Immune Network Dysregulation Predicts Adverse Outcomes in Infective Endocarditis.
5 affiliations
- 1Programa de Pós-Graduação em Ciências Aplicadas à Saúde do Adulto, Faculdade de Medicina da Universidade Federal de Minas Gerais, Avenida Professor Alfredo Balena, 190, Santa Efigênia, Belo Horizonte 30130-100, MG, Brazil.
- 2Hospital das Clínicas da Universidade Federal de Minas Gerais, Avenida Professor Alfredo Balena, 110, Santa Efigênia, Belo Horizonte 30130-100, MG, Brazil.
- 3Departamento de Clínica Médica, Faculdade de Medicina da Universidade Federal de Minas Gerais, Avenida Professor Alfredo Balena, 190, Santa Efigênia, Belo Horizonte 30130-100, MG, Brazil.
- 4Diagnostic and Monitoring Biomarkers Laboratory of the Fundação Oswaldo Cruz, Instituto René-Rachou, Avenida Augusto de Lima, 1715-Barro Preto, Belo Horizonte 30190-002, MG, Brazil.
- 5Department of Statistics, Universidade Federal do Paraná, R. XV de Novembro, 1299, Centro, Curitiba 81530-015, PR, Brazil.
Abstract
Infective endocarditis (IE) is characterized by systemic inflammation, yet the contribution of cytokine network dysregulation to clinical outcomes remains poorly understood. We aimed to evaluate cytokine co-expression patterns in IE and identify immune network signatures associated with in-hospital mortality and major complications. We conducted a prospective cohort study of adult patients hospitalized with IE at a quaternary public hospital in Brazil (2012-2024). Serum cytokines and chemokines were measured at one to three time points during hospitalization. Weighted topological overlap (wTO) and Co-expression Differential Network Analysis (CoDiNA) were used to characterize cytokine interactions in baseline. Logistic mixed-effects models assessed associations between individual cytokines and in-hospital mortality. Of 305 screened patients, 160 met inclusion criteria (41 deaths; in-hospital mortality 25.6%). Survivors exhibited dense, integrated cytokine interaction networks, whereas non-survivors showed markedly fragmented networks with loss of connectivity across multiple cytokines. IFN-γ and IL-1RA formed a preserved but isolated axis in fatal cases, while IL-7 displayed outcome-specific connectivity in patients with infectious complications. A distinct triad involving IFN-γ, IL-1RA, and IL-6 differentiated patients with cardiac complications. In multivariable models adjusted for age, sex, and sampling time, CCL2 was independently associated with in-hospital mortality. Immune network disruption is strongly associated with adverse outcomes in IE. Distinct cytokine signatures, including altered interactions of IFN-γ, IL-1RA, IL-6, IL-7, and CCL2, identify high-risk patients and reveal potential biological pathways underlying clinical deterioration.
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BibTeX
@article{fae2026immune,
title = {{Immune Network Dysregulation Predicts Adverse Outcomes in Infective Endocarditis.}},
author = {Isabela Galizzi Fae and Pedro Henrique Oliveira Murta Pinto and Gustavo Brandão Oliveira and Roni Arley Silva Duque and Fernanda Sophya Leite Cambraia and Lucas Chaves Diamante and Guilherme Lelis Costa and Andréa Teixeira-Carvalho and Deisy Morselli Gysi and José Luiz Padilha da Silva and Teresa Cristina Abreu Ferrari and Maria Carmo Pereira Nunes},
journal = {Tropical medicine and infectious disease},
year = {2026},
month = sep,
doi = {10.3390/tropicalmed11100265},
url = {https://europepmc.org/article/MED/42931450},
note = {CC BY},
}
RIS
TY - JOUR
TI - Immune Network Dysregulation Predicts Adverse Outcomes in Infective Endocarditis.
AU - Isabela Galizzi Fae
AU - Pedro Henrique Oliveira Murta Pinto
AU - Gustavo Brandão Oliveira
AU - Roni Arley Silva Duque
AU - Fernanda Sophya Leite Cambraia
AU - Lucas Chaves Diamante
AU - Guilherme Lelis Costa
AU - Andréa Teixeira-Carvalho
AU - Deisy Morselli Gysi
AU - José Luiz Padilha da Silva
AU - Teresa Cristina Abreu Ferrari
AU - Maria Carmo Pereira Nunes
PY - 2026
DA - 2026/09/24
JO - Tropical medicine and infectious disease
DO - 10.3390/tropicalmed11100265
UR - https://europepmc.org/article/MED/42931450
AB - Infective endocarditis (IE) is characterized by systemic inflammation, yet the contribution of cytokine network dysregulation to clinical outcomes remains poorly understood. We aimed to evaluate cytokine co-expression patterns in IE and identify immune network signatures associated with in-hospital mortality and major complications. We conducted a prospective cohort study of adult patients hospitalized with IE at a quaternary public hospital in Brazil (2012-2024). Serum cytokines and chemokines were measured at one to three time points during hospitalization. Weighted topological overlap (wTO) and Co-expression Differential Network Analysis (CoDiNA) were used to characterize cytokine interactions in baseline. Logistic mixed-effects models assessed associations between individual cytokines and in-hospital mortality. Of 305 screened patients, 160 met inclusion criteria (41 deaths; in-hospital mortality 25.6%). Survivors exhibited dense, integrated cytokine interaction networks, whereas non-survivors showed markedly fragmented networks with loss of connectivity across multiple cytokines. IFN-γ and IL-1RA formed a preserved but isolated axis in fatal cases, while IL-7 displayed outcome-specific connectivity in patients with infectious complications. A distinct triad involving IFN-γ, IL-1RA, and IL-6 differentiated patients with cardiac complications. In multivariable models adjusted for age, sex, and sampling time, CCL2 was independently associated with in-hospital mortality. Immune network disruption is strongly associated with adverse outcomes in IE. Distinct cytokine signatures, including altered interactions of IFN-γ, IL-1RA, IL-6, IL-7, and CCL2, identify high-risk patients and reveal potential biological pathways underlying clinical deterioration.
SN - 2414-6366
ER -