Jörg Wendler

Genetic Variants of the IL-23R Pathway: Association with Psoriatic Arthritis and Psoriasis Vulgaris, but No Specific Risk Factor for Arthritis

Variants in two genes of the IL-23 receptor (R) pathway have recently been shown to be associated with psoriasis vulgaris (PV). We were interested whether the risk conferred by these variants differs between psoriatic skin and joint disease. Four variants of the IL12B and IL23R genes were analyzed in 1,114 PV patients, 748 patients with psoriatic arthritis (PA) and 937 healthy controls before and after stratification for the major psoriasis risk allele at psoriasis susceptibility locus 1 (PSORS1). For both PA and PV, we detected the strongest association with two IL12B single-nucleotide polymorphisms and the corresponding haplotype as reflected by minimal P-values of 10(-7) and highest odds ratios of 1.50 (1.28-1.75) for rs6887695 in PA patients and 1.50 (1.27-1.76) for rs3212227 in the PV cohort, respectively. For IL23R, only rs11209026 showed an association. The results remained significant after correction for multiple testing. No difference was observed after stratification for the PSORS1 risk allele. While confirming recent reports on variants of the IL-23R pathway as susceptibility factors for PV, our study is the first to extend analysis of both genes to PA. However, our results indicate that these variants are not specific risk factors for arthritis, but relevant for susceptibility to psoriasis in general.

Deletion of LCE3C and LCE3B genes at PSORS4 does not contribute to Susceptibility to Psoriatic Arthritis in German patients

Introduction Psoriasis susceptibility locus 4 (PSORS4) is a susceptibility locus for psoriasis vulgaris (PsV), a common inflammatory, hyperproliferative skin disorder. Recently, a deletion of 2 late cornified envelope (LCE) genes within epidermal differentiation complex on chromosome 1 was shown to be enriched in 1426 patients with PsV, suggesting compromised barrier function in deletion carriers. This genetic association was subsequently confirmed in a German cohort. Methods In order to investigate whether this variant also predisposes to psoriatic arthritis (PsA), this deletion and 3 single nucleotide polymorphisms (SNPs) in strong linkage disequilibrium with it were genotyped in a case-control cohort of 650 patients and 937 control individuals of German origin. Results LCE deletion frequency did not significantly differ between patients with PsA and controls (65.0% vs 65.5%). Similarly, no evidence for association to the three SNPs was observed. Discussion This is the first non-human leucocyte antigen (HLA) risk factor predisposing only to skin type of psoriasis, supporting the concept of partially overlapping but different aetiological factors underlying skin and joint manifestations.

Patients with rheumatoid arthritis adapt differently to repetitive painful stimuli compared to healthy controls

The aim of the study was to investigate whether there are changes of the nociceptive system in patients with chronic inflammatory joint pain. A pain model was used which is based on the recording of cortical chemo-somatosensory event-related potentials (CSSERP) after nociceptive stimulation of the nasal mucosa with gaseous carbon dioxide (CO(2)). Twenty-five patients with rheumatoid arthritis (RA) were compared to healthy controls matched for age and gender. Responses to both different intensities of painful stimuli and constant intensities of series of 4 stimuli were analysed. When testing increasing CO(2) concentrations ratings and CSSERP amplitudes increased for both patients and controls. However, when repetitive stimulation was performed with an interval of 2s CSSERP amplitudes N1 were significantly greater in RA patients. It is hypothesized that chronic inflammatory joint pain changes nociceptive processing in terms of generalized changes of the nociceptive system which may amplify chronic pain.

Peripheral and central nervous changes in patients with rheumatoid arthritis in response to repetitive painful stimulation

It has been observed that patients with rheumatoid arthritis (RA) respond differently to repetitive painful stimulation. The present study investigated whether this is related to the peripheral or central nervous nociceptive system. EEG-derived potentials and the negative mucosal potential (NMP) from the respiratory epithelium were recorded in response to painful intranasal stimulation with gaseous CO(2). Differences between groups (12 RA patients, 12 controls) were found when stimuli were presented at short intervals. While the NMP did not differ between groups, patients had larger cortical responses to the first stimuli of a series of painful stimuli. This may indicate that in RA central nervous changes of nociceptive processing are present.

Safety of 15-deoxyspergualin in the treatment of glomerulonephritis associated with active systemic lupus erythematosus

Optimal treatment for patients with relapsing lupus nephritis remains unclear. The ability of 15-deoxyspergualin (gusperimus; 15-DSG) to suppress systemic lupus erythematosus (SLE)-like diseases has been demonstrated in animals and humans.1–4 15-DSG exerted no nephrotoxicity or hepatotoxicity but reversibly induced leucocytopenia.5,6 In this study we aimed at evaluating the safety of 15-DSG in the treatment of glomerulonephritis associated with SLE. Table 1 shows the patient characteristics. View this table: Table 1  Details of the patients’ history, especially previous immunosuppressive treatment, signs of SLE-GN activity or general SLE activity at entry, and indicators for response during/after 15-DSG treatment 15-DSG was provided by Nippon Kayaku Co Ltd, Tokyo, Japan. Patients gave their informed consent, and 15-DSG 0.5 mg/kg normal body weight (height in cm minus 100)/day was self administered subcutaneously for 14 days, followed by a break of 7 days ( = 1 cycle). The dose was adjusted (dependent on efficacy or safety, or both) after cycles 4 and 6 to 0.35 mg/kg and 0.25 mg/kg, or 0.7 mg/kg and 1.0 mg/kg. ### Patient 1 After a bolus, daily …

AB1014 The Value of an Automated Ultrasound System in the Detection of Synovitis

Background The detection of joint swelling caused by synovitis is important for the diagnosis and assessment of inflammatory arthritis. Ultrasound (US) and MRI have proven to be more sensitive and reliable than physical examination, but a comprehensive examination of affected joints with these techniques is time consuming and expensive. The automated breast volume scanner (ABVS) was developed to acquire serial B-mode pictures of the female breast and these data can be analysed in all three dimensions. Objectives To analyse the value of automated grey scale B mode US employing the ABVS system in detecting synovitis of the finger joints compared to manual ultrasound and physical examination, using MRI as gold standard. Methods 19 consecutive patients suffering from rheumatoid (n=15) or psoriatic (n=4) arthritis with at least one swollen finger joint were included. Automated and manual US were conducted using the ACUSON S2000™. The ABVS transducer was equipped with a linear array used with a frequency of 11 MHz. Each automatic sweep of the scanner generated 15.4 x 16.8 x 2.5 cm volume data sets. The system was set to perform an automatic scanning time of 65 s per scan with a slice thickness of 0.5 mm. The dorsal and palmar side of each hand were scanned separately. Multiplanar reconstruction enabled examination of the images at multiple levels for the presence of synovitis. Results Automated US detected 12.0, manual ultrasound 14.2, MRI 13.4, and clinical examination 4.1 swollen joints on average, respectively, per patient. The inter-observer reliability of both assessors for automated and manual US, MRI, and physical examination, was 66.9%, 72.7%, 95.1%, and 88.9%, respectively. A double assessor detection of joint swelling with MRI was used as gold standard. For the other methods, single observer detection was chosen. 84.3% of the joints classified as positive on MRI were confirmed by automated ultrasound, 85.5% on manual US, and 36.0 on physical examination. This translated into a sensitivity of 83.5%, 85.5%, and 36.0% for the three methods, respectively. Conclusions Automated US is a simple and time sparing option for the effective detection of synovitis in patients with inflammatory arthritis. Disclosure of Interest R. Mueller: None declared, M. Gruenke: None declared, J. Wendler: None declared, F. Schuch: None declared, H.-P. Karina: None declared, I. Boettger: None declared, R. Jakobs Employee of: Siemens, H. Schulze-Koops: None declared, J. von Kempis: None declared DOI 10.1136/annrheumdis-2014-eular.2059

Immunstatus bei HIV-Infizierten: Hat das Bewältigungsverhalten Einfluß?

Seit ca. 15 Jahren gibt es auch im deutschsprachigen Raum in Anlehnung an Bemuhungen in angloamerikanischen Landern eine eigenstandige Forschung zur Bewaltigung kritischer Lebensereignisse. Die Diagnose “HIV-positiv” stellt ein solches „kritisches Lebensereignis“ dar, durch das bei vielen Betroffenen Angst, Abwehrreaktionen und Panikhandlungen ausgelost werden. Im Gegensatz zu normalen Alltagsproblemen kann das Individuum nun nicht mehr auf ritualisierte Reaktionsschemata zuruckgreifen, sondern benotigt mitgesteuerte neue Verhaltenseinheit. Der Betroffene pruft deshalb die Tragfahigkeit seiner sozialen Beziehungen und die Moglichkeiten der Problem- und Krankheitsbewaltigung.

AB0189 Anti-Modified Protein Antibody Response Pattern Influences The Risk for Disease Relapse in Rheumatoid Arthritis Patients Tapering Disease Modifying Anti-Rheumatic Drugs

Background Autoimmunity is still present in rheumatoid arthritis patients in sustained disease remission. In the absence of inflammation the pattern of autoimmunity against post-translationally modified proteins could potentially impact the course of disease of rheumatoid arthritis patients, espepcially their risk to experience relapse of disease when disease modifying anti-rheumatic drugs (DMARDs) are tapered or stopped Objectives To perform a detailed analysis of the autoantibody response against post-translationally modified proteins in rheumatoid arthritis (RA) patients in sustained remission and to test whether its composition influences the risk for disease relapse when tapering DMARD therapy. Methods Immune responses against 10 citrullinated, homocitrullinated/carbamylated and acetylated peptides, as well as unmodified vimentin (control) and cyclic citrullinated peptide 2 (CCP2) were tested in baseline serum samples from 94 patients of the RETRO study. Patients were classified according to the number of autoantibody reactivities (0–1/10, 2–5/10 and >5/10) or specificity groups (citrullination, carbamylation and acetylation; 0 to 3) and tested for their risk to develop relapses after DMARD tapering. Demographic and disease-specific parameters were included in multivariate logistic regression analysis for defining the role of autoantibodies in predicting relapse. Results Patient varied in their anti-modified protein antibody response with the extremes from recognition of no (0/10) to all antigens (10/10). Antibodies against citrullinated vimentin (51%), acetylated ornithine (46%) and acetylated lysine (37%) were the most frequently observed sub-specificities. Relapse risk significantly (p=0.011) increased from 18% (0–1/10 reactivities) to 34% (2–5/10) and 55% (>5/10). With respect to specificity groups (0 to 3), relapse risk significantly (p=0.021) increased from 18% (no reactivity) to 28%, 36% and finally to 52% with one, two or three antibody specificity groups, respectively. Conclusions The data suggest that the pattern of anti-modified protein antibody response determines the risk of disease relapse in RA patients tapering DMARD therapy. Disclosure of Interest C. Figueiredo: None declared, H. Bang Employee of: Organtec Diagnostica, J. Cobra: None declared, M. Englbrecht: None declared, A. Hueber: None declared, J. Haschka: None declared, B. Manger: None declared, A. Kleyer: None declared, M. Reiser: None declared, S. Finzel: None declared, H.-P. Tony: None declared, S. Kleinert: None declared, J. Wendler: None declared, F. Schuch: None declared, M. Ronneberger: None declared, M. Feuchtenberger: None declared, M. Fleck: None declared, K. Manger: None declared, W. Ochs: None declared, M. Schmitt-Haendle: None declared, H.-M. Lorenz: None declared, H. Nuesslein: None declared, R. Alten: None declared, J. Henes: None declared, K. Krueger: None declared, J. Rech: None declared, G. Schett: None declared

Effects of Concomitant Conventional and Previous Biological Disease Modifying Anti-Rheumatic Drugs Treatment on the Efficacy of Tocilizumab to Induce Remission in Patients with Rheumatoid Arthritis An Observational Real-Life Study

Objectives: To investigate remission rates in rheumatoid arthritis patients exposed to tocilizumab treatment in real life clinical practice and to test whether concomitant conventional and previous biological disease modifying anti-rheumatic drugs treatment affects the efficacy of tocilizumab to reach remission. Methods: Between January 2009 and December 2012 disease activity was analyzed in 272 rheumatoid arthritis patients exposed to tocilizumab at the onset of treatment and sequentially thereafter, i.e. every four weeks at the time of infusion. Aside from demographic and disease-specific variables, previous and concomitant conventional and biologic disease modifying anti-rheumatic drugs therapy was documented in all patients. Multivariate logistic regression analyses were conducted to identify factors influencing Disease Activity Score 28 remission and attrition to tocilizumab treatment. Results: 219 (80.5%) of all patients were female. Mean Age was 55.48 ± 13.23 years and our patients had mean disease duration of 12.48 ± 9.30 years. Disease Activity Score 28 significantly decreased from 5.00 ± 1.52 at baseline to 3.09 ± 1.49 at the latest infusion. Mean treatment period was 58.28 ± 43.95 weeks. A total of 101 patients (42.8%) achieved Disease Activity Score 28 remission, which was significantly associated to the length of tocilizumab exposure. Achievement of Disease Activity Score 28 remission was independent from the concomitant use of conventional disease modifying anti-rheumatic drugs. Previous exposure to tumour necrosis factor inhibitors but not rituximab significantly reduced the likelihood to achieve Disease Activity Score 28 remission. Two logistic regression analyses revealed baseline disease activity and duration of tocilizumab therapy as independent factors for Disease Activity Score 28 remission, whereas age and concomitant methotrexate therapy were linked to attrition to tocilizumab treatment. Conclusion: Remission rates found in this observational study are comparable to those of randomized controlled trials and those of big post-marketing surveillance studies. Remission rates of rheumatoid arthritis patients treated with tocilizumab in clinical practice are not influenced by concomitant disease modifying anti-rheumatic drugs use. Previous exposure to tumour necrosis factor inhibitors but not to rituximab decreases the chance to reach remission with tocilizumab.

SAT0517 Automated Ultrasound for the Detection of Joint Swelling in Arthritic Diseases

Background The detection of joint swelling is a key feature in the diagnosis and assessment of arthritic diseases. Ultrasound and MRI have proven to be more sensitive and reliable than clinical examination, but a comprehensive examination of the small joints with these techniques is either time consuming or expensive. The automated breast volume scanner (ABVS) was developed to acquire series of consecutive B-mode pictures of the female breast and these data can be analysed in all three dimensions. Objectives To analyse the value of ABVS in detecting swelling of the finger joints compared to clinical examination and manual ultrasound. Methods 19 consecutive patients suffering from psoriatic (n=4) or rheumatoid (n=15) arthritis with at least 1 swollen MCP (metacarpophalangeal) or PIP (proximal interphalangeal) joint were included. ABVS and manual ultrasound were conducted using the ACUSON S2000™ (Siemens Medical Solutions, Mountain View, USA). The ABVS transducer was equipped with a linear array (5 – 14 MHz band width); the frequency was set at 11 MHz. Each automatic sweep of the scanner generated 15.4 x 16.8 cm x maximum 3 cm volume data sets. The system was set to perform an automatic scanning time of 65 s per scan with a slice thickness of 0.5 mm. The dorsal and palmar side of each hand were scanned separately. Multiplanar reconstruction enabled examination of the images at multiple levels for the presence of lesions or joint swelling (figure) Results Clinical examination of MCP, PIP, and DIP joints detected in average 4.1 swollen joints, manual ultrasound 13.7 joints, and ABVS 10.6 joints per patient. The interobserver reliability for detection of joint swelling were 73.3%, 72.5% and 85.9% for manual ultrasound, ABVS, and clinical examination, respectively. The sensitivities and specificities were 30.7% and 91.3% for clinical examination and 59.9% and 63.4% for ABVS using manual ultrasound as gold standard. Image/graph Conclusions ABVS is a simple and time sparing option for effective detection of joint swelling in patients suffering from arthritis with good sensitivity and specificity compared to manual ultrasound. Disclosure of Interest None Declared