Dataset Information

Machine-learning algorithms define pathogen-specific local immune fingerprints in peritoneal dialysis patients with bacterial infections.

ABSTRACT: The immune system has evolved to sense invading pathogens, control infection, and restore tissue integrity. Despite symptomatic variability in patients, unequivocal evidence that an individual's immune system distinguishes between different organisms and mounts an appropriate response is lacking. We here used a systematic approach to characterize responses to microbiologically well-defined infection in a total of 83 peritoneal dialysis patients on the day of presentation with acute peritonitis. A broad range of cellular and soluble parameters was determined in peritoneal effluents, covering the majority of local immune cells, inflammatory and regulatory cytokines and chemokines as well as tissue damage-related factors. Our analyses, utilizing machine-learning algorithms, demonstrate that different groups of bacteria induce qualitatively distinct local immune fingerprints, with specific biomarker signatures associated with Gram-negative and Gram-positive organisms, and with culture-negative episodes of unclear etiology. Even more, within the Gram-positive group, unique immune biomarker combinations identified streptococcal and non-streptococcal species including coagulase-negative Staphylococcus spp. These findings have diagnostic and prognostic implications by informing patient management and treatment choice at the point of care. Thus, our data establish the power of non-linear mathematical models to analyze complex biomedical datasets and highlight key pathways involved in pathogen-specific immune responses.

SUBMITTER: Zhang J

PROVIDER: S-EPMC5484022 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Machine-learning algorithms define pathogen-specific local immune fingerprints in peritoneal dialysis patients with bacterial infections.

Zhang Jingjing J Friberg Ida M IM Kift-Morgan Ann A Parekh Gita G Morgan Matt P MP Liuzzi Anna Rita AR Lin Chan-Yu CY Donovan Kieron L KL Colmont Chantal S CS Morgan Peter H PH Davis Paul P Weeks Ian I Fraser Donald J DJ Topley Nicholas N Eberl Matthias M

Kidney international 20170317 1

The immune system has evolved to sense invading pathogens, control infection, and restore tissue integrity. Despite symptomatic variability in patients, unequivocal evidence that an individual's immune system distinguishes between different organisms and mounts an appropriate response is lacking. We here used a systematic approach to characterize responses to microbiologically well-defined infection in a total of 83 peritoneal dialysis patients on the day of presentation with acute peritonitis. ...[more]

PMID: 28318629

Similar Datasets

Project description:Bacterial infections and the concurrent inflammation have been associated with increased long-term cardiovascular (CV) risk. In patients receiving peritoneal dialysis (PD), bacterial peritonitis is a common occurrence, and each episode further increases late CV mortality risk. However, the underlying mechanism(s) remains to be elucidated before safe and efficient anti-inflammatory interventions can be developed. Damage-Associated Molecular Patterns (DAMPs) have been shown to contribute to the acute inflammatory response to infections, but a potential role for DAMPs in mediating long-term vascular inflammation and CV risk following infection resolution in PD, has not been investigated. We found that bacterial peritonitis in mice that resolved within 24h led to CV disease-promoting systemic and vascular immune-mediated inflammatory responses that were maintained up to 28 days. These included higher blood proportions of inflammatory leukocytes displaying increased adhesion molecule expression, higher plasma cytokines levels, and increased aortic inflammatory and atherosclerosis-associated gene expression. These effects were also observed in infected nephropathic mice and amplified in mice routinely exposed to PD fluids. A peritonitis episode resulted in elevated plasma levels of the DAMP Calprotectin, both in PD patients and mice, here the increase was maintained up to 28 days. In vitro, the ability of culture supernatants from infected cells to promote key inflammatory and atherosclerosis-associated cellular responses, such as monocyte chemotaxis, and foam cell formation, was Calprotectin-dependent. In vivo, Calprotectin blockade robustly inhibited the short and long-term peripheral and vascular consequences of peritonitis, thereby demonstrating that targeting of the DAMP Calprotectin is a promising therapeutic strategy to reduce the long-lasting vascular inflammatory aftermath of an infection, notably PD-associated peritonitis, ultimately lowering CV risk.

Project description:BackgroundLimited data exist on the association between gut permeability, circulating bacterial fragment and volume overload in peritoneal dialysis (PD) patients. We measured circulating bacterial fragments, N-terminal pro B-type natriuretic peptide (NT-proBNP), calprotectin and zonulin levels, and evaluate their association with the clinical outcomes in PD patients.MethodsThis was a single-center prospective study on 108 consecutive incident PD patients. Plasma endotoxin and bacterial DNA, and serum NT-proBNP, calprotectin and zonulin levels were measured. Primary outcomes were technique and patient survival, secondary outcomes were hospitalization data.ResultsThere was no significant correlation between plasma endotoxin and bacterial DNA, and serum NT-proBNP, calprotectin and zonulin levels. The Homeostatic Model Assessment for Insulin Resistance (HOMA)-2β index, which represents insulin resistance, positively correlated with plasma bacterial DNA (r = 0.421, P < .001) and calprotectin levels (r = 0.362, P = .003), while serum NT-proBNP level correlated with the severity of volume overload and residual renal function. Serum NT-proBNP level was associated with technique survival even after adjusting for confounding factors [adjusted hazard ratio (aHR) 1.030, 95% confidence interval 1.009-1.051]. NT-proBNP level was also associated with patient survival by univariate analysis, but the association became insignificant after adjusting for confounding factors (aHR 1.010, P = .073). Similarly, NT-proBNP correlated with the number of hospitalizations and duration of hospitalization by univariate analysis, but the association became insignificant after adjusting for confounding factors.ConclusionThere was no correlation between markers of gut permeability, circulating bacterial fragments and measures of congestion in PD patients. Bacterial fragments levels and gut permeability are both associated with insulin resistance. Serum NT-proBNP level is associated with the severity of volume overload and technique survival. Further studies are required to delineate the mechanism of high circulating bacterial fragment levels in PD patients.

Project description:Infections are major complications in peritoneal dialysis (PD) with a multifactorial etiology that comprises patient, microbial and dialytic factors. This study aimed at investigating the contribution of microbial biofilms on PD catheters to recalcitrant infections and their interplay with PD related-factors. A prospective observational study was performed on 47 patients attending Centro Hospitalar of Porto and Vila Nova de Gaia/Espinho to whom the catheter was removed due to infectious (n = 16) and non-infectious causes (n = 31). Microbial density on the catheter was assessed by culture methods and the isolated microorganisms identified by matrix-assisted laser desorption/ionization time-of-flight intact cell mass spectrometry. The effect of conventional and three biocompatible PD solutions on 16 Coagulase Negative Staphylococci (CNS) and 10 Pseudomonas aeruginosa strains planktonic growth and biofilm formation was evaluated. Cultures were positive in 87.5% of the catheters removed due infectious and 90.3% removed due to non-infectious causes. However, microbial yields were higher on the cuffs of catheters removed due to infection vs. non-infection. Staphylococci (CNS and Staphylococcus aureus) and P. aeruginosa were the predominant species: 32% and 20% in the infection and 43.3% and 22.7% in the non-infection group, respectively. In general, PD solutions had a detrimental effect on planktonic CNS and P. aeruginosa strains growth. All strains formed biofilms in the presence of PD solutions. The solutions had a more detrimental effect on P. aeruginosa than CNS strains. No major differences were observed between conventional and biocompatible solutions, although in icodextrin solution biofilm biomass was lower than in bicarbonate/lactate solution. Overall, we show that microbial biofilm is universal in PD catheters with the subclinical menace of Staphylococci and P. aeruginosa. Cuffs colonization may significantly contribute to infection. PD solutions differentially impact microbial species. This knowledge is important for the development of infection diagnosis, treatment and preventive strategies.

Dataset Information

Machine-learning algorithms define pathogen-specific local immune fingerprints in peritoneal dialysis patients with bacterial infections.

Publications

Machine-learning algorithms define pathogen-specific local immune fingerprints in peritoneal dialysis patients with bacterial infections.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets