CCR7 and CD48 as Predicted Targets in Acute Rejection Related to M1 Macrophage after Pediatric Kidney Transplantation.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:38957433", "kind": "science-record", "revision": 3, "content_hash": "sha256:8a612b99cc37563773ba9d8c254566e115f748e4592f17e02df5ae2b3d7f3372", "created_at": "2026-11-01T20:29:01Z", "updated_at": "2026-11-01T22:12:10Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "CCR7 and CD48 as Predicted Targets in Acute Rejection Related to M1 Macrophage after Pediatric Kidney Transplantation.", "doi": "10.1155/2024/6908968", "pmid": "38957433", "authors": ["Jie Zhang", "Jun Pei", "Chengjun Yu", "Jin Luo", "Yifan Hong", "Yi Hua", "Guanghui Wei"], "journal": "Journal of immunology research", "year": 2024, "abstract": "Background: Kidney transplantation (KT) is the best treatment for end-stage renal disease. Although long and short-term survival rates for the graft have improved significantly with the development of immunosuppressants, acute rejection (AR) remains a major risk factor attacking the graft and patients. The innate immune response plays an important role in rejection. Therefore, our objective is to determine the biomarkers of congenital immunity associated with AR after KT and provide support for future research.\nMaterials and Methods: A differential expression genes (DEGs) analysis was performed based on the dataset GSE174020 from the NCBI gene Expression Synthesis Database (GEO) and then combined with the GSE5099 M1 macrophage-related gene identified in the Molecular Signatures Database. We then identified genes in DEGs associated with M1 macrophages defined as DEM1Gs and performed gene ontology (GO) and Kyoto Encyclopedia of Genomes (KEGG) enrichment analysis. Cibersort was used to analyze the immune cell infiltration during AR. At the same time, we used the protein-protein interaction (PPI) network and Cytoscape software to determine the key genes. Dataset, GSE14328 derived from pediatric patients, GSE138043 and GSE9493 derived from adult patients, were used to verify Hub genes. Additional verification was the rat KT model, which was used to perform HE staining, immunohistochemical staining, and Western Blot. Hub genes were searched in the HPA database to confirm their expression. Finally, we construct the interaction network of transcription factor (TF)-Hub genes and miRNA-Hub genes.\nResults: Compared to the normal group, 366 genes were upregulated, and 423 genes were downregulated in the AR group. Then, 106 genes related to M1 macrophages were found among these genes. GO and KEGG enrichment analysis showed that these genes are mainly involved in cytokine binding, antigen binding, NK cell-mediated cytotoxicity, activation of immune receptors and immune response, and activation of the inflammatory NF-κB signaling pathway. Two Hub genes, namely CCR7 and CD48, were identified by PPI and Cytoscape analysis. They have been verified in external validation sets, originated from both pediatric patients and adult patients, and animal experiments. In the HPA database, CCR7 and CD48 are mainly expressed in T cells, B cells, macrophages, and tissues where these immune cells are distributed. In addition to immunoinfiltration, CD4+T, CD8+T, NK cells, NKT cells, and monocytes increased significantly in the AR group, which was highly consistent with the results of Hub gene screening. Finally, we predicted that 19 TFs and 32 miRNAs might interact with the Hub gene.\nConclusions: Through a comprehensive bioinformatic analysis, our findings may provide predictive and therapeutic targets for AR after KT.", "claims": [{"id": "claim-method", "statement": "The absolute value of log2fold > 1.0 and adj. P < 0.05 were used as significance indicators.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38957433", "locator": "sections[3] \"2.1. Dataset Sources and Processing\" paragraph 2", "quote": "The absolute value of log2fold > 1.0 and adj. P < 0.05 were used as significance indicators."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The data sets presented in this study can be found in online repositories. The original data of the animal experiments can be found in the Supplementary Materials section (Supplementary 3).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38957433", "locator": "sections[20] \"Data Availability\" paragraph 2", "quote": "The data sets presented in this study can be found in online repositories. The original data of the animal experiments can be found in the Supplementary Materials section (Supplementary 3)."}], "state": "complete"}, {"id": "claim-target-result", "statement": "CCR7 and CD48 were identified as the two hub genes associated with M1 macrophages in acute rejection after kidney transplantation and were elevated in acute-rejection groups.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:38957433", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "Two Hub genes, namely CCR7 and CD48, were identified by PPI and Cytoscape analysis."}, {"asset": "source:pmid:38957433", "locator": "sections[13] \"3.2. Identification of the Hub Gene Based on the PPI Network and Cytoscape\" paragraph 2", "quote": "The protein expression levels of CCR7 and CD48 were statistically analyzed, and it was found that the expression levels of CCR7 and CD48 in patients with AR were higher than those of the normal group, and the difference was statistically significant (Figure 3(h))."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "CCR7 and CD48 were identified as the two hub genes associated with M1 macrophages in acute rejection after kidney transplantation and were elevated in acute-rejection groups.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:38957433"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE138034"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "blocked", "blocked_on": "method:student_t", "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE138034"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": ["step:run_analysis blocked on method:student_t"]}, "data": {"state": "partial", "assets": [{"id": "source:pmid:38957433", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1155/2024/6908968", "sha256": "sha256:8544a28d5387b4abfcb55d40d7e6f3ec3f4fb85daf76023d3e1c5e56179aeada", "bytes": 35560, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1155/2024/6908968", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC11217580", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE138034", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE138034", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE138034", "version": null, "note": "The data sets presented in this study can be found in online repositories. 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