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Featured researches published by Heidi Lausten Munk.


BMJ Open | 2018

Efficacy and safety of faecal microbiota transplantation in patients with psoriatic arthritis: protocol for a 6-month, double-blind, randomised, placebo-controlled trial

Maja Skov Kragsnaes; Jens Kjeldsen; Hans Christian Horn; Heidi Lausten Munk; Finn M o̸ ller Pedersen; Hanne Marie Holt; Jens Kristian Pedersen; Dorte Kinggaard Holm; Henning Glerup; Vibeke Andersen; Ulrich Fredberg; Karsten Kristiansen; Robin Christensen; Torkell Ellingsen

Introduction An unbalanced intestinal microbiota may mediate activation of the inflammatory pathways seen in psoriatic arthritis (PsA). A randomised, placebo-controlled trial of faecal microbiota transplantation (FMT) infused into the small intestine of patients with PsA with active peripheral disease who are non-responsive to methotrexate (MTX) treatment will be conducted. The objective is to explore clinical aspects associated with FMT performed in patients with PsA. Methods and analysis This trial is a randomised, two-centre stratified, double-blind (patient, care provider and outcome assessor), placebo-controlled, parallel-group study. Eighty patients will be included and randomised (1:1) to either placebo (saline) or FMT provided from an anonymous healthy donor. Throughout the study, both groups will continue the weekly self-administered subcutaneous MTX treatment, remaining on the preinclusion dosage (15–25 mg/week). The clinical measures of psoriasis and PsA disease activity used include the Short (2-page) Health Assessment Questionnaire, the Dermatology Quality of Life Index, the Spondyloarthritis Research Consortium of Canada Enthesitis Index, the Psoriasis Area Severity Index, a dactylitis digit count, a swollen/tender joint count (66/68), plasma C reactive protein as well as visual analogue scales for pain, fatigue and patient and physician global assessments. The primary end point is the proportion of patients who experience treatment failure during the 6-month trial period. The number of adverse events will be registered throughout the study. Ethics and dissemination This is a proof-of-concept clinical trial and will be performed in agreement with Good Clinical Practice standards. Approvals have been obtained from the local Ethics Committee (DK-S-20150080) and the Danish Data Protection Agency (15/41684). The study has commenced in May 2017. Dissemination will be through presentations at national and international conferences and through publications in international peer-reviewed journal(s). Trial registration number NCT03058900; Pre-results.


Scandinavian Journal of Rheumatology | 2017

No diagnostic utility of antibody patterns against Klebsiella pneumoniae capsular serotypes in patients with axial spondyloarthritis vs. patients with non-specific low back pain: a cross-sectional study

Louise Thuesen Hermansen; Anne Loft; Alice Christiansen; Heidi Lausten Munk; Leona Gilbert; Anne Grethe Jurik; Bodil Arnbak; Claus Manniche; U Weber; Mikkel Østergaard; Susanne Juhl Pedersen; Torben Barington; Peter Junker; Kim Hørslev-Petersen; Oliver Hendricks

Objectives: To investigate whether antibody response patterns against Klebsiella pneumoniae capsular serotypes can discriminate patients with axial spondyloarthritis (axSpA) from patients with non-specific low back pain (LBP). Method: Immunoglobulin (Ig)G and IgA antibodies against K. pneumoniae capsular serotypes K2, K26, K36, and K50 were measured, and antibody seropositivity compared between groups and analysed for patient correlation in five different groups: (a) 96 patients fulfilling the Assessment of SpondyloArthritis International Society (ASAS) classification criteria for axSpA; (b) 38 patients with either a positive magnetic resonance imaging (MRI) scan as defined by ASAS or a positive human leucocyte antigen (HLA)-B27 status plus one clinical SpA feature, characterized as ‘non-axSpA’; (c) 82 non-specific LBP patients; (d) 40 healthy blood donors and (e) 43 patients with diagnosed ankylosing spondylitis (AS) served as the negative and positive control groups. Results: There was no difference in IgG and IgA seropositivity against all serotypes between the axSpA, non-axSpA, and LBP groups. No significant correlations were found between anti-Klebsiella antibodies and age, gender, HLA-B27, or high-sensitivity C-reactive protein (hsCRP). IgG seropositivity against K50 was more frequent in AS (25.6%) than in axSpA (13.5%, p < 0.05). axSpA patients with radiographic sacroiliitis and AS controls concordantly had the highest frequency of seropositivity for ≥ 2 serotypes (21%). Conclusions: The antibody patterns against K. pneumoniae serotypes K2, K26, K36, and K50 did not discriminate between early axSpA and non-specific LBP.


Osteoarthritis and Cartilage | 2014

Heritability assessment of cartilage metabolism. A twin study on circulating procollagen IIA N-terminal propeptide (PIIANP).

Heidi Lausten Munk; Anders Jørgen Svendsen; Jacob von Bornemann Hjelmborg; Grith Lykke Sørensen; Kirsten Ohm Kyvik; Peter Junker

OBJECTIVE The aim of this investigation was to estimate the heritability of circulating collagen IIA N-terminal propeptide (PIIANP) by studying mono- and dizygotic healthy twin pairs at different age and both genders. DESIGN 598 monozygotic (MZ) and dizygotic (DZ) twin individuals aged 18-59 years were recruited from the Danish Twin Registry. PIIANP was measured by competitive ELISA. The similarity of circulating PIIANP among MZ and DZ twins was assessed by intraclass correlations according to traits. The heritability was estimated by variance component analysis accounting for additive and dominant genetic factors as well as shared and non-shared environment but ignoring epistasis (genetic inter-locus interaction) and gene-environment interaction. RESULTS The intraclass correlation of PIIANP in MZ and DZ twins was 0.69 (0.60-0.76) and 0.46 (0.34-0.58) respectively indicating a significant genetic impact on PIIANP in serum. Additive genetic effects explained 45% (21-70%), shared environment 24% (7-53%) and non-shared environment 31% (24-39%) of the total variance. The heritability estimate did not differ across ages and between genders. CONCLUSIONS The study shows that approximately 45% of the collagen IIA synthesis as assessed by the collagen IIA N-terminal propeptide in serum is attributable to genetic effectors while individual and shared environment account for 24% and 31% respectively. The heritability does not differ between genders or according to age.


Rheumatology | 2018

Surfactant protein-D, a potential mediator of inflammation in axial spondyloarthritis

Heidi Lausten Munk; Dalia Fakih; Lene Christiansen; Qihua Tan; Anne Friesgaard Christensen; Anne Loft; Kirsten Junker; Kirsten Ohm Kyvik; Rania Jounblat; Uffe Holmskov; Grith Lykke Sørensen; Peter Junker

Objectives Surfactant protein-D (SP-D), an innate immune defence molecule of the collectin family, is expressed in lungs and additional extrapulmonary epithelia. SP-D has immune modulatory and anti-microbial effects depending on its oligomerization. The ratio of high molecular weight (HMW): low molecular weight (LMW) SP-D in serum is mainly determined by the Met11Thr polymorphism (SNP rs721917). We aimed to study the SP-D serum level and the molecular size distribution in patients with untreated axial spondyloarthritis (axSpA) as compared with control subjects. Methods Thirty-four patients with disease modifier untreated axSpA according to the ASAS criteria, age 19-63 years, disease duration 3.9 (2.2-5.6) years were included. Demographics, smoking habits, HLA-B27 status, ASDAS, BASDAI, BASFI, BASMI and visual analogue scale scores were recorded. SP-D in serum was measured by ELISA. DNA was isolated from whole blood and single nucleotide polymorphism rs721917 was genotyped. SP-D molecular size distribution was determined using gel filtration chromatography. Results SP-D in serum did not differ between patients with axSpA and healthy controls, 1177 (869, 1536) vs 910 (494, 1682) (P = 0.35) and SP-D did not correlate with disease activity. However, the HMW/LMW ratio of SP-D in serum was significantly lower in axSpA, 0.38 (0.18, 0.53) compared with controls 1.49 (0.37, 3.24) when adjusting for the Met11Thr polymorphism, gender, age, BMI and smoking (P = 0.0004). There was no correlation between HMW/LMW ratio and CRP or composite diseases outcome measures. Conclusion We suggest that predominance of LMW oligomeric variants of SP-D may enhance local or systemic inflammatory responses in axSpA.


BMJ Open | 2018

Impact of red and processed meat and fibre intake on treatment outcomes among patients with chronic inflammatory diseases: protocol for a prospective cohort study of prognostic factors and personalised medicine

Robin Christensen; Berit L. Heitmann; Karina Winther Andersen; Ole Haagen Nielsen; Signe Bek Sørensen; Mohamad Jawhara; Anette Bygum; Lone Hvid; Jakob Grauslund; Jimmi Wied; Henning Glerup; Ulrich Fredberg; Jan Alexander Villadsen; Søren Geill Kjær; Jan Fallingborg; Seyed A G R Moghadd; Torben Knudsen; Jacob Broder Brodersen; Jesper Frøjk; Jens Frederik Dahlerup; Anders Bojesen; Grith Lykke Sørensen; Steffen Thiel; Nils J. Færgeman; Ivan Brandslund; Tue Bjerg Bennike; Allan Stensballe; Erik Berg Schmidt; Andre Franke; David Ellinghaus

Introduction Chronic inflammatory diseases (CIDs) are frequently treated with biological medications, specifically tumour necrosis factor inhibitors (TNFi)). These medications inhibit the pro-inflammatory molecule TNF alpha, which has been strongly implicated in the aetiology of these diseases. Up to one-third of patients do not, however, respond to biologics, and lifestyle factors are assumed to affect treatment outcomes. Little is known about the effects of dietary lifestyle as a prognostic factor that may enable personalised medicine. The primary outcome of this multidisciplinary collaborative study will be to identify dietary lifestyle factors that support optimal treatment outcomes. Methods and analysis This prospective cohort study will enrol 320 patients with CID who are prescribed a TNFi between June 2017 and March 2019. Included among the patients with CID will be patients with inflammatory bowel disease (Crohn’s disease and ulcerative colitis), rheumatic disorders (rheumatoid arthritis, axial spondyloarthritis, psoriatic arthritis), inflammatory skin diseases (psoriasis, hidradenitis suppurativa) and non-infectious uveitis. At baseline (pretreatment), patient characteristics will be assessed using patient-reported outcome measures, clinical assessments of disease activity, quality of life and lifestyle, in addition to registry data on comorbidity and concomitant medication(s). In accordance with current Danish standards, follow-up will be conducted 14–16 weeks after treatment initiation. For each disease, evaluation of successful treatment response will be based on established primary and secondary endpoints, including disease-specific core outcome sets. The major outcome of the analyses will be to detect variability in treatment effectiveness between patients with different lifestyle characteristics. Ethics and dissemination The principle goal of this project is to improve the quality of life of patients suffering from CID by providing evidence to support dietary and other lifestyle recommendations that may improve clinical outcomes. The study is approved by the Ethics Committee (S-20160124) and the Danish Data Protecting Agency (2008-58-035). Study findings will be disseminated through peer-reviewed journals, patient associations and presentations at international conferences. Trial registration number NCT03173144; Pre-results.


Annals of the Rheumatic Diseases | 2016

SAT0028 Circulating Surfactant Protein-D (SP-D) Molecular Size Profile Differs between Patients with Untreated Axial Spondyloarthritis and Healthy Control Subjects

Heidi Lausten Munk; D. Fakih; Grith Lykke Sørensen; Qihua Tan; Lene Christiansen; Anne Friesgaard Christensen; Anne Loft; Kirsten Ohm Kyvik; R. Jounblat; Uffe Holmskov; Peter Junker

Background Surfactant protein-D (SP-D), an innate immune defence molecule of the collectin family has immune modulatory and anti-microbial effects and is expressed in lungs and on mucosal surfaces. The molecule consists of subunits ordered as trimers, dodecamers and even higher multimers. In healthy adults genes are responsible for the majority of the quantitative variation of SP-D in serum as well as its molecular size distribution1. High Molecular weight (HMw) SP-D is suggested to have anti-inflammatory properties, while low Mw (LMw) variants lack this capacity. In spondyloarthritis (SpA) SP-D correlates negatively with hsCRP and positively with patient global assessment. LMw variants have been shown to prevail in serum during inflammatory flares in chronic obstructive pulmonary disease. Objectives To investigate the distribution of SP-D HMw and LMw variants in serum among patients with SpA and controls according to the Met11Thr polymorphism. Methods 34 patients with SpA (age 22–63) according to the ASAS criteria, receiving NSAIDs only and 57 healthy controls (age 10–75) were included (Table 1). Total SP-D in serum was measured by ELISA and SNP rs721917 was genotyped. SP-D molecular size distribution was assessed using gel filtration chromatography. Integration of the area under the curves was performed to determine the ratio between HMw and LMw SP-D in serum. Results SP-D in SpA was in the normal range, 1092 ng/ml (725;1541) vs. controls, 910 ng/ml (494; 1682). Whereas the ratio of HMw:LMw serum SP-D was lower in SpA patients, 0.38 (0.18;0.53) compared to controls 1.49 (0.37; 3.24) even when adjusting for the Met11Thr polymorphism, gender, age, BMI and smoking (Table 2). Tabel 1. Characteristics of patients and controls SpA (n=34) Control (n=57) P-value Sex (% male) 71% 42% <0.0001 (Fisher test) Age (y) 36.4 (33.3- 39.6) 39.7 (35.8–43.6) 0.13 (Unpaired t-test) Smoker 32% 51% 0.006 (Fisher test) BMI (kg/m2) 25.3 (23.7–26.9) 25.6 (24.0–27.3) 0.69 (Mann-Whitney test) HLA-B27 82% – – NSAID 88% – – Met11/Met11 8 (24%) 21 (37%) Met11/Thr11 19 (58%) 18 (32%) Thr11/Thr11 6 (18%) 18 (32%) SP-D (ng/ml) 1092 (725; 1541) 910 (494; 1682) 0.35 H/L Mw SP-D ratio 0.38 (0.18; 0.53) 1.49 (0.37; 3.24) 0.0004 Age, BMI: mean with 95% CI. SP-D and H/L Mw SP-D ratio: median with 25 and 75% percentile. Mann-Whitney test was used to compare SP-D levels and H/L Mw SP-D ratios. Tabel 2. Ratio of HMw and LMw serum SP-D ratio between controls and SpA according to Met11Thr polymorphism H/L Mw SP-D ratio Control SpA Difference 95% CI P-value Met11/Met11 4,14 1,38 −2,76 −3.60 to −1.93 P<0.001 Met11/Thr11 1,51 0,36 −1,15 −1.84 to −0.46 P<0.001 Thr11/Thr11 0,22 0,06 −0,16 −1.15 to 0.83 P>0.05 Conclusions The molecular size distribution of circulating SP-D in patients with SpA is skewed towards preponderance of small size molecular variants. SpA related disease mechanisms may disrupt the multimeric state of SP-D, thereby amplifying the inflammatory burden of the disease. References Leth-Larsen R. J Immunol 2005;174:1532–8 Disclosure of Interest None declared


Arthritis & Rheumatism | 2015

Fingerprint biomarkers of type I and III collagen in axial spondyloarthropathy (axspa) and psoriatic arthritis (psa). Association with disease activity and diagnostic capacity

N. S. Gudman; Anne Friesgaard Christensen; Grith Lykke Sørensen; Anne-Christine Bay Jensen; Anne Sofie Siebuhr; Morten A. Karsdal; Heidi Lausten Munk; Anne Loft; Peter Junker

Are Ankylosing Spondylitis, Psoriatic Arthritis and Undifferentiated Spondylarthritis Associated with an Increased Risk of Cardiovascular Disease?For a searchable version of these abstracts, please visit www.acrabstracts.org. Please Note: It may take several minutes for this file to download.Background/Purpose: Person-centred care (PCC) is a holistic approach with respectful and individualized care allowing negotiation of care where persons with health problems are empowered to be involved in health decisions. Patients’ illness narratives constitute a starting point for building a collaboration with health care professionals and to empower them to play an active role in their health care. Little is known of the impact of PCC vs. regular care on patients’ skills as health care consumers. The aim was to study the impact on effective consumers’ skills over 6 and 12 months as measured by the Effective Consumer Scale (EC17) in patients undergoing biological therapy and randomly assigned to either a nurse-led rheumatology clinic (NLC) based on PCC or to a rheumatologist-led clinic (RLC) based on regular care.Methods: A 12 month RCT in 107 patients with chronic inflammatory arthritis1. Inclusion criteria were ongoing biological therapy and a DAS28 ≤3.2. All patients met a rheumatologist at inclusion and after 12 months, while the 6 month follow-up was randomized to either at an NLC (PCC) or at an RLC (regular care). Outcome measure was the EC17, developed and endorsed by the OMERACT, including five subscales; 1. Use of health information, 2. Clarifying personal priorities, 3. Communicating with others, 4. Negotiating roles and 5. Deciding and taking action. EC17 total score ranges from 0-100, worse to best. Differences between and within NLC and RLC were analyzed with Friedmans’ test or Mann Whitney U-test.Results: After 12 months 97 patients completed the RCT (NLC n=47, RLC n=50), mean (SD) age 55.4 (12.7) years, disease duration 16.7 (11.5) years, DAS28 2.1 (0.7), HAQ 0.54 (0.38), global health 20.4 (17.1), pain 21.1 (18.0) and 56% were women. There were no statistically significant differences within or between the two intervention groups at baseline nor in EC17 total score mean (SD) at baseline (NLC 83.5 (9.4) vs. RLC 83.2 (10.8), 6 months (NLC 85.4 (10.4) vs. RLC 82.9 (10.9) and 12 months (NLC 85.3 (11.1) vs. RLC 82.3 (10.9)). However, in NLC there was a statistically significant improvement in EC17 subscale “1. Use of health information” at both 6 and 12 months (p=0.041 and p=0.004 respectively).Conclusion: Replacing just one of three visits over 12 months to an NLC based on PCC instead of an RLC based on regular care resulted in more effective consumers concerning the use of health information. Larger studies over longer time frames focusing on PCC are needed to better understand its full impact on effective consumer skills measured by EC17.References:1. Larsson I, et al. Randomized controlled trial of a nurse-led rheumatology clinic for monitoring biological therapy. J Adv Nurs 2014;70:164-75.Background/Purpose: Chronic widespread pain (CWP), one of the hallmarks of fibromyalgia, is not uncommon in adolescents and it has previously been shown that adolescents with pain often become young adults with pain. CWP often co-varies with anxiety, depression, and stress symptoms in adults, but the knowledge regarding this is small in youth and young adults.The aim was to study the associations between CWP, anxiety, depression and stress in adolescents attending first year of high school.Methods: A computerized questionnaire to 296 adolescents attending Swedish high school, with validated questions regarding presence and distribution of pain (Epipain mannequin), stress symptoms (ELO question), anxiety and depression (Hospital Anxiety and Depression Scale – HADS), and health related quality of life (HRQL as measured by EQ5D). Pain was considered chronic when persistent for more than three months, and the subgroup CWP was defined according to the 1990 ACR criteria for fibromyalgia. Statistical analyses in SPSS v21 with comparison of means by Student’s t-test and proportions by chi2-test or Fischer’s exact test.Results: 257 (87%) out of 296 eligible students, mean (SD) age 16.1 (0.7) and 65.8% girls, responded to the questionnaire. Prevalence of chronic pain was 20.8% and that of the subgroup CWP was 4.7%, without any gender differences (boys 18.2% vs girls 22.2%; p=0.224, and 3.4% vs 5.4%; p=0.692). High level (4 or 5 on a 5 point scale) of stress symptoms were less common in boys (16.0% vs 28.2%; p=0.015), as was possible or probable anxiety (17.1% vs 44.4%; p<0.001), but not depression (10.3% vs 12.5%; p=0.764). Students with high level of stress reported CWP five times more often than those with less stress (30.4% vs 5.8%; p=0.001). Students with probable anxiety reported CWP ten times more often than students with no anxiety (17.6% vs 1.8%; p=0.001), and CWP was also more common, but not statistically significant, in students with probable depression (20.0% vs 3.1%; p=0.163). Those reporting CWP had significantly lower HRQL (0.58 vs 0.87; p=0.038) than students with no chronic pain.Conclusion: The high prevalence of chronic pain and the strong associations between CWP and reports of stress and anxiety in adolescents highlights that a multifactorial background to chronic pain must be considered early in life. An apparent lower score in EQ5D also indicates that the presence of CWP has an marked impact on HRQL also in adolescents.Background/Purpose: The treatment target for axial spondyloarthritis (SpA) is to maximize health-related quality of life (HRQoL) by controlling disease activity and improving functioning. The treatment cornerstones are a combination of patient education, pharmacological and non-pharmacological treatment. Health professionals are familiar with providing patient education but the knowledge is scarce concerning how this education is experienced by the patients.The aim was to describe patients’ experiences of education in SpA management.Methods: The study had a descriptive design with a qualitative conventional content analysis approach performed in seven steps in accordance with Graneheim & Lundman (1). The analysis aimed to describe and preserve contextual meanings. After coding and subgrouping meaningful parts of the text were merged into categories. Eleven interviews were conducted between 2014-2015 in patients with SpA based on a strategic sampling in order to achieve variation with regard to sex (7 men, 4 women), age (38-66 years), subdiagnoses (5 patients with AS, 6 with USpA), quality of life (EQ5D 0.29-1.0), disease activity (BASDAI 1-6), physical function (BASFI 0-5), and global health (BASG 0-7) .Results: Three categories representing patients’ experiences of patient education in disease management emerged; guiding education, reliable education and available education. Guiding education comprised SpA management including disease knowledge such as symptoms, prognosis, treatment, self-management, climate impact, heredity, and assisting devices. Reliable education meant how and by whom the education was communicated and was considered reliable if it was based on science and communicated by specialists, for example by physician, nurse, PT, dietician and senior patients with experience of rheumatic diseases. The patients experienced difficulties in assessing the large flow of education coming from various sources. Individualized education also increased the reliability. Available education meant that the education can and should be presented in varied formats, and that the amount of information could be chosen. The education could be given orally (through meetings, videos, lectures), in writing (by pamphlets, e-mails, journals, webpages) or obtained through own personal experiences. There were requests to utilize newer media like skype, video and chat forums. Furthermore, individual contacts with healthcare professionals when needed were of importance.Conclusion: This study highlights the importance of obtaining a guiding, reliable and available patient education for management of SpA. Health care professionals need to consider the importance of presenting varied formats of education based on patients’ experiences and expectations.References:1.Graneheim UH, Lundman B. Qualitative content analysis in nursing research: concepts, procedures and measures to achieve trustworthiness. Nurse education today 2004;24(2):105-12.PMN Reactivity Contribute to Acute Onset Joint Inflammation By Increasing CXCL8 Production in Joints of RA Patients with Anti-Collagen II AntibodiesBig Data International Primary Sjogren Syndrome Registry : Baseline Characterization and Diagnostic Approach in 6047 Patients Fulfilling the 2002 AE CriteriaThe Link Between DAS28 and the Short-Term Risk of Acute Coronary Syndrome in RA, and Its Driving FactorsHypomethylation in Enhancer and Promoter Regions of Interferon Regulated Genes in Multiple Tissues Is Associated with Primary Sjogrens SyndromeReceptor Activator of Nuclear Factor Kappa-B Ligand (RANKL) and Sclerostin Are Related to Joint Destruction in Early Rheumatoid Arthritis Unrelated to Polymorphisms of the Genes


Annals of the Rheumatic Diseases | 2014

THU0512 Surfactant Protein-D, A Component of the Innate Immune Defence, in Patients with Axial Spondyloarthritis or Psoriatic Arthritis

Heidi Lausten Munk; Grith Lykke Sørensen; Anne Friesgaard Christensen; Anne Loft; Uffe Holmskov; Peter Junker

Background Surfactant protein-D (SP-D) belongs to the collectin family of the innate immune system. It has pro- and anti-inflammatory activities according to its oligomerization. Microbial opsonization and scavenging of nuclear debris are among its important properties. Serum SP-D exhibits a biphasic course with acute bacterial infections and increases during flares of COPD. Conversely, in rheumatoid arthritis (RA) we recently reported that individuals with newly diagnosed disease had subnormal circulating levels of SP-D at baseline and 4 years on despite a treatment to target strategy. In addition we found that SP-D and CRP were inversely correlated at baseline suggesting that SP-D is implicated in the RA pathogenesis. Spondyloarthritis (SpA) and psoriatic arthritis (PsA) are chronic and usually seronegative arthritides belonging to the SpA complex. The etiopathogenesis is incompletely understood although there is evidence for an effect of genes and environmental triggers, HLA-B27 and bacterial antigens in particular. The present investigation was conducted to extend our previous studies on SP-D in RA by assessing the pattern of SP-D expression in serum among patients with SpA and PsA. Objectives To compare the serum level of SP-D in SpA and PsA with that in healthy controls. Methods Patients with SpA according to the ASAS criteria, age 18-63 years (n=108) and PsA patients fulfilling the CASPAR criteria, age 21-53 years (n=98) were included. Demographic and clinical disease measures were recorded including HAQ, BAS and hs-CRP. Healthy twin individuals, age 18-67 years (n=1476) served as controls. SP-D in serum was quantified by ELISA. SP-D was compared across patient groups and with controls using non parametric statistics. Stepwise multiple linear regression with a significance level of 0.05 was performed to study associations between SP-D, patient characteristics and disease activity measures. The model fit was assessed using appropriate residual and goodness of fit statistics. Results SP-D did not differ between patients with SpA, 1054 ng/ml (677;1462 p=0.23) and PsA patients, 962 ng/ml (730;1506 p=0.57) or healthy controls, 913 ng/ml (680;1387). Linear regression analysis showed that SP-D was positively associated with sex, patient global (VAS) and negatively associated with BMI and hs-CRP in SpA. By contrast, SP-D was only associated with smoking in PsA patients (Table). Conclusions Serum SP-D did not differ between patients with SpA, PsA and healthy controls. However, while SP-D did not associate with disease activity measures in PsA, SP-D correlated positively with clinical disease activity, and negatively with hs-CRP in axial SpA. These distinctive association profiles may relate to underlying pathogenetic disparities. The negative association between SP-D and hs-CRP in SpA may reflect that SP-D and hs-CRP are regulated in a coordinated manner, increased consumption or complex formation with inflammatory debris in active disease. Disclosure of Interest : None declared DOI 10.1136/annrheumdis-2014-eular.1540


Annals of the Rheumatic Diseases | 2013

FRI0043 Heritability assessment of cartilage collagen metabolism. a twin study on circulating pro-collagen iia n-terminal pro-peptide (piianp)

Heidi Lausten Munk; Anders Jørgen Svendsen; Kirsten Ohm Kyvik; Grith Lykke Sørensen; Jacob V. Hjelmborg; Peter Junker

Background Collagen is produced and secreted as a precursor molecule with C-and N-terminal extensions termed procollagen peptides. In the extracellular space these are cleaved off by specific C- and N-peptidases after which collagen can participate in fibril formation. Since procollagen propeptides are released from the parent molecule in a stoichiometric manner, the concentration of these peptides provides an opportunity to assess the current biosynthetic activity of the parent collagen species. Recently, the heritability of cartilage oligomeric matrix protein (COMP) in serum was estimated to 40%. (1) Objectives The aim of the investigation was to estimate heritability on circulating collagen IIA N-propeptide (PIIANP) by studying mono- and dizygotic twin pairs. Methods A total of 602 healthy monozygotic (MZ) and dizygotic (DZ) twin individuals aged 18-55 years were recruited from the Danish Twin Registry. PIIANP was measured by competitive ELISA. The similarity of circulating PIIANP among MZ and DZ twins was assessed by means of intraclass correlations for the traits. The extent to which variation in a trait is attributable to genetics (heritability) can be estimated quantitatively through variance components analysis. The phenotypic (P) variance in a trait can be separated into four variance components: variance due to additive genetic effects (A), genetic dominance (D), shared (family) environment (C) and non-shared (individual) environment (E), e.i., P = A + D + C + E. In agreement with standard practice, we assume no epistasis (genetic inter-locus interaction) and no gene-environment interaction or correlation. Results The intraclass correlation for PIIANP in MZ twins and DZ twins was 0.69 vs. 0.46. In the variance component analysis, ACE was the best fitting model. Additive genetic effects explained 45%, shared environment 24% and non-shared environment 31% of the total variance. Conclusions Our findings suggest that genetic factors have a considerable impact on the serum level of PIIANP. However, shared and common environmental factors are important modifiers as well. The close similarity between the heritability figures of PIIANP and COMP indicate that the expression of these two integral constituents of hyaline cartilage is coordinated or that they are processed in the extracellular space by shared metabolic pathways. References Williams FM, Andrew T, Saxne T, Heinegard D, Spector TD, MacGregor AJ. The heritable determinants of cartilage oligomeric matrix protein. Arthritis and rheumatism. 2006 Jul;54(7):2147-51. Disclosure of Interest None Declared


Rheumatology International | 2016

Cartilage collagen type II seromarker patterns in axial spondyloarthritis and psoriatic arthritis: associations with disease activity, smoking and HLA-B27.

Heidi Lausten Munk; Natasja Stæhr Gudmann; Anne Friesgaard Christensen; Grith Lykke Sørensen; Anne Loft; Anne C. Bay-Jensen; Anne Sofie Siebuhr; Peter Junker

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Grith Lykke Sørensen

University of Southern Denmark

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Peter Junker

Odense University Hospital

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Kirsten Ohm Kyvik

University of Southern Denmark

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Morten A. Karsdal

University of Southern Denmark

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Anders Jørgen Svendsen

University of Southern Denmark

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Natasja Stæhr Gudmann

University of Southern Denmark

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Uffe Holmskov

University of Southern Denmark

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A.-C. Bay-Jensen

University of Southern Denmark

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