Introduction: Variants in collagen-related genes COL1A1, COL3A1, COL5A1 and COL5A2 are associated with Ehlers-Danlos syndrome (EDS), a heterogeneous group of connective tissue disorders strongly associated with increased bleeding. Of patients with incompletely explained bleeding diathesis, a relativ...
November 20, 2020
Journal:
Haemophilia
Author:
Fager Ferrari M, Zetterberg E, Rossing M, Manon-Jensen T, Pehrsson M, Karsdal MA, Lykkesfeldt J, Leinoe E
Background: Chronic obstructive pulmonary disease (COPD) is characterized by abnormal epithelial repair resulting in a hypercoagulable state with intra-alveolar accumulation of fibrin and alveolar basement membrane destruction. This study aimed to investigate if the combination of two serological bi...
November 19, 2020
Journal:
Lancet Respir Med
Author:
Sand JMB, Rønnow SR, Langholm LL, Karsdal MA, Manon-Jensen T, Tal-Singer R, Miller BE, Vestbo J, Leeming DJ
Introduction: Anti-tumor necrosis factor (TNF) therapy is effective in inducing remission in Crohn's disease in 60% of patients. No serological biomarkers are available, which can predict response to anti-TNF. We aimed to investigate serological markers of collagen turnover reflecting tissue inflamm...
September 11, 2020
Journal:
Clin Transl Gastroenterol
Author:
van Haaften WT, Mortensen JH, Dige AK, Grønbæk H, Hvas CL, Bay-Jensen AC, Karsdal MA, Olinga P, Manon-Jensen T, Dijkstra G
Introduction: Anti-tumor necrosis factor (TNF) therapy is effective in inducing remission in Crohn's disease in 60% of patients. No serological biomarkers are available, which can predict response to anti-TNF. We aimed to investigate serological markers of collagen turnover reflecting tissue inflamm...
September 11, 2020
Journal:
Clin Transl Gastroenterol
Author:
van Haaften WT, Mortensen JH, Dige AK, Grønbæk H, Hvas CL, Bay-Jensen AC, Karsdal MA, Olinga P, Manon-Jensen T, Dijkstra G
Introduction: Anti-tumor necrosis factor (TNF) therapy is effective in inducing remission in Crohn's disease in 60% of patients. No serological biomarkers are available, which can predict response to anti-TNF. We aimed to investigate serological markers of collagen turnover reflecting tissue inflamm...
September 11, 2020
Journal:
Clin Transl Gastroenterol
Author:
van Haaften WT, Mortensen JH, Dige AK, Grønbæk H, Hvas CL, Bay-Jensen AC, Karsdal MA, Olinga P, Manon-Jensen T, Dijkstra G
Background & aims: Primary sclerosing cholangitis (PSC), primary biliary cholangitis (PBC) and autoimmune hepatitis (AIH) are phenotypically distinct autoimmune liver diseases that progress to cirrhosis and liver failure; however, their histological fibrosis distribution differs. We investigated...
September 3, 2020
Journal:
JHEP Rep
Author:
Vesterhus M, Nielsen MJ, Hov JR, Saffioti F, Manon-Jensen T, Leeming DJ, Moum B, Boberg KM, Pinzani M, Karlsen TH, Karsdal MA, Thorburn D
Background: In Crohn's disease (CD), 10% to 40% of patients do not respond to anti-tumor necrosis factor-α (TNFα) treatment. Currently, there are no biomarkers with adequate sensitivity to separate responders from nonresponders at an early stage. Aim: The aim of this study was to investigated wheth...
April 14, 2020
Journal:
J Clin Gastroenterol
Author:
Mortensen JH, Van Haaften WT, Karsdal MA, Bay-Jensen AC, Olinga P, Grønbæk H, Hvas CL, Manon-Jensen T, Dijkstra G, Dige A
Chronic obstructive pulmonary disease (COPD) is characterized by a slow heterogeneous progression. Therefore, improved biomarkers that can accurately identify patients with the highest likelihood of progression and therefore the ability to benefit from a given treatment, are needed. Elastin is an es...
March 11, 2020
Journal:
Sci Rep
Author:
Rønnow S, Langholm LL, Sand JMB, Thoracius-Using J, Leeming DJ, Manon-Jensen T, Tal-Singer R, Miller BE, Karsdal MA, Vestbo J
Background: Chronic obstructive pulmonary disease (COPD) is characterized by chronic inflammation and lung tissue deterioration. Given the high vascularity of the lung, von Willebrand factor (VWF), a central component of wound healing initiation, has previously been assessed in COPD. VWF processing,...
March 9, 2020
Journal:
Int J Chron Obstruct Pulmon
Author:
Langholm LL, Rønnow S, bülow Sand JM, Leeming DJ, Talsinger R, Miller BE, Vestbo J, Karsdal MA, Manon-Jensen T
Background: Chronic obstructive pulmonary disease (COPD) is characterized by abnormal epithelial repair process that may result in intra-airway accumulation of fibrin. Given that plasma fibrinogen is the only FDA approved biomarker that predicts mortality and COPD exacerbations, we hypothesized that...
December 2, 2019
Journal:
Lancet Respir Med
Author:
Manon-Jensen T, Langholm LL, Ronnow SR, Karsdal MA, Tal-Singer R, Vestbo J, Leeming DJ, Miller BE, bülow Sand JM
Vascular remodeling associated with hemophilic arthropathy (HA) may contribute to bleed propagation, but the mechanisms remain poorly understood. OBJECTIVES: To explore molecular mechanisms of HA and the effects of hemostasis correction on synovial vascular remodeling after joint injury in hypocoag...
November 1, 2019
Journal:
J Thromb Haemost
Author:
Cooke EJ, Wyseure T, Zhou JY, Gopal S, Nasmran CA, Fisch KM, Manon-Jensen T, Karsdal MA, Mosnier LO, Von Drygalski A
Introduction: Extracellular matrix (ECM) remodeling of the intestinal tissue is important in inflammatory bowel disease (IBD) due to the extensive mucosal remodeling. There are still gaps in our knowledge as to how ECM remodeling is related to intestinal epithelium homeostasis and healing of the int...
October 22, 2019
Journal:
Expert Rev Gastroenterol Hepatol
Author:
Mortensen JH, Lindholm M, Langholm LL, Kjeldsen J, Bay-Jensen AC, Karsdal MA, Manon-Jensen T
BACKGROUND AND AIMS: Crohns disease (CD) is a chronic inflammatory condition characterized by continuous mucosal damage and ongoing wound healing of the intestines. The fibrinolytic system is involved in early parts of the wound healing process. Fibrin is a key mediator of primary blood clot formati...
June 1, 2019
Journal:
J Gastrointestin Liver Dis
Author:
Sun S, Karsdal MA, Mortensen JH, Luo Y, Kjeldsen J, Krag A, Jensen MD, Bay-Jensen AC, Manon-Jensen T
Chronic obstructive pulmonary disease (COPD) is characterized by a slow heterogeneous progression. Therefore, improved biomarkers that can accurately identify patients with the highest likelihood of progression and therefore the ability to benefit from a given treatment, are needed. Elastin is an es...
March 9, 2019
Journal:
Sci Rep
Author:
Ronnow SR, Langholm LL, Sand JMB, Thoracius-Ussing J, Leeming DJ, Manon-Jensen T, Tal-Singer R, Miller BE, Karsdal MA, Vestbo J
C-telopeptide of type II collagen (CTX-II) has been shown to be a highly relevant biomarker of cartilage degradation in human rheumatic diseases, if measured in synovial fluid or urine. However, serum or plasma CTX-II have not been demonstrated to have any clinical utility to date. Here, we describe...
February 28, 2019
Journal:
Sci Rep
Author:
Löfvall H, Katri A, Dabrowska A, Karsdal MA, Luo Y, He Y, Manon-Jensen T, Dziegiel MH, Bay-Jensen AC, Thudium CS, Henriksen K
OBJECTIVES: Portal hypertension in cirrhosis is associated with endothelial dysfunction, impaired wound healing, and decreased platelet count. Increased von Willebrand factor (VWF) formation has been suggested as a compensatory mechanism, but the role of VWF processing has not been directly assessed...
February 12, 2019
Journal:
Eur J Gastroenterol Hepatol
Author:
Langholm LL, Manon-Jensen T, Karsdal MA, Bendtsen F, Leeming DJ, Møller S
Background: Crohn’s disease (CD) is a chronic inflammatory condition of the intestinal tract resulting in severe intestinal tissue damage. The concept of mucosal healing has therefore gained significant interest as a therapeutic end point in the treatment of inflammatory bowel disease (IBD). Given t...
January 31, 2019
Journal:
EC Gastroenterology and Digestive
Author:
Manon-Jensen T, Langholm LL, Sun S, Mortensen JH, He Y, Krag A, Jensen MD, Bay-Jensen AC, Kjeldsen J, Karsdal MA
OBJECTIVE: Phenotypic changes of chondrocytes toward hypertrophy might be fundamental in the pathogenesis of OA, of which type X collagen (Col10) is a well-known marker. The purpose was to develop a specific immunoassay for blood quantification of a newly identified neo-epitope of type X collagen to...
January 14, 2019
Journal:
Osteoarthritis Cartilage
Author:
He Y, Manon-Jensen T, Arendt-Nielsen L, Petersen KK, Christiansen T, Samuels J, Abramson S, Karsdal MA, Attur M, Bay-Jensen AC
Chronic obstructive pulmonary disease (COPD) is characterized by high levels of protease activity leading to degradation of elastin followed by loss of elasticity of the lung and the development of emphysema. Elastin is an essential structural component of the lung parenchyma to support the expansio...
September 10, 2018
Journal:
Biochem Biophys Res Commun
Author:
Gudmann NS, Manon-Jensen T, Sand JMB, Diefenbach C, Sun S, Danielsen A, Karsdal MA, Leeming DJ
Chronic obstructive pulmonary disease (COPD) is characterized by high levels of protease activity leading to degradation of elastin followed by loss of elasticity of the lung and the development of emphysema. Elastin is an essential structural component of the lung parenchyma to support the expansio...
September 10, 2018
Journal:
Biochem Biophys Res Commun
Author:
Gudmann NS, Manon-Jensen T, Sand JM, Diefenbach C, Sun S, Danielsen A, Karsdal MA, Leeming DJ
The matricellular protein SPARC (secreted proteome acidic and rich in cysteine) is known to bind collagens and regulate fibrillogenesis. Cleavage of SPARC at a single peptide bond, increases the affinity for collagens up to 20-fold. To investigate if this specific cleavage has pathological relevance...
August 1, 2018
Journal:
Cancer biology therapy
Author:
Kehlet SN, Manon-Jensen T, Sun S, Brix S, Karsdal MA, Leeming DJ, Willumsen N
OBJECTIVES: Fibrosis and cancer are characterized by extracellular matrix (ECM) remodeling. The basement membrane is mainly composed by collagen type IV and laminin. Tumstatin is a matrix metalloproteinase-9 (MMP-9) generated matrikine of collagen type IV α3 chain. We evaluated the potential of tums...
March 7, 2018
Journal:
Transl Oncol
Author:
Nielsen SH, Willumsen N, Brix S, Sun S, Manon-Jensen T, Karsdal MA, Genovese F
INTRODUCTION: The medical need in the haemophilic (HF) field to reduce bleeding incidents requires measurement of the annual bleeding rate (ABR) in haemophiliacs. Vascular rupture is associated with damage to the vascular endothelium causing exposure of the basement membrane. Endothelial cells and m...
BACKGROUND:Increased protease activity is a key pathological feature of inflammatory bowel disease (IBD). However, the differences in extracellular matrix remodelling (ECM) in Crohn\u0027s disease (CD) and ulcerative colitis (UC) are not well described. An increased understanding of the inflammatory...
October 13, 2017
Journal:
PLoS One
Author:
Bay-Jensen AC, Karsdal MA, Krag A, Kjeldsen J, Klinge LG, Hägglund P, Jensen MD, Manon-Jensen T, Mortensen JH
Altered extracellular matrix (ECM) turnover is a central pathological feature of many diseases. The ECM is a meshwork of molecules that provides structural support to cells throughout the body. It consists mainly of two membranes: the interstitial matrix, which is present between parenchymal cells i...
August 29, 2017
Journal:
Haemophilia
Author:
Manon-Jensen T, Hua BL, Olsen EHN, Sun S, Gudme CN, Li J, Lei W, Vandahl B, Roepstorff K, Kjelgaard-Hansen M, Zhao Y, Karsdal MA
Usually the dense extracellular structure in fibrotic tissues is described as extracellular matrix (ECM) or simply as collagen. However, fibrosis is not just fibrosis, which is already exemplified by the variant morphological characteristics of fibrosis due to viral versus cholestatic, autoimmune or...
July 21, 2017
Journal:
Adv Drug Deliv Rev
Author:
Karsdal MA, Nielsen SH, Leeming DJ, Langholm LL, Nielsen MJ, Manon-Jensen T, Siebuhr AS, Gudmann NS, Rønnow S, Sand JM, Daniels SJ, Mortensen JH, Schuppan D
Introduction: Progressive arthropathy caused by recurrent joint bleeds is a severe complication in haemophilia. Aim: We investigated whether biomarkers of cartilage and bone degradation, and inflammation were altered in haemophilia patients and whether these biomarkers could identify haemophilia pa...
April 24, 2017
Journal:
Haemophilia
Author:
Hua B, Olsen EHN, Sun S, Gudme CN, Wang L, Vandahl B, Roepstorff K, Kjelgaard-Hansen M, Sørensen BB, Zhao Y, Karsdal MA, Manon-Jensen T
ESSENTIALS: Joint bleeding in hemophilia may induce significant remodeling of the extracellular matrix. Biomarkers of collagen turnover were investigated in a F8-/- rat model of hemophilic arthropathy. Biomarkers of cartilage degradation increased significantly during development of arthropathy. Bas...
October 28, 2016
Journal:
J Thromb Haemost.
Author:
Manon-Jensen T, Karsdal MA, Nielsen LN, Kjelgaard-Hansen M, Vandahl B, Olsen EHN, Enoksson M, Roepstorff K
OBJECTIVE: Recurrent flares constitute the main clinical burden of gout. Our aim was to assess whether biomarkers measuring MMP tissue degradation could be used as markers of frequent gout flares. METHODS: Fasting plasma samples from 112 men with gout and 170 controls, along with serum samples from...
June 2, 2016
Journal:
Rheumatology (Oxford)
Author:
Valdes AM, Manon-Jensen T, Abhishek A, Jenkins W, Siebuhr AS, Karsdal MA, Doherty S, Zhang W, Richardson H, Doherty M, Bay-Jensen AC
Collagens mediate essential hemostasis by maintaining the integrity and stability of the vascular wall. Imbalanced turnover of collagens by uncontrolled formation and/or degradation may result in pathologic conditions such as fibrosis. Thickening of the vessel wall because of accumulation of collage...
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