In the Original article, the legend of Figures 3 and 4 are interchanged and line number 387 is incomplete.

Objectives Impaired vascular pathophysiology and increased cardiovascular (CV) mortality are associated with rheumatoid arthritis (RA). To date, no genomic analysis of RA- and RA treatment-related vascular pathophysiology has been published. In this pilot study, we performed gene expression profiling in association with vascular pathophysiology in RA patients. Methods Sixteen and 19 biologic-naïve RA patients were included in study 1 and study 2, respectively. In study 1, genetic signatures determined by microarray were related to flow-mediated vasodilation (FMD), pulse-wave velocity (PWV), and common carotid intima-media thickness (IMT) of patients. In study 2, clinical response (cR) vs non-response (cNR) to 1-year etanercept (ETN) or certolizumab pegol (CZP) treatment, as well as “vascular” response (vR) vs non-response (vNR) to biologics, were also associated with genomic profiles. Multiple testing could not be performed due to the relatively small number of patients; therefore, our pilot study may lack power. Results In study 1, multiple genes were up- or downregulated in patients with abnormal vs normal FMD, IMT, and PWV. In study 2, there were 13 cR and 6 cNR anti-tumor necrosis factor (TNF)-treated patients. In addition, 10, 9, and 8 patients were FMD-20%, IMT-20%, and PWV-20% responders. Again, vascular responder status was associated with changes of the expression of various genes. The highest number of genes showing significant enrichment were involved in positive regulation of immune effector process, regulation of glucose transport, and Golgi vesicle budding. Conclusion Differential expression of multiple genetic profiles may be associated with vascular pathophysiology associated with RA. Moreover, distinct genetic signatures may also be associated with clinical and vascular responses to 1-year anti-TNF treatment.

Background: Increased cardiovascular (CV) morbidity and mortality and abundant angiogenesis have been associated with rheumatoid arthritis (RA) and ankylosing spondylitis (AS).Biologics may influence both vascular function and angiogenesis.Here, vascular function, markers of atherosclerosis angiogenesis and the effects of anti-TNF therapy on these biomarkers were assessed arthritides.Patients and methods: Altogether 53 arthritis patients including 36 RA patients treated with etanercept (ETN) or certolizumab pegol (CZP) and 17 AS patients treated with ETN were included in a 12-month follow-up study.Angiogenesis markers including vascular endothelial (VEGF) and platelet-derived growth factor (PDGF-BB), angiopoetin 1 and 2 (Ang1, Ang2) and thrombospondin 1 (TSP-1) were assessed by ELISA.Anti-CCP and anti-citrullinated enolase peptide (CEP) antibodies were also determined by ELISA.Flow-mediated vasodilation (FMD), common carotid intima-media thickness (ccIMT) and pulse-wave velocity (PWV) were assessed by ultrasound.All assessments were performed at baseline, as well as 6 and 12 months after treatment initiation.Results: One-year anti-TNF therapy significantly decreased VEGF, PDGF-BB and Ang2 serum levels.In uni-and multivariate analyses, PDGF-BB levels correlated with smoking, disease duration and ccIMT.Moreover, Ang1 correlated with CRP, Ang2 with disease duration, CRP and positive CV history.Finally, TSP-1 levels correlated with disease duration, anti-CCP, anti-CEP and ccIMT. Conclusions:In our arthritis cohort, the levels of angiogenic markers correlated with disease duration, CRP, ACPA and ccIMT.Anti-TNF therapy attenuated the production of angiogenic markers in these arthritides.Some angiogenic mediators may be used as surrogate biomarkers that link angiogenesis, inflammation and atherosclerosis in arthritides.

Objectives Rheumatoid arthritis (RA) and ankylosing spondylitis (AS) have been associated with generalized and localized bone loss. We conducted a comprehensive study using imaging (dual-energy X-ray absorptiometry, DXA) and laboratory biomarkers in order to determine bone health and to study the effects of anti-tumor necrosis factor (TNF) biologics in RA and AS. Patients and methods Thirty-six RA and 17 AS patients undergoing 1-year etanercept (ETN) or certolizumab-pegol (CZP) therapy were studied. Bone density was assessed by DXA at baseline and after 12 months. Serum C-reactive protein (CRP), calcium, phosphate, parathyroid hormone (PTH), vitamin D3, osteocalcin, procollagen type I N-propeptide (P1NP), C-terminal telopeptide (βCTX), osteoprotegerin, sclerostin (SOST), Dickkopf-1 (DKK-1), soluble receptor activator nuclear kappa B ligand (sRANKL), and cathepsin K (cathK) levels were determined at baseline and after 6 and 12 months. Results TNF-α inhibition was clinically effective. Anti-TNF-α halted further bone loss over 1 year. In general, anti-TNF therapy significantly increased P1NP, SOST levels, and the P1NP/βCTX ratios, while decreased DKK-1 and CathK production at different time points in most patient subsets. In the full cohort and in RA, baseline and/or 12-month bone mineral density (BMD) at multiple sites exerted inverse relationships with CRP and βCTX, and positive correlation with SOST. In AS, L2-4 BMD after 1-year biologic therapy inversely correlated with baseline βCTX, while femoral neck BMD rather showed inverse correlations with CRP. Conclusions Anti-TNF therapy slowed down generalized bone loss, in association with clinical improvements, in both diseases. TNF blockade may enhance bone formation and suppress joint destruction. Anti-TNF therapy may act inversely on DKK-1 and SOST. Independent predictors of BMD were SOST and βCTX in RA, whilst CRP in AS. Key Points • One-year anti-TNF therapy halted generalized bone loss in association with clinical improvement in arthritides. • Anti-TNF therapy may inversely act on DKK-1 and SOST. • Independent predictors of BMD were SOST and βCTX in RA, while CRP in AS.

Background Accelerated atherosclerosis and cardiovascular (CV) disease have been associated with rheumatoid arthritis (RA). Many genes have been implicated in atherosclerosis, RA or both. However, most of these studies described SNPs in CD40, SMAD3, HLADR, CTLA4 and other alleles. Very few studies on genetic signatures have been performed that would link RA and CV pathology. We have previously associated some genomic profiles with pathological carotid atherosclerosis (ccIMT), arterial stiffness (PWV) and brachial artery flow-mediated vasodilation (FMD). In other studies we have also found 165 genes that separated anti-TNF responder patients from non-responders. Objectives Here we looked for associations between clinical and “vascular” response to biologics and vascular pathology in RA patients. Methods In this study, 19 RA patients were treated with either etanercept (ETN) or certolizumab pegol (CZP) for one year. We separated responders (R) and non-responders (NR) according to EULAR response criteria. Microarray gene expression study was performed (Affymetrix) followed by analysis using the GeneSpring software, hierarchy clustering and principal component analysis (PCA). “Vascular response” (VR) to biologics was defined as an at least 20% improvement in FMD, ccIMT or PWV. Good Vascular Response (GVR) was defined as an at least 20% improvement in two or three of these variables. Results Among the 19 patients, 13 were R and 6 were NR. With respect to VR, FMD, ccIMT and PWV responded to anti-TNF treatment in 10, 9 and 8 patients, respectively. GVR was observed in 8 patients and 5 patients had VR in all 3 parameters. When comparing clinical response and VR, 7 out of 8 patients showing GVR also had good clinical response to biologics. Up-regulation of 99 and down-regulation of 67 genes separated clinical R and NR patients. Significant correlation was found between ccIMT improvement upon biological therapy and clinical response (R=0.418, p=0.04). Conclusions Genomic signature analysis may be able to separate clinical responders and non-responders to biologics, as well as patients that show or do not show imporvement of vascular pathology. Disclosure of Interest None declared

Background Genetic signatures may be involved in the pathogenesis of rheumatoid arthritis (RA) and ankylosing spondylitis (AS). In addition, such genetic patterns may change overtime upon treatment with anti-TNF biologics. With respect to pharmacogenomics, pre-treatment genomics may predict response or non-response to biological therapy. Objectives In the present study, we wished to determine gene expression changes due to anti-TNF therapy. Furthermore, we wished to study associations between baseline genetic signature and response to TNF blockade. Patients and methods Altogether 23 RA and 17 AS patients were recruited for the study. Among RA patients, 10 received certolizumab pegol (CZP), and 13 etanercept (ETN). All AS patients were treated with ETN. Gene expression analysis using Affymetrix microarray and PrimeView array was performed at baseline and after 2 weeks of treatment. EULAR response criteria were used to differentiate responders (R) from non-responders (NR) after 12 weeks of treatment using GeneSpring software. Principal Component Analysis (PCA) was also performed. Changes in gene expression patterns were also determined between baseline and 2 weeks. Results In the CZP-treated RA group, 4 patients were R and 6 were NR. Altogether 453 genes showed significantly differential expression between N and NR. In the RA-ETN group, 10 patients were R, and 3 were NR. Here, 836 genes exerted differential expression. When a CZP- and ETN-treated patients, were pooled, 165 genes separated R from NR. In the AS population, 14 patients were R and 3 were NR. 177 genes differentiated between R and NR. When changes in gene expression patterns from baseline to week 2 were determined, in the RA-CZP, RA-ETN, RA-all and AS groups 370, 79, 24 and 76 genes showed significant changes in expression. Conclusions Using microarray, genetic signatures may differentiate RA patients responding or not responding to anti-TNF therapy. Furthermore, a large set of genes show differential expression before versus 2 weeks after biologic treatment.

Rheumatoid arthritis (RA) has been associated with osteoporosis. Quantitative computed tomography (QCT) is capable of assessing bone density and composition. We found lower bone density in RA compared to controls. Age and RA duration influenced bone density. QCT may be useful to assess bone metabolism in RA.

Absztrakt Idiopathias inflammatorikus myopathiaban szenvedő betegeknel a jelenleg alkalmazott gyogyszeres kezeles mellett izomkarosodas es egeszsegromlas alakul ki. A gyogytornanak az izomteljesitmenyre, az aerob kapacitasra es az egeszsegre gyakorolt jotekony hatasait vizsgaltak kronikus polymyositises es dermatomyositises betegeknel, es a kisebb mertekben aktiv betegsegben, inclusion body myositisben szenvedő betegeknel. Randomizalt vizsgalatok arra utalnak, hogy a fokozott aerob kapacitas egeszsegjavulassal es a klinikai betegsegaktivitas csokkenessel jar egyutt. Jelenleg kutatjak azokat a mechanizmusokat, amelyek a gyogytornanak a vazizomzatra kifejtett hatasai mogott allnak (fokozott mitokondrialis kapacitas es kapillarisdenzitas, csokkent laktatszint, aerob fenotipusu genaktivacio, izomnovekedesi programok, gyulladashoz kapcsolhato genek csokkent kifejeződese). Osszessegeben a gyogytorna hozzajarul mind a szisztemas, mind az izmon beluli adaptaciohoz. Aktiv betegsegben es inclusion body myositisben szenvedő betegeknel a gyogytorna hatasanak tanulmanyozasara randomizalt klinikai vizsgalatok szuksegesek. Orv. Hetil., 2016, 157(39), 1557–1562. | Abstract Using current recommended treatment, a majority of patients with idiopathic inflammatory myopathy develop muscle impairment and poor health. Beneficial effects of exercise have been reported on muscle performance, aerobic capacity and health in chronic polymyositis and dermatomyositis, as well as in active disease and inclusion body myositis to some extent. Importantly, randomized controlled trials indicate that improved health and decreased clinical disease activity could be mediated through increased aerobic capacity. Recently, reports seeking pathomechanisms of the underlying effects of exercise on skeletal muscle indicate increased aerobic capacity (i.e. increased mitochondrial capacity and capillary density, reduced lactate levels), activation of genes of aerobic phenotype and muscle growth programs and down regulation of genes related to inflammation. Exercise contributes to both systemic and within-muscle adaptations demonstrating that it is fundamental for improving muscle performance and health in patients with idiopathic inflammatory myopathy. There is a need for randomized controlled trials to study the effects of exercise in patients with active disease and inclusion body myositis. Orv. Hetil., 2016, 157(39), 1557–1562.

Using current recommended treatment, a majority of patients with idiopathic inflammatory myopathy develop muscle impairment and poor health. Beneficial effects of exercise have been reported on muscle performance, aerobic capacity and health in chronic polymyositis and dermatomyositis, as well as in active disease and inclusion body myositis to some extent. Importantly, randomized controlled trials indicate that improved health and decreased clinical disease activity could be mediated through increased aerobic capacity. Recently, reports seeking pathomechanisms of the underlying effects of exercise on skeletal muscle indicate increased aerobic capacity (i.e. increased mitochondrial capacity and capillary density, reduced lactate levels), activation of genes of aerobic phenotype and muscle growth programs and down regulation of genes related to inflammation. Exercise contributes to both systemic and within-muscle adaptations demonstrating that it is fundamental for improving muscle performance and health in patients with idiopathic inflammatory myopathy. There is a need for randomized controlled trials to study the effects of exercise in patients with active disease and inclusion body myositis.

Background Rheumatoid arthritis is characterized by painful joint swelling, cartilage and bone destruction, chronic inflammation of the synovium (synovitis) with the accumulation of synovial fluid into the joint cavity. Within the synovial fluid the number of MSC-like cells (SYF-MSC) is increasing during the active phase of the disease. MSC are able to mediate immunosuppression via cell-cell contact and secreted factors respectively. Objectives Our goal was to screen the secreted proteins by SYF-MSCs under pro-inflammatory conditions. Methods Synovial fluid was harvested from patients with active RA (according to the Guidelines of the Helsinki Declaration). The isolated fluid/cells were cultured in vitro, their expression of well-known MSC markers as well as their differentiation potential was tested. SYF-MSCs were treated with human recombinant TNF alpha (TNFa) for 24 hour than the secreted cytokines were determined by high throughput protein array. Results SYF-MSCs secreted aggrecan, angiogenin, chitinase 3 like-1, Dkk-1, DPPIV, EMMPRIN, FGF-19, GM-CSF, IGFBP-3, IL-6, IL-17A, MCP-1, PDGF-AA, Pentraxin-3, Resistin, SDF-1α and Thrombospondin-1 under normal condition. Treatment by TNFa decreased the level of the secreted chitinase 3 like-1 (544003±56200.85; Pixel density, Mean±SD) and Dkk-1 (388062.5±10488.51) compared to untreated controls (721671.5±10434.77 and 705830±16013.14). Beside this phenomenon the pro-inflammatory provocation increased the secretion of IL-6 (from 79140±6940.96 to 615191±73256.26), MCP-1 (283985.5±25964.25 to 846348±81354.05), furthermore induced the release of IL-(8743315±71580.42) IL-24 (32189±29555.65) and RANTES (641698±26383.57). Unlike untreated cells no resistin, empirin and SDF-1 could be detected after TNFa exposure. Conclusions The in vitro data suggest that TNFa is able to turn SYF-MSCs to a pro-inflammatory phenotype, which may play a role in the inflammatory processes of RA prolonging the active phase of the disease. Disclosure of Interest None declared

Using current recommended treatment, a majority of patients with idiopathic inflammatory myopathy develop muscle impairment and poor health. Beneficial effects of exercise have been reported on muscle performance, aerobic capacity and health in chronic polymyositis and dermatomyositis, as well as in active disease and inclusion body myositis to some extent. Importantly, randomized controlled trials indicate that improved health and decreased clinical disease activity could be mediated through increased aerobic capacity. Recently, reports seeking pathomechanisms of the underlying effects of exercise on skeletal muscle indicate increased aerobic capacity (i.e. increased mitochondrial capacity and capillary density, reduced lactate levels), activation of genes of aerobic phenotype and muscle growth programs and down regulation of genes related to inflammation. Exercise contributes to both systemic and within-muscle adaptations demonstrating that it is fundamental for improving muscle performance and health in patients with idiopathic inflammatory myopathy. There is a need for randomized controlled trials to study the effects of exercise in patients with active disease and inclusion body myositis. Orv. Hetil., 2016, 157(39), 1557-1562.

Background Genetic signatures may be involved in the pathogenesis of rheumatoid arthritis (RA) and ankylosing spondylitis (AS). In addition, such genetic patterns may change overtime upon treatment with anti-TNF biologics. With respect to pharmacogenomics, pre-treatment genomics may predict response or non-response to biological therapy. Objectives In the present study, we wished to determine gene expression changes due to anti-TNF therapy. Furthermore, we wished to study associations between baseline genetic signature and response to TNF blockade. Methods Altogether 23 RA and 17 AS patients were recruited for the study. Among RA patients, 10 received certolizumab pegol (CZP), and 13 etanercept (ETN). All AS patients were treated with ETN. Gene expression analysis using Affymetrix microarray and PrimeView array was performed at baseline and after 2 weeks of treatment. EULAR response criteria were used to differentiate responders (R) from non-responders (NR) after 12 weeks of treatment using GeneSpring software. Principal Component Analysis (PCA) was also performed. Changes in gene expression patterns were also determined between baseline and 2 weeks. Results In the CZP-treated RA group, 4 patients were R and 6 were NR. Altogether 453 genes showed significantly differential expression between N and NR. In the RA-ETN group, 10 patients were R, and 3 were NR. Here, 836 genes exerted differential expression. When a CZP- and ETN-treated patients, were pooled, 165 genes separated R from NR. In the AS population, 14 patients were R and 3 were NR. 177 genes differentiated between R and NR. When changes in gene expression patterns from baseline to week 2 were determined, in the RA-CZP, RA-ETN, RA-all and AS groups 370, 79, 24 and 76 genes showed significant changes in expression. Conclusions Using microarray, genetic signatures may differentiate RA patients responding or not responding to anti-TNF therapy. Furthermore, a large set of genes show differential expression before versus 2 weeks after biologic treatment. Disclosure of Interest None declared

Myositis, which means inflammation of the muscles, is a general term used for inflammatory myopathies. Myositis is a rare idiopathic autoimmune disease. It is believed that environmental factors such as virus, bacteria, parasites, direct injuries, drugs side effect can trigger the immune system of genetically susceptible individuals to act against muscle tissues. There are several types of myositis with the same systemic symptoms such as muscle weakness, fatigue, muscle pain and inflammation. These include dermatomyositis, juvenile dermatomyositis, inclusion-body myositis, polymyositis, orbital myositis and myositis ossificans. Juvenile and adult dermatomyositis are chronic, immune-mediated inflammatory myopathies characterized by progressive proximal muscle weakness and typical skin symptoms. The aim of the authors was to compare the symptoms, laboratory and serological findings and disease course in children and adult patients with idiopathic inflammatory myopathy. Early diagnosis and aggressive immunosuppressive treatment improve the mortality of these patients. Myositis-specific autoantibodies have predictive and prognostic values regarding the associated overlap disease, response to treatment and disease course. The authors intend to lighten the clinical and pathogenetic significance of the new target autoantigens. Orv. Hetil., 2016, 157(29), 1179-1184.

Background and objectives Accelerated atherosclerosis, increased cardiovascular (CV) morbidity and mortality, as well as the perpetuation of angiogenesis and abundant production of angiogenic factors have been associated with rheumatoid arthritis (RA) and ankylosing spondylitis (AS). Biologics may influence both vascular function and angiogenesis. However, the effects of targeted therapies on vascular function and angiogenesis have been poorly studied in a comparative manner. Therefore, vascular function, markers of atherosclerosis and angiogenesis, as well as the effects of anti-TNF therapy on these biomarkers were assessed in the very same arthritis patient cohort. Patients and methods Altogether 31 arthritis patients including 18 RA patients treated with either etanercept (ETN) or certolizumab pegol (CZP) and 13 AS patients treated with ETN were included in a 12-month follow-up study. Ultrasonography was performed to determine flow-mediated vasodilation (FMD), a marker of endothelial dysfunction; common carotid intima-media thickness (ccIMT), a marker of atherosclerosis and pulse-wave velocity (PWV), an arterial stiffness parameter in all patients. Furthermore, circulating markers of angiogenesis including vascular endothelial growth factor (VEGF), platelet-derived growth factor-BB (PDGF-BB), angiopoetin 1 and 2(Ang1, Ang2) and thrombospondin 1 (TSP-1) were assessed in the sera by ELISA. DAS28, BASDAI and CRP, markers of disease activity, were also determined. All assessments were performed at baseline, as well as 6 and 12 months after treatment initiation. Results Anti-TNF treatment was highly effective in both diseases, as the mean DAS28 decreased from 5.00 to 2.97 (p < 0.001) in RA, mean BASDAI decreased from 5.99 to 1.82 (p < 0.001) in AS and CRP decreased from 13.8 to 3.9 mg/l (p = 0.021) in RA+AS over a 12-month period. Anti-TNF treatment resulted in significant improvement in FMD (from 7.15% to 9.11%; p = 0.009) and a tendency of improvement in PWV (from 7.57 to 6.82 m/sec; p = 0.190). Among markers of angiogenesis, mean VEGF (from 268.3 to 222.6 pg/ml; p = 0.006) and PDGF-BB (from 8187 to 6020 pg/ml; p = 0.012) levels significantly decreased after 12 months of therapy. Moreover, PDGF levels after 12 months, as well as Ang2 levels at all time points correlated with disease duration (p < 0.05) and Ang1, Ang2 and TSP1 levels all correlated with CRP at baseline (p < 0.05). When markers of vascular function and angiogenesis were compared, baseline PDGF levels correlated with baseline ccIMT (p < 0.05). Conclusions In a mixed cohort of RA and AS patients, anti-TNF therapy improved endothelial function and decreased the circulating levels of some angiogenic markers. Both impaired vascular function and the perpetuation of angiogenesis may be due to active systemic inflammation associated with these arthritides.

BackgroundMesenchymal stem cells (MSC) are the stromal cells of bone marrow, but they can also be found in other tissues including the synovia.ObjectivesOur goal was to isolate and cultivate human synovial fluid-derived MSC-like cells (SYF-MSC) and study their role in immunity and angiogenesis with relevance to rheumatoid arthritis (RA).MethodsSynovial fluid was harvested from patients with active RA (according to the Guidelines of the Helsinki Declaration). The isolated fluid/cells were cultured in vitro, and the expression of well-known MSC, hematopoietic, endothelial markers as well as high-end glycosylation products were measured by flow cytometry. In vitro differentiation assays were used to determine the stemness of SYF-MSCs. The immunosuppressive function of these cells was studied by mitogen-activated lymphocyte reaction, and their immunophenotype was investigated by cell activation with TLR ligands and pro-inflammatory cytokines; the secreted cytokines were measured by ELISA.ResultsThe cells isolated from synovial fluid of patients with RA grew as monolayers in vitro and could be maintained in culture for more than 10 passages. The cells expressed the most important MSC markers (CD44, CD73, CD90 and CD105) with absence of endothelial (CD31, VEGFR2) or hematopoietic cell markers (CD34, CD45, CD69, CD133), respectively. SYF-MSCs were able to differentiate into bone, fat and cartilage tissue in vitro fulfilling the ISCT criteria, and could suppress the proliferation of mitogen activated peripheral blood lymphocytes. Furthermore, SYF-MSCs secreted increased amount of IL-6 after 12 and 24 hrs treatment by LPS (15423.61±9348.61 pg/ml at 12h; 17479.17±3848.63 pg/ml at 24h time points), Poly:IC (15215.28±10834.72 and 24090.28±3626.40 pg/ml), TNFα (7437.5±1168.06 and 11562.5±845.83 pg/ml) and IL-1β (19465.28±2306.94 and 21229.17±12.5 pg/ml) compared to untreated controls (1590.28±1015.28 and 2187.50±640.28 pg/ml), respectively. IL-8 could be detected in the supernatants of SYF-MSC only upon LPS (10876.76±7553.24 and 12117.94±2912.06 pg/ml), Poly:IC (8972.35±8707.65 and 30567.94±3637.94 pg/ml) TNFα (5516.47±1336.47 and 110325.29±5645.29 pg/ml) and IL-1β (18063.53±3083.53 and 24970.88±9940.88 pg/ml) treatment, but not in the untreated controls.ConclusionsThe in vitro data suggest that SYF-MSC may play a role in the inflammatory processes of RA, and their activation could lead to the release of pro-angiogenic cytokines as well.Disclosure of InterestNone declared

Background Prediction of responsiveness in biological therapies is an important and challenging issue in different diseases. Analyzing glycosylation pattern changes of key serum glycoproteins is one of the possible avenues to follow disease remission. Objectives The aim of this study was to investigate the changes of serum IgG glycoforms in rheumatoid arthritis (RA) and Crohn9s disease (CD) patients in response to anti-tumor necrosis factor alpha (TNFα) treatment. Methods IgG was isolated from patient serum samples using Protein A affinity pull-down, followed by the release of N-glycans with peptide-N-glycanase F. The released glycans were fluorescently tagged with aminopyrene-trisulfonate and analyzed by capillary gel electrophoresis with laser induced fluorescent detection. Results Significant alterations were detected between responders and non-responders in both disease groups. In RA, three low abundant galactosylated structures were found to be significantly different before the treatment where in all of the cases responders showed higher galactosylation level. Unfortunately, no significant alteration was detected in RA in response to the treatment. In CD significant differences were detected in galactosylation level between responders and non-responders before the treatment (higher in the responder group). FA2G2S1 level was significantly increased in response to anti-TNFα therapy, thus being a possible candidate marker for responder identification. Interestingly, the level of this structure was not significantly altered in any of the RA groups suggesting disease specificity for CD. Conclusions IgG N-glycomics and corresponding transcriptomics may be useful to reveal disease-specific alterations when assessing responses to anti-TNFα therapy in chronic inflammatory diseasaes, such as RA or CD. Disclosure of Interest None declared

Background and objectives Uncoupling of bone resorption and formation has been associated with rheumatoid arthritis (RA) and ankylosing spondylitis (AS). Generalised bone loss and erosions are characteristic for RA, while in AS, bone formation overrides resorption. The RANKL/OPG and the Wnt/DKK-1/sclerostin systems have been implicated in disturben bone homeostasis in arthritides. Anti-TNF biologics may beneficially influence erosions and bone loss in RA, however, they have little effect on bone formation in AS. In the present study, we assessed the effects of 1-year anti-TNF treatment on various bone biomarkers. Patients and methods Altogether 43 arthritis patients including 30 RA patients treated with either etanercept (ETN) or certolizumab pegol (CZP) and 13 AS patients treated with ETN were included in a 12-month follow-up study. Disease activity (DAS28 or BASDAI), CRP, IgM rheumatoid factor, anti-CCP, calcium (Ca), phosphate (P), osteocalcin (OC), P1NP, CTX, BNP, sclerostin (SOST), DKK-1, soluble RANKL (sRANKL), cathepsin K (cathK) and vitamin D3 (vitD) levels were assessed at baseline, as well as 6 and 12 months after treatment initiation. Results Anti-TNF treatment was highly effective in both diseases, as the mean DAS28 decreased from 6.32 to 3.16 (p = 0.02) in RA, mean BASDAI decreased from 5.87 to 1.84 (p < 0.001) in AS. In RA, anti-TNF treatment significantly decreased DKK-1 (60.5 ± 28.9 pM and 54.7 ± 20.8 pM, p = 0.036) and CathK (28.7 ± 6.2 pm and 26.8 ± 4.0 pm, p = 0.014) but increased SOST (107.0 ± 47.5 pM and 131.2 ± 85.2 pM, p = 0.04) levels from baseline to 12 months, respectively. In RA, ETN and CZP treatment also increased OPG/sRANKL ratio after 6 months (51.9) vs. baseline (43.9) (p = 0.01). In AS, ETN therapy significantly increased the bone formation marker P1NP (49.4 ± 19.0 pM and 56.9 ± 28.7 pM, p = 0.03) and SOST (70.6 ± 29.0 pM and 82.4 ± 48.3 pM, p = 0.022) levels from baseline to 12 months, respectively. ETN therapy also increased OPG/sRANKL ratio after 6 months (44.5) and 12 months (46.9) compared to baseline (34.5) in AS (p < 0.01). Both baseline and 12-month SOST levels were significantly lower in AS compared to RA (p < 0.001). When RA and AS data were pooled, TNF inhibition resulted in significantly decreased DKK-1 (p = 0.035) and cathK (p = 0.008) but increased P1NP (p = 0.04) and SOST (p = 0.04) after 12 months. In this study, biologics did not affect Ca, P, OC, CTX, BNP, vitD levels. Conclusions In a mixed cohort of RA and AS patients, anti-TNF therapy resulted in a restoration of bone homeostasis by decreasing DKK-1 and CathK, increasing P1NP, SOST and OPG/sRANKL ratio. Lower SOST levels in AS compared to RA, as well as the induction of bone formation over resorption may account for the inefficacy of TNF inhibitors on syndesmophyte formation in AS.

Background Accelerated atherosclerosis, increased cardiovascular (CV) morbidity and mortality, as well as the perpetuation of angiogenesis and abundant production of angiogenic factors have been associated with rheumatoid arthritis (RA) and ankylosing spondylitis (AS). Biologics may influence both vascular function and angiogenesis. However, the effects of targeted therapies on vascular function and angiogenesis have been poorly studied in a comparative manner. Objectives Therefore, vascular function, markers of atherosclerosis and angiogenesis, as well as the effects of anti-TNF therapy on these biomarkers were assessed in the very same arthritis patient cohort. Methods Altogether 31 arthritis patients including 18 RA patients treated with either etanercept (ETN) or certolizumab pegol (CZP) and 13 AS patients treated with ETN were included in a 12-month follow-up study. Ultrasonography was performed to determine flow-mediated vasodilation (FMD), a marker of endothelial dysfunction; common carotid intima-media thickness (ccIMT), a marker of atherosclerosis and pulse-wave velocity (PWV), an arterial stiffness parameter in all patients. Furthermore, circulating markers of angiogenesis including vascular endothelial growth factor (VEGF), platelet-derived growth factor-BB (PDGF-BB), angiopoetin 1 and 2 (Ang1, Ang2) and thrombospondin 1 (TSP-1) were assessed in the sera by ELISA. DAS28, BASDAI and CRP, markers of disease activity, were also determined. All assessments were performed at baseline, as well as 6 and 12 months after treatment initiation. Results Anti-TNF treatment was highly effective in both diseases, as the mean DAS28 decreased from 5.00 to 2.97 (p<0.001) in RA, mean BASDAI decreased from 5.99 to 1.82 (p<0.001) in AS and CRP decreased from 13.8 to 3.9 mg/l (p=0.021) in RA+AS over a 12-month period. Anti-TNF treatment resulted in significant improvement in FMD (from 7.15% to 9.11%; p=0.009) and a tendency of improvement in PWV (from 7.57 to 6.82 m/sec; p=0.190). Among markers of angiogenesis, mean VEGF (from 268.3 to 222.6 pg/ml; p=0.006) and PDGF-BB (from 8187 to 6020 pg/ml; p=0.012) levels significantly decreased after 12 months of therapy. Moreover, PDGF levels after 12 months, as well as Ang2 levels at all time points correlated with disease duration (p<0.05) and Ang1, Ang2 and TSP1 levels all correlated with CRP at baseline (p<0.05). When markers of vascular function and angiogenesis were compared, baseline PDGF levels correlated with baseline ccIMT (p<0.05). Conclusions In a mixed cohort of RA and AS patients, anti-TNF therapy improved endothelial function and decreased the circulating levels of some angiogenic markers. Both impaired vascular function and the perpetuation of angiogenesis may be due to active systemic inflammation associated with these arthritides. Disclosure of Interest None declared

Background Accelerated atherosclerosis, increased cardiovascular (CV) morbidity and mortality have been associated with rheumatoid arthritis (RA) and ankylosing spondylitis (AS). Oxidized LDL (oxLDL) and beta 2 glycoprotein I (beta2gpI) antigens have been implicated in atherosclerosis, as well as antiphospholipid syndrome. High circulating oxLDL/beta2gpI levels may reflect vascular damage in acute coronary, syndrome, SLE, and other autoimmune diseases. However, the role of these complexes in RA and AS has not yet been evaluated in relation to therapy. Objectives Circulating complex levels, as well as the effects of anti-TNF therapy on these complexes were assessed in RA and AS patients. Complex levels were also correlated with various autoimmune-innflammatory and metabolic markers. Methods Altogether 43 arthritis patients including 30 RA patients treated with either etanercept (ETN) or certolizumab pegol (CZP) and 13 AS patients treated with ETN were included in a 12-month follow-up study. Circulating oxLDL/beta2gpI complexes were assessed by an AtherOx® ELISA system (Corgenix). In addition, disease activity (DAS28 or BASDAI), CRP, IgM rheumatoid factor, anti-CCP, and lipid levels (total cholesterol, TC; LDL-C, HDL-C and triglyceride) were also assessed. Assessments were performed at baseline, as well as 6 and 12 months after treatment initiation. Results Anti-TNF treatment was highly effective in both diseases, as the mean DAS28 decreased from 6.32 to 3.16 (p=0.02) in RA, mean BASDAI decreased from 5.87 to 1.84 (p Conclusions In a mixed cohort of RA and AS patients, anti-TNF therapy suppressed the circulating levels of oxLDL/beta2gpI complexes, markers of atherosclerosis and vascular disease in SLE or APS. Moreover, oxLDL/beta2gpI levels correlated with TC and LDL-C in arthritides. oxLDL/beta2gpI complexes do not seem to be markers of disease activity in RA or AS. Disclosure of Interest None declared