scores should be used for peripheral blood (PB) and BM.METHODSDay 90 plasma proteomics from PB and BM recipients developing cGVHD revealed 5 risk markers that were added to 8 previous cGVHD markers to screen 982 HCT samples of 2 multicenter Blood and Marrow Transplant Clinical Trials Network (BMTCTN) cohorts. Each marker was tested for its association with cause-specific hazard ratios (HRs) of cGVHD using Cox-proportional-hazards models. We paired these clinical studies with biomarker measurements in a mouse model of cGVHD.RESULTSSpearman correlations between DKK3 and MMP3 were significant in both cohorts. In BMTCTN 0201 multivariate analyses, PB recipients with 1-log increase in CXCL9 and DKK3 were 1.3 times (95% CI: 1.1-1.4, P = 0.001) and 1.9 times (95%CI: 1.1-3.2, P = 0.019) and BM recipients with 1-log increase in CXCL10 and MMP3 were 1.3 times (95%CI: 1.0-1.6, P = 0.018 and P = 0.023) more likely to develop cGVHD. In BMTCTN 1202, PB patients with high CXCL9 and MMP3 were 1.1 times (95%CI: 1.0-1.2, P = 0.037) and 1.2 times (95%CI: 1.0-1.3, P = 0.009) more likely to develop cGVHD. PB patients with high biomarkers had increased likelihood to develop cGVHD in both cohorts (22%-32% versus 8%-12%, P = 0.002 and P < 0.001, respectively). Mice showed elevated circulating biomarkers before the signs of cGVHD.CONCLUSIONBiomarker levels at 3 months after HCT identify patients at risk for cGVHD occurrence.FUNDINGNIH grants R01CA168814, R21HL139934, P01CA158505, T32AI007313, and R01CA264921.","journal":"Journal of Clinical Investigation","year":2023,"id":329249,"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":20,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9604,"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":887996,"name":"Denggang Fu","orcid":"0000-0003-0779-7975","position":1,"is_corresponding":false},{"id":526854,"name":"Alan Howard","orcid":"0009-0003-7273-6906","position":2,"is_corresponding":false},{"id":550339,"name":"Mingwei Fei","orcid":"0000-0002-5627-4102","position":3,"is_corresponding":false},{"id":443055,"name":"Jianqun Kou","orcid":null,"position":4,"is_corresponding":false},{"id":818032,"name":"Morgan R. Little","orcid":"0009-0009-3713-6132","position":5,"is_corresponding":false},{"id":944171,"name":"Djamilatou Adom","orcid":"0000-0002-5225-2205","position":6,"is_corresponding":false},{"id":707520,"name":"Fathima A. Mohamed","orcid":"0000-0003-4270-8560","position":7,"is_corresponding":false},{"id":52067,"name":"Bruce R. Blazar","orcid":"0000-0002-9608-9841","position":8,"is_corresponding":false},{"id":720936,"name":"Philip R. Gafken","orcid":"0000-0001-6092-4828","position":9,"is_corresponding":false},{"id":348770,"name":"Sophie Paczesny","orcid":"0000-0001-5571-2775","position":10,"is_corresponding":false},{"id":244899,"name":"Brent R. Logan","orcid":"0000-0002-4473-4044","position":0,"is_corresponding":true}],"reference_count":53,"raw_metadata":null,"created_at":"2026-07-19T01:09:01.509601Z","pmid":"37526081","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":[]}