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Background:Angiogenesis is an important contributor to the development of Rheumatoid arthritis (RA). Tocilizumab (TCZ), an anti-IL-6 receptor antibody, is an immunosuppressant used in the treatment of RA patients, but its effects on angiogenesis and the molecular mechanisms regulating new blood vessel formation are not fully elucidated.Objectives:To evaluate the concentrations of pro- and anti-angiogenic factors in serum samples of RA patients, before and after the initiation of TCZ treatment and to explore in an in vitro co-culture system the mechanisms of TCZ action.Methods:We evaluated the concentrations of EMMPRIN, VEGF, MMP-9, IL-6, NGAL, endostatin and thrombospondin-1 (Tsp-1) using commercial ELISA kits from 40 RA patients, before and 4 months after the initiation of TCZ treatment. The levels of secreted EMMPRIN, VEGF MMP-9 and Tsp-1 were measured in an in vitro co-culture system of HT1080 fibroblasts and U937 monocytes with and without addition of anti-EMMPRIN blocking antibody. In the tube formation assay serum samples and supernatnats from the co-cultures were added to endothelial layer. Images were obtained after 6 hours of incubation and the number of closed lumens were counted in two separate fields. In the wound assay, supernatants from the co-cultures, with or without the addition of the anti-EMMPRIN antibody were added to the endothelial layer after scratching. The scratch site area was measured immediately and compared to the area after 24 hours of incubation to assess the distance of cell migration.Results:Study population included 40 RA patients, 33 (82.5%) females, mean age of 57.5±11.1 years, disease duration of 7.7±5.6 years, and 53.9% positive for rheumatoid factor initiating treatment with TCZ. In this patient cohort, 25/40 (62.5%) patients were classified as “responders” according to EULAR criteria.Following 4 mounts of treatment, statistically significant reductions in the levels of EMMPRIN/CD147 (p=0.035), without significant changes in serum levels of MMP-9, VEGF, MMP-3 and MMP-7 and of the anti-angiogenetic factors Tsp-1 and endostatin were found. A statistically significant decrease in the ratio between the pro-angiogenic factor EMMPRIN and the anti-angiogenic factor Tsp-1 that was calculated for each patient 4 months after initiating TCZ was found(p=0.031). The decrease in angiogenesis was manifested by the reduced number of closed lumen tube-like structures formed by EaHy926 endothelial cell line after incubation with serum samples 4 months after initiation of TCZ, relative to the number of closed lumens formed prior to TCZ initiation (p=0.007). The ratio between EMMPRIN and Tsp-1 was significantly reduced in the responding patients versus non-responders (p=0.033), while the levels of VEGF, MMP-9, Tsp-1, and EMMPRIN were unchanged.In vitro, the accumulation of the pro-angiogenic factors EMMRPIN, VEGF and MMP-9 in the supernatants was increased in the co-culture, while the accumulation of the anti-angiogenic factor Tsp-1 was decreased. When EMMPRIN was neutralized with a blocking antibody, supernatants derived from these co-cultures exhibited reduced migration, proliferation, and tube-like structure formation in functional assays.Conclusion:Our findings suggest an important role for EMMPRIN in mediating pro-angiogenic signals in RA patients, with EMMPRIN/Tsp-1 ratio serving as a marker of angiogenesis in RA. When administered to RA patients, TCZ in turn, exerts an anti-angiogenic effect through its regulation of EMMRPIN/CD147 levels.Disclosure of Interests:None declared

We appreciate the interest of Akiyama et al in our report and thank them for the data presented in their letter.1 2 Akiyama et al have presented a thorough literature review and have described a positive and efficacious effect of tocilizumab in 11 cases of refractory polyarteritis nodosa (PAN) described in 6 case series. Indeed, the use of tocilizumab, an interleukin (IL)-6 inhibitor, in vasculitis is gaining evidence in the literature, specifically in large vessel vasculitis including giant cell arteritis and Takayasu arteritis.3 4 Nevertheless, it should be noted that although the …

Background:Elevated serum levels of interleukin (IL)-22 were reported in patients with ankylosing spondylitis (AS).[1]IL-22 was also reported to drive the osteogenic differentiation of mesenchymal stem cells.[2]Objectives:To confirm the fact that serum levels of IL-22 are elevated in AS patients and to examine the relationship between concentrations of IL-22 and degree of radiographic progression in AS patients.Methods:Seventeen male patients with established AS of more than 4 years duration signed the informed consent and donated 10 ml of peripheral blood. Demographic data was collected from patient’s charts. Disease activity indices were calculated for all patients and radiographic disease progression was calculated as mSASS. A control group included 6 healthy persons and 4 patients with advanced diffuse idiopathic skeletal hyperostosis (DISH). Serum levels of IL-22 were tested using enzyme-linked immunosorbent assay. Intergroup differences were examined using the Mann-Whitney test, while correlations were calculated using Pearson correlation coefficient.Results:Serum IL-22 levels were remarkably elevated in patients with AS, comparing to healthy individuals and patients with DISH (p=0.005). However, increased concentrations of IL-22 did not correlate with the degree of radiographic progression or AS disease activity indices, nor with disease duration or patient’s age. Presence of diarrhea, psoriasis, uveitis, or elevated levels of C-reactive protein did not influence the levels of IL-22 as well. More AS patients with elevated serum IL-22 were smokers (p=0.05).Fig. 1.Serum levels of interleukin 22 (pg/ml)Conclusion:The serum levels of IL-22 are elevated in patients with AS. It seems that smoking can be related to the elevated levels of serum IL-22 in AS. The significance of this data is unclear and further research is needed.References:[1]Zhang L, Li Y gang, Li Y hua, Qi L, Liu X guang, Yuan C zhong, et al. Increased frequencies of th22 cells as well as th17 cells in the peripheral blood of patients with ankylosing spondylitis and rheumatoid arthritis. PLoS One. 2012;7(4).[2]El-Zayadi AA, Jones E, Churchman S, Baboolal T, Cuthbert R, El-Jawhari J, et al. Interleukin-22 drives the proliferation, migration and osteogenic differentiation of mesenchymal stem cells: a novel cytokine that could contribute to new bone formation in spondyloarthropathies. Rheumatology. 2016 Dec 10;56.Disclosure of Interests:None declared

Tofacitinib is a novel inhibitor of Janus kinase (JAK) 3 and JAK1 is recently introduced as treatment for rheumatoid arthritis.1 The JAK inhibitors are at the focus of research in a myriad of other inflammatory diseases2 ,3 as the JAK-(signal transducer and activator of transcription) STAT pathway has a central role in cytokine signal transduction. We herein describe a case of refractory polyarteritis nodosa (PAN) successfully treated with tofacitinib. A 28-year-old man had been diagnosed with PAN at age 14. He presented with livedo reticularis, arthritis and skin nodules with arteritis/fibrinoid necrosis confirmed on biopsy. Immunological panel at the time of diagnosis was negative for antineutrophil cytoplasmic antibodies, anti-nuclear antibodies, anti-Ro/SS-A antibodies, anti-La/SS-B antibodies, rheumatoid factor, with normal complement levels. He was treated with azathioprine and methotrexate for several years with drug-controlled complete remission. At age 24, his disease flared and he began to suffer from necrotic lesions of the scrotum and calves, excruciating abdominal pain and polyarthritis, with high C-reactive protein (CRP) levels (160–300 mg/L) for which he received recurrent intravenous methylprednisolone pulses and oral …

Objective: To assess changes in macrophage phenotype and function after rituximab-induced B cell depletion in patients with rheumatoid arthritis (RA). Methods: 10 patients with RA were treated with rituximab, achieving significant B cell depletion 4 months later. Clinical improvement, rheumatoid factor (RF), anti-cyclic citrullinated peptide (anti-CCP) antibodies, mRNA of B cell activating factor (BAFF), interleukin (IL) 10 and CD86 in human monocyte-derived macrophages (HMDMs) and tumour necrosis factor α (TNFα) secretion from cultured HMDMs were assessed at baseline and after the depletion. Results: A clinical response of American College of Rheumatology (ACR) 50% improvement was noted in six patients, and another two patients responded with moderate improvement, equivalent to ACR 20–50% improvements. RF and anti-CCP antibodies were positive at baseline in seven of ten patients. RF disappeared or declined in six patients 4 months after treatment, correlating with clinical improvement. By contrast, anti-CCP remained unchanged in six patients. After rituximab treatment, and in association with clinical improvement, BAFF, IL10 and CD86 mRNA expression in HMDM were significantly upregulated compared with values at baseline. A significant decrease in TNFα in the supernatant of cultured HMDM was also noted. Conclusions: In addition to B cell depletion and attenuation in some of the specific autoantibodies, clinical improvement in rituximab-treated patients with RA occurred in association with changes in macrophage function.

Background Previous studies have showed that structural abnormalities such as erosions and geodes could be detected in wrist of patients with Rheumatoid Arthritis (RA) using high-field MRI whereas corresponding anomalies were invisible using conventional 1.5 T MRI. Similar observations have not been reported so far for patients with either an early form of RA or patients with axial and peripheral forms of spondyloarthritis (SpA). Objectives In the present study, we compared wrist MRI investigations performed at 1.5 and 3 T in SpA and early RA patients (less than one-year disease evolution). We aimed at determining whether synovitis, geodes and erosions are similarly observed in both cases. Methods The study was conducted in the wrist of 9 SpA patients (6 with ankylosing spondyloarthritis (AS) and 3 with psoriatic arthritis) and in 7 early RA patients. Age in the RA group ranged from 35 to 54 (6 females, 1 male) while it ranged between 22 and 64 in the SpA group (7 females, 2 males). All the patients provided their written informed consent before their inclusion in the protocol which was approved by the local ethics committee. MRI investigations were performed at 1.5T (Philips Achieva) using a Flex-M coil and at 3T (Siemens Verio) using a 4-channel flexible coil. In both cases, subjects were asked to lie down in the supine position inside the scanner and wrist was scanned at 1.5T using a T1-SE and a PD-FS-SE and at 3T using both a VIBE and a DESS sequences. MR images were analyzed by one senior radiologist (CC). Results In the RA group, we identified more abnormalities at 3T as compared to 1.5T for 1 patient while for 5 patients the number of abnormalities was identical in both cases. 1 patient did show no abnormality. Similarly, in the SpA group, more abnormalities were observed at 3T as compared to 1.5T for 2 patients. In those cases, more erosions were identified whereas geodes, synovitis and oedema were similar. These two patients had AS with peripheral and axial pain without psoriasis. For 1 patient with structural abnormalities, the results at both fields were similar. In 6 patients, (including 2 patients with psoriatic arthritis), we did not detect any structural abnormality. Conclusions In the present study, we illustrated that for both RA and SpA patients, MRI investigations performed at high-field can detect wrist abnormalities which were not detectable at 1.5T. Disclosure of Interest None declared

Background Fibrosis and vasculopathy are the major concerns in systemic sclerosis (SSc), the pathogenesis of which is not clear. Lysyl oxidase (LOX) is an extracellular copper enzyme that cross-links collagen and elastin, thus stabilizing collagen fibrils [1]. In a preliminary study, LOX was found to be overexpressed in SSc patients and was suggested to be related to diffuse disease [2]. We evaluated skin and lung biopsies from 11 SSc patients and were able to show LOX located in the epidermis in the skin and in the endothelium of blood vessels within the dermis and in lung tissue. It is not clear whether the source of elevated LOX levels in SSc is damaged vascular endothelium or fibrotic tissues. Objectives To evaluate LOX serum level of patients with SSc compared to patients with very early diagnosis of SSc (VEDOSS), patients with primary Raynaud9s phenomena (PRP) and healthy controls in order to validate the elevated levels in SSc and to delineate its source. Methods We prospectively evaluated patients for demographics, clinical manifestations and laboratory results including blood count, chemistry, urine examination, autoantibodies and serum LOX concentration determined by ELISA. We further evaluated lung function tests, echocardiography, lung high resolution CT scans, as needed, and determined lung involvement, modified Rodnan skin score (mRSS), Medsger disease severity scale and Valentini activity index [3]. Results 86 SSC patients (76 women and 10 men) at a mean age of 49±12.4 were evaluated and compared with 110 patients with VEDOSS, 86 patients with PRP, and 80 age and gender matched healthy controls. Of the SSc patients, 42 had diffuse disease- 23 of them with lung fibrosis, and 44 had limited disease. LOX concentration in SSc was higher than VEDOSS, PRP and healthy controls, 12.8±7.5 ng/ml vs. 9.7±7.4 ng/ml vs. 8.1±5.4 vs. 8.9±5.1 ng/ml, respectively (p Conclusions LOX level was found to be high in the serum of patients with SSc correlating with disease severity and inversely correlated with lung diffusion, suggesting a vascular source of LOX excretion in SSc. LOX was not elevated in patients with VEDOSS or PRP. Our study confirms our former observation of elevated LOX level in SSc and suggests LOX to be a possible biomarker of disease severity and vasculopathy in SSC. References Csiszar K, et al. Lysyl oxidases: a novel multifunctional amine oxidase family. Prog. Nucleic Acid Res. Mol. Biol. 2001;70: 1–322. Rimar D et al. Brief report: lysyl oxidase is a potential biomarker of fibrosis in systemic sclerosis. Arthritis Rheumatol. 2014;66(3):726–30 Hudson M, et al. Update on indices of disease activity in systemic sclerosis. Semin Arthritis Rheum 2007;37(2):93–8. Disclosure of Interest None declared

Background Tofacitinib is a novel inhibitor of Janus kinase (JAK) 3 and JAK1 [1]. The JAK inhibitors are in the focus of research in myriad of other inflammatory diseases as it seems the JAK- (signal transducer and activator of transcription) STAT pathway has a central role in cytokines9 signal transduction. We herein describe a case of refractory polyarteritis nodosa (PAN) successfully treated with tofacitinib.Preliminary evidence for the role of JAK-STAT pathway in vasculitis has been recently published [2]. A 28 years-old man had been diagnosed with PAN at the age of 14. He presented with livedo reticularis, arthritis and skin nodules with fibrinoid necrosis, as confirmed by biopsy. Immunologic panel at the time of diagnosis was negative for ANCA, ANA, SSA, SSB, RF, and complement levels were normal. He was treated with azathioprine and methotrexate for several years and was in complete remission. Three years prior the initiation of tofacitinib his disease flared and he began suffering from necrotizing vasculitis of the scrotum and calves, abdominal pain and polyarthritis with high CRP levels (160–300 mg/l) for which he received recurrent intravenous solumedrol pulses and oral prednisone therapy of 40–60 mg daily in between pulses. Numerous treatments including, infliximab, adalimumab, rituximab, etanercept, tocilizumab, potassium iodide and cyclophosphamide intravenous and oral failed to achieve remission. Subsequently, he was hospitalized for reevaluation and was treated by plasma exchange for 3 weeks with partial remission, but had to discontinue the treatment due to central line sepsis. At this point he was in severe long standing inflammatory state for 3 years with high CRP levels low albumin (3 mg/dl) and ongoing leukocytosis. Objectives To evaluate the activity of the JAK-STAT pathway guiding the treatment with tofacitinib. Methods We have profiled his peripheral blood cells using mass cytometry (CyTOF), a single cell proteomics platform capable of simultaneously measuring the expression up to 45 proteins on each cell and on millions of cells. This provided a high-dimensional immune cell type profile of his immune system, both in cell abundance as well as the activity of the JAK1 and 3 along with STAT 3 pathways in response to stimulation with interleukin 6, specifically in CD4+ and CD8+ T cells subsets (figure 1). Results We initiated treatment with tofacitinib 10 mg BID that resulted in prompt normalization of his CRP, albumin and leukocyte count, resolution of skin ulcers and relief of pain. Prednisone therapy was soon tapered from 60 mg to 10 mg daily. Reevaluating the response of the JAK-STAT pathway to IL-6 stimulation after treatment confirmed attenuated response of the CD8+T and CD4+T cell (figure 1). After one year of follow-up the patient remained in complete remission. Conclusions In conclusion, this is the first report in the literature of treatment of refractory PAN vasculitis with tofacitinib. Using high resolution mass cytometry technology we were able to tailor and monitor therapy. References Vadasz Z, Rimar D, Toubi E. The new era of biological treatments. Isr Med Assoc J. 2014 Dec;16(12):793–8 Hartmann B, et al. The STAT1 Signaling Pathway In Giant Cell Arteritis. 2013 ACR/ARHP Annual Meeting, Plenary Session II, abstract number: 1691. Disclosure of Interest None declared

Three patients presented with septal fasciitis and panniculitis, associated with clinical and laboratory features which precluded straight-forward classification into eosinophilic fasciitis, localised scleroderma, or lupus erythematosus profundus. Treatment with cimetidine caused the remission of cutaneous manifestations and the extracutaneous abnormalities, such as nailfold capillary disturbances and the presence of antithyroid antibodies, improved. It is concluded that features of eosinophilic fasciitis or localised scleroderma and certain additional atypical elements should be categorised as atypical fasciitis-panniculitis syndrome.

Background and objectives B cells function as regulatory cells by producing inhibitory cytokines such as transforming growth factor β (TGF-β) and interleukin 10 (IL-10). Human CD25high B cells were shown to secrete higher levels of IL-10 versus CD25low B cells, suggesting this subset of cells to be immune-regulatory. Tocilizumab, a monoclonal antibody that acts as an IL-6R antagonist thus inhibiting IL-6 activity, and its autocrine growth activity on B cells is currently used for treatment of rheumatoid arthritis (RA). Following this treatment, one might expect a reduction in B cell activity status, and on the other hand increase of their regulatory properties. Methods Freshly purified B lymphocytes were isolated from 10 active RA patients, with inadequate response to methotrexate, at baseline and 3 months following add on tocilizumab. Clinical status was assessed by DAS 28 score and erythrocyte sedimentation rate (ESR). Using flow cytometry, B cells were stained for the expression of intracellular TGF-β, IL-10, membrane CD69, and MHC-II. These markers were assessed in primary (no-stimulated) CD25high B cells and expressed in MFI, with results given in mean ± SEM. Results Three months following initiation of tocilizumab, the expression of intracellular TGF-β in CD25high B cells was significantly increased (from 5.2 ± 2.3 at baseline to 8.1 ± 2.8; p Conclusions Our unique finding of a shift in B cell properties following tocilizumab treatment, namely the increase in TGF-β expression and the alteration in their activation status and APC properties in CD25high B cells, suggests that the induction/expansion of B regulatory cells may be one of the mechanisms by which tocilizumab may possibly produce its beneficial clinical effects.

Background Familial Mediterranean Fever (FMF) is an autoinflammatory disease characterized by recurrent attacks of fever and serositis. A relation between FMF and Ankylosing Spondylitis (AS) has been suggested in small cohort studies, although there is no consensus regarding the role of HLA B27. Colchicine, the mainstay treatment in FMF, does not improve the axial or peripheral symptoms due to spondylarthropathy. There are controversial data about the efficacy of Tumor Necrosis Factor Alpha (TNF α) blockade in FMF patients (1). Objectives Efficacity of Tumor Necrosis Factor Alpha in FMF patients with axial spondyloarthropathy. Methods We report our experience in 4 patients with intractable FMF treated with oral colchicine and supplemental IV colchicine (2), that were treated with TNF α blockade for symptomatic axial spondylarthropathy). Results A 26- year-a old man with MEFV mutations V726A and E148Q, negative for HLAB27, with concomitant ulcerative colitis was treated with infliximab and then with adalimumab; and 3 women (42, 48 and 55 years old), two of them treated with infliximab and one treated with adalimumab. The three women were homozygous for the M694V mutation. All developed severe to moderate adverse events: exacerbation of FMF in 2 of them, and myositis and ulcerative colitis exacerbation in the male patient, and staphylococcus aureus sepsis in another patient. Three of them had to stop the TNF α blockade treatment. One patient developed psoriatic rash, with no need to stop the treatment. Conclusions In our limited experience, TNF α blockade in patients with both intractable FMF and AS is not very effective and may be associated with severe adverse events. Little is known about the possible interaction between intravenous colchicine and anti-TNF treatment. References 1. Bilgen SA, Kilic L, Akdogan A, Kiraz S, Kalyoncu U, Karadag O, Ertenli I, Dogan I, Calguneri M. Effects of anti-tumor necrosis factors agents for familial Mediterranean fever patients with chronic arthritis and/or sacroiliitis who were resistant to colchicine treatment. J clin Rheumatol 2011;7:358-62. 2. Rozenbaum M, Boulman N, Feld J, Avshovich N, Petrovich S, Elias M, Slobodin G, Rosner I. Intravenous colchicine treatment for six months: adjunctive therapy in Familial Mediterranean fever (FMF) unresponsive to oral colchicine. Clin Exp Rheumatol 2009; 27 (2 suppl 53) S 105. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.1994

Background Semaphorin 3A (sema 3A), is now recognized as a potent immuno-regulator during all stages of the immune response. Sema 3A expression has been recognized on T regulatory cells as a suppressive marker, contributing to the regulatory properties of these cells [1]. Decreased expression of sema 3A and correlation with disease activity has been reported in rheumatoid arthritis patients and systemic lupus erthematosus (SLE) [2,3]. The expression of sema 3A hasn9t been evaluated in systemic sclerosis (SSc) thus far. Objectives To compare sema 3A serum levels in patients with SSc to SLE patients (disease control) and healthy controls. To measure expression of sema 3A in whole blood and on regulatory T-cells and correlate it with demographic, clinical and laboratory parameters in SSc. Methods 27 SSc patients were evaluated for demographics, clinical manifestations, routine laboratory results, serum autoantibodies, sema 3A serum levels (measured by commercial ELISA kit) and expression on regulatory T cells CD 4+ CD 25 bright (by flow cytometry), nailfold videocapillaroscopy patterns, pulmonary function tests, echocardiograms, high resolution lung CT scans, modified Rodnan skin score (mRSS), Medsger disease severity scale and Valentini activity index. Sema 3A serum levels were also evaluated in 42 sex and age matched SLE patients (disease control) and 28 healthy controls. Results Twenty seven SSc patients (10 with diffuse cutaneous disease) were evaluated and compared with healthy controls and disease controls (SLE). Sema 3A expression in SSc patients was lower than healthy controls as measured by flow cytometry on regulatory T cells 61.7% ±15.7 vs. 88.7% ±3.6 (p Conclusions The expression of sema 3A is reduced in SSc patients and inversely correlates with disease duration and scl-70 antibodies production. Sema 3A role in the prevention of autoimmunity has been suggested to be mediated by its effect on regulatory T cells. Regulatory T cells have been reported in the literature to be reduced and functionally impaired in SSc. Our finding of low levels of sema 3A in SSc correlating with disease duration is in line with the literature and may serve to explain the impairment regulatory T cells in SSc. Further studies are needed to assess the cause-effect relations between sema 3A, regulatory T cells and disease progression in SSc. References Vadasz Z, Toubi E. Semaphorins: Their Dual Role in Regulating Immune-Mediated Diseases.Clin Rev Allergy Immunol. 2013 Feb 9. [Epub ahead of print]. Takagawa S, Nakamura F, Kumagai K, et al. Decreased semaphorin3A expression correlates with disease activity and histological features of rheumatoid arthritis.BMC Musculoskelet Disord. 2013;14:40. Vadasz Z, Haj T, Halasz K, et al. Semaphorin 3A is a marker for disease activity and a potential immunoregulator in systemic lupus erythematosus.Arthritis Res Ther. 2012 14;14(3):R146. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.3403

Background Thickening of the aortic wall, probably the earliest computed tomography (CT)-seen sign of aortitis, is frequently missed as there are no accepted criteria for normal aortic wall thickness (AWT). As aortitis can affect patients in a wide range of ages and with different co-morbidities, information on the normal values for AWT for various age groups, as well as for the presence of co-morbid background, may be essential. Objectives The present study was conducted to assess the relationship of CT-measured AWT with patient-related and disease-related variables in a large cohort of patients without aortitis. Methods CT scans of 250 consecutive patients without known aortitis, hospitalized at Bnai Zion Medical Center were reviewed and AWT manually measured at three levels: 1. thoracic descending aorta at the level of the bifurcation of the pulmonary artery; 2. abdominal aorta at the level of celiac artery origin; 3. abdominal aorta one slice below the level of the origin of renal arteries. Patients9 charts were analyzed and demographic data and data on co-morbidities extracted. Correlations with measured AWT were calculated. Results By multivariate regression analysis, AWT had significant positive correlation with patient age (p Conclusions The “normal” range of AWT varies with age, gender and may also vary with co-morbidities. The data presented may serve as a reference and should be considered in the interpretation of the CT-appearance of the aortic wall when assessing for aortitis. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.1116

Background Because of its reduced thickness at the carpus level, the MRI identification of cartilage abnormalities has been initially discarded from the usual rheumatologic diagnostic scores and just recently introduced as a qualitative variable related to joint space narrowing. Objectives In the present study we aimed at determining whether carpal cartilage area can be measured using high-field MRI area through a semi-automatic method. We also compared the results related to two different MRI sequences. Methods The study was conducted in 14 healthy volunteers after they provided their written informed consent. MRI investigations were performed at 3T using two 3D sequences i.e. VIBE and DESS for the analysis of carpal cartilage. Cartilage surface was measured on a three-dimensional reconstruction using a conventional image processing radiology software. The protocol received the agreement from the local ethics committee. Results Cartilage measurements performed by two different operators and twice by the same operator showed a very good reproducibility regardless the MRI sequence used. A 15% interindividual variability for the cartilage area was quantified within this control group. Interestingly, the wrist cartilage area was linearly related to the carpal bone height and so for results obtained with both MRI sequences. Conclusions Using high-field MRI, we reported a very reproducible semi-automatic method of cartilage surface measurement in wrist. The measurements were performed on a MRI section accurately defined thanks to 3D acquisitions. The large variability of the corresponding measurements illustrated that cartilage area cannot be used as a stand-alone diagnostic criterion. The standardized linear relationship between wrist cartilage area and carpal bone height captures the natural diversity of these measurements and provides a promising index for future diagnostic and therapeutic studies in the field of rheumatologic diseases. Disclosure of Interest None Declared

Background Fibrosis is a major concern in patients with systemic sclerosis (SSc), the pathogenesis of which is not clear. Lysyl oxidase (LOX) is an extracellular copper enzyme that cross-links collagen and elastin, thus stabilizing collagen fibrils [1]. LOX was found to be overexpressed in patients with primary myelofibrosis (PMF), a disease with severe fibrosis [2]. In SSc, LOX was found to be elevated in the skin but has not been evaluated in the serum [3] in correlation with clinical parameters. Objectives To evaluate LOX serum level of patients with SSc compared to normal controls and to patients with PMF. To correlate this serum level to clinical parameters. Methods We prospectively evaluated patients with SSc for demographics, clinical manifestations and laboratory results including blood count, chemistry, urine examination, autoantibodies and serum LOX concentration determined by ELISA. We further evaluated lung function tests, echocardiography, lung high resolution CT scans, as needed, and determined lung involvement, modifies Rodnan skin score (mRSS), Medsger disease severity scale and Valentini activity index [4]. Results Twenty four women and 2 men with SSc at a mean age of 48±12.6 were evaluated and compared with 25, age and gender matched healthy controls and 9 patients with PMF. Of the SSc patients, 10 had diffuse disease- 8 of them with lung fibrosis, and 17 had limited disease. LOX concentration in SSc was higher than healthy controls and similar to PMF, 58.4±4.8 ng/ml vs. 28.4±2.5 ng/ml vs. 44.6±9.4 ng/ml (p Conclusions This is the first study to demonstrate high serum levels of LOX in SSc patients. These levels specifically correlate with skin fibrosis, lung fibrosis and disease severity - which reflects organ damage including fibrosis. We suggest that LOX has an important role in the pathophysiology of SSc and may serve as an objective assay for evaluation of disease severity. Our results suggest that LOX may be a promising future target of therapy in SSc. Future studies are warranted in order to determine the precise effects of such therapy. References Csiszar K et al. “Lysyl oxidases: a novel multifunctional amine oxidase family”. Prog. Nucleic Acid Res. Mol. Biol. 2001;70: 1–322. Papadantonakis N, Matsuura S, Ravid K. Megakaryocyte pathology and bone marrow fibrosis: the lysyl oxidase connection. Blood 2012;120(9):1774-81 Chanoki M, et al. Increased expression of lysyl oxidase in skin with scleroderma. Br J Dermatol 1995;133(5):710-5. Hudson M, et al. Update on indices of disease activity in systemic sclerosis. Semin Arthritis Rheum 2007;37(2):93-8. Disclosure of Interest None Declared

Goossens et al reported on a patient in whom a remission of Behcet's syndrome was induced with tumour necrosis factor (TNF) blocking treatment.1 We would like to add our experience in a patient with Behcet's disease associated with rheumatoid arthritis (RA), treated with infliximab (Remicade). A 47 year old male patient, born in Morocco, living in Israel, was diagnosed 14 years earlier with severe, progressive polyarthritis of hands, feet, and knees. Radiography showed …

Serum anticollagen antibodies to the native and denatured interstitial collagens were measured by solid phase radioimmunoassay (RIA) in a rabbit model of IgG-induced immune synovitis. Serum antibodies binding the native interstitial collagens and denatured type II collagen were observed in 100% of the animals tested (n = 6). Titerable antibodies to the alpha 1 (III) collagen polypeptide chain were observed in 83% of the animals, whereas serum antibodies to denatured type I collagen were observed in 33%. Inhibition studies showed that the observed serum anticollagen antibodies were conformationally dependent and collagen type specific. In addition these antibody populations varied in their affinities by as much as a factor of 2.81 for the specific substrates. Mean value of the average binding constants (Ka) for synovitis anticollagen antibodies binding native type II collagen was 5.47 X 10(6)mol; while the Ka determined for synovitis antibodies binding denatured type III collagen was 1.94 X 10(6)/mol. The data indicate that unique anticollagen antibody populations are expressed in the serum of animals with experimental IgG-induced chronic immune synovitis.