Uncoupling of Collagen II Metabolism in Newly Diagnosed, Untreated Rheumatoid Arthritis Is Linked to Inflammation and Antibodies Against Cyclic Citrullinated Peptides

Christensen, Anders Lyhne; Hørslev‐Petersen, Kim; Stephan, Carsten; Lindegaard, Hanne; Lottenburger, Tine; Junker, Kirsten; Hetland, Merete Lund; Stengaard‐Pedersen, Kristian; Jacobsen, Søren; Ellingsen, Torkell; Andersen, Lis Smedegaard; Hansen, I.; Skjødt, Henrik; Pedersen, J. Boiden; Lauridsen, Ulrik Birk; Svendsen, Anders Jørgen; Tarp, Ulrik; Pødenphant, Jan; Heegaard, Niels H. H.; Vestergaard, Aage; Jurik, Anne Grethe; Østergaard, Mikkel; Junker, Peter

doi:10.3899/jrheum.091265

Cited by 13 publications

(16 citation statements)

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“…However, the CIMESTRA study reports on a correlation between markers of cartilage catabolism (Ctelopeptide of collagen II) and disease [42]. DAS 28 and CRP represent systemic inflammation beyond the single joint examined in MRI and are not specific; involvement of MCP II was an inclusion criterion in the present study and severe inflammation of other joints did not lead to exclusion.…”

Section: Discussionmentioning

confidence: 76%

Cartilage quality in rheumatoid arthritis: comparison of T2* mapping, native T1 mapping, dGEMRIC, ΔR1 and value of pre-contrast imaging

et al. 2011

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Section: Discussionmentioning

confidence: 76%

Cartilage quality in rheumatoid arthritis: comparison of T2* mapping, native T1 mapping, dGEMRIC, ΔR1 and value of pre-contrast imaging

et al. 2011

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“…There was no difference between anti-CCP-positive and anti-CCP-negative patients with respect to demographic or clinical variables, except that anti-CCP-positive patients had fewer tender joints [8 (5-15) vs 11 (7)(8)(9)(10)(11)(12)(13)(14)(15)(16); p = 0.02] and were more frequently carriers of the SE [82/93 (88%) vs 34/65 (52%); p < 0.001] compared with anti-CCP-negative individuals.…”

Section: Rheumatologymentioning

confidence: 99%

“…Thus, Turesson, et al recently reported increased COMP levels in individuals who developed RA within 1-2 years, and elevated COMP was more likely in anti-CCP-negative subjects than in anti-CCP-posi tive individuals 11 . We recently reported that the N-propeptide of collagen IIA (PIIANP), a marker of cartilage collagen anabolism, is significantly lower in anti-CCP-positive compared to anti-CCP-negative patients with RA 12 . As well, we found a negative correlation between PIIANP and anti-CCP titer in serum 12 .…”

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confidence: 99%

“…We recently reported that the N-propeptide of collagen IIA (PIIANP), a marker of cartilage collagen anabolism, is significantly lower in anti-CCP-positive compared to anti-CCP-negative patients with RA 12 . As well, we found a negative correlation between PIIANP and anti-CCP titer in serum 12 . These observations indicate that autoimmunity reflected by anti-CCP is implicated in the pathogenesis of RA by suppressing collagen II formation.…”

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confidence: 99%

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Cartilage Oligomeric Matrix Protein Associates Differentially with Erosions and Synovitis and Has a Different Temporal Course in Cyclic Citrullinated Peptide Antibody (Anti-CCP)-positive versus Anti-CCP-negative Early Rheumatoid Arthritis

Christensen¹,

Lindegaard²,

Hørslev‐Petersen³

et al. 2011

J Rheumatol

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Objective.Cyclic citrullinated peptide antibody (anti-CCP)-positive and anti-CCP-negative rheumatoid arthritis (RA) have been suggested as 2 distinctive disease subsets with respect to disease activity and prognosis. Previously, we proposed that anti-CCP antibodies might have a chondrocyte-suppressive effect. We aimed to compare circulating cartilage oligomeric matrix protein (COMP), a marker of cartilage turnover, in untreated anti-CCP-positive and anti-CCP-negative RA, and to study the temporal pattern of COMP through 4 years of treatment, including the relationship to imaging and clinical findings.Methods.A total of 160 patients with newly diagnosed RA who were naive to disease-modifying antirheumatic drugs were included in the CIMESTRA trial. Ninety healthy blood donors served as controls. Demographic and disease measures including Disease Activity Score in 28 joints, IgM rheumatoid factor, anti-CCP, Health Assessment Questionnaire, visual analog scale scores for pain and global and physician assessment, and magnetic resonance imaging (MRI) of the nondominant hand were recorded at baseline. COMP in serum was measured by ELISA at inclusion and serially through 4 years.Results.Median baseline COMP was higher in patients with RA [9.8 U/l (interquartile range 8.96, 10.5)] compared with controls [8.3 U/l (IQR 7.84, 8.9); p < 0.001] and remained elevated at 4 years [10.8 U/l (IQR 10.2, 11.7); p < 0.001]. At baseline, anti-CCP-positive patients had lower COMP than anti-CCP-negative patients (p = 0.048). In anti-CCP-positive patients, COMP exhibited a parabolic course over 4 years, while COMP in anti-CCP-negative patients had an almost linear course. In anti-CCP-positive patients, COMP was associated with MRI edema and erosion score, while COMP was correlated with synovitis score in anti-CCP-negative individuals.Conclusion.Our study provides additional evidence for the existence of different disease pathways in anti-CCP-positive and anti-CCP-negative subsets of RA, and evidence that anti-CCP antibodies may be implicated in the disease process by modifying cartilage metabolism.

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“…Furthermore, galectin-3 was associated with bone marrow edema score of the wrist at baseline and remained elevated during 12 months of follow-up despite a targeted, synovitis-suppressive treatment strategy [15]. Conversely, we have previously reported that a seromarker of cartilage regeneration (type IIA collagen N-terminal propeptide (PIIANP)) is decreased in newly diagnosed RA [16–18] while hyaluronan (HYA), a marker of synovial swellings, is increased [19, 20]. …”

Section: Introductionmentioning

confidence: 99%

Increased galectin-3 may serve as a serologic signature of pre-rheumatoid arthritis while markers of synovitis and cartilage do not differ between early undifferentiated arthritis subsets

et al. 2017

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BackgroundUndifferentiated arthritis (UA) is a label applied to patients with joint complaints which cannot be classified according to current criteria, which implies a need for precision diagnostic technologies. We studied serum galectin-3, a proinflammatory mediator, and seromarkers of structural joint elements in patients with early, UA and their associations with disease profile and biochemical and imaging findings.MethodsOne hundred and eleven UA patients were followed-up for at least 12 months and reclassified according to appropriate criteria (TUDAR). At baseline, demographics and laboratory and clinical disease measures, as well as wrist magnetic resonance imaging (MRI) synovitis, erosion, and bone marrow edema scorings, were recorded. Galectin-3, the type IIA collagen N-terminal propeptide (PIIANP), which is a marker of regenerative cartilage formation, and hyaluronan (HYA), which is prevalent in synovial tissue swellings, were measured by enzyme-linked immunosorbent assay (ELISA). Receiver operating characteristic (ROC) curve analysis was carried out to assess the discriminant capacity of galectin-3 against arthritis subsets.ResultsGalectin-3 was increased in pre-rheumatoid arthritis (RA) (4.6 μg/l, interquartile range (IQR) 3.8–5.5) versus non-RA (4.0 μg/l, IQR 3.1–4.9; p = 0.03) and controls (3.8 μg/l, IQR 3.0–4.8; p = 0.009). PIIANP was equally depressed in either subset (p < 0.01). Galectin-3 in non-RA and HYA in UA did not differ from healthy controls. In the entire UA cohort, galectin-3 correlated with the MRI bone marrow edema score, while PIIANP correlated with the MRI erosion score, and HYA with the synovitis and erosion scores. ROC curve analysis showed that baseline galectin-3 discriminated well between pre-RA and non-RA with univariate area under the curve (AUC) of 0.64 (95% confidence interval (CI) 0.53–0.76) while AUC for galectin-3 + anti-CCP increased to 0.71 (95% CI 0.59–0.83).ConclusionsGalectin-3 in serum was increased in patients with early UA of pre-RA origin. Cartilage remodeling assessed by PIIANP was diminished in UA irrespective of subsequent clinical differentiation, while HYA did not differ from controls. ROC analysis showed a potential for galectin-3 to discriminate between pre-RA and non-RA.Trial registrationKF 11 315829. Registered 25 July 2006.

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Uncoupling of Collagen II Metabolism in Newly Diagnosed, Untreated Rheumatoid Arthritis Is Linked to Inflammation and Antibodies Against Cyclic Citrullinated Peptides

Cited by 13 publications

References 45 publications

Cartilage quality in rheumatoid arthritis: comparison of T2* mapping, native T1 mapping, dGEMRIC, ΔR1 and value of pre-contrast imaging

Cartilage quality in rheumatoid arthritis: comparison of T2* mapping, native T1 mapping, dGEMRIC, ΔR1 and value of pre-contrast imaging

Cartilage Oligomeric Matrix Protein Associates Differentially with Erosions and Synovitis and Has a Different Temporal Course in Cyclic Citrullinated Peptide Antibody (Anti-CCP)-positive versus Anti-CCP-negative Early Rheumatoid Arthritis

Increased galectin-3 may serve as a serologic signature of pre-rheumatoid arthritis while markers of synovitis and cartilage do not differ between early undifferentiated arthritis subsets

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