Reference - Detail
| RRC ID | 88564 |
|---|---|
| Author | Ambite I, Chao SM, Rosenblad T, Hopkins R, Storm P, Ng YH, Ganesan I, Lindén M, Haq F, Tran TH, Ahmadi S, Lee B, Chen SL, Godaly G, Brandström P, Connolly JE, Svanborg C. |
| Title | Molecular analysis of acute pyelonephritis-excessive innate and attenuated adaptive immunity. |
| Journal | Life Sci Alliance |
| Abstract |
This study investigated the molecular basis of disease severity in acute pyelonephritis (APN), a common and potentially life-threatening bacterial infection. Two cohorts of infants with febrile urinary tract infection were included. Renal involvement was defined by DMSA scans and molecular disease determinants by gene expression analysis and proteomic screens, at diagnosis and after 6 mo. Innate immune hyper-activation, systemically and locally in the urinary tract, was defined as a cytokine storm. Neutrophil degranulation and renal toxicity genes were strongly regulated, with overexpression in the APN group (first DMSA+). Adaptive immune attenuation in the APN group further supported the notion of an immune imbalance. DNA exome genotyping identified APN and febrile urinary tract infection as genetically distinct and scarring associated genes, but the activation of renal toxicity genes during acute infection was unrelated to the development of renal scarring. The results define APN as a hyper-inflammatory disorder with the characteristics of a cytokine storm combined with adaptive immune attenuation. The findings are consistent with innate immune dysfunctions and neutrophil disorders identified as determinants of APN susceptibility in genetic models. |
| Volume | 8(3) |
| Published | 2025-3-1 |
| DOI | 10.26508/lsa.202402926 |
| PII | 8/3/e202402926 |
| PMID | 40036168 |
| PMC | PMC11662066 |
| MeSH | Acute Disease Adaptive Immunity* / genetics Adaptive Immunity* / immunology Cytokines / metabolism Female Humans Immunity, Innate* / genetics Immunity, Innate* / immunology Infant Kidney / immunology Kidney / pathology Male Neutrophils / immunology Neutrophils / metabolism Proteomics / methods Pyelonephritis* / genetics Pyelonephritis* / immunology Urinary Tract Infections / genetics Urinary Tract Infections / immunology |
| IF | 2.622 |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | X(Twitter) |
| Total number of mentions | 3 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Mice | RBRC00858 |