Category: Scientific Posters

Results from the Phase IIb RECITAL Trial

Posted on by Claire Hornung

Reduction of PRO-C3 and PRO-C6 fibrogenesis biomarkers in connective tissue disease-associated interstitial lung disease: results from the Phase IIb RECITAL trial

Introduction

Interstitial lung disease (ILD) is a major cause of morbidity and mortality in connective tissue disease (CTD). While cyclophosphamide is often an effective treatment for CTD-ILD, its use is limited by side effects.

In this study, Rituximab was tested as an alternative in the RECITAL phase IIb trial (NTC1862926). Both drugs improved 24- and 48-week lung function with rituximab showing fewer adverse events.

Poster

ICLAF2024 Phase IIb RECITAL Trial_Nordic BioscienceDownload

Conclusion

The decrease in nordicPRO-C6™ and nordicPRO-C3™ suggest that, besides their immunomodulatory effects, these drugs may also reduce fibrogenesis. NordicPRO-C3™ and nordicPRO-C6™, measured at baseline and as % change from baseline, are associated with an FVC response. These findings highlight nordicPRO-C3™ and nordicPRO-C6™ as promising biomarkers for CTD-ILD.

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    C1SIG Is a Risk Predictor for All-Cause Mortality at Admission With STEMI

    Posted on by Claire Hornung

    Introduction

    ST-elevated myocardial infarction (STEMI) damages local cardiac tissue and leads to acute inflammation-driven tissue remodelling immediately after injury. A collagen type I (COL1) matricryptin cleaved
    by MMP-2 and MMP-9 was previously identified as being involved in left ventricular remodelling after a MI. We aimed to develop, technically evaluate, and quantify this COL1- derived matricryptin, named C1SIG, as a serological biomarker in a clinical cohort of STEMI patients.

    Poster

    MBE2024_C1SIG in STEMI_Nordic BioscienceDownload

    Conclusion

    C1SIG was developed as a technically robust biomarker and demonstrated as an independent predictor of
    mortality at 30 days and 1-year after STEMI, even when adjusted for multiple clinically-relevant variables.
    This COL1 biomarker could be helpful in assessing acute extracellular matrix processing in individuals after suffering a STEMI and could identify a subset of patients at increased risk of long-term outcome.

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      Treprostinil Reduces Fibrosis Biomarkers in the Scar-in-a-Jar Model Using a Fibrotic Cocktail

      Posted on by Claire Hornung

      Treprostinil reduces clinically relevant fibrosis biomarkers in the Scar-in-a-Jar model using a fibrotic cocktail

      Introduction

      The activation of fibroblasts and the subsequent deposition of extracellular matrix (ECM) play a pivotal role in the development of interstitial lung disease (ILD), making it crucial for novel anti-fibrotic drugs.

      In this study, we investigated the effects of a fibrotic cocktail (FC) that consists of eight pro-fibrotic and pro-inflammatory cytokines and one growth factor in the Scar-in-a-Jar fibroblast model, thereby mimicking the complex microenvironment associated with fibrotic ILDs.

      Poster

      ERS2024_Treprostinil_ScarInAJar_Nordic BioscienceDownload

      Conclusion

      The FC effectively stimulated fibrogenesis in the Scar-in-a-Jar in-vitro model, leading to elevated
      levels of the fibrosis biomarkers nordicPROC3 TM, nordicPRO-C6™ and nordicFBN-CT™. Treprostinil significantly inhibited fibrogenesis and collagen deposition quantified by ELISA. In conclusion, the Scar-in-a-Jar model is a useful tool for screening novel anti-fibrotic drugs.

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        ELP-3 as a Potential Serological Biomarker to Distinguish Fibrotic from Non-Fibrotic HP

        Posted on by Claire Hornung

        A specific elastin fragment (ELP-3) as a potential serological biomarker to distinguish fibrotic from non-fibrotic hypersensitivity pneumonitis

        Introduction

        Hypersensitivity Pneumonitis (HP) is defined by an exaggerated immune response to antigens that may develop into pulmonary fibrosis. Elastin, a structural lung protein, is susceptible to degradation by activated neutrophils during inflammation via proteinase-3. This process releases elastin fragments into circulation that can be quantified by the nordicELP-3 TM assay. This study aimed to evaluate serum ELP-3 in HP and compare it with healthy, IPF and chronic obstructive pulmonary disease (COPD).

        Poster

        ERS2024_ELP3_HP_Nordic BioscienceDownload

        Conclusion

        The serum ELP-3 is elevated in patients with different chronic lung diseases, particularly in HP. Notably, ELP-3 was able to separate non-fibrotic from fibrotic HP patients. These findings highlight the potential value of ELP-3 as a biomarker that provides additional clinical information beyond conventional inflammation markers.

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          CC16-HNE is Associated With Mortality and Pulmonary Hypertension in IPF

          Posted on by Claire Hornung

          A marker of human neutrophil elastase mediated club cell secretary protein-16 degradation in (CC16-HNE) is associated with mortality and pulmonary hypertension in idiopathic pulmonary fibrosis

          Introduction

          Idiopathic pulmonary fibrosis (IPF) is characterized by epithelial injury, fibrosis, and an aberrant immune response. Club cells are essential for lung homeostasis by repairing the injured epithelium and secreting the anti-inflammatory club cell secretory protein-16 (CC16). Additionally, activated neutrophils release human neutrophil elastase (HNE) during inflammation. Our aim was to investigate if serum measurements of CC16 degradation by HNE (CC16-HNE) were related to IPF mortality and pulmonary hypertension (PH).

          Poster

          ERS2024_CC16HNE_Mortality_IPF_Nordic BioscienceDownload

          Conclusion

          Low serum CC16-HNE at baseline was associated with increased risk of mortality and a PH complication in IPF. These results indicate that a neutrophil immune response and degradation of CC16 is relevant for disease outcome. CC16 degradation by HNE could serve as a prognostic biomarker for IPF and diagnostic for a PH complication.

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            NordicPRO-C6™ is Prognostic for Liver-Related Events in Cirrhosis from Hepatitis C

            Posted on by Claire Hornung

            Fibroblast activity kills – circulating endotrophin (nordicPRO-C6™) is prognostic for liver-related events in patients with cirrhosis from chronic hepatitis C

            Introduction

            Prognostic markers for patients with compensated cirrhosis at increased risk of developing liver-related events are required. Endotrophin, a potential driver of fibroblast activation and mediator of fibroinflammatory disease, can be assessed non-invasively using nordicPRO-C6™. Blood-based collagen extracellular matrix remodeling markers may provide novel prognostic information to identify patients with cirrhosis at higher risk of developing a liver-related event.

            Our aims were to investigate the ability of nordicPRO-C6™ to predict liver-related events in The Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis Trial (HALT-C).

            Poster

            EASL2024_Fibroblast_Activity_Kills_Nordic BioscienceDownload

            Conclusion

            NordicPRO-C6™, a biomarker of circulating endotrophin, was primarily associated with an increased risk of developing a liver-related event in patients with cirrhosis from Chronic Hepatitis C (CHC). It is a potential monitoring blood-based biomarker that may also provide prognostic information in treatment-naive CHC patients with moderate-advanced fibrosis at higher risk of developing a liver-related event. The prognostic utility of nordicPRO-C6™ in CHC patients after sustained virologic response and other advanced stage chronic liver disease is required.

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              NordicPRO-C3™ as a Predictor of Liver Related Outcomes in Chronic Hepatitis C

              Posted on by Claire Hornung

              PRO-C3 determined active fibrogenesis is a predictor of liver-related outcomes in patients with chronic hepatitis C

              Introduction

              Patients with untreated chronic hepatitis C (CHC) infection are at increased risk of developing a liver related outcome. Despite the availability of simplified direct-acting antiviral therapy, the prevalence of CHC remains unchanged in many industrialized countries. Biomarkers that can predict which chronic liver disease patients with inflammatory injury are at greatest risk of developing a clinical outcome are required. In this study we aim to investigate the ability of PRO-C3 as a marker of active fibrogenesis to predict liver-related outcomes compared to METAVIR fibrosis stage on biopsy in patients with hepatitis C.

              Poster

              EASL2024_Active_Fibrogenesis_Nordic BioscienceDownload

              Conclusion

              We conclude that fibrosis activity (nordicPRO-C3™) is associated with an increased risk of developing a liver-related outcome in patients with untreated HCV infection. NordicPRO-C3™ provides a higher risk predictor for outcomes than METAVIR fibrosis stage on biopsy. A pro-fibrogenic marker such as nordicPRO-C3™ could provide prognostic utility in other chronic liver disease patients with ongoing inflammatory injury.

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                Endotrophin as an Early Marker of Kidney Outcomes in Type 2 Diabetes

                Posted on by Claire Hornung

                Endotrophin as an early marker of kidney outcomes in persons with type 2 diabetes: findings from the PROVALID study

                Introduction

                Diabetic kidney disease (DKD) is driven by pathophysiological processes, including fibrosis. Endotrophin (ETP), a pro-fibrotic fragment generated during collagen type VI formation, has previously been shown to be a biomarker of DKD progression1,2,3,4,5. The aim of this study was to investigate, for the first time, circulating ETP as a risk marker for kidney outcomes in persons with type 2 diabetes (T2D) being taken care of at the primary level of healthcare.

                Poster

                ERA2024 Endotrophin in Type 2 Diabetes_Nordic BioscienceDownload

                Conclusion

                Plasma ETP (endotrophin) has been identified as an independent risk marker for kidney outcomes in individuals with type 2 diabetes (T2D) with early-stage kidney disease. Higher levels of ETP were associated with a significantly increased risk of developing the kidney endpoint in persons with eGFR >90 ml/min/1.73 m2. These findings demonstrate that markers of fibrosis, such as ETP, may serve as early markers for kidney disease progression or kidney failure in persons with T2D and apparently normal kidney function.

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                  LG1M is Prognostic for Long-Term Readmission After AKI

                  Posted on by Claire Hornung

                  The novel fibrosis biomarker LG1M is prognostic for long-term readmission after AKI

                  Introduction

                  Acute Kidney Injury (AKI), survivors are at increased risk of long-term adverse outcomes, including readmission to hospital. Pathophysiological consequences of AKI, include extracellular matrix (ECM) remodeling. Tools to monitor the long-term health risk of patients after AKI are needed to improve
                  patient outcome.

                  Poster

                  ERA2024 LG1M in AKI_Nordic BioscienceDownload

                  Conclusion

                  Circulating levels of LG1M were elevated in AKI patients 1 year after the AKI episode and correlated with markers of kidney function in the AKI group and to a lower extent in the CKD control group. In the AKI group, LG1M was associated with the risk of readmission, even though the significance of the association was lost in adjusted analyses. This biomarker, quantifying circulating levels of a laminin fragment, may reflect injury to the basement membrane (of which laminin is a major component) after AKI, which was associated with an increased risk of worse outcome in patients that experienced an episode of AKI.

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                    Advancing Diagnostic Precision of Emphysema COPD

                    Posted on by Claire Hornung

                    Machine-learning classification integrating non-invasive biomarkers, clinical characteristics and pulmonary function

                    Introduction

                    Computed tomography (CT) is used for evaluating phenotypic abnormalities in chronic obstructive
                    pulmonary disease (COPD), yet its cost and time-intensive nature limit routine use. Developing an
                    easily implementable technique for classifying emphysema extent is thus essential.

                    This study aimed to develop a diagnostic model to classify emphysema extent in COPD
                    patients relying solely on easily obtained measures such as clinical characteristics and
                    non-invasive biomarkers.

                    Poster

                    ATS2024_Emphysema_Model Nordic BioscienceDownload

                    Conclusion

                    Diagnostic models incorporating easily obtainable measures effectively
                    distinguished COPD patients with high emphysema extent from those with
                    low extent. Such models for classifying emphysema patterns have the
                    potential for clinical implementation, aiding in diagnosis or serving as a
                    decision-making tool to determine the necessity of further CT scans.

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