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Analysis of the Innate Immune Response to Febrile UTI in Infants : Evidence of an Acute Cytokine Storm

Ahmadi, Shahram LU ; Rosenblad, Therese LU ; Sabari, Samudra LU ; Linden, Magnus ; Brandström, Per LU ; Chao, Sing Ming ; Svanborg, Catharina LU and Ambite, Ines LU orcid (2025) In Pediatric Infectious Disease Journal
Abstract

Background: Infections trigger complex immune responses, with conserved as well as disease-specific characteristics. Methods: Proteomic screening technology and gene expression analysis were used here to define the immune response in infants, with their first episode of febrile urinary tract infection. Urine and peripheral blood samples were obtained at enrollment and at follow-up, after 6 months. Results: Pair-wise proteomic analysis of urine samples detected a broad local cytokine response in urine; 20 of the 24 proteins were strongly activated during acute infection compared with follow-up. Functional profiling identified the response as a cytokine storm, and major innate immune response regulators and effector molecules were... (More)

Background: Infections trigger complex immune responses, with conserved as well as disease-specific characteristics. Methods: Proteomic screening technology and gene expression analysis were used here to define the immune response in infants, with their first episode of febrile urinary tract infection. Urine and peripheral blood samples were obtained at enrollment and at follow-up, after 6 months. Results: Pair-wise proteomic analysis of urine samples detected a broad local cytokine response in urine; 20 of the 24 proteins were strongly activated during acute infection compared with follow-up. Functional profiling identified the response as a cytokine storm, and major innate immune response regulators and effector molecules were activated, such as IL-1α, IL-1β, IL-1RA, IL-33, IL-8, IP-10, MCP-1, MIP-1α, MIP-1β, GM-CSF, IL-6, IL-17, TNF-α and IFN-γ. In addition, the adaptive immune response was activated, including CD40L, IL-2, Granzyme B, IL-10, IL-15 and PD-L1. Gene expression analysis of peripheral blood RNA detected a systemic cytokine storm profile, which was more pronounced in infants with renal involvement, defined by positive acute dimercaptosuccinic acid scans, than in infants with febrile urinary tract infection without renal involvement. Conclusions: Local and systemic hyperactivation of innate immunity characterizes acute pyelonephritis, a common and severe bacterial infection in childhood and a significant cause of urosepsis and mortality in adults. The results define a transient cytokine storm response, resembling that induced during severe acute respiratory syndrome coronavirus 2 infection, as characteristic of acute pyelonephritis, rather than individual protein biomarkers.

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author
; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
in press
subject
keywords
COVID-19, cytokine storm, febrile urinary tract infection, gene expression, immune response, urine proteomics
in
Pediatric Infectious Disease Journal
publisher
Lippincott Williams & Wilkins
external identifiers
  • pmid:40856487
  • scopus:105015070630
ISSN
0891-3668
DOI
10.1097/INF.0000000000004914
language
English
LU publication?
yes
id
075e3ae0-3612-4b42-96be-e572c76f6a82
date added to LUP
2025-11-14 13:55:46
date last changed
2025-11-15 03:00:02
@article{075e3ae0-3612-4b42-96be-e572c76f6a82,
  abstract     = {{<p>Background: Infections trigger complex immune responses, with conserved as well as disease-specific characteristics. Methods: Proteomic screening technology and gene expression analysis were used here to define the immune response in infants, with their first episode of febrile urinary tract infection. Urine and peripheral blood samples were obtained at enrollment and at follow-up, after 6 months. Results: Pair-wise proteomic analysis of urine samples detected a broad local cytokine response in urine; 20 of the 24 proteins were strongly activated during acute infection compared with follow-up. Functional profiling identified the response as a cytokine storm, and major innate immune response regulators and effector molecules were activated, such as IL-1α, IL-1β, IL-1RA, IL-33, IL-8, IP-10, MCP-1, MIP-1α, MIP-1β, GM-CSF, IL-6, IL-17, TNF-α and IFN-γ. In addition, the adaptive immune response was activated, including CD40L, IL-2, Granzyme B, IL-10, IL-15 and PD-L1. Gene expression analysis of peripheral blood RNA detected a systemic cytokine storm profile, which was more pronounced in infants with renal involvement, defined by positive acute dimercaptosuccinic acid scans, than in infants with febrile urinary tract infection without renal involvement. Conclusions: Local and systemic hyperactivation of innate immunity characterizes acute pyelonephritis, a common and severe bacterial infection in childhood and a significant cause of urosepsis and mortality in adults. The results define a transient cytokine storm response, resembling that induced during severe acute respiratory syndrome coronavirus 2 infection, as characteristic of acute pyelonephritis, rather than individual protein biomarkers.</p>}},
  author       = {{Ahmadi, Shahram and Rosenblad, Therese and Sabari, Samudra and Linden, Magnus and Brandström, Per and Chao, Sing Ming and Svanborg, Catharina and Ambite, Ines}},
  issn         = {{0891-3668}},
  keywords     = {{COVID-19; cytokine storm; febrile urinary tract infection; gene expression; immune response; urine proteomics}},
  language     = {{eng}},
  publisher    = {{Lippincott Williams & Wilkins}},
  series       = {{Pediatric Infectious Disease Journal}},
  title        = {{Analysis of the Innate Immune Response to Febrile UTI in Infants : Evidence of an Acute Cytokine Storm}},
  url          = {{http://dx.doi.org/10.1097/INF.0000000000004914}},
  doi          = {{10.1097/INF.0000000000004914}},
  year         = {{2025}},
}