Accelerated extracellular matrix remodeling in psoriatic arthritis & value of ECM-related biomarkers

Samra Sardar, Salome Kristensen, Anne Sofie Siebuhr, Jeppe Christensen, Morten Karsdal, Annette Mortensen, Anne-Christine Bay-Jensen

Publikation: Bidrag til tidsskriftKonferenceabstrakt i tidsskriftForskningpeer review

Resumé

Background With our increasing understanding of cross-talk between the immune system (immune cells, cytokines) and extracellular matrix (ECM) of the affected tissues, ECM destruction and turnover has gained a lot of attention in inflammatory arthritis. ECM mainly consists of interstitial matrix (rich in type I and III collagens) and basement membrane (mainly composed of type IV collagen), both of which are affected in inflammatory arthritis. We hypothesize that inflammatory milieu in Psoriatic Arthritis (PsA) leads to accelerated ECM destruction and remodeling, and the release of ECM metabolites into circulation, that can be measured in serum as biomarkers of tissue remodeling and may give insight to pathological process at the tissue level.Objectives This prospective study aimed to use serological biomarkers for evaluation of the extent of damage to, and changes in turnover of ECM in patients with PsA and to investigate their relation to inflammatory biomarkers and disease activity.Methods Patients with PsA (n=145) fulfilling the CASPAR criteria and above 18 years of age with any disease activity were recruited through outpatient department in Aalborg University Hospital, Denmark. Exclusion criteria were pregnancy, treatment with biological DMARD, or with oral corticosteroids and other comorbidities. Clinical disease parameters were recorded, and blood samples were collected at baseline and 24 weeks follow-up. Inflammation-related ECM remodelling was measured by serological biomarkers of type I, III and IV collagen formation (Pro-C1, Pro-C3 and Pro-C4, respectively) and MMP-mediated degradation (C1M, C3M and C4M respectively). The chronic inflammation was measured by CRPM (MMP degraded metabolite of CRP). All biomarkers were measured by competitive ELISAs and levels were compared to the reference levels of healthy individuals. The biomarker data was log2 transformed for normalization and standard parametric statistical methods were applied.Results We found that there was an increase in the degradation of interstitial matrix (represented by C1M and C3M) which was uncompensated with either decreased (Pro-C1) or unaltered (Pro-C3) formation in patients with PsA as compared to healthy individuals. On the contrary, there was a compensated increase in basement membrane remodeling in patients with PsA as represented by increase in both C4M and Pro-C4 in comparison to healthy individuals (Table 1). Interestingly, there was a strong correlation between baseline C4M and Pro-C4 (r=0.703, p<0.0001), and 24-week changes in both biomarkers (r=0.468, p<0.0001) pointing towards coupling between the two processes which was either lost or was weak in case of interstitial collagens. As baseline values and changes in C1M, C3M, C4M and Pro-C4 showed a strong correlation with changes in inflammatory biomarkers, we believe that ECM remodeling in PsA is, at least partly, driven by inflammation. Furthermore, baseline values and changes in these ECM turnover biomarkers correlated positively with changes in composite disease activity scores (Table 2) that may indicate their clinical importance as potential diagnostic or disease activity markers.Conclusion Chronic inflammation underlying PsA pathology results in an increased amount of ECM turnover that correlates with clinical progression and can be measured by serological biomarkers.References NoneDisclosure of Interests Samra Sardar Employee of: I am a full time employee at Nordic Bioscience, Salome Kristensen: None declared, Anne Sofie Siebuhr Employee of: I am a full-time employee in Nordic Bioscience, Jeppe Christensen: None declared, Morten Karsdal Shareholder of: I own shares of Nordic Bioscience, Employee of: I am a full-time employee in Nordic Bioscience, Annette Mortensen: None declared, Anne-Christine Bay-Jensen Shareholder of: I own shares of Nordic Bioscience, Employee of: I am a full-time employee in Nordic Bioscience
OriginalsprogEngelsk
ArtikelnummerFRI0370 
TidsskriftAnnals of the Rheumatic Diseases
Vol/bind78
Udgave nummerSuppl. 2
Sider (fra-til)867-867
Antal sider1
ISSN0003-4967
DOI
StatusUdgivet - jun. 2019
BegivenhedAnnual European Congress of Rheumatology, EULAR 2019 - Madrid, Spanien
Varighed: 12 jun. 201915 jun. 2019
https://www.congress.eular.org/

Konference

KonferenceAnnual European Congress of Rheumatology, EULAR 2019
LandSpanien
ByMadrid
Periode12/06/201915/06/2019
Internetadresse

Citer dette

Sardar, Samra ; Kristensen, Salome ; Siebuhr, Anne Sofie ; Christensen, Jeppe ; Karsdal, Morten ; Mortensen, Annette ; Bay-Jensen, Anne-Christine. / Accelerated extracellular matrix remodeling in psoriatic arthritis & value of ECM-related biomarkers. I: Annals of the Rheumatic Diseases. 2019 ; Bind 78, Nr. Suppl. 2. s. 867-867.
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title = "Accelerated extracellular matrix remodeling in psoriatic arthritis & value of ECM-related biomarkers",
abstract = "Background With our increasing understanding of cross-talk between the immune system (immune cells, cytokines) and extracellular matrix (ECM) of the affected tissues, ECM destruction and turnover has gained a lot of attention in inflammatory arthritis. ECM mainly consists of interstitial matrix (rich in type I and III collagens) and basement membrane (mainly composed of type IV collagen), both of which are affected in inflammatory arthritis. We hypothesize that inflammatory milieu in Psoriatic Arthritis (PsA) leads to accelerated ECM destruction and remodeling, and the release of ECM metabolites into circulation, that can be measured in serum as biomarkers of tissue remodeling and may give insight to pathological process at the tissue level.Objectives This prospective study aimed to use serological biomarkers for evaluation of the extent of damage to, and changes in turnover of ECM in patients with PsA and to investigate their relation to inflammatory biomarkers and disease activity.Methods Patients with PsA (n=145) fulfilling the CASPAR criteria and above 18 years of age with any disease activity were recruited through outpatient department in Aalborg University Hospital, Denmark. Exclusion criteria were pregnancy, treatment with biological DMARD, or with oral corticosteroids and other comorbidities. Clinical disease parameters were recorded, and blood samples were collected at baseline and 24 weeks follow-up. Inflammation-related ECM remodelling was measured by serological biomarkers of type I, III and IV collagen formation (Pro-C1, Pro-C3 and Pro-C4, respectively) and MMP-mediated degradation (C1M, C3M and C4M respectively). The chronic inflammation was measured by CRPM (MMP degraded metabolite of CRP). All biomarkers were measured by competitive ELISAs and levels were compared to the reference levels of healthy individuals. The biomarker data was log2 transformed for normalization and standard parametric statistical methods were applied.Results We found that there was an increase in the degradation of interstitial matrix (represented by C1M and C3M) which was uncompensated with either decreased (Pro-C1) or unaltered (Pro-C3) formation in patients with PsA as compared to healthy individuals. On the contrary, there was a compensated increase in basement membrane remodeling in patients with PsA as represented by increase in both C4M and Pro-C4 in comparison to healthy individuals (Table 1). Interestingly, there was a strong correlation between baseline C4M and Pro-C4 (r=0.703, p<0.0001), and 24-week changes in both biomarkers (r=0.468, p<0.0001) pointing towards coupling between the two processes which was either lost or was weak in case of interstitial collagens. As baseline values and changes in C1M, C3M, C4M and Pro-C4 showed a strong correlation with changes in inflammatory biomarkers, we believe that ECM remodeling in PsA is, at least partly, driven by inflammation. Furthermore, baseline values and changes in these ECM turnover biomarkers correlated positively with changes in composite disease activity scores (Table 2) that may indicate their clinical importance as potential diagnostic or disease activity markers.Conclusion Chronic inflammation underlying PsA pathology results in an increased amount of ECM turnover that correlates with clinical progression and can be measured by serological biomarkers.References NoneDisclosure of Interests Samra Sardar Employee of: I am a full time employee at Nordic Bioscience, Salome Kristensen: None declared, Anne Sofie Siebuhr Employee of: I am a full-time employee in Nordic Bioscience, Jeppe Christensen: None declared, Morten Karsdal Shareholder of: I own shares of Nordic Bioscience, Employee of: I am a full-time employee in Nordic Bioscience, Annette Mortensen: None declared, Anne-Christine Bay-Jensen Shareholder of: I own shares of Nordic Bioscience, Employee of: I am a full-time employee in Nordic Bioscience",
author = "Samra Sardar and Salome Kristensen and Siebuhr, {Anne Sofie} and Jeppe Christensen and Morten Karsdal and Annette Mortensen and Anne-Christine Bay-Jensen",
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Accelerated extracellular matrix remodeling in psoriatic arthritis & value of ECM-related biomarkers. / Sardar, Samra; Kristensen, Salome; Siebuhr, Anne Sofie; Christensen, Jeppe; Karsdal, Morten; Mortensen, Annette; Bay-Jensen, Anne-Christine.

I: Annals of the Rheumatic Diseases, Bind 78, Nr. Suppl. 2, FRI0370 , 06.2019, s. 867-867.

Publikation: Bidrag til tidsskriftKonferenceabstrakt i tidsskriftForskningpeer review

TY - ABST

T1 - Accelerated extracellular matrix remodeling in psoriatic arthritis & value of ECM-related biomarkers

AU - Sardar, Samra

AU - Kristensen, Salome

AU - Siebuhr, Anne Sofie

AU - Christensen, Jeppe

AU - Karsdal, Morten

AU - Mortensen, Annette

AU - Bay-Jensen, Anne-Christine

PY - 2019/6

Y1 - 2019/6

N2 - Background With our increasing understanding of cross-talk between the immune system (immune cells, cytokines) and extracellular matrix (ECM) of the affected tissues, ECM destruction and turnover has gained a lot of attention in inflammatory arthritis. ECM mainly consists of interstitial matrix (rich in type I and III collagens) and basement membrane (mainly composed of type IV collagen), both of which are affected in inflammatory arthritis. We hypothesize that inflammatory milieu in Psoriatic Arthritis (PsA) leads to accelerated ECM destruction and remodeling, and the release of ECM metabolites into circulation, that can be measured in serum as biomarkers of tissue remodeling and may give insight to pathological process at the tissue level.Objectives This prospective study aimed to use serological biomarkers for evaluation of the extent of damage to, and changes in turnover of ECM in patients with PsA and to investigate their relation to inflammatory biomarkers and disease activity.Methods Patients with PsA (n=145) fulfilling the CASPAR criteria and above 18 years of age with any disease activity were recruited through outpatient department in Aalborg University Hospital, Denmark. Exclusion criteria were pregnancy, treatment with biological DMARD, or with oral corticosteroids and other comorbidities. Clinical disease parameters were recorded, and blood samples were collected at baseline and 24 weeks follow-up. Inflammation-related ECM remodelling was measured by serological biomarkers of type I, III and IV collagen formation (Pro-C1, Pro-C3 and Pro-C4, respectively) and MMP-mediated degradation (C1M, C3M and C4M respectively). The chronic inflammation was measured by CRPM (MMP degraded metabolite of CRP). All biomarkers were measured by competitive ELISAs and levels were compared to the reference levels of healthy individuals. The biomarker data was log2 transformed for normalization and standard parametric statistical methods were applied.Results We found that there was an increase in the degradation of interstitial matrix (represented by C1M and C3M) which was uncompensated with either decreased (Pro-C1) or unaltered (Pro-C3) formation in patients with PsA as compared to healthy individuals. On the contrary, there was a compensated increase in basement membrane remodeling in patients with PsA as represented by increase in both C4M and Pro-C4 in comparison to healthy individuals (Table 1). Interestingly, there was a strong correlation between baseline C4M and Pro-C4 (r=0.703, p<0.0001), and 24-week changes in both biomarkers (r=0.468, p<0.0001) pointing towards coupling between the two processes which was either lost or was weak in case of interstitial collagens. As baseline values and changes in C1M, C3M, C4M and Pro-C4 showed a strong correlation with changes in inflammatory biomarkers, we believe that ECM remodeling in PsA is, at least partly, driven by inflammation. Furthermore, baseline values and changes in these ECM turnover biomarkers correlated positively with changes in composite disease activity scores (Table 2) that may indicate their clinical importance as potential diagnostic or disease activity markers.Conclusion Chronic inflammation underlying PsA pathology results in an increased amount of ECM turnover that correlates with clinical progression and can be measured by serological biomarkers.References NoneDisclosure of Interests Samra Sardar Employee of: I am a full time employee at Nordic Bioscience, Salome Kristensen: None declared, Anne Sofie Siebuhr Employee of: I am a full-time employee in Nordic Bioscience, Jeppe Christensen: None declared, Morten Karsdal Shareholder of: I own shares of Nordic Bioscience, Employee of: I am a full-time employee in Nordic Bioscience, Annette Mortensen: None declared, Anne-Christine Bay-Jensen Shareholder of: I own shares of Nordic Bioscience, Employee of: I am a full-time employee in Nordic Bioscience

AB - Background With our increasing understanding of cross-talk between the immune system (immune cells, cytokines) and extracellular matrix (ECM) of the affected tissues, ECM destruction and turnover has gained a lot of attention in inflammatory arthritis. ECM mainly consists of interstitial matrix (rich in type I and III collagens) and basement membrane (mainly composed of type IV collagen), both of which are affected in inflammatory arthritis. We hypothesize that inflammatory milieu in Psoriatic Arthritis (PsA) leads to accelerated ECM destruction and remodeling, and the release of ECM metabolites into circulation, that can be measured in serum as biomarkers of tissue remodeling and may give insight to pathological process at the tissue level.Objectives This prospective study aimed to use serological biomarkers for evaluation of the extent of damage to, and changes in turnover of ECM in patients with PsA and to investigate their relation to inflammatory biomarkers and disease activity.Methods Patients with PsA (n=145) fulfilling the CASPAR criteria and above 18 years of age with any disease activity were recruited through outpatient department in Aalborg University Hospital, Denmark. Exclusion criteria were pregnancy, treatment with biological DMARD, or with oral corticosteroids and other comorbidities. Clinical disease parameters were recorded, and blood samples were collected at baseline and 24 weeks follow-up. Inflammation-related ECM remodelling was measured by serological biomarkers of type I, III and IV collagen formation (Pro-C1, Pro-C3 and Pro-C4, respectively) and MMP-mediated degradation (C1M, C3M and C4M respectively). The chronic inflammation was measured by CRPM (MMP degraded metabolite of CRP). All biomarkers were measured by competitive ELISAs and levels were compared to the reference levels of healthy individuals. The biomarker data was log2 transformed for normalization and standard parametric statistical methods were applied.Results We found that there was an increase in the degradation of interstitial matrix (represented by C1M and C3M) which was uncompensated with either decreased (Pro-C1) or unaltered (Pro-C3) formation in patients with PsA as compared to healthy individuals. On the contrary, there was a compensated increase in basement membrane remodeling in patients with PsA as represented by increase in both C4M and Pro-C4 in comparison to healthy individuals (Table 1). Interestingly, there was a strong correlation between baseline C4M and Pro-C4 (r=0.703, p<0.0001), and 24-week changes in both biomarkers (r=0.468, p<0.0001) pointing towards coupling between the two processes which was either lost or was weak in case of interstitial collagens. As baseline values and changes in C1M, C3M, C4M and Pro-C4 showed a strong correlation with changes in inflammatory biomarkers, we believe that ECM remodeling in PsA is, at least partly, driven by inflammation. Furthermore, baseline values and changes in these ECM turnover biomarkers correlated positively with changes in composite disease activity scores (Table 2) that may indicate their clinical importance as potential diagnostic or disease activity markers.Conclusion Chronic inflammation underlying PsA pathology results in an increased amount of ECM turnover that correlates with clinical progression and can be measured by serological biomarkers.References NoneDisclosure of Interests Samra Sardar Employee of: I am a full time employee at Nordic Bioscience, Salome Kristensen: None declared, Anne Sofie Siebuhr Employee of: I am a full-time employee in Nordic Bioscience, Jeppe Christensen: None declared, Morten Karsdal Shareholder of: I own shares of Nordic Bioscience, Employee of: I am a full-time employee in Nordic Bioscience, Annette Mortensen: None declared, Anne-Christine Bay-Jensen Shareholder of: I own shares of Nordic Bioscience, Employee of: I am a full-time employee in Nordic Bioscience

U2 - 10.1136/annrheumdis-2019-eular.5576

DO - 10.1136/annrheumdis-2019-eular.5576

M3 - Conference abstract in journal

VL - 78

SP - 867

EP - 867

JO - Annals of the Rheumatic Diseases

JF - Annals of the Rheumatic Diseases

SN - 0003-4967

IS - Suppl. 2

M1 - FRI0370 

ER -