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Molecular analysis of acute pyelonephritis—excessive innate and attenuated adaptive immunity

Ambite, Ines LU orcid ; Chao, Sing Ming ; Rosenblad, Therese LU ; Hopkins, Richard ; Storm, Petter LU orcid ; Ng, Yong Hong ; Ganesan, Indra ; Lindén, Magnus ; Haq, Farhan LU and Tran, Thi Hien LU , et al. (2025) In Life Science Alliance 8(3).
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... (More)

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.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Life Science Alliance
volume
8
issue
3
article number
e202402926
publisher
Rockefeller University Press
external identifiers
  • scopus:85213967550
  • pmid:40036168
ISSN
2575-1077
DOI
10.26508/lsa.202402926
language
English
LU publication?
yes
additional info
Publisher Copyright: © 2024 Ambite et al.
id
46312aae-5bce-4670-9aac-7460fcec49c9
date added to LUP
2025-03-14 15:17:48
date last changed
2025-06-06 22:41:50
@article{46312aae-5bce-4670-9aac-7460fcec49c9,
  abstract     = {{<p>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.</p>}},
  author       = {{Ambite, Ines and Chao, Sing Ming and Rosenblad, Therese and Hopkins, Richard and Storm, Petter and Ng, Yong Hong and Ganesan, Indra and Lindén, Magnus and Haq, Farhan and Tran, Thi Hien and Ahmadi, Shahram and Lee, Bernett and Chen, Swaine L. and Godaly, Gabriela and Brandström, Per and Connolly, John E. and Svanborg, Catharina}},
  issn         = {{2575-1077}},
  language     = {{eng}},
  number       = {{3}},
  publisher    = {{Rockefeller University Press}},
  series       = {{Life Science Alliance}},
  title        = {{Molecular analysis of acute pyelonephritis—excessive innate and attenuated adaptive immunity}},
  url          = {{http://dx.doi.org/10.26508/lsa.202402926}},
  doi          = {{10.26508/lsa.202402926}},
  volume       = {{8}},
  year         = {{2025}},
}