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ObjectiveBone formation is a hallmark of osteoarthritis (OA). It has been speculated that bone formation may occur because of ossification at the bone-cartilage unit, that is, bone formation directly involving the calcified cartilage (CC). This study aimed to investigate the thickness of the CC and subchondral bone (SCB) in relation to the severity of the overlying articular cartilage (AC) degeneration.DesignWe investigated femoral heads from 20 patients with OA and 15 healthy subjects with design-based stereology using systematic uniform random sampling of the entire joint surface. This was combined with the Osteoarthritis Research Society International (OARSI) OA cartilage histopathology assessment system, thus obtaining focal OARSI grades paired with thickness measurements of AC, CC and the SCB.ResultsThe patients with OA had thicker CC (mean 159; 95% CI 144 to 177 µm) compared with the healthy subjects (mean 132; 95% CI 113 to 1550 µm; p=0.036), and this difference was even higher in areas without loss of AC thickness (OARSI grade ≤3); 187 (95% CI 164 to 214) µm vs 132 (95% CI 113 to 155) µm (p=0.001). In the patients with OA, a thicker SCB was observed in areas with loss of AC thickness (OARSI grade ≥4), but not in areas without loss of AC thickness (OARSI grade ≤3).ConclusionThe study showed that thicker CC is present in early stages of OA, suggesting that bone formation by endochondral ossification is an early phenomenon of OA. Thickening of the SCB was present, but only in areas with denuded bone. Suggesting that also appositional bone growth occurs and that it may be a consequence of changed biomechanics.

Background M-ficolin is a pattern recognition molecule that collaborates with associated serine proteases as an activator of the complement system. High M-ficolin levels are strongly associated with high disease activity in early RA and low levels at baseline are strong predictors of both remission and low disease activity after one year (1). Single nucleotide polymorphisms (SNPs) in the M-ficolin gene FCN1 have been shown to influence the concentration and function of M-ficolin (2) and are associated with outcome in patients with systemic inflammation. Objectives To investigate the associations of 7 FCN1 SNPs with DAS28, modified Total Sharp Score (mTSS), low disease activity (LDA, DAS28 Methods 180 DMARD naive RA patients with disease duration Results Baseline characteristics were similar in the two groups, table 1. Table 2 states the four SNPs of which the minor allele was previously shown to be associated with higher plasma M-ficolin levels in healthy adults (2). Homozygosity of the minor allele in any of these 4 SNPs was associated with higher DAS28 at both baseline (p Conclusions Homozygosity of the minor allele of 4 FCN1 SNPs is associated with higher DAS28 levels and modified Total Sharp Score in early RA. The four SNPs were the only variables capable of predicting LDA and the strongest predictors of DAS28 remission. These data consolidate our previous findings that M-ficolin, a molecule of the innate immune system, is a strong prognostic marker at both the protein and gene level. References Arthritis Rheum.2013 Dec;65(12):3045-50. PLoS One.2012;7(11):e50585 Ann Rheum Dis. 2014 Apr;73(4):654-61. Acknowledgements The authors would like to thank all participating patients, study nurses and coinvestigators Disclosure of Interest None declared

Background Single nucleotide polymorphisms (SNPs) in the C-reactive protein ( CRP) gene are implicated in the regulation of the constitutional CRP expression and its response to pro-inflammatory stimuli. Previous reports suggest that these effects may influence instruments for clinical decision-making based on CRP, e.g. DAS28. Objectives To investigate the associations between 7 CRP SNPs, their haplotypes, the serum level of CRP and DAS28 in recent onset, treatment naive RA (rheumatoid arthritis) patients. Methods 315 DMARD and steroid naive RA patients with disease duration Results The minor allele of rs1205 C>T was associated with decreased CRP levels at baseline (p=0.03). The TT genotype showed a 50% reduction in CRP from 16.7 to 8.4 mg/l (p=0.005) compared to the CC genotype. This association was not observed after one year of active treatment (p=0.38) (Table 1). The common H2 haplotype, characterized by the T allele of rs1205, was associated with a 26% reduction in CRP at baseline (p=0.04), but no effect was observed at year 1 (p=0.47) (Table 2). No other SNP or haplotype were associated with CRP at baseline or year 1 (p≥0.09). We observed no associations between SNPs or haplotypes and DAS28 scores at baseline or year 1 (p≥0.10) Conclusions This study shows that DAS28 can be used for clinical decision-making without adjustment for CRP gene variants, as CRP genotypes and haplotypes were only marginally associated with CRP levels and without any association to the DAS28 score. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.1357

The aim of the present study was to study the sensibility in the area of saline-induced muscle pain. In three experiments, ten subjects were exposed to computer-controlled infusion of 0.5 ml isotonic (0.9%) or hypertonic (9%) saline into the anterior tibial muscle. The pain intensity was assessed on a visual analogue scale (VAS). The pain threshold (PT) to pressure and electrical stimulation in muscle and subcutaneous tissues was determined. Three experiments were performed in which infusion of hypertonic saline produced significantly higher VAS scores than isotonic saline. In all three experiments, there was no significant difference in PT obtained after infusion of isotonic saline compared with infusion of hypertonic saline. In experiment 1, the PT was determined at the infusion site and 4 cm from the infusion site. At the infusion site, the pressure PT decreased (-19 +/- 2%) 1, 3, 5, 7 and 9 min after infusion of isotonic and hypertonic saline, but remained unchanged 4 cm from the infusion site. The intramuscular electrical PT at the infusion site and 4 cm from the infusion site increased significantly (29 +/- 6%) 5, 7 and 9 min after saline infusion. In experiment 2, the pressure PT and the intramuscular electrical PT were recorded after two infusions of saline separated by 1 day. The day after the first infusion, the pressure PT was decreased compared with the PT before the first infusion, but the electrical PT was not affected. Moreover, the hypertonic saline infusion given on the second day produced significantly higher (130 +/- 50%) VAS scores than the infusion given on the first day. In experiment 3, the PT was determined in the subcutaneous tissue, but no significant effects of saline infusion were found. The present placebo-controlled experiments failed to show muscular or subcutaneous hyperalgesia after saline-induced muscle pain per se.

Objectives: Pressure algometry [PA] is widely used for the study of muscle sensitivity, but this method can not distinguish between the sensitivity of superficial and deep structures. Electrical stimulation of muscle has been suggested as a method to study muscle sensitivity. At present, it is still unknown whether electrically evoked pain thresholds [PT] from muscle correlate with PT determined by percutaneous PA.Methods: Three experiments were performed to study the correlation between percutaneous pressure and electrical stimulation of the anterior tibial muscle in healthy volunteers.In the first experiment the correlation between electrical and pressure PT In the muscle was studied. In the second experiment the correlation between visual analog scale [VAS] ratings after graded stimulation with PA and electrical stimulation was examined. In the third experiment electrical and pressure PT were recorded before and after cutaneous anesthesia with lidocaine.Results: Muscle PT assessed by electrical stimula...

Background Rheumatoid arthritis (RA) is an autoimmune disease characterised by the presence of autoantibodies and autoreactive T cells, leading to synovitis and progressive destruction of the joints. The TNF-family members OX40 and OX40L are crucial for the generation of memory T cells, which can lead to persistence of immunity, if the T cells are autoreactive (1), Both molecules exist in a soluble form (s), and have previously been connected to autoimmune diseases (2). Furthermore, sOX40 have been suggested to be antagonistic to the membrane bound form, and thereby have an anti-inflammatory function (3). Objectives To investigate the presence and bioactivity of sOX40 and sOX40L and their association with disease activity and progression in RA Methods Plasma samples from early RA patients (eRA, n=76) randomised to conventional DMARD treatment with or without 12 months of adalimumab treatment were obtained from the OPERA study. Correlations between plasma levels of sOX40 and sOX40L (analysed by ELISA; detection limits 5.97 pg/ml and 1.16 ng/ml, respectively) at 0, 3, and 12 months after treatment initiation and DAS28, HAQ, IgM-RF, and anti-CCP were calculated. The results were compared with a transverse sample set of chronic RA patients (cRA, n=12, disease duration > 8 years) and with healthy volunteers (HV, n=32). All data are expressed as median. Results eRA had a low amount of sOX40 at baseline (5.97 pg/ml), which increased to 11.47 pg/ml at 12 months (p Conclusions The findings of this study showed, that sOX40L was markedly elevated in eRA compared with HV and cRA, suggesting that sOX40L plays a key role in early RA. The level of sOX40L remained high despite adalimumab treatment, and sOX40 levels increased, indicating that anti-TNFα treatment does not affect memory generation. Combined with the predictive values of the sOX40L/sOX40 ratio to risk of disease flare this dysfunction in the OX40 system could explain why many patients experience relapse after anti-TNF discontinuation References : Ishii et al., OX40-OX40L interaction in T-cell mediated immunity and immunopathology , Advances in immunology, chapter 3, 2010 M. Croft, Control of immunity by the TNFR-Related molecule OX40 (CD134 ), Annu. Rev. Immunol 2010, 28. 57-78 R Sibliano et al., Technical advance: soluble OX40 molecule mimics regulatory T cell modulatory activity on FCeRI-dependent mast cell degranulation , J Leukoc Biol. 2011 Disclosure of Interest None Declared