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Article: Inflammatory Biomarkers of Extracellular Matrix Remodeling and Disease Activity in Crohn's Disease and Ulcerative Colitis.

Domislovic, Viktor / Høg Mortensen, Joachim / Lindholm, Majken / Kaarsdal, Morten Asser / Brinar, Marko / Barisic, Ana / Manon-Jensen, Tina / Krznaric, Zeljko

Journal of clinical medicine

2022 Volume 11, Issue 19

Abstract: Extracellular matrix (ECM) homeostasis is highly affected in active inflammatory bowel disease (IBD). The aim of the study was to investigate serological biomarkers of type III, IV, and V collagen degradation and formation, and their association with ... ...

Abstract	Extracellular matrix (ECM) homeostasis is highly affected in active inflammatory bowel disease (IBD). The aim of the study was to investigate serological biomarkers of type III, IV, and V collagen degradation and formation, and their association with disease activity in IBD. ECM remodeling serum biomarkers were measured in 162 IBD patients, 110 with Crohn's disease (CD) and 52 with ulcerative colitis (UC), and in 29 healthy donors. Biomarkers of type III collagen degradation (C3M) and formation (PRO-C3), type IV collagen degradation (C4M) and formation (PRO-C4), and type V collagen formation (PRO-C5) were measured using ELISA. Inflammatory activity was assessed using endoscopic, clinical, and biochemical activity indices. The highest diagnostic value was identified in discriminating endoscopically moderate to severe disease in CD (PRO-C3, C3M/PRO-C3, and C4M with AUC of 0.70, 0.73, and 0.69, respectively) and UC (C3M, C3M/PRO-C3, and C4M with AUC of 0.86, 0.80, and 0.76, respectively). C4M and C3M/PRO-C3 in combination yielded AUC of 0.93 (0.66-0.90) in CD and 0.94 (0.65-0.99) in UC. This study confirmed that ECM remodeling reflected disease activity in CD and UC. A combination of C4M, C3M, and PRO-C3 biomarkers may potentially be considered as a biomarker differentiating moderate to severe endoscopic disease.
Language	English
Publishing date	2022-10-07
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662592-1
ISSN	2077-0383
ISSN	2077-0383
DOI	10.3390/jcm11195907
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Article ; Online: Evaluation of collagen turnover biomarkers as an objective measure for efficacy of treatment with rurioctocog alfa pegol in patients with hemophilia A: a secondary analysis of a randomized controlled trial.

Manon-Jensen, Tina / Tangada, Srilatha / Bager, Cecilie / Chowdary, Pratima / Klamroth, Robert / von Drygalski, Annette / Windyga, Jerzy / Escobar, Miguel / Frederiksen, Peder / Engl, Werner / Ewenstein, Bruce / Karsdal, Morten

Journal of thrombosis and haemostasis : JTH

2023 Volume 22, Issue 1, Page(s) 90–100

Abstract: Background: Patients with hemophilia who have recurrent hemarthroses develop hemophilic arthropathy (HA). Regular prophylaxis with factor (F) VIII (FVIII) can reduce HA, but there is a need for objective outcome measures to evaluate treatment efficacy.!# ...

Abstract	Background: Patients with hemophilia who have recurrent hemarthroses develop hemophilic arthropathy (HA). Regular prophylaxis with factor (F) VIII (FVIII) can reduce HA, but there is a need for objective outcome measures to evaluate treatment efficacy. Objectives: Evaluate and assess collagen turnover biomarkers in patients with hemophilia A to determine the efficacy of rurioctocog alfa pegol treatment and understand their potential as tools for guiding treatment decisions and monitoring outcomes. Methods: Joint remodeling was assessed by analyzing serum levels of collagen remodeling products at baseline and months 3, 6, 9, and 12 in a 98 patient subset receiving pharmacokinetics-guided prophylaxis with rurioctocog alfa pegol, targeting FVIII trough levels of 1 to 3 International Units (IU)/dL or 8 to 12 IU/dL (PROPEL study, NCT0285960). Results: Basement membrane metabolism-related type 4 collagen remodeling products (C4M and PRO-C4) decreased after 3 months at all time points by up to 25% at 1 to 3 IU/dL (P = .049, P < .0001) and 8 to 12 IU/dL FVIII trough levels (P = .0002, P < .0001). Interstitial tissue metabolism-related type 3 (C3M) and 5 (PRO-C5) collagen remodeling products decreased after 3 months, by up to 19% at 1 to 3 IU/dL FVIII trough level (P = .0001, P = .009) and 23% at 8 to 12 IU/dL FVIII trough level (P = .0002, P = .001). An increase of up to 12% was seen for cartilage metabolism-related type 2 collagen product (PRO-C2, not C2M) after 6 months at both trough levels (P = .01, P = .005). When stratified by prior treatment, changes in C3M (P = .03) and C4M (P = .02) levels were observed between trough levels for prior on-demand treatment but not for prophylaxis prior to study entry. Conclusion: Joint improvement measured by collagen remodeling biomarkers specific to the basement membrane, interstitial matrix, and cartilage was seen with pharmacokinetics-guided prophylaxis. These collagen remodeling biomarkers warrant further exploration as biomarkers to guide treatment toward improvement in HA.
MeSH term(s)	Humans ; Hemophilia A/diagnosis ; Hemophilia A/drug therapy ; Factor VIII/therapeutic use ; Collagen ; Vascular Diseases/complications ; Biomarkers
Chemical Substances	BAX 855 (5X3GF74R79) ; Factor VIII (9001-27-8) ; Collagen (9007-34-5) ; Biomarkers
Language	English
Publishing date	2023-09-16
Publishing country	England
Document type	Randomized Controlled Trial ; Journal Article
ZDB-ID	2112661-6
ISSN	1538-7836 ; 1538-7933
ISSN (online)	1538-7836
ISSN	1538-7933
DOI	10.1016/j.jtha.2023.08.035
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Article ; Online: Endotrophin and C6Ma3, serological biomarkers of type VI collagen remodelling, reflect endoscopic and clinical disease activity in IBD.

Lindholm, Majken / Godskesen, Line E / Manon-Jensen, Tina / Kjeldsen, Jens / Krag, Aleksander / Karsdal, Morten A / Mortensen, Joachim H

Scientific reports

2021 Volume 11, Issue 1, Page(s) 14713

Abstract: In inflammatory bowel disease (IBD), the chronic inflammation deeply affects the intestinal extracellular matrix. The aim of this study was to investigate if remodeling of the intestinal basement membrane type VI collagen was associated with ... ...

Abstract	In inflammatory bowel disease (IBD), the chronic inflammation deeply affects the intestinal extracellular matrix. The aim of this study was to investigate if remodeling of the intestinal basement membrane type VI collagen was associated with pathophysiological changes in Crohn's disease (CD) and ulcerative colitis (UC). Serum from IBD patients (CD: n = 65; UC: n = 107; irritable bowel syndrome: n = 18; healthy subjects: n = 20) was investigated in this study. The serological biomarkers C6Ma3 (a matrix metalloproteinase (MMP) generated fragment of the type VI collagen α3 chain) and PRO-C6, also called endotrophin (the C-terminus of the released C5 domain of the type VI collagen α3 chain) were measured by ELISAs. Serum C6Ma3 was increased in CD patients with moderate to severe and mild endoscopically active disease compared to endoscopic remission (p = 0.002, p = 0.0048), respectively, and could distinguish endoscopically active disease from remission with an AUC of 1.0 (sensitivity: 100%, specificity: 100%) (p < 0.0001), which was superior to CRP. C6Ma3 was increased in CD patients with moderate to severe clinical disease compared to mild and remission (p = 0.04; p = 0.009). Serum PRO-C6, endotrophin, was increased in CD patients in clinically remission compared to mild disease (p = 0.04) and moderate to severe disease (p = 0.065). In UC, fecal calprotectin was the only marker that alone could distinguish both clinical and endoscopic active and inactive disease. Type VI collagen degradation of the α3 chain mediated by MMPs was increased in CD patients with endoscopically active disease, measured by the serological biomarker C6Ma3, which was able to distinguish endoscopically active from inactive CD.
MeSH term(s)	Adolescent ; Adult ; Aged ; Aged, 80 and over ; Biomarkers/blood ; Case-Control Studies ; Collagen Type VI/analysis ; Collagen Type VI/blood ; Collagen Type VI/metabolism ; Denmark ; Disease Progression ; Endoscopy, Gastrointestinal ; Extracellular Matrix/metabolism ; Female ; Humans ; Inflammatory Bowel Diseases/diagnosis ; Inflammatory Bowel Diseases/metabolism ; Inflammatory Bowel Diseases/pathology ; Male ; Middle Aged ; Peptide Fragments/analysis ; Peptide Fragments/blood ; Prognosis ; Protein Processing, Post-Translational ; Young Adult
Chemical Substances	Biomarkers ; Collagen Type VI ; Peptide Fragments ; endotrophin
Language	English
Publishing date	2021-07-19
Publishing country	England
Document type	Journal Article ; Observational Study ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-021-94321-2
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Article ; Online: The activation fragment of PAR2 is elevated in serum from patients with rheumatoid arthritis and reduced in response to anti-IL6R treatment.

Kalogera, Stefania / He, Yi / Bay-Jensen, Anne-Christine / Gantzel, Thorbjørn / Sun, Shu / Manon-Jensen, Tina / Karsdal, Morten Asser / Thudium, Christian S

Scientific reports

2021 Volume 11, Issue 1, Page(s) 24285

Abstract: Osteoarthritis (OA) and rheumatoid arthritis (RA) are serious and painful diseases. Protease-activated receptor 2 (PAR2) is involved in the pathology of both OA and RA including roles in synovial hyperplasia, cartilage destruction, osteophyogenesis and ... ...

Abstract	Osteoarthritis (OA) and rheumatoid arthritis (RA) are serious and painful diseases. Protease-activated receptor 2 (PAR2) is involved in the pathology of both OA and RA including roles in synovial hyperplasia, cartilage destruction, osteophyogenesis and pain. PAR2 is activated via cleavage of its N-terminus by serine proteases. In this study a competitive ELISA assay was developed targeting the 36-amino acid peptide that is cleaved and released after PAR2 activation (PRO-PAR2). Technical assay parameters including antibody specificity, intra- and inter-assay variation (CV%), linearity, accuracy, analyte stability and interference were evaluated. PRO-PAR2 release was confirmed after in vitro cleavage of PAR2 recombinant protein and treatment of human synovial explants with matriptase. Serum levels of 22 healthy individuals, 23 OA patients and 15 RA patients as well as a subset of RA patients treated with tocilizumab were evaluated. The PRO-PAR2 antibody was specific for the neo-epitope and intra-inter assay CV% were 6.4% and 5.8% respectively. In vitro cleavage and matriptase treated explants showed increased PRO-PAR2 levels compared to controls. In serum, PRO-PAR2 levels were increased in RA patients and decreased in RA patients treated with tocilizumab. In conclusion, PRO-PAR2 may be a potential biomarker for monitoring RA disease and pharmacodynamics of treatment.
MeSH term(s)	Adult ; Aged ; Antibodies/chemistry ; Antibodies, Monoclonal/chemistry ; Antibodies, Monoclonal, Humanized/therapeutic use ; Arthritis, Rheumatoid/blood ; Arthritis, Rheumatoid/immunology ; Arthritis, Rheumatoid/therapy ; Biomarkers/metabolism ; Cartilage/metabolism ; Epitopes/chemistry ; Female ; Humans ; Immunoassay ; Linear Models ; Male ; Middle Aged ; Osteoarthritis/metabolism ; Receptor, PAR-2/blood ; Receptors, Interleukin-6/antagonists & inhibitors ; Reproducibility of Results ; Serine Endopeptidases ; Synovial Fluid/metabolism ; Synovial Membrane/metabolism ; Young Adult
Chemical Substances	Antibodies ; Antibodies, Monoclonal ; Antibodies, Monoclonal, Humanized ; Biomarkers ; Epitopes ; F2RL1 protein, human ; IL6R protein, human ; Receptor, PAR-2 ; Receptors, Interleukin-6 ; Serine Endopeptidases (EC 3.4.21.-) ; matriptase (EC 3.4.21.-) ; tocilizumab (I031V2H011)
Language	English
Publishing date	2021-12-20
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-021-03346-0
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Article ; Online: Enzymatic cross-linking of collagens in organ fibrosis - resolution and assessment.

Pehrsson, Martin / Mortensen, Joachim Høg / Manon-Jensen, Tina / Bay-Jensen, Anne-Christine / Karsdal, Morten Asser / Davies, Michael Jonathan

Expert review of molecular diagnostics

2021 Volume 21, Issue 10, Page(s) 1049–1064

Abstract: ... ...

Abstract	Introduction
MeSH term(s)	Collagen ; Extracellular Matrix ; Fibrosis ; Humans
Chemical Substances	Collagen (9007-34-5)
Language	English
Publishing date	2021-08-24
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2112530-2
ISSN	1744-8352 ; 1473-7159
ISSN (online)	1744-8352
ISSN	1473-7159
DOI	10.1080/14737159.2021.1962711
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Article ; Online: A serologically assessed neo-epitope biomarker of cellular fibronectin degradation is related to pulmonary fibrosis.

Hansen, Annika Hummersgaard / Breisnes, Helene Wallem / Prior, Thomas Skovhus / Hilberg, Ole / Rasmussen, Daniel Guldager Kring / Genovese, Federica / Lukassen, Marie Vestergaard / Svensson, Birte / Langholm, Lasse Løcke / Manon-Jensen, Tina / Karsdal, Morten Asser / Leeming, Diana Julie / Bendstrup, Elisabeth / Sand, Jannie Marie Bülow

Clinical biochemistry

2023 Volume 118, Page(s) 110599

Abstract: Background: Idiopathic pulmonary fibrosis (IPF) is characterized by excessive extracellular matrix (ECM) remodeling, herein ECM degradation. Fibronectin (FN) is an important component of the ECM that is produced by multiple cell types, including ... ...

Abstract	Background: Idiopathic pulmonary fibrosis (IPF) is characterized by excessive extracellular matrix (ECM) remodeling, herein ECM degradation. Fibronectin (FN) is an important component of the ECM that is produced by multiple cell types, including fibroblasts. Extra domain B (EDB) is specific for a cellular FN isoform which is found in the ECM. We sought to develop a non-invasive test to investigate whether matrix metalloproteinase 8 (MMP-8) degradation of EDB in cellular FN results in a specific protein fragment that can be assessed serologically and if levels relate to pulmonary fibrosis. Method: Cellular FN was cleaved in vitro by MMP-8 and a protein fragment was identified by mass spectrometry. A monoclonal antibody (mAb) was generated, targeting a neo-epitope originating from EDB in cellular FN. Utilizing this mAb, a neo-epitope specific enzyme-linked immunosorbent assay (FN-EDB) was developed and technically validated. Serum FN-EDB was assessed in an IPF cohort (n = 98), registered at clinicaltrials.gov (NCT02818712), and in healthy controls (n = 35). Results: The FN-EDB assay had high specificity for the MMP-8 degraded neo-epitope and was technically robust. FN-EDB serum levels were not influenced by age, sex, ethnicity, or BMI. Moreover, FN-EDB serum levels were significantly higher in IPF patients (median 31.38 [IQR 25.79-46.84] ng/mL) as compared to healthy controls (median 28.05 [IQR 21.58-33.88] ng/mL, p = 0.023). Conclusion: We developed the neo-epitope specific FN-EDB assay, a competitive ELISA, as a tool for serological assessment of MMP-8 mediated degradation of EDB in cellular FN. This study indicates that degradation of EDB in cellular FN is elevated in IPF and warrants further investigation.
MeSH term(s)	Humans ; Pulmonary Fibrosis ; Matrix Metalloproteinase 8 ; Fibronectins/chemistry ; Fibronectins/metabolism ; Epitopes ; Antibodies, Monoclonal ; Biomarkers
Chemical Substances	Matrix Metalloproteinase 8 (EC 3.4.24.34) ; Fibronectins ; Epitopes ; Antibodies, Monoclonal ; Biomarkers
Language	English
Publishing date	2023-06-19
Publishing country	United States
Document type	Journal Article
ZDB-ID	390372-2
ISSN	1873-2933 ; 0009-9120
ISSN (online)	1873-2933
ISSN	0009-9120
DOI	10.1016/j.clinbiochem.2023.110599
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Article ; Online: A Specific Calprotectin Neo-epitope [CPa9-HNE] in Serum from Inflammatory Bowel Disease Patients Is Associated with Neutrophil Activity and Endoscopic Severity.

Mortensen, Joachim Høg / Sinkeviciute, Dovile / Manon-Jensen, Tina / Domislović, Viktor / McCall, Kathryn / Thudium, Christian S / Brinar, Marko / Önnerfjord, Patrik / Goodyear, Carl S / Krznarić, Željko / Karsdal, Morten Asser / Bay-Jensen, Anne-Christine

Journal of Crohn's & colitis

2022 Volume 16, Issue 9, Page(s) 1447–1460

Abstract: Background and aims: Endoscopy and the use of faecal calprotectin [faecal CP] are among the least-favoured methods for assessing disease activity by inflammatory bowel disease [IBD] patients; the handling/processing of faecal samples is also impractical. ...

Abstract	Background and aims: Endoscopy and the use of faecal calprotectin [faecal CP] are among the least-favoured methods for assessing disease activity by inflammatory bowel disease [IBD] patients; the handling/processing of faecal samples is also impractical. Therefore, we sought to develop a novel neo-epitope serum calprotectin enzyme-linked immunosorbent assay [ELISA], CPa9-HNE, with the aim of quantifying neutrophil activity and neutrophil extracellular trap [NET]-osis and proposing a non-invasive method for monitoring disease activity in IBD patients. Methods: In vitro cleavage was performed by mixing calprotectin [S100A9/S100A8] with human neutrophil elastase [HNE], and a novel HNE-derived calprotectin neo-epitope [CPa9-HNE] was identified by mass spectrometry for ELISA development. The CPa9-HNE ELISA was quantified in supernatants from ex vivo activated neutrophils and serum samples from patients with ulcerative colitis [UC, n = 43], Crohn's disease [CD, n = 93], and healthy subjects [HS, n = 23]. For comparison, faecal CP and MRP8/14 biomarkers were also measured. Results: CPa9-HNE was specific for activated neutrophils ex vivo. Serum CPa9-HNE levels were 4-fold higher in CD [p <0.0001] and UC [p <0.0001] patients than in HS. CPa9-HNE correlated well with the Simple Endoscopic Score [SES]-CD score [r = 0.61, p <0.0001], MES [r = 0.46, p = 0.0141], and the full Mayo score [r = 0.52, p = 0.0013]. CPa9-HNE was able to differentiate between CD and UC patients in endoscopic remission and moderate/severe disease activity (CD: area under the curve [AUC] = 0.82 [p = 0.0003], UC: AUC = 0.87 [p = 0.0004]). The performance of CPa9-HNE was equipotent or slightly better than that of faecal CP. Conclusions: Serum CPa9-HNE levels were highly associated with CD and UC patients. CPa9-HNE correlated with the SES-CD score and the full Mayo score, indicating a strong association with disease activity.
MeSH term(s)	Biomarkers ; Colitis, Ulcerative/diagnosis ; Endoscopy, Gastrointestinal ; Epitopes/analysis ; Feces/chemistry ; Humans ; Inflammatory Bowel Diseases/diagnosis ; Leukocyte Elastase ; Leukocyte L1 Antigen Complex/analysis ; Neutrophils/chemistry ; Severity of Illness Index
Chemical Substances	Biomarkers ; Epitopes ; Leukocyte L1 Antigen Complex ; Leukocyte Elastase (EC 3.4.21.37)
Language	English
Publishing date	2022-03-18
Publishing country	England
Document type	Journal Article
ZDB-ID	2390120-2
ISSN	1876-4479 ; 1873-9946
ISSN (online)	1876-4479
ISSN	1873-9946
DOI	10.1093/ecco-jcc/jjac047
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Article ; Online: Type XX Collagen Is Elevated in Circulation of Patients with Solid Tumors.

Thorlacius-Ussing, Jeppe / Jensen, Christina / Madsen, Emilie A / Nissen, Neel I / Manon-Jensen, Tina / Chen, Inna M / Johansen, Julia S / Diab, Hadi M H / Jørgensen, Lars N / Karsdal, Morten A / Willumsen, Nicholas

International journal of molecular sciences

2022 Volume 23, Issue 8

Abstract: In the tumor microenvironment, the extracellular matrix (ECM) has been recognized as an important part of cancer development. The dominant ECM proteins are the 28 types of collagens, each with a unique function in tissue architecture. Type XX collagen, ... ...

Abstract	In the tumor microenvironment, the extracellular matrix (ECM) has been recognized as an important part of cancer development. The dominant ECM proteins are the 28 types of collagens, each with a unique function in tissue architecture. Type XX collagen, however, is poorly characterized, and little is known about its involvement in cancer. We developed an ELISA quantifying type XX collagen, named PRO-C20, using a monoclonal antibody raised against the C-terminus. PRO-C20 and PRO-C1, an ELISA targeting the N-terminal pro-peptide of type I collagen, was measured in sera of 219 patients with various solid cancer types and compared to sera levels of 33 healthy controls. PRO-C20 was subsequently measured in a separate cohort comprising 36 patients with pancreatic ductal adenocarcinoma (PDAC) and compared to 20 healthy controls and 11 patients with chronic pancreatitis. PRO-C20 was significantly elevated in all cancers tested: bladder, breast, colorectal, head and neck, kidney, lung, melanoma, ovarian, pancreatic, prostate, and stomach cancer (p < 0.01−p < 0.0001). PRO-C1 was only elevated in patients with ovarian cancer. PRO-C20 could discriminate between patients and healthy controls with AUROC values ranging from 0.76 to 0.92. Elevated levels were confirmed in a separate cohort of patients with PDAC (p < 0.0001). High PRO-C20 levels (above 2.57 nM) were predictive of poor survival after adjusting for the presence of metastasis, age, and sex (HR: 4.25, 95% CI: 1.52−11.9, p-value: 0.006). Circulating type XX collagen is elevated in sera of patients with various types of cancer and has prognostic value in PDAC. If validated, PRO-C20 may be a novel biomarker for patients with solid tumors and can help understand the ECM biology of cancer.
MeSH term(s)	Biomarkers, Tumor/metabolism ; Carcinoma, Pancreatic Ductal/pathology ; Collagen/metabolism ; Extracellular Matrix/metabolism ; Female ; Humans ; Male ; Non-Fibrillar Collagens/metabolism ; Pancreatic Neoplasms/pathology ; Tumor Microenvironment ; Pancreatic Neoplasms
Chemical Substances	Biomarkers, Tumor ; Non-Fibrillar Collagens ; Collagen (9007-34-5)
Language	English
Publishing date	2022-04-08
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms23084144
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Article ; Online: An MMP-degraded and cross-linked fragment of type III collagen as a non-invasive biomarker of hepatic fibrosis resolution.

Pehrsson, Martin / Manon-Jensen, Tina / Sun, Shu / Villesen, Ida F / Castañé, Helena / Joven, Jorge / Patel, Keyur / Goodman, Zachary / Nielsen, Mette J / Bay-Jensen, Anne-Christine / Leeming, Diana J / Mortensen, Joachim H / Karsdal, Morten A

Liver international : official journal of the International Association for the Study of the Liver

2022 Volume 42, Issue 7, Page(s) 1605–1617

Abstract: Background and aims: Liver fibrosis results from a prolonged wound healing response to continued injury with excessive production of extracellular proteins. In patients with chronic liver disease, the monitoring of liver fibrosis dynamics is of high ... ...

Abstract	Background and aims: Liver fibrosis results from a prolonged wound healing response to continued injury with excessive production of extracellular proteins. In patients with chronic liver disease, the monitoring of liver fibrosis dynamics is of high interest. Whilst markers of fibrogenesis exist, markers of hepatic fibrosis resolution remain an unmet clinical need. Thus, we sought to develop an assay quantifying a circulating proteolytic fragment of cross-linked type III collagen as a biomarker of fibrolysis, testing its utility in two clinical cohorts of liver fibrosis of distinct aetiology and regressing endotype METHODS: We used a monoclonal antibody targeting the C-telopeptide of type III collagen following C-proteinase cleavage to develop and validate a neo-epitope-specific enzyme-linked immunosorbent assay (CTX-III). A potential fibrosis resolution marker, CTX-III, was measured in two clinical cohorts of patients with obesity-associated non-alcoholic fatty liver disease undergoing bariatric surgery or hepatitis C virus infection from a clinical trial study evaluating the anti-fibrotic effect of farglitazar. Results: CTX-III was robust and specific for the targeted neo-epitope with good reproducibility in EDTA plasma. We assessed type III collagen remodelling using a panel of biomarkers, including a type III collagen formation marker (PRO-C3), degradation (C3M), and CTX-III (fibrolysis). Net fibrolysis was increased in patients with non-alcoholic fatty liver disease following bariatric surgery (p < .001). Moreover, net fibrolysis identified spontaneous fibrotic regressors from stable and progressors (p < .05 and p < .001) among hepatitis C virus infection patients. Conclusion: Circulating CTX-III as a marker of fibrolysis indicates the biomarker's beneficial use in assessing hepatic fibrosis resolution.
MeSH term(s)	Biomarkers ; Collagen Type III ; Epitopes ; Fibrosis ; Humans ; Liver Cirrhosis ; Matrix Metalloproteinases ; Non-alcoholic Fatty Liver Disease ; Reproducibility of Results
Chemical Substances	Biomarkers ; Collagen Type III ; Epitopes ; Matrix Metalloproteinases (EC 3.4.24.-)
Language	English
Publishing date	2022-04-12
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2102783-3
ISSN	1478-3231 ; 1478-3223
ISSN (online)	1478-3231
ISSN	1478-3223
DOI	10.1111/liv.15270
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Article: Serum Type XIX Collagen is Significantly Elevated in Non-Small Cell Lung Cancer: A Preliminary Study on Biomarker Potential.

Thorlacius-Ussing, Jeppe / Manon-Jensen, Tina / Sun, Shu / Leeming, Diana J / Sand, Jannie M / Karsdal, Morten / Willumsen, Nicholas

Cancers

2020 Volume 12, Issue 6

Abstract: Type XIX collagen is a poorly characterized collagen associated with the basement membrane. It is abnormally regulated during breast cancer progression and the NC1 (XIX) domain has anti-tumorigenic signaling properties. However, little is known about the ...

Abstract	Type XIX collagen is a poorly characterized collagen associated with the basement membrane. It is abnormally regulated during breast cancer progression and the NC1 (XIX) domain has anti-tumorigenic signaling properties. However, little is known about the biomarker potential of collagen XIX in cancer. In this study, we describe a competitive ELISA, named PRO-C19, targeting the C-terminus of collagen XIX using a monoclonal antibody. PRO-C19 was measured in serum of patients with a range of cancer types and was elevated in non-small cell lung cancer (NSCLC) (
Language	English
Publishing date	2020-06-09
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers12061510
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In stock of ZB MED Cologne/Königswinter

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In stock of ZB MED Cologne/Königswinter

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Order via subito

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In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito