Serological Extracellular Matrix Fragments May Serve as Early Kidney Damage Biomarkers

Serological extracellular matrix fragments may serve as early kidney damage biomarkers in children with defects in Alport genes

Introduction

Alport syndrome is a genetic disorder caused by variants in COL4A3, COL4A4, or COL4A5, which encode type IV collagen. The α3.α4.α5(IV) collagen network is a critical structural component of the glomerular and tubular basement membranes within the kidney’s extracellular matrix (ECM). Variants in this network compromise basement membrane integrity, leading to cell injury, inflammation, and fibrotic remodeling of the surrounding interstitial matrix, which contributes to progressive kidney dysfunction.

We aim to identify serological protease-generated fragments of the ECM as potential early biomarkers of kidney damage.

Poster

Conclusion

The following biomarkers were altered in children with Alport syndrome, compared to healthy donors, before the onset of detectable proteinuria:


These biomarkers could potentially indicate early kidney damage and enable earlier initiation of kidney-protective treatments in children with Alport syndrome.

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    Hidradenitis Suppurutiva Awareness Week: Biomarkers for Hidradenitis Suppurutiva

    The Hidradenitis Suppurutiva Awareness Week is held annually to spread knowledge about the disease and how it affects patients. Affecting roughly 1% of the population, HS causes significant physical and emotional challenges that are often overlooked.

    Hidradenitis Suppurativa Awareness Week is held annually to raise awareness about this systemic skin disease

    HS is believed to result from a complex mix of genetic predisposition, lifestyle factors, and immune system dysfunction, driving a continuous cycle of inflammation. It commonly presents as painful nodules, abscesses, draining tunnels beneath the skin, and scarring.

    These symptoms often cause physical discomfort and disability, affecting quality of life, personal relationships, and career opportunities. People living with HS respond differently to treatments, and we believe that raising awareness and supporting research is key to developing tailored treatment strategies that truly address their challenges.

    Our dermatology biomarkers enable precision medicine by providing information about ongoing pathological processes, such as damage and repair, within the ECM. This can guide targeted treatments and therapies, enhancing patient outcomes and personalized medicine approaches. At the same time, our markers, supported by our long history of experience and expertise, expedite drug development by specifically identifying target populations and reducing costs, over proteomic providers’ hopes to hit the right target by chance.

    Type III and VI Collagen Have the Potential to Distinguish Between IPF and HP

    Type III and VI Collagen remodeling biomarkers have the potential to distinguish between IPF and HP

    Introduction

    IPF and HP are two ILDs with similar clinical phenotype but distinct management, making their precise separation critical. Serological biomarkers may assist in distinguishing the two. In this study we assessed the clinical value of type III and VI collagen remodeling biomarkers and their potential to act as a tool to distinguish between HP and IPF in two separate, independent cohorts.

    Poster

    Conclusion

    We conclude that nordicPRO-C3™ could distinguish between HP and IPF in the AUH-ILD cohort. Furthermore, the distinct collagen remodeling takes place in each disease. In conclusion, these findings suggest that ECM remodeling biomarkers could act as potential tools to distinguish between HP and IPF.

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      NordicPRO-C3™NordicPRO-C6™ in CTD-ILD: Results From the Phase IIb RECITAL Trial

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

      Introduction

      ILD is a major cause of morbidity and mortality in connective tissue disease (CTD). Cyclophosphamide is an effective treatment for CTD-ILD, but is limited by side effects. Rituximab was tested as an alternative in the RECITAL phase IIb trial. The result was that both drugs improved lung function, but rituximab showed fewer adverse events.

      The aim of this study was to evaluate the effect of cyclophosphamide and rituximab on fibrogenesis in CTD-ILD.

      Poster

      Conclusion

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

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        Type III and VI Collagen Remodeling Biomarkers’ Potential to Distinguish Between IPF and HP

        Type III and VI collagen remodeling biomarkers have the potential to distinguish
        between IPF and HP

        Introduction

        IPF and HP are two ILDs with similar clinical phenotype but distinct management, making their precise separation critical. Serological biomarkers may assist in this distinction. Extracellular matrix (ECM) remodeling is a hallmark of fibrosis. Collagen formation and degradation processes release peptide fragments into the blood that can be quantified by the nordicPRO-C3™ and nordicPRO-C6™ (type III and VI collagen formation), or the C3M and C6M (type III and VI collagen degradation) assays.

        In this study we assessed the clinical value of Type III and VI collagen remodeling biomarkers and their potential to act as a tool to distinguish between HP and IPF in two separate, independent cohorts.

        Poster

        Conclusion

        These findings suggest that ECM remodeling biomarkers such as nordicPRO-C3™ could act as potential tools to distinguish between HP and IPF.

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          NordicPRO-C3™ and NordicPRO-C6™ in Connective Tissue Disease-Associated Interstitial Lung Disease

          NordicPRO-C3™ and nordicPRO-C6™ fibrogenesis biomarkers in connective tissue disease-associated interstitial lung disease: results from the phase IIb RECITAL trial

          Introduction

          ILD is a major cause of morbidity and mortality in connective tissue disease (CTD). Cyclophosphamide is an effective treatment for CTD-ILD, but limited by side effects. In this study, we additionally tested rituximab as an alternative in the RECITAL phase IIb trial. Both drugs improved the lung function with rituximab showing fewer adverse events (Maher, 2022. Lancet Resp Med)

          Poster

          Conclusion

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

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            Identifying Patients with Mild-Stage Emphysema in COPD via Machine Learning

            Identifying biomarkers of mild-stage emphysema in COPD patients via interpretable machine learning

            Introduction

            Emphysema results from alveolar damage—causing abnormal extracellular matrix (ECM) remodeling and impaired lung function. Early detection in mild, often asymptomatic stages is key to timely intervention. Although computed tomography (CT) scans are the most accurate detection method, pathological changes may occur before emphysema becomes visible, highlighting the need for non-invasive early detection approaches.

            This study aimed to develop a proof-of-concept machine learning (ML) pipeline to identify patients with mild-stage emphysema using circulating biomarkers.

            Poster

            Conclusion

            ML demonstrates potential for early-stage emphysema diagnosis through biomarker-driven methods. Quantifying fragments of ECM remodeling—driven by immune cell activity and collagen formation—could potentially serve as early diagnostic biomarkers in patients without lung function decline.

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              Tankyrase Inhibitor OM153 Exhibits Anti-Fibrotic Effects in a Scar-in-a-Jar Pulmonary Fibrosis Model

              Introduction

              Idiopathic pulmonary fibrosis (IPF) is a progressive, chronic and fatal lung disease with limited
              treatment options. Fibroblast activation and ECM deposition is pivotal in development of IPF, thus
              inhibiting fibrogenesis and ECM deposition is crucial for anti-fibrotic approaches to treat IPF.

              This study aims to prove that tankyrase inhibition reduces fibrogenesis induced by a fibrotic cocktail (FC) in primary human lung fibroblasts derived from IPF patients and decreases extracellular matrix biomarkers nordicPRO-C3™ and nordicPRO-C6™.

              Poster

              Conclusion

              These findings highlight the potential of tankyrase inhibiton as a therapeutic target for IPF and
              support the use of the Scar–in-a-Jar model as an effective tool for IPF drug screening.

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                Engineering Liver Fibrosis in a Three-Dimensional, ECM-Hydrogel Disease Model

                Engineering liver fibrosis in a three-dimensional, extracellular matrix-hydrogel disease model

                Introduction

                Modeling fibrosis requires replicating the mechano-chemical cues of the extracellular matrix (ECM), including binding sites, three-dimensionality, and biomechanics. To engineer a liver fibrosis model based on native, decellularized ECM with spatial and compositional integrity, layered on a hydrogel of poly(ethylene glycol) diacrylate (PEGDA) that provides tunable mechanical properties.

                This model aims to support cell recolonization and facilitate the investigation of cell-matrix interactions, fibrogenic remodeling, and therapeutic screening in a physiologically relevant context.

                Poster

                Conclusion

                HSCs colonize porcine liver ECM and synthesize new collagen. Biochemical signaling and biomechanical properties drive ECM deposition, recapitulating key features of the fibrotic niche. Upon treatment with relaxin-2, HSCs display an ECM-degrading activity. The ECM-hydrogel constructs exhibit no cytotoxicity, and polymer concentration can be tuned to modulate the mechanical properties of the ECM. Due to its anatomical similarity to human tissue, porcine ECM offers a biologically relevant scaffold for in vitro fibrosis modeling without the ethical concerns associated with live animal use.

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                  Bile Acids Drive Fibroblast Activation and Fibrogenesis in PSC

                  Bile acids drive fibroblast activation, fibrogenesis, interstitial matrix fibrosis and outcomes in PSC

                  Introduction

                  Fibrosis often originates from a persistent insult that damages epithelial and endothelial cells and activates chronic pro-inflammatory processes that impair the regular course of tissue repair.

                  A hallmark of fibrosis is the activation of fibroblasts leading to excessive production of type I, III, and VI collagens in the interstitial space of the extracellular matrix (ECM). Several drivers, including transforming growth factor-beta (TGF-β), have been identified as key drivers of fibroblast activation. While bile acids (BA) have been shown to correlate with the fibroblast activation marker nordicPRO-C3™ in biliary diseases, their precise role in the process of fibrogenesis remains unclear.

                  The present work aims to investigate the relationship between bile acids and markers of ECM formation and degradation during anti-fibrotic therapy (an engineered FGF-19; NCT02704364 analogue;) and related prognostic ability of biomarkers reflecting fibroblast activity in PSC.

                  Poster

                  Conclusion

                  Fibroblast activation and collagen formation play a crucial role in determining outcomes in PSC. The data suggests that bile acids activate fibroblast driving fibrogenesis, and that lowering of bile acids attenuate the fibrotic drive. Lowering fibroblast activity may have positive effects on liver related outcomes in PSC.

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