Association of Circulating Proteins with Death or Lung Transplant in Patients with Idiopathic Pulmonary Fibrosis in the IPF-PRO Registry Cohort

Todd, Jamie L.; Neely, Megan L.; Overton, Robert; Mulder, Hillary; Roman, Jesse; Lasky, Joseph A.; Andrade, Joao A. de; Gulati, Mridu; Huang, Howard J.; Leonard, Thomas B.; Heßlinger, Christian; Noth, Imre; Belperio, John A.; Flaherty, Kevin R.; Palmer, Scott M.

doi:10.1007/s00408-021-00505-y

Cited by 7 publications

(3 citation statements)

References 13 publications

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“…Aptamer-based technologies have also been successfully used to define markers of injury and are only emerging in transplant medicine. [50][51][52][53][54][55][56][57] Other protein-based methods that will be briefly discussed include proximity extension assay technology and protein microarrays.…”

Section: Technical Considerations and Biological Samplesmentioning

confidence: 99%

Proteomics: Its Promise and Pitfalls in Shaping Precision Medicine in Solid Organ Transplantation

2023

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Solid organ transplantation is an established treatment of choice for end-stage organ failure. However, all transplant patients are at risk of developing complications, including allograft rejection and death. Histological analysis of graft biopsy is still the gold standard for evaluation of allograft injury, but it is an invasive procedure and prone to sampling errors. The past decade has seen an increased number of efforts to develop minimally invasive procedures for monitoring allograft injury. Despite the recent progress, limitations such as the complexity of proteomics-based technology, the lack of standardization, and the heterogeneity of populations that have been included in different studies have hindered proteomic tools from reaching clinical transplantation. This review focuses on the role of proteomics-based platforms in biomarker discovery and validation in solid organ transplantation. We also emphasize the value of biomarkers that provide potential mechanistic insights into the pathophysiology of allograft injury, dysfunction, or rejection. Additionally, we forecast that the growth of publicly available data sets, combined with computational methods that effectively integrate them, will facilitate a generation of more informed hypotheses for potential subsequent evaluation in preclinical and clinical studies. Finally, we illustrate the value of combining data sets through the integration of 2 independent data sets that pinpointed hub proteins in antibodymediated rejection.

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Section: Technical Considerations and Biological Samplesmentioning

confidence: 99%

Proteomics: Its Promise and Pitfalls in Shaping Precision Medicine in Solid Organ Transplantation

2023

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“…Two anti-fibrotic drugs, nintedanib and pirfenidone, slow decline in lung function in patients with IPF [ 4 , 5 ], and have been licensed for its treatment, but the disease remains progressive. The rate of disease progression among patients with IPF is variable [ 6 , 7 ] and while some circulating biomarkers have shown promise as predictors of progression [ 8 – 11 ], for an individual patient, it remains challenging to predict the rate at which their disease will progress.…”

Section: Introductionmentioning

confidence: 99%

Circulating metabolic profile in idiopathic pulmonary fibrosis: data from the IPF-PRO Registry

Summer,

Todd,

Neely

et al. 2024

Respir Res

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Background The circulating metabolome, reflecting underlying cellular processes and disease biology, has not been fully characterized in patients with idiopathic pulmonary fibrosis (IPF). We evaluated whether circulating levels of metabolites correlate with the presence of IPF, with the severity of IPF, or with the risk of clinically relevant outcomes among patients with IPF. Methods We analyzed enrollment plasma samples from 300 patients with IPF in the IPF-PRO Registry and 100 individuals without known lung disease using a set of targeted metabolomics and clinical analyte modules. Linear regression was used to compare metabolite and clinical analyte levels between patients with IPF and controls and to determine associations between metabolite levels and measures of disease severity in patients with IPF. Unadjusted and adjusted univariable Cox regression models were used to evaluate associations between circulating metabolites and the risk of mortality or disease progression among patients with IPF. Results Levels of 64 metabolites and 5 clinical analytes were significantly different between patients with IPF and controls. Among analytes with greatest differences were non-esterified fatty acids, multiple long-chain acylcarnitines, and select ceramides, levels of which were higher among patients with IPF versus controls. Levels of the branched-chain amino acids valine and leucine/isoleucine were inversely correlated with measures of disease severity. After adjusting for clinical factors known to influence outcomes, higher levels of the acylcarnitine C:16-OH/C:14-DC were associated with all-cause mortality, lower levels of the acylcarnitine C16:1-OH/C14:1DC were associated with all-cause mortality, respiratory death, and respiratory death or lung transplant, and higher levels of the sphingomyelin d43:2 were associated with the risk of respiratory death or lung transplantation. Conclusions IPF has a distinct circulating metabolic profile characterized by increased levels of non-esterified fatty acids, long-chain acylcarnitines, and ceramides, which may suggest a more catabolic environment that enhances lipid mobilization and metabolism. We identified select metabolites that were highly correlated with measures of disease severity or the risk of disease progression and that may be developed further as biomarkers. Trial registration ClinicalTrials.gov; No: NCT01915511; URL: www.clinicaltrials.gov.

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“…Appropriate to their significance in pulmonary medicine, interstitial lung diseases (ILD) and idiopathic pulmonary fibrosis (IPF) were well represented in the journal. Studies of IPF investigated potential mechanisms [ 41 ], animal models of induced fibrosis [ 42 ], potential biomarkers [ 43 ] and clinical outcomes [ 44 ]. Contributions on the subject of ILD included evaluation of potential biomarkers [ 45 ], diagnostic cryobiopsy [ 24 ], pediatric ILD [ 46 ], ILD outcomes [ 47 ], as well as investigations of hypersensitivity pneumonitis [ 48 ] and bronchiectasis [ 49 , 50 ].…”

mentioning

confidence: 99%

LUNG Year in Review: 2022

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2023

Lung

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Association of Circulating Proteins with Death or Lung Transplant in Patients with Idiopathic Pulmonary Fibrosis in the IPF-PRO Registry Cohort

Cited by 7 publications

References 13 publications

Proteomics: Its Promise and Pitfalls in Shaping Precision Medicine in Solid Organ Transplantation

Proteomics: Its Promise and Pitfalls in Shaping Precision Medicine in Solid Organ Transplantation

Circulating metabolic profile in idiopathic pulmonary fibrosis: data from the IPF-PRO Registry

LUNG Year in Review: 2022

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