Protein Signatures of Remodeled Airways in Transplanted Lungs with Bronchiolitis Obliterans Syndrome Obtained Using Laser-Capture Microdissection

Müller, Catharina; Rosmark, Oskar; Åhrman, Emma; Brunnström, Hans; Wassilew, Katharina; Nybom, Annika; Michaliková, Barbora; Larsson, Hillevi; Eriksson, Leif; Schultz, Hans Henrik Lawaetz; Perch, Michael; Malmström, Johan; Wigén, Jenny; Iversen, Martin; Westergren‐Thorsson, Gunilla

doi:10.1016/j.ajpath.2021.05.014

Cited by 7 publications

(5 citation statements)

References 58 publications

(60 reference statements)

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“…Individual proteins have been singled out instead [ 14 , 28 , 29 ], and thus this study demonstrates a novel use of proteomic profiling using mass spectrometry as a means to investigate the disease state through broader changes within the proteome. Mass spectrometry has rarely been utilized in lung transplantation research, with the exception of a few studies focusing on long-term outcomes in bronchiolitis obliterans syndrome [ 17 , 30 , 31 ]. This study therefore represents a novel approach to the study of PGD.…”

Section: Discussionmentioning

confidence: 99%

Proteomic Analysis of Primary Graft Dysfunction in Porcine Lung Transplantation Reveals Alveolar-Capillary Barrier Changes Underlying the High Particle Flow Rate in Exhaled Breath

Niroomand,

Hirdman,

Bèchet

et al. 2024

Transpl Int

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Primary graft dysfunction (PGD) remains a challenge for lung transplantation (LTx) recipients as a leading cause of poor early outcomes. New methods are needed for more detailed monitoring and understanding of the pathophysiology of PGD. The measurement of particle flow rate (PFR) in exhaled breath is a novel tool to monitor and understand the disease at the proteomic level. In total, 22 recipient pigs underwent orthotopic left LTx and were evaluated for PGD on postoperative day 3. Exhaled breath particles (EBPs) were evaluated by mass spectrometry and the proteome was compared to tissue biopsies and bronchoalveolar lavage fluid (BALF). Findings were confirmed in EBPs from 11 human transplant recipients. Recipients with PGD had significantly higher PFR [686.4 (449.7–8,824.0) particles per minute (ppm)] compared to recipients without PGD [116.6 (79.7–307.4) ppm, p = 0.0005]. Porcine and human EBP proteins recapitulated proteins found in the BAL, demonstrating its utility instead of more invasive techniques. Furthermore, adherens and tight junction proteins were underexpressed in PGD tissue. Histological and proteomic analysis found significant changes to the alveolar-capillary barrier explaining the high PFR in PGD. Exhaled breath measurement is proposed as a rapid and non-invasive bedside measurement of PGD.

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Section: Discussionmentioning

confidence: 99%

Proteomic Analysis of Primary Graft Dysfunction in Porcine Lung Transplantation Reveals Alveolar-Capillary Barrier Changes Underlying the High Particle Flow Rate in Exhaled Breath

Niroomand,

Hirdman,

Bèchet

et al. 2024

Transpl Int

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“…The main trigger of BOS is a fibro-proliferative process called the epithelial–mesenchymal transition, derived from self-perpetuating activation of fibroblasts and massive release of collagen leading to peribronchiolar fibrosis and a decline in lung function [ 12 , 13 ].…”

Section: Introductionmentioning

confidence: 99%

“…The protein signature of BOS lesions concerns extracellular matrix organization, wound healing, and aberrant basement membrane composition. Basement membrane components, such as epitopes on collagens and laminins, are targeted by auto-antibodies and lymphocytes in bronchiolitis obliterans syndrome arising after lung transplant [ 13 , 14 ].…”

Section: Introductionmentioning

confidence: 99%

“…Thickening of the lamina reticularis impairs airway distensibility and patency [ 16 ]. Collagen types IV and VI are two proteins abundant in basement membrane; their loss of integrity causes abnormal lung architecture followed by fibrosis [ 13 ]. Collagen types I and V are two collagens of the lamina reticularis, a thin layer below the basement membrane [ 17 , 18 ].…”

Section: Introductionmentioning

confidence: 99%

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Collagen Type IV Alpha 5 Chain in Bronchiolitis Obliterans Syndrome After Lung Transplant: The First Evidence

Armati

Cattelan

Guerrieri

et al. 2023

Lung

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Introduction Bronchiolitis obliterans syndrome (BOS) is the most common form of CLAD and is characterized by airflow limitation and an obstructive spirometry pattern without parenchymal opacities. The protein signature of BOS lesions concerns extracellular matrix organization and aberrant basement membrane composition. In this pilot study, we investigated the presence of COL4A5 in the serum of patients with BOS. Methods 41 patients who had undergone LTX were enrolled. Of these, 27 developed BOS and 14 (control group) were considered stable at the time of serum sampling. Of BOS patients, serum samples were analysed at the time of BOS diagnosis and before the clinical diagnosis (pre-BOS). COL4A5 levels were detected through the ELISA kit. Results Serum concentrations of COL4A5 were higher in pre-BOS than in stable patients (40.5 ± 13.9 and 24.8 ± 11.4, respectively, p = 0.048). This protein is not influenced by comorbidities, such as acute rejection or infections, or by therapies. Survival analysis also reveals that a higher level of COL4A5 was also associated with less probability of survival. Our data showed a correlation between concentrations of COL4A5 and FEV1 at the time of diagnosis of BOS. Conclusion Serum concentrations of COL4A5 can be considered a good prognostic marker due to their association with survival and correlation with functional parameters.

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“…When viruses infect cells, the tran-scription of host protein-coding genetic makeup and microRNAs are altered to facilitate the virus's growth and replication. Viruses have acquired the ability to encapsulate miRNAs, which they exploit to dampen the host antiviral response (Müller et al, 2021, Shibata et al, 1990. Viruses have a distinct advantage in using miRNAs as weapons due to their small size, non-antigenic nature, and ability to influence host and own genomes.However, only infections with DNA sequences have been proven to synthesize miRNAs, which means that not all infections transmit miRNA.…”

Section: Introductionmentioning

confidence: 99%

DIVERSITY OF RIBONUCLEIC ACID (RNA) VIRUS ENDOGENOUS VIRAL ELEMENTS (EVEs) IN INSECT GENETIC MATERIAL

Saqib

Bibi

2022

Dahot Publications Pakistan Journal of Biotechnology

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Many different RNA viruses infect insects, but the capacity to transmit to a single or numerous host species sets them apart. Through recipient transcription and replication, viral chromosomes may be incorporated into their host genes, resulting in the emergence of endogenous viral elements (EVEs). It has proven possible to find RNA virus EVEs in various of insect genomes with varying evolutionary paths, from extremely damaged genetic remnants to partial and full viral coding sections, in several different insects.Insect–virus contact has benefited much from research on these EVE, such as developing a novel kind of intuitive antiviral immunity . From a functional standpoint, RNA EVEs' effects on hosts and migratory viruses are still mostly unknown,However, new research shows that they are involved in a complicated arms race that affects the genetic path of these interdependent organisms. As additional insect genotypes and extrinsic viral are decoded, the variety of insect EVEs will continue to grow, making paleovirology an exciting study area for insects in the coming years

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Protein Signatures of Remodeled Airways in Transplanted Lungs with Bronchiolitis Obliterans Syndrome Obtained Using Laser-Capture Microdissection

Cited by 7 publications

References 58 publications

Proteomic Analysis of Primary Graft Dysfunction in Porcine Lung Transplantation Reveals Alveolar-Capillary Barrier Changes Underlying the High Particle Flow Rate in Exhaled Breath

Proteomic Analysis of Primary Graft Dysfunction in Porcine Lung Transplantation Reveals Alveolar-Capillary Barrier Changes Underlying the High Particle Flow Rate in Exhaled Breath

Collagen Type IV Alpha 5 Chain in Bronchiolitis Obliterans Syndrome After Lung Transplant: The First Evidence

DIVERSITY OF RIBONUCLEIC ACID (RNA) VIRUS ENDOGENOUS VIRAL ELEMENTS (EVEs) IN INSECT GENETIC MATERIAL

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