Proteinase-3 mRNA expressed by glomerular epithelial cells correlates with crescent formation in Wegener's granulomatosis

Proteinase-3 mRNA expressed by glomerular epithelial cells correlates with crescent formation in Wegener's granulomatosis. Background Wegener's granulomatosis (WG) is characterized by systemic vasculitis with crescentic glomerulonephritis (CGN) and circulating autoantibodies directed against neutrophil cytoplasmic antigens (ANCA). Proteinase 3 (PR-3), a neutral serine proteinase in neutrophils implicated in the growth control of myeloid cells, has been identified as the target antigen for ANCA in WG. Since the kidneys are frequently involved in WG, we studied the in situ expression of PR-3 by renal parenchymal cells. Methods We assessed the expression of PR-3 in kidney biopsies of 15 patien…

Safety and clinical outcomes of rituximab therapy in patients with different autoimmune diseases: experience from a national registry (GRAID)

Introduction: Evidence from a number of open-label, uncontrolled studies has suggested that rituximab may benefit patients with autoimmune diseases who are refractory to standard-of-care. The objective of this study was to evaluate the safety and clinical outcomes of rituximab in several standard-of-care-refractory autoimmune diseases (within rheumatology, nephrology, dermatology and neurology) other than rheumatoid arthritis or non-Hodgkin's lymphoma in a real-life clinical setting. Methods: Patients who received rituximab having shown an inadequate response to standard-of-care had their safety and clinical outcomes data retrospectively analysed as part of the German Registry of Autoimmune…

Efficacy and Safety of Subcutaneous Belimumab in Anti–Double-Stranded DNA–Positive, Hypocomplementemic Patients With Systemic Lupus Erythematosus

Objective: To investigate the efficacy and safety of belimumab, a human immunoglobulin monoclonal antibody against B lymphocyte stimulator, in a subset of patients with systemic lupus erythematosus (SLE) who were hypocomplementemic (C3 <90 mg/dl and/or C4 <10 mg/dl) and anti–double-stranded DNA (anti-dsDNA) positive (≥30 IU/ml) at baseline. Methods: In this phase III, double-blind, placebo-controlled study (BEL112341; ClinicalTrials.gov identifier: NCT01484496), patients with moderate to severe SLE (Safety of Estrogens in Lupus Erythematosus National Assessment version of the Systemic Lupus Erythematosus Disease Activity Index [SELENA–SLEDAI] score ≥8) were randomized (2:1) to receive weekl…

SAT0571 OPTICAL SPECTRAL TRANSMISSION TO ASSESS THERAPY RESPONSE IN PATIENTS WITH ARTHRITIS: A COMPARATIVE STUDY WITH CLINICAL, LABORATORY AND ULTRASONOGRAPHIC ACTIVITY MARKERS.

Background:Valid assessment of disease activity leads to outcome improvement in patients with rheumatoid arthritis (RA) (1). Optical spectral transmission (OST) is a modern diagnostic tool able to assess the blood-specific absorption of light transmitted through a tissue, promising quantification of inflammation in the finger and wrist joints of RA patients (commercial device: HandScan - Hemics, The Netherlands) (2).Objectives:To our knowledge, there are no data regarding the diagnostic value of OST in the evaluation of inflammatory activity changes during arthitis follow up.Thus, aims of this study were to examine the ability of OST to detect response to anti-inflammatory therapy in patien…

Anti-PR-3 antibodies induce endothelial IL-8 release

Background It has been shown that interaction of anti-PR-3 antibodies with human endothelial cells (EC) leads to an activation of EC in vitro, i.e. induction of adhesion molecules like E-selectin, VCAM-1 and tissue factor. The aim of this study was to investigate the effect of anti-PR-3 antibodies on endothelial IL-8 expression. Materials and methods EC were cultured in 96-well plates and stimulated with TNF-α and IL-1β for 1 h to induce membrane expression of endothelial PR-3. Anti-PR-3 antibodies were purified from sera from patients with clinically active Wegener's granulomatosis. Purified anti-Ro, anti-centromere, anti-dsDNA antibodies and a monoclonal anti-PR-3 antibody (WGM2) served a…

AB0691 INCREASED CARDIOVASCULAR RISK IN MIXED CONNECTIVE TISSUE DISEASE: EVALUATION OF MACROVASCULAR INVOLVEMENT AND ITS PREDICTORS BY AORTIC PULSE WAVE VELOCITY

Background: Macrovascular involvement and cardiovascular (CV) risk have not been sufficiently studied in patients with mixed connective tissue disease (MCTD). In particular, the gold standard assessment method of aortic stiffness carotid-femoral pulse wave velocity (cfPWV) (1) has never been evaluated in patients with this disease. Objectives: Aims of the present study were to examine cfPWV in MCTD and to evaluate its associations with MCTD associated parameters and traditional CV risk factors. Methods: cfPWV measurements were performed in 43 MCTD patients and 107 healthy controls. The difference between cfPWV in the two groups was statistically examined and subsequently controlled for the …

Correlation of renal tubular epithelial cell-derived interleukin-18 up-regulation with disease activity in MRL-Faslpr mice with autoimmune lupus nephritis.

Objective MRL-Faslpr mice spontaneously develop an autoimmune disease that mimics systemic lupus erythematosus in humans. Infiltrating T cells expressing interferon-γ (IFNγ) are responsible for the autoimmune kidney destruction in MRL-Faslpr mice, and interleukin-18 (IL-18) released by mononuclear phagocytes stimulates T cells to produce the IFNγ. Since MRL-Faslpr T cells are characterized by an overexpression of the IL-18 receptor accessory chain, we sought to determine the impact of IL-18 on the progression of lupus nephritis in MRL-Faslpr mice. Methods IL-18 expression in sera and kidney tissues from MRL-Faslpr mice was determined by enzyme-linked immunosorbent assay (ELISA), reverse tra…

P172 Mainzer lupus score (MLS) a new questionnaire for lupus treatment

Background For the diagnosis and treatment of the systemic lupus erythematosus (SLE), numerous scores and indices already exist with different focal points, which are mostly extensive and time consuming. The MLS is a short newly developed questionnaire consisting out of four items to consider whether it is necessary to adjust current therapy: Occurrence of new lupus-specific symptoms, subjective measurement of quality of life (Qol), change of serological abnormalities and the occurrence of organ damage accrual. Methods Patients who had at least 3 visits since 2016 in our clinic were able to participate. Spearman-correlation was used to correlate MLS and several other well established scores…

Implementation of a Web-Based Work-Related Psychological Aftercare Program Into Clinical Routine: Results of a Longitudinal Observational Study

Background: As inpatient medical rehabilitation serves to promote work ability, vocational reintegration is a crucial outcome. However, previous Web-based trials on coping with work-related stress have been limited to Web-based recruitment of study participants. Objective: The aim of our study was to evaluate the implementation of an empirically supported transdiagnostic psychodynamic Web-based aftercare program GSA (Gesund und Stressfrei am Arbeitsplatz [Healthy and stress-less at the workplace])-Online plus into the clinical routine of inpatient medical rehabilitation, to identify characteristics of patients who have received the recommendation for GSA-Online plus, and to determine helpfu…

Genetic predisposition—is lupus nephritis a question of copy numbers?**Copy number polymorphism in Fcgr3 predisposes to glomerulonephritis in rats and humans. Comment on Aitman TJ, Dong R, Vyse TJ et al. Nature 2006; 439: 851–855.

Control Of Organ Transplant-Associated Graft-versus-Host Disease By Activated Host Lymphocyte Infusions

Background Prolonged persistence of donor-derived T cells after organ transplantation has been proposed to improve long-term allograft survival. However, surviving transplant-derived T cells are also able to mediate devastating graft-versus-host disease (GvHD). Currently, GvHD after organ transplantation is usually refractory to conventional therapy and the disease outcome fatal. Methods Graft-reactive host T cells were generated ex vivo from a patient suffering from a severe and refractory liver-transplant-associated GvHD. To control GvHD, activated alloreactive host T cells were repetitively retransferred into the patient (activated host lymphocyte infusion [aHLI]). Results Adoptive trans…

Fabry nephropathy: 5 years of enzyme replacement therapy-a short review.

Fabry disease is an X-linked lysosomal storage disease, resulting from a deficiency of the enzyme α-galactosidase A and subsequent cellular storage of the enzyme substrate globotriaosylceramide (Gb3) [1]. Estimates of the incidence of Fabry disease vary markedly, from 1:<5000 male births in a newborn screening study in Italy [2] to 1:117 000 male births in Australia [3] and 1:833 000 male births in northern Portugal [4]. In general, hemizygous males are more severely affected than heterozygous females. In males, life expectancy is reduced by an average of 20 years [5] and in females by 15 years [6]. Although males tend to suffer symptoms earlier than females, both boys and girls can be affe…

Anti-Endothelzell-Antikörper

Fatigue in SLE: diagnostic and pathogenic impact of anti-N-methyl-D-aspartate receptor (NMDAR) autoantibodies.

ObjectivesWe explored the impact of circulating anti-N-methyl-D-aspartate receptor (NMDAR) antibodies on the severity of fatigue in patients with systemic lupus erythematosus (SLE).MethodsSerum samples of 426 patients with SLE were analysed for the presence of antibodies to the NR2 subunit of the NMDAR. In parallel, the severity of fatigue was determined according to the Fatigue Scale for Motor and Cognitive functions questionnaire. In a subgroup of patients with SLE, the hippocampal volume was correlated with the levels of anti-NR2 antibodies. Isolated immunoglobulin G from patients with anti-NR2 antibodies were used for murine immunohistochemical experiments and functional assays on neuro…

CSF-1 signals directly to renal tubular epithelial cells to mediate repair in mice

金沢大学医薬保健研究域医学系

AB1299-HPR THE RHEUMA-VOR APP: OPTIMIZING THE EARLY DIAGNOSIS OF RHEUMATIC DISEASES

Background:The proof-of-concept network study “Rheuma-VOR” aims to improve the quality of rheumatological care through coordinated cooperation. In particular, rheumatic diseases should be diagnosed as early as possible and treated quickly in a targeted manner [3]. Smartphone apps have a potential to improve the management of chronic diseases. For example, they can be used to provide health information, or to offer self-monitoring and self-screening options [1, 2].Objectives:The Rheuma-VOR Screening-App study examines whether a smartphone-based app can increase the detection rate of the three most common chronic inflammatory rheumatic diseases: rheumatoid arthritis, psoriatic arthritis and s…

Genetics and novel aspects of therapies in systemic lupus erythematosus.

Autoimmune diseases, such as rheumatoid arthritis, multiple sclerosis, autoimmune hepatitis and inflammatory bowel disease, have complex pathogeneses and the factors which cause these disorders are not well understood. But all have in common that they arise from a dysfunction of the immune system, interpreting self components as foreign antigens. Systemic lupus erythematosus (SLE) is one of these complex inflammatory disorders that mainly affects women and can lead to inflammation and severe damage of virtually any tissue and organ. Recently, the application of advanced techniques of genome-wide scanning revealed more genetic information about SLE than previously possible. These case-contro…

P125 Internet-based exercise therapy in patients with systemic lupus erythematodes – systemic lupus erythematodes exercise program (SLEEP)

Background The SLEEP study examines the effect of an exercise therapy against a control group with TAU therapy (Treatment as usual) in SLE to identify the effect of regular physical activity on muscular development. Furthermore, we investigate the effect of physical activity on disease activity and especially on fatigue syndrome. Molecular biological markers such as cfDNA and exosomes also detect the degree of the prostration of the patients. Methods Thirty SLE patients with laboratory as well as clinically stable status were included. The intervention group initially consisted of 24 patients, of which 12 were aerobically and 12 anaerobically active. In contrast, eight patients were include…

Role of Human Leukocyte Antigens (HLA) in Autoimmune Diseases

Since the discovery of HLA 60 years ago, it has contributed to the understanding of the immune system as well as of the pathogenesis of several diseases. Aside from its essential role in determining donor-recipient immune compatibility in organ transplantation, HLA genotyping is meanwhile performed routinely as part of the diagnostic work-up of certain autoimmune diseases. Considering the ability of HLA to influence thymic selection as well as peripheral anergy of T cells, its role in the pathogenesis of autoimmunity is understandable. The aim of this paper is to provide a brief overview of the role and current clinical relevance of HLA-B27 in spondyloarthritis and HLA-B51 in Behçet's disea…

sj-docx-1-tan-10.1177_17562864211051497 – Supplemental material for Association of serum neurofilament light chain levels and neuropsychiatric manifestations in systemic lupus erythematosus

Supplemental material, sj-docx-1-tan-10.1177_17562864211051497 for Association of serum neurofilament light chain levels and neuropsychiatric manifestations in systemic lupus erythematosus by Sinah Engel, Simone Boedecker, Paul Marczynski, Stefan Bittner, Falk Steffen, Arndt Weinmann, Andreas Schwarting, Frauke Zipp, Julia Weinmann-Menke and Felix Luessi in Therapeutic Advances in Neurological Disorders

Thymoma and pure red cell aplasia in a patient with systemic lupus erythematosus.

We present the case of a female patient with a diagnosis of systemic lupus erythematosus (SLE) at the age of 54 years. At the age of 63 years, she suffered from malignant thymoma and 3 years after removal of the thymoma a diagnosis of pure red cell aplasia (PRCA) was established. This is, to our knowledge, the first report of the occurrence of SLE, thymoma and PRCA in the same patient. The case is discussed with regard to the already known associations between these diseases.

Inducible Co-Stimulator Null MRL-Fas lpr Mice

MRL/MpJ-Tnfrsf6lpr (MRL-Faslpr) mice develop a spontaneous T cell-dependent autoimmune disease that shares features with human lupus, including fatal nephritis, systemic pathology, and autoantibodies (autoAb). The inducible co-stimulator (ICOS) is upregulated on activated T cells and modulates T cell-mediated responses. To investigate whether ICOS has an essential role in regulating autoimmune lupus nephritis and the systemic illness in MRL-Faslpr mice, ICOS null (-/-) MRL Faslpr and ICOS intact (+/+) MRL-Faslpr strains (wild-type [WT]) were generated and compared. It was determined that in ICOS-/- MRL-Faslpr as compared with the WT strain, (1) there is a significant reduction in circulatin…

FRI0189 POOLED ANALYSIS OF THE REAL-WORLD EFFECTIVENESS OF BELIMUMAB IN TREATMENT OF SYSTEMIC LUPUS ERYTHEMATOSUS USING MULTI-COUNTRY DATA FROM THE OBSERVE STUDIES

Background: Real-world evidence of belimumab effectiveness in patients with systemic lupus erythematosus (SLE) has been reported separately for several countries through the OBSErve (evaluation Of use of Belimumab in clinical practice SEttings) programme. Objectives: To evaluate the effectiveness of belimumab in patients with SLE using pooled data from the individual OBSErve studies. Methods: This was a post hoc meta-analysis (GSK study 206351) of patient level data pooled from six retrospective observational cohort studies (Argentina, Canada, Germany, Spain, Switzerland, United States of America). Physicians provided data for adults (≥18 years; clinical diagnosis of SLE) who had initiated …

FRI0318 Health care resource utilisation (HCRU) and cost analyses of systemic lupus erythematosus (SLE) as a function of disease severity: analysis of real-world claims data from a german sickness fund

Background SLE is a severe, chronic autoimmune disease of the connective tissue involving multiple organ systems. Understanding the economic burden of SLE in the context of disease severity is important when considering new therapeutic options. Objectives HCRU and costs associated with SLE were examined retrospectively using anonymized data from a German Sickness Fund database. Methods Real-world claims for adult (≥18 years old) patients (pts) with SLE from a German Sickness Fund database of company health insurance schemes were analysed. HCRU and costs were assessed annually for 2009–2014 for pts diagnosed with SLE in 2009 and validated using repeated SLE-related claims, co-diagnosis codes…

Realität der Versorgungssituation der Gicht: Daten zur Klinik, Epidemiologie und Komorbiditäten von 4016 Patienten in Rheinland-Pfalz

Zusammenfassung Einleitung Ziel dieser Datenerhebung war die Untersuchung der klinischen, demografischen und Komorbidität-assoziierten Daten der Gicht sowie der klinischen Praxis der hausärztlichen Gichtversorgung in Rheinland-Pfalz (RL-P). Methoden Gicht-spezifische Fragebögen wurden über die kassenärztliche Vereinigung an alle Hausarztpraxen in RL-P versendet. Die Fragebögen setzten sich aus Items zur Erfassung von Epidemiologie, Medikation und Komorbiditäten zusammen. Darüber hinaus wurden Fragen zur klinischen Manifestation der Gicht mit einem besonderen Fokus auf therapierefraktäre Fälle eingebunden. Schließlich wurden die Hausärzte angehalten, den aktuellen Versorgungsstatus anhand ei…

Interaction of antibodies to proteinase 3 (classic anti-neutrophil cytoplasmic antibody) with human renal tubular epithelial cells: impact on signaling events and inflammatory mediator generation.

Abstract Among the anti-neutrophil cytoplasmic Abs (ANCA), those targeting proteinase 3 (PR3) have a high sensitivity and specificity for Wegener’s granulomatosis (WG). A pathogenetic role for these autoantibodies has been proposed due to their capacity of activating neutrophils in vitro. Recently, PR3 was also detected in human renal tubular epithelial cells (TEC). In the present study, the effect of murine monoclonal anti-PR3 Abs (anti-PR3) and purified c-ANCA targeting PR3 from WG serum on isolated human renal tubular cell signaling and inflammatory mediator release was characterized. Priming of TEC with TNF-α resulted in surface expression of PR3, as quantified in immunofluorescence stu…

B cell activating factor (BAFF): Structure, functions, autoimmunity and clinical implications in Systemic Lupus Erythematosus (SLE)

The B cell activating factor (BAFF), or B lymphocyte stimulator (BLyS), is a B cell survival factor which supports autoreactive B cells and prevents their deletion. BAFF expression is closely linked with autoimmunity and is enhanced by genetic alterations and viral infections. Furthermore, BAFF seems to be involved in adipogenesis, atherosclerosis, neuro-inflammatory processes and ischemia reperfusion (I/R) injury. BAFF is commonly overexpressed in Systemic Lupus Erythematosus (SLE) and strongly involved in the pathogenesis of the disease. The relationship between BAFF levels, disease activity and damage accrual in SLE is controversial, but growing evidence is emerging on its role in renal …

Absence of Anti-Glomerular Basement Membrane Antibodies in 200 Patients With Systemic Lupus Erythematosus With or Without Lupus Nephritis: Results of the GOODLUPUS Study

IntroductionAnti-glomerular basement membrane (GBM) antibodies are pathogenic antibodies first detected in renal-limited anti-GBM disease and in Goodpasture disease, the latter characterized by rapidly progressive crescentic glomerulonephritis combined with intra-alveolar hemorrhage. Studies have suggested that anti-GBM antibody positivity may be of interest in lupus nephritis (LN). Moreover, severe anti-GBM vasculitis cases in patients with systemic lupus erythematosus (SLE) have been described in the literature, but few studies have assessed the incidence of anti-GBM antibodies in SLE patients.ObjectiveThe main study objective was to determine if positive anti-GBM antibodies were present …

Cytotoxic effects of antibodies to proteinase 3 (C-ANCA) on human endothelial cells.

SUMMARY Autoantibodies directed against cytoplasmic antigens of neutrophils (ANCA), especially those with specificity for proteinase 3 (PR-3) and myeloperoxidase, are valuable markers for differential diagnosis and monitoring of disease activity in Wegener's granulomatosis (WG) and other vasculitides. Till now, several concepts concerning a direct role of antibodies against PR-3 in the pathogenesis of WG have been discussed. Recently we were able to show that these antibodies recognize PR-3 translocated into the membrane of human endothelial cells. The aim of this study was to investigate putative cytotoxic effects of antibodies to PR-3 on human endothelial cells. Antibodies were obtained b…

THU0366 SYSTEMATIC CORONARY RISK EVALUATION (SCORE) MISCLASSIFIES CARDIOVASCULAR RISK IN ANTISYNTHETASE SYNDROME: RESULTS OF THE PILOT MULTICENTRIC STUDY RI.CAR.D.A.

Background:Antisynthetase Syndrom (ASyS) is an autoimmune overlap disease characterized by antiaminoacyl-tRNA-synthetase (anti-ARS) antibodies and the classic triad of arthritis, myositis and interstitial lung disease (ILD) (1). Markers of cardiovascular (CV) or cerebrovascular (CVB) risk have never been examined in ASyS.Objectives:Aim of this study (RIsk of CARdiovascular Disease in ASyS: RI.CAR.D.A.) was to test the ability of an established traditional CV risk prediction score (Systematic Coronary Risk Evaluation-SCORE) and its EULAR modified version (mSCORE) to identify ASyS patients at high CV risk. Moreover, we sought to examine for the first time associations of CV surrogate markers …

New perspectives on the renal slit diaphragm protein podocin.

Podocin is a critical component of the glomerular filtration barrier, its mutations causing recessive steroid-resistant nephrotic syndrome. A GenBank analysis of the human podocin (NPHS2) gene resulted in the possible existence of a new splice variant of podocin in the kidney, missing the in-frame of exon 5, encoding the prohibitin homology domain. Using RT–polymerase chain reaction and immunoblotting followed by sequence analysis, we are for the first time able to prove the expression of a novel podocin isoform (isoform 2), exclusively and constitutively expressed in human podocytes. Furthermore, we reveal singular extrarenal podocin expression in human and murine testis. Our data show the…

Circulating CSF-1 Promotes Monocyte and Macrophage Phenotypes that Enhance Lupus Nephritis

Macrophages mediate kidney disease and are prominent in a mouse model (MRL- Fas lpr ) of lupus nephritis. Colony stimulating factor-1 (CSF-1) is the primary growth factor for macrophages, and CSF-1 deficiency protects MRL- Fas lpr mice from kidney disease and systemic illness. Whether this renoprotection derives from a reduction of macrophages and whether systemic CSF-1, as opposed to intrarenal CSF-1, promotes macrophage-dependent lupus nephritis remain unclear. Here, we found that increasing systemic CSF-1 hastened the onset of lupus nephritis in MRL- Fas lpr mice. Using mutant MRL- Fas lpr strains that express high, moderate, or no systemic CSF-1, we detected a much higher tempo of kidne…

Targeting transcription factor Stat4 uncovers a role for interleukin-18 in the pathogenesis of severe lupus nephritis in mice

Polymorphisms in the transcription factor Stat4 gene have been implicated as risk factors for systemic lupus erythematosus. Although some polymorphisms have a strong association with autoantibodies and nephritis, their impact on pathophysiology is still unknown. To explore this further we used signal transducers and activators of transcription 4 (Stat4) knockout MRL/MpJ-Fas(lpr)/Fas(lpr) (MRL-Fas(lpr)) mice and found that they did not differ in survival or renal function from Stat4-intact MRL-Fas(lpr) mice. Circulating interleukin (IL)-18 levels, however, were elevated in Stat4-deficient compared to Stat4-intact mice, suggesting that this interleukin might contribute to the progression of l…

Interferon-α Abrogates the Suppressive Effect of Apoptotic Cells on Dendritic Cells in anIn VitroModel of Systemic Lupus Erythematosus Pathogenesis

Objective.An increased incidence of apoptotic cells and an increased activation of dendritic cells (DC) may be involved in the pathogenesis of systemic lupus erythematosus (SLE). We investigated the characteristics of apoptotic neutrophils and monocyte-derived DC of patients with SLE, their interaction, and the influence of autoantibodies and inflammatory cytokines on this interaction.Methods.Kinetics of neutrophil apoptosis and DC activation were studied by flow cytometry. To analyze the interaction of apoptotic cells with phagocytes, crossover coculture experiments were performed with DC from patients with SLE and apoptotic Jurkat T cells as well as with apoptotic neutrophils from patient…

Impact of switching from mycophenolate mofetil to enteric-coated mycophenolate sodium on gastrointestinal side effects in patients with autoimmune disease: a Phase III, open-label, single-arm, multicenter study

Bernhard Manger,1 Falk Hiepe,2 Matthias Schneider,3 Margitta Worm,4 Peter Wimmer,5 Eva-Maria Paulus,5 Andreas Schwarting6 1University Hospital Erlangen, Med Clinic III Polyclinic, Erlangen, 2Rheumatology, University Hospital Charit&amp;eacute;, Campus Mitte, Berlin, 3Policlinic of Rheumatology, Heinrich-Heine-Universit&amp;auml;t, D&amp;uuml;sseldorf, 4Department of Dermatology, Venereology and Allergology, University Hospital Charit&amp;eacute;, Campus Mitte, Berlin, 5Novartis Pharma GmbH, N&amp;uuml;rnberg, 6Department of Internal Medicine, Johannes Gutenberg University, Mainz, Germany Background: The purpose of this study was to assess changes in gastrointestinal symptom severity in pati…

Arthrosonografische, klinische, laborchemische und radiologische Aspekte des Löfgren-Syndroms: Eine retrospektive Analyse

Possible misclassification of cardiovascular risk by SCORE in antisynthetase syndrome: results of the pilot multicenter study RI.CAR.D.A

Abstract Objectives To test the ability of an established traditional cardiovascular (CV) risk prediction score [Systematic COronary Risk Evaluation (SCORE)] and its EULAR modified version (mSCORE) to identify antisynthetase syndrome (ASyS) patients at high CV risk and to examine for the first time associations of CV and cerebrovascular surrogate markers with clinical and immunological ASyS parameters. Methods SCORE/mSCORE and the gold standard marker of aortic stiffness [carotid-femoral pulse wave velocity (cfPWV)] were examined in ASyS patients and healthy controls. Moreover, sonography of the common- (CCA) and internal- (ICA) carotid arteries was performed in subsets of both groups, eval…

Association of serum neurofilament light chain levels and neuropsychiatric manifestations in systemic lupus erythematosus

Background: The aim was to evaluate the diagnostic potential of serum neurofilament light chain (sNfL) measurements in patients with neuropsychiatric systemic lupus erythematosus (NPSLE). Methods: sNfL levels were determined by single molecule array assay in a retrospective cross-sectional cohort of 144 patients with systemic lupus erythematosus (SLE). After log-transformation of sNfL levels, mean sNfL levels were compared between NPSLE patients and SLE patients without neuropsychiatric disease using Student’s t test. Furthermore, the association of different neuropsychiatric manifestations with sNfL levels was assessed using a one-way analysis of variance (ANOVA) with post hoc analysis. As…

Renal tubular epithelial cell-derived BAFF expression mediates kidney damage and correlates with activity of proliferative lupus nephritis in mouse and men.

B-cell activating factor of the tumour necrosis factor family (BAFF) is a cytokine, mainly produced by hematopoietic cells (e.g. monocytes/macrophages, dendritic cells), indispensable for B-cell maturation. The BLISS studies have demonstrated that blocking BAFF by the human monoclonal antibody belimumab is a valuable therapeutic approach in patients with clinically and serologically active systemic lupus erythematosus (SLE). However, the defined sources of BAFF, which contributes to SLE, are still unclear. Recent findings show that BAFF expression is not restricted to myeloid cells. Since lupus nephritis is the main cause of morbidity and mortality for SLE patients, the aim of this study wa…

Effects of Th1 and Th2 cytokines on cytokine production and ICAM-1 expression on synovial fibroblasts

OBJECTIVES--To investigate the influence of the Th1 and Th2 lymphokines interleukins (IL)-4 and IL-13, interferon gamma (IFN gamma), and several monokines on the adhesion of mononuclear cells to synovial fibroblasts and intercellular adhesion molecule-1 (ICAM-1) expression and cytokine production of synovial fibroblasts in patients with osteoarthritis. METHODS--Synovial fibroblasts were isolated from patients with osteoarthritis and stimulated with IL-1 beta, IL-4, IL-6, IL-10, IL-12, IL-13, tumour necrosis factor alpha (TNF alpha), and IFN gamma. Subsequently, we determined the production of IL-1 alpha, IL-1 beta, IL-6, IL-10, IL-12, IFN alpha and TNF alpha, and the expression of ICAM-1 ly…

Clinical outcomes and safety of rituximab treatment for patients with systemic lupus erythematosus (SLE) – results from a nationwide cohort in Germany (GRAID)

Objective The objective of this article is to evaluate the safety and clinical outcome of rituximab treatment in systemic lupus erythematosus (SLE) patients refractory to standard of care therapy in a real-life setting in Germany. Methods The GRAID registry included patients with different autoimmune diseases who were given off-label treatment with rituximab. Data on safety and clinical response were collected retrospectively. In SLE patients, clinical parameters included tender and swollen joint counts, fatigue, myalgia, general wellbeing, Raynaud’s and the SLEDAI index. Laboratory tests included dsDNA antibody titres, complement factors, hematologic parameters and proteinuria. Finally, th…

FRI0265 Selexipag in Raynaud's Phenomenon Secondary To Systemic Sclerosis: A Randomised, Placebo-Controlled, Phase II Study

Background Raynaud9s phenomenon (RP) occurs in >95% of patients (pts) with systemic sclerosis (SSc) and contributes to digital ischaemia that may lead to digital ulcers (DUs) and gangrene.1,2 Empirical treatment of SSc-associated RP includes oral vasodilators, particularly calcium channel blockers and intermittent intravenous prostacyclin analogues.3,4 However, there is a need to identify oral therapies that are more efficacious than those currently available. Objectives To determine the activity of selexipag, an oral, selective, prostacyclin receptor agonist, on RP attack frequency in pts with SSc. Methods The study comprised a placebo single-blind run-in phase of 2–4-weeks followed by an …

The fungal lactone oxacyclododecindione is a potential new therapeutic substance in the treatment of lupus-associated kidney disease.

Recently oxacyclododecindione (Oxa), a macrocyclic lactone isolated from the imperfect fungus Exserohilum rostratum, has been described as a potent transcription inhibitor of inducible proinflammatory and profibrotic genes in cell culture models. As kidney disease in systemic lupus erythematosus is characterized by aberrant expression of inflammatory mediators and infiltration of immune cells, we investigated the effect of Oxa in MRL-Fas(lpr) mice, a model of systemic lupus erythematosus. These mice develop a spontaneous T-cell and macrophage-dependent autoimmune disease including severe glomerulonephritis that shares features with human lupus. Comparable to the results of in vitro models, …

Diagnostic Value of Optical Spectral Transmission in Rheumatoid Arthritis: Associations with Clinical Characteristics and Comparison with Joint Ultrasonography

Objective.To examine the value of optical spectral transmission (OST) in detecting joint inflammation in patients with rheumatoid arthritis (RA) and to evaluate whether OST correlates with certain patient characteristics.Methods.OST measurements were performed in the metacarpophalangeal, proximal intraphalangeal, and wrist joints of 168 patients with RA and 114 controls. OST difference between the 2 groups was statistically examined and subsequently controlled for the effect of possible confounding factors. Diagnostic OST performance was tested by receiver-operating characteristics. Moreover, associations of OST with clinical and serological activity markers (patient group), joint ultrasoun…

Interferon-beta: a therapeutic for autoimmune lupus in MRL-Faslpr mice.

Type I interferons are associated with lupus. Genes that are regulated by IFN-alpha are upregulated in pediatric lupus patients. Gene deletion of the IFN-alpha/beta receptor in experimental lupus-like NZB mice results in reduced disease activity. Conversely, IFN-beta is a well-established treatment in multiple sclerosis, another autoimmune disease. For determining whether IFN-beta treatment is harmful or beneficial in lupus, MRL-Fas(lpr) mice were injected with this type I IFN. Treatment was initiated in MRL-Fas(lpr) mice with mild and advanced disease. IFN-beta was highly effective in prolonging survival and ameliorating the clinical (renal function, proteinuria, splenomegaly, and skin les…

FRI0628 DIAGNOSTIC VALUE OF OPTICAL SPECTRAL TRANSMISSION IN PATIENTS WITH RHEUMATOID ARTHRITIS: CORRELATIONS WITH DISEASE ACTIVITY, EPIDEMIOLOGIC AND ANTHROPOMETRIC PARAMETERS

Background Valid assessment of disease activity leads to improvement of long-term outcomes in patients with rheumatoid arthritis (RA) (1). Clinical disease activity assessment tools such as the Disease Activity Score 28 (DAS28) are partially subjective and do not always depict the real inflammatory burden. Ultrasound (US) and Hand-MRI are important diagnostic modalities which can nevertheless be time consuming (US, MRI), expensive (MRI) or usually performed unilaterally (MRI). Thus, further diagnostic tools are needed. Optical spectral transmission (OST) is a new modality able to assess the blood-specific absorption of light transmitted through a tissue promising quantification of inflammat…

PS7:145 Il-34, not csf-1, similarly mediates rheumatoid and lupus arthritis in patients

While Myeloid cells are abundant in lupus arthritis (LA) and rheumatoid arthritis (RA), based on clinical presentation LA and RA are considered distinct diseases. Although inflammatory arthritis is common in patients with lupus, the pivotal mechanisms leading to joint damage have not been investigated. We tested the hypothesis that IL-34, but not CSF-1, is a predictive biomarker that is integral in perpetuating synovial destructive inflammation in both LA and RA. We report the novel findings that: using longitudinally tracked patients, IL–34, not CSF–1, is a clinical predictive biomarker for both LA and RA; and IL–34 is more robustly expressed in the synovial tissue, cells and fluid compare…

AB0210 Quality of Life Indexes in Patients with Very Early Rheumatoid Arthritis (VERA): A Two Center Subgroup Analysis from The Adapthera Cohort: Table 1.

Background The significance of early diagnosis and early therapy initiation in patients with RA is tremendous. ADAPTHERA is a state wide rheumatology network based in Rhineland-Palatinate, Germany. ADAPTHERA aims to improve RA prognosis and quality of patients` life by reducing the time-to-RA-diagnosis. While there have been a lot of studies regarding quality of life in patients with established RA 1,2 , adequate data concerning very early rheumatoid arthritis (VERA) (disease duration Objectives To study quality of life in VERA patients and to investigate its associations with various RA associated clinical and laboratory parameters. Methods In a two center subgroup analysis from the ADAPTH…

Dr. Triantafyllias, et al reply

To the Editor: We have read with great interest the letter of Verhoeven, et al ,1 referring to our recent publication on the diagnostic value of optical spectral transmission (OST) in rheumatoid arthritis (RA).2 In our work we had described for the first time, to our knowledge, that OST values could be influenced not only by disease-associated factors (i.e., inflammatory activity) but also by patient-associated characteristics, such as sex, BMI, and age. …

Efficacy and Safety of Selexipag in Adults With Raynaud's Phenomenon Secondary to Systemic Sclerosis:A Randomized, Placebo-Controlled, Phase II Study

Objective To determine the effect of selexipag, an oral, selective IP prostacyclin receptor agonist, on the frequency of attacks of Raynaud's phenomenon (RP) in patients with systemic sclerosis (SSc). Methods Patients with SSc-related RP were randomized 1:1 to placebo (n = 38) or selexipag (n = 36) in individualized doses (maximum of 1,600 μg twice daily) during a 3-week titration period. The primary end point was the weekly average number of RP attacks during the study maintenance period, analyzed using a Bayesian approach with a negative binomial model adjusted for baseline number of RP attacks. Other outcome measures included Raynaud's Condition Score (RCS), RP attack duration, and treat…

AB1358 Infectious antibodies repertoire in rheumatoid arthritis

Background The incidence of infectious diseases in the RA ADAPTHERA study by ELISA antibody screening and the differences in infectious distribution in active or low active disease patients was explored. Methods Sera from 88 naive RA patients out of the ADAPTHERA study cohort, disease duration Results 82% RA patients were found to be positive for HSV1 +2 IgG (2% IgM positive), 8% for Adenovirus (IgA), 77% (IgG), and 1% (IgM). 99% for EBV-IgG (no IgM positive). 53% (IgG), and 26% (IgM) for CMV. 38% for HP-IgG and 15% for IgA and 79% for P-B19-IgG (3% IgM). 6% for Borrelia-IgM and 14% for IgG. A slightly increase was found for EBV sera positivity (99% IgG), compared to the normal population. …

Correlation between cell free DNA levels and medical evaluation of disease progression in systemic lupus erythematosus patients

High levels of cell free DNA (cfDNA) in human blood plasma have been described in patients with autoimmune diseases. The aim of this study was to determine the levels of cfDNA in systemic lupus erythematosus (SLE) patients and to assess fluctuations of cfDNA concentrations compared to the course of disease progression under standard treatment. Therefore, nuclear cfDNA concentrations in plasma were measured in 59 SLE patients and 59 healthy controls. Follow-up blood plasma was collected from 27 of the 59 SLE patients. Patients were characterised by clinical parameters (antinuclear antibodies (ANA), anti-dsDNA-antibodies, C3, C4, and CRP), SLE disease activity index (SLEDAI) and medical thera…

AB1209 THE RHEUMA-BUS-TOUR: TWO WEEK OPEN-ACCESS SCREENING FOR EARLY RHEUMATIC DISEASES

Background Early diagnosis is crucial for patients with rheumatic diseases. Studies show that early stage patients already show reduced mental and physical health [2, 3]. However, early diagnosis is often delayed due to the severe lack of rheumatologists in Germany. Objectives The cross-sectional study compares data on physical and mental health of known and suspected early rheumatic patients, collected from participants of the bus tour. Methods The Rheuma-Bus-Tour is an annual, two week open-access screening event in three states (Rhineland-Palatine, Saarland, Lower Saxony) that raises awareness for rheumatic diseases and identifies people with potential early cases of RA, SpA and PsA. All…

AB1232 RHEUMA-VOR: A PROOF-OF-CONCEPT NETWORK STUDY FOR THE IMPROVEMENT OF RHEUMATOLOGICAL HEALTH CARE THROUGH COORDINATED COOPERATION

Background Rheumatoid arthritis (RA), psoriasis arthritis (PsA) and spondyloarthritis (SpA) are the most common chronic autoimmune rheumatic diseases. For all 3, the so-called “window of opportunity” [1-3] has been identified as the decisive factor affecting the outcome. Objectives The aim of the prospective study is to improve early diagnosis of RA, PsA and SpA and thus positively impact the quality of care for patients with the help of coordinating centers. The primary endpoint is the number of cases with an actual indication for immediate referral to a specialist in proportion to all reported cases. Methods The project establishes a network of the University Medical Center Mainz, the Med…

Twelve-Week Internet-Based Individualized Exercise Program in Adults With Systemic Lupus Erythematosus: Protocol for a Randomized Controlled Trial

Background Systemic lupus erythematosus is a systemic autoimmune disease, which is associated with high cardiovascular risk, a predisposition to metabolic disorders, muscle wasting, and fatigue. Exercise therapy has become an important part of the long-term treatment of comorbidities in systemic lupus erythematosus. Exercise can lead to various benefits in patients with systemic lupus erythematosus such as increased aerobic capacity and exercise tolerance, resulting in an increased quality of life, decreased depression, and decreased fatigue. At the moment, no evidence-based treatment guidelines that recommend exercise for patients with systemic lupus erythematosus exist. Also, the efficac…

The Mainz Severity Score Index: a new instrument for quantifying the Anderson-Fabry disease phenotype, and the response of patients to enzyme replacement therapy

Anderson-Fabry disease (AFD) is an X-linked disorder caused by deficient activity of the lysosomal enzyme alpha-galactosidase A. The availability of enzyme replacement therapy (ERT) for this debilitating condition has led to the need for a convenient and sensitive instrument to monitor clinical effects in an individual patient. This study aimed to develop a scoring system--the Mainz Severity Score Index (MSSI)--to measure the severity of AFD and to monitor the clinical course of the disease in response to ERT. Thirty-nine patients (24 males and 15 females) with AFD were assessed using the MSSI immediately before and 1 year after commencing agalsidase alfa ERT. Control data were obtained fro…

Downregulation of alpha-galactosidase A upregulates CD77: functional impact for Fabry nephropathy.

Anderson-Fabry disease, an inherited deficiency in the lysosomal enzyme alpha-galactosidase A, is characterized by the progressive accumulation of globotriaosylceramide (Gb3), also known as CD77. We sought to clarify the pathogenesis of Fabry disease by establishing a cell model of this disorder. The expression of alpha-galactosidase A was transiently silenced by RNA interference in HK2 and primary human renal epithelial cells and stably silenced in HK2 cells by retroviral transfection with small hairpin RNA. All of the silenced cells had histological similarities to cells of patients with Fabry disease. The cells had reduced viability, significant accumulation of intracellular Gb3, and a m…

Antibodies to proteinase 3 mediate expression of vascular cell adhesion molecule-1 (VCAM-1).

SUMMARY VCAM-1 was first identified as an adhesion molecule induced on human endothelial cells (HEC) by inflammatory cytokines such as IL-1, tumour necrosis factor (TNF), and lipopolysaccharide (LPS). The molecule binds to a variety of leucocytes, including B cells, T cells, basophils, eosinophils and monocytes. Vascular expression of VCAM-1 has been associated with a number of disease states, including rheumatoid arthritis and vasculitis. The detection of antineutrophil cytoplasmic antibodies (ANCA), especially to proteinase 3 (PR3), has become important in the diagnosis of Wegener’s granulomatosis (WG) and related vasculitides. Recently we were able to demonstrate a direct effect of anti-…

Endothelin-1 modulates the expression of adhesion molecules on fibroblast-like synovial cells (FLS)

Endothelin-1 is known to possess various biological properties. In the present study we have investigated the effects of Endothelin-1 (Et-1) on the expression of adhesion molecules ICAM-1, VCAM-1 and CD-44 by fibroblast-like synoviocytes. Cultured fibroblast-like synoviocytes were treated with Et-1 in the absence or presence of C1306, a specific endothelin-A-receptor antagonist. Cell surface expression of ICAM-1, VCAM-1 and CD-44 was determined by immunofluorescence studies, Cyto-ELISA and FACS-analysis. ICAM-1, VCAM-1 and CD-44 were constitutively expressed on cultured FLS. After incubation with Et-1 the expression of ICAM-1, VCAM-1 and CD-44 increased. The level of expression of adhesion …

sj-docx-1-tan-10.1177_17562864211051497 – Supplemental material for Association of serum neurofilament light chain levels and neuropsychiatric manifestations in systemic lupus erythematosus

Supplemental material, sj-docx-1-tan-10.1177_17562864211051497 for Association of serum neurofilament light chain levels and neuropsychiatric manifestations in systemic lupus erythematosus by Sinah Engel, Simone Boedecker, Paul Marczynski, Stefan Bittner, Falk Steffen, Arndt Weinmann, Andreas Schwarting, Frauke Zipp, Julia Weinmann-Menke and Felix Luessi in Therapeutic Advances in Neurological Disorders

OP0048 Outcomes in Systemic Lupus Erythematous (SLE) Patients Treated with Belimumab in Clinical Practice Settings: Results from the Observe Study in Germany

Background Large-scale clinical trials have demonstrated clinical efficacy of belimumab in SLE patients. Objectives This study examined the clinical outcomes associated with belimumab in clinical practice settings in Germany. Methods OBSErve (GSK 117214) is a multi-center retrospective medical chart review study. Twenty-one rheumatologists from Germany treating >10 SLE-patients annually and with at least >5 yrs of practice experience were selected for data reporting. Adult SLE patients meeting the ACR classification criteria who received belimumab (10mg/kg) as part of usual care were identified for chart abstraction. Index date was the date of belimumab initiation. The primary outcome measu…

THU0520 Assessment of cardiovascular risk in patients with fibromyalgia by carotid-femoral pulse wave velocity – results of a prospective study

Background Autonomic dysfunction, a basic element of fibromyalgia (FM), has been in some cases related to increased risk of cardiovascular (CV) disease. CV risk associates with aortic stiffness, which can be reliably assessed by carotid-femoral pulse wave velocity (cfPWV). Objectives Aims of this study were to test the hypothesis of increased cfPWV in a group of patients with FM and to examine its association with FM associated parameters and selected traditional CV risk factors. Methods We performed measurements of cfPWV in 99 FM patients and 102 healthy controls. The difference between cfPWV values in the two groups after controlling for possible confounding factors was evaluated through …

PS8:160 Health care resource use (hru) and medical cost analyses as a function of systemic lupus erythematosus (sle) disease severity: analysis of claims data of a german sickness fund

Purpose Real-world HRU and medical cost analyses support drug development in SLE. The economic burden of SLE as a function of disease severity was quantified for a German cohort. Methods HRU and cost analyses were performed for patients (≥18 years old) with SLE and compared with those of matched controls for 2009–2014 using the Betriebskrankenkassen (BKK) German Sickness Fund Database. BKK is a branch of the statutory German health insurance. SLE was confirmed in 2009 using the diagnosing physician’s specialty, repeated SLE-related claims, co-diagnosis codes, laboratory tests, or prescriptions. At least 3 years’ data was also required prior to 2009. SLE cases were control matched by age, se…

Hepatische Manifestation eines Makrophagen-Aktivierungs-Syndroms (MAS)

Hintergrund Leberwerterhohungen gehoren zu den haufigsten pathologischen Laborbefunden in Deutschland. Haufige Ursachen einer Leberwerterhohung stellen neben einer nutritiv- und medikamentos-toxischen Schadigung, vor allem bei jungeren Patienten, virale oder autoimmune Ursachen dar. Das MAS kann sich ahnlich einer viralen Infektionserkrankung mit Fieber, Hepatosplenomegalie und Panzytopenie manifestieren und ist mit einer hohen Mortalitat assoziiert. Zugrunde liegt eine verstarkte Aktivierung der Makrophagen mit gesteigerter Zytokinausschuttung, was zu Endorganschaden mit Multiorganversagen fuhren kann. Neben genetischen Ursachen findet sich ein MAS haufig im Zusammenhang mit Infekten und r…

Effects of enzyme replacement therapy with agalsidase alfa on glomerular filtration rate in patients with Fabry disease: preliminary data

Progressive deposition of globotriaosylceramide results in severe complications involving the kidney, heart and brain in both hemizygous male and heterozygous female patients with Fabry disease. Analysis of renal data from FOS - the Fabry Outcome Survey - suggests that enzyme replacement therapy with agalsidase alfa can significantly improve renal function in patients with Fabry disease, at least in those with a mild decrease in glomerular filtration rate, and may also be able to slow down the natural decline in renal function in patients with a moderate reduction in glomerular filtration rate. Conclusion: Initial results from the large cohort of patients within FOS indicate that treatment …

The relationship between BAFF serum levels, anti-NMDAR autoantibodies and fatigue in patients with systemic lupus erythematosus and multiple sclerosis.

Soluble E-Selectin Enhances Intercellular Adhesion Molecule-1 (ICAM-1) Expression in Human Tumor Cell Lines

E-selectin mediates neovascularization via its soluble form, while its membrane-bound form initiates binding of tumor cells to vascular endothelium. Therefore, it was studied whether soluble E-selectin regulates further adhesion molecules on tumor cells. In tumor cells but not in related nonmalignant cells, intercellular adhesion molecule (ICAM)-1 expression was strikingly increased from 5 to 68% positive cells by in vitro inoculation of a recombinant E-selectin-IgG1 within 24 h, as analyzed by flow cytometry. The absence of changes in the expression of vascular cell adhesion molecule, integrin ligands (CD11a, CD18, integrin alpha 4), and sialyl-Lewis X indicates a specific effect of solubl…

Genetics and pathophysiology of granulomatosis with polyangiitis (GPA) and its main autoantigen proteinase 3.

Granulomatosis with polyangiitis (GPA) is a severe autoimmune disease and one of the small vessel anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides. Although its etiology and pathophysiology are still widely unknown, it is accepted that infections, environmental factors, epigenetic modifications, and a genetic predisposition provide the basis for this systemic disorder. GPA typically evolves into two phases: an initial phase characterized by ear, nose and throat (ENT) manifestations, such as chronic sinusitis and otitis, ulceration of the oral cavity and pharynx, as well as pulmonary nodules and a severe generalized phase, defined by the occurrence of rapidly progressive g…

Human renal tubular epithelial cells as target cells for antibodies to proteinase 3 (c-ANCA)

Intronic promoters and their noncoding transcripts: A new source of cancer-associated genes

Recent studies of mammalian genomes suggest that alternative promoters are associated with various disorders, including cancer. Here we present an intronic promoter of the murine proteinase 3 gene, which drives the expression of an alternative mRNA in intron 2 of the prtn3 gene. The proximal promoter sequences were identified and a series of promoter deletion constructs were used to identify the sequence elements that are required for basal promoter activity. Expression of the homeobox transcription factor CUX1 p75 isoform was found to suppress the activity of the alternative PR3 promoter. Data base analyses, multiple alignments and expression data showed that the intronic PR3 promoter is a…

Influence of Antisynthetase Antibodies Specificities on Antisynthetase Syndrome Clinical Spectrum Time Course

Antisynthetase syndrome (ASSD) is a rare clinical condition that is characterized by the occurrence of a classic clinical triad, encompassing myositis, arthritis, and interstitial lung disease (ILD), along with specific autoantibodies that are addressed to different aminoacyl tRNA synthetases (ARS). Until now, it has been unknown whether the presence of a different ARS might affect the clinical presentation, evolution, and outcome of ASSD. In this study, we retrospectively recorded the time of onset, characteristics, clustering of triad findings, and survival of 828 ASSD patients (593 anti-Jo1, 95 anti-PL7, 84 anti-PL12, 38 anti-EJ, and 18 anti-OJ), referring to AENEAS (American and Europea…

Colony-Stimulating Factor-1

A noninvasive means to predict the onset and recurrence of lupus nephritis (LN) before overt renal injury is needed to optimize and individualize treatment. Colony-stimulating factor-1 (CSF-1) is expressed by kidney tubules at the onset of LN, increases with disease progression, and spills into the circulation in lupus-prone mice. We tested the hypothesis that amplified expression of CSF-1 detected in the serum or urine correlates with intrarenal CSF-1 expression and histopathology (increased macrophage accumulation, activity indices) and clinical kidney disease activity and predicts the onset and recurrence of nephritis in patients with systemic lupus erythematosus (SLE). We found increase…

Immunoadsorption with tryptophan columns: A therapeutic option for the treatment of rheumatoid arthritis with septic complications

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease affecting multiple organs and tissues. Although there is a wide range of therapeutic applications, the coexistence of severe side effects and contraindications outlines the necessity of new therapeutic options in the treatment of severe RA. We report on the case of a 71-year-old patient with successful treatment of a complicated RA with tryptophan immunoadsorption combined with low-dose steroids. Bacterial spondylitis developed in this patient during long-term treatment with infliximab and methotrexate. Weekly immunoadsorption sessions with tryptophan columns resulted in continuous suppression of RA activity over a perio…

Mitomycininduziertes hämolytisch-urämisches Syndrom

HISTORY AND CLINICAL FINDINGS A 58-year-old patient suffered from rapidly progressing renal insufficiency and 11 kg weight-loss three months after adjuvant treatment of a carcinoma of the lower bowel (G 2 T 3 N 1 M 0 ) with mitomycine C. At the point of hospitalisation the patient was anuric while suffering from pulmonary oedema, hemolytic anemia and thrombocytopenia. INVESTIGATIONS Computed tomography and bronchial endoscopy showed pulmonary haemorrhage. Recurrence of carcinoma or metastases were excluded. Renal biopsy revealed mesangiolysis and concentric intimaproliferation (onion skinning). Beside haemolytic anaemia and fragmentocytes toxic damage of the bone marrow was found. TREATMENT…

Signal transduction pathways of membrane expression of proteinase 3 (PR‐3) in human endothelial cells

At present, the exact mechanism of the pathogenic effect of anti-PR-3 antibodies remains unknown. Interaction of anti-neutrophil cytoplasmic antibodies (ANCAs) with human umbilical vein endothelial cells (HUVECs) may play a key role. Recently we were able to show that ANCAs recognize their target antigen, PR-3, translocated into the membrane of HUVECs. The objective of this study was to investigate regulation, i.e. signal transduction pathways, of PR-3 expression in endothelial cells. HUVECs were isolated according to the method of Jaffe et al. and cultured under standard conditions. A cyto-enzyme-linked immunosorbent assay (ELISA) with unfixed cells was performed. Membrane-expressed PR-3 w…

SAT0132 DOES JANUS KINASE INHIBITION INDUCED HYPERLIPIDAEMIA ASSOCIATE WITH AN INCREASE OF AORTIC STIFFNESS IN PATIENTS WITH ARTHRITIS? PRELIMINARY RESULTS OF A PROSPECTIVE PILOT STUDY ON CARDIOVASCULAR RISK

Background:Treatment with Janus Kinase inhibitors (JAK-i) (Tofacitinib, Baricitinib) can cause an increase of serum lipids such as total cholesterol, low- (LDL) and high- (HDL) density lipoproteins in patients with arthritis (1). On the other hand, JAK-i can reduce systemic inflammation and have therefore a beneficial effect on the cardiovascular system of treated patients. However, the effects of JAK-i on the CV system have not been adequately examined. In particular, we are not aware of any ’’real world’’ data concerning CV risk of patients receiving JAK-i treatment.Stiffness of the aortic vasculature is a modifiable, valid and independent surrogate predictor of CV risk and can be measure…

Prevalence of Uncontrolled Hypertension in Patients With Fabry Disease

Background Fabry disease is a rare X-linked disease arising from deficiency of α-galactosidase A. It results in early death related to renal, cardiac, and cerebrovascular disease, which are also important outcomes in patients with elevated blood pressure (BP). The prevalence of uncontrolled hypertension, as well as the effect of enzyme replacement therapy on BP, in patients with Fabry disease is unknown. Methods We examined uncontrolled hypertension (systolic BP [SBP] ≥130 mm Hg or diastolic BP [DBP] ≥80 mm Hg) among 391 patients with Fabry disease who were participating in the Fabry Outcome Survey (FOS). Results Uncontrolled hypertension was present in 57% of men and 47% of women. In patie…

Interleukin 6 (IL-6) deficiency delays lupus nephritis in MRL-Faslpr mice: the IL-6 pathway as a new therapeutic target in treatment of autoimmune kidney disease in systemic lupus erythematosus.

Objective.To investigate the pathophysiological effect of interleukin 6 (IL-6) on lupus nephritis in MRL-Faslprmice.Methods.We generated IL-6-deficient MRL-Faslprmice using a backcross/intercross breeding scheme. Renal pathology was evaluated using immunohistochemistry detection for macrophages, lymphocytes, vascular cell adhesion molecule-1 (VCAM-1), and TUNEL (terminal deoxynucleotide transferase-mediated dUTP nick end-labeling) for apoptotic cells, and renal IgG and C3 deposition by immunofluorescence staining. Expression of inflammatory markers in the spleen was analyzed by quantitative real-time reverse transcription-polymerase chain reaction. Serum cytokine concentrations were detecte…

P68 A diet rich in wheat alpha-amylase/trypsin inhibitors (ATIs) enhances disease progression in the MRL-Fas(lpr) mouse model of systemic lupus erythematosus

Background Wheat alpha-amylase/trypsin inhibitors (ATIs) are the second most prevalent proteins in wheat (3–4% vs 80–90% for gluten) and potent activators of the innate immune system via the toll like receptor 4 (TLR4)-MD2-CD14 complex in cells of the mononuclear phagocyte system (Junker Y et al, J Exp Med 2012), triggering several autoimmune/inflammatory diseases. In contrast, pure gluten that is de-enriched of ATIs shows no stimulatory activity. MRL-Fas(lpr) mice develop progressive and spontaneous glomerular, tubulointerstitial and perivascular kidney disease, arthritis, lymphadenopathy, splenomegaly and circulating autoantibodies in a syndrome that resembles systemic lupus erythematosus…

The Aspect of Anti-Proteinase 3 Antibodies as AECA

Publisher Summary The discovery of anti-neutrophil cytoplasmic antibodies (ANCA) has caused a great impact on the diagnostic procedure and clinical observation of systemic necrotizing vasculitides like Wegener's granulomatosis (WG), microscopic polyangiitis, Churg- Strauss syndrome and necrotizing glomerulonephritis. There is persuasive circumstantial evidence for a pathogenic role of ANCA in ANCA-related vasculitides involving both neutrophils and vascular endothelial cells. The major stepthrough in the pathogenesis of ANCA related diseases was the identification of proteinase-3 (PR-3) as the main target antigen of ANCA in Wegener's Granulomatosis. PR-3 has been described as a constituent …

Enormous hemangiosarcoma of the heart

This report describes a 26-year-old patient with hemangiosarcoma of the heart and summarizes the clinicopathological features in previous reports of patients with cardiac angiosarcoma. The patient was admitted to our hospital because of a syncope and one episode of nocturnal dyspnea and hemoptysis. In his history he complained of progressive weakness and loss of weight over the past 2 months. Echocardiography and computed tomography of the chest showed inhomogeneous masses in the pericardial cavity completely surrounding the heart and involving the ascending aorta and the superior vena cava. Histological examination of the tissue obtained from the mass by fine needle technique revealed a po…

PS5:100 Patophysiological role of type i and iii interferons in systemic lupus erythematosus (sle)

Systemic Lupus erythematosus (SLE) is an autoimmune disease characterised by activated autoreactive lymphocytes and autoantibodies, resulting in tissue damage in multiple organs. An important factor for the disease´s mortality is the development of Lupus nephritis (LN). Type I and III interferons, which are both part of the antiviral defense, have both been associated with the disease´s activity. In sera and urine of SLE patients an enhanced level of IL28/29 was described, but their distinct functional role in the course of disease need to be further investigated. To determine the role of type I and III interferons during onset and progression of autoimmunity – with focus on the development…