Per-protocol repeat kidney biopsy portends relapse and long-term outcome in incident cases of proliferative lupus nephritis

2019

Abstract Objectives In patients with LN, clinical and histological responses to treatment have been shown to be discordant. We investigated whether per-protocol repeat kidney biopsies are predictive of LN relapses and long-term renal function impairment. Methods Forty-two patients with incident biopsy-proven active proliferative (class III/IV±V) LN from the database of the UCLouvain were included in this retrospective study. Per-protocol repeat biopsies were performed after a median [interquartile range (IQR)] time of 24.3 (21.3–26.2) months. The National Institutes of Health activity index (AI) and chronicity index (CI) scores were assessed in all biopsies. Results Despite a moderate corre…

Immunoadsorption for treatment of severe atopic dermatitis.

2017

Atopic dermatitis (AD) is a common disease affecting up to 10-20% of the population with the largest disease burden in childhood. Treatment options include basic emollient treatment, topical as well as systemic immunosuppressants. The pathogenesis is complex and among various triggers, genetic predisposition and immunological alterations contribute to development of disease. Atopy is common in patients with AD and many patients have high levels of Immunoglobulin E (IgE), some of which recognizes exogenous or auto/self-allergens. Treatment options targeting IgE such as specific immunotherapy against e.g. house dust mites or using anti-IgE antibodies (omalizumab) showed variable results that …

Validating quantitative PCR assays for cell-free DNA detection without DNA extraction: Exercise induced kinetics in systemic lupus erythematosus pati…

2021

ABSTRACTCirculating cell-free DNA (cfDNA) has been investigated as a screening tool for many diseases. To avoid expensive and time-consuming DNA isolation, direct quantification PCR assays can be established. However, rigorous validation is required to provide reliable data in the clinical and non-clinical context. Considering International Organization for Standardization, as well as bioanalytical method validation guidelines we provide a comprehensive procedure to validate assays for cfDNA quantification from unpurified blood plasma. A 90 and 222 bp assay was validated to study the kinetics of cfDNA after exercise in patients with systemic lupus erythematosus. The assays showed ultra-low …

TD-09 IL-34 promotes macrophage-mediated lupus nephritis in MRL-Faslpr mice

2018

Background Nephritis is the major cause of mortality and morbidity in patients with lupus. Macrophages (Mo) are central to kidney destruction in lupus-prone mice and patients. CSF-1, and the newly identified IL-34, mediate Mo survival and proliferation. However, IL-34 and CSF-1 differ during development and disease. While CSF-1 and IL-34 share the CSF-1 receptor (cFMS), expressed by Mo, IL-34 binds to a second receptor, Protein-Tyrosine Phosphatase ζ (PTPRZ) in inflamed kidneys. Intra-renal IL-34, cFMS, and PTPRZ are increased during the progression of lupus nephritis in MRL-Faslpr mice. Therefore, we hypothesized that IL-34 is a potential therapeutic target for lupus nephritis. Methods and…

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

2019

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 …

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

2020

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…

Non‐bacterial thrombotic endocarditis in a patient with pancreatic carcinoma

2021

Nonbacterial thrombotic endocarditis (NBTE) is a rare condition that most often accompanies a malignant disease and involves a hypercoagulable state. We report the incidental finding of a rare case of an NBTE affecting the tricuspid valve in a patient with metastatic pancreatic carcinoma complicated by severe venous and arterial thromboembolisms.

IL-34–Dependent Intrarenal and Systemic Mechanisms Promote Lupus Nephritis in MRL-Faslpr Mice

2019

Background In people with SLE and in the MRL- Fas lpr lupus mouse model, macrophages and autoantibodies are central to lupus nephritis. IL-34 mediates macrophage survival and proliferation, is expressed by tubular epithelial cells (TECs), and binds to the cFMS receptor on macrophages and to a newly identified second receptor, PTPRZ. Methods To investigate whether IL-34–dependent intrarenal and systemic mechanisms promote lupus nephritis, we compared lupus nephritis and systemic illness in MRL- Fas lpr mice expressing IL-34 and IL-34 knockout (KO) MRL- Fas lpr mice. We also assessed expression of IL-34 and the cFMS and PTPRZ receptors in patients with lupus nephritis. Results Intrarenal IL-3…

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

2019

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…

Non-alcoholic fatty liver disease increases the risk of incident chronic kidney disease

2020

BACKGROUND AND AIM: Non-alcoholic fatty liver disease (NAFLD) is a highly prevalent chronic liver disease. Its role in the development of extrahepatic co-morbidities is under investigation. The impact of NAFLD on the development of chronic kidney disease (CKD) is incompletely understood. The aim of this study was to explore the potential contribution of NAFLD on CKD in Germany. METHODS: The Disease Analyzer Database covering 7.49 million cases in Germany was explored for patients diagnosed with NAFLD between 2000 and 2015 and was matched 1:1 to a cohort without NAFLD. Matching criteria included age, sex, physician, index year and co-diagnoses associated with CKD. The primary outcomes of thi…

Genetics and novel aspects of therapies in systemic lupus erythematosus.

2015

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)

2020

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…

Rapid Steroid Withdrawal after Renal Transplantation Reduces Mortality: Five Year Follow-Up of a Randomized Controlled Trial (Harmony Study) Confirms…

2021

Background: We previously reported excellent efficacy and improved safety aspects of rapid steroid withdrawal (RSWD) in the randomized controlled one year “Harmony” trial, in which 587 predominantly deceased-donor kidney transplant recipients were randomized either to basiliximab or rabbit ATG induction therapy and compared to standard immunosuppressive therapy consisting of basiliximab, low tacrolimus once daily, mycophenolate mofetil, and corticosteroids. Methods: Following the end of the original one-year study period, patients were asked to participate in the observational follow-up (FU) study examining most of the end points of the original study. Hereby, de novo incidences between yea…

sj-docx-1-tan-10.1177_17562864211051497 – Supplemental material for Association of serum neurofilament light chain levels and neuropsychiatric manife…

2021

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

O33 Per-protocol repeat kidney biopsy portends relapse and long-term outcome in incident cases of proliferative lupus nephritis

2020

Background In patients with Lupus Nephritis (LN), clinical response to treatment and renal histopathology have been shown to be discordant. We investigated whether per-protocol repeat renal biopsies are predictive of LN relapses and long-term impairment of renal function. Methods Forty-two patients with an incident biopsy-proven active proliferative (class III/IV ± V) LN from the LN database of the Universite catholique de Louvain were included in the present retrospective study. Per-protocol repeat kidney biopsies were performed in all patients after a median time of 24.3 (IQR: 21.3–26.2) months. The NIH activity index (AI) and chronicity index (CI) scores were assessed in both baseline an…

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

2020

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 …

The KH-type splicing regulatory protein (KSRP) regulates type III interferon expression post-transcriptionally.

2019

Abstract Type III interferons (IFNs) are the latest members of the IFN family. They play an important role in immune defense mechanisms, especially in antiviral responses at mucosal sites. Moreover, they control inflammatory reactions by modulating neutrophil and dendritic cell functions. Therefore, it is important to identify cellular mechanisms involved in the control of type III IFN expression. All IFN family members contain AU-rich elements (AREs) in the 3′-untranslated regions (3′-UTR) of their mRNAs that determine mRNA half-life and consequently the expressional level of these cytokines. mRNA stability is controlled by different proteins binding to these AREs leading to either stabili…

Improved prediction of survival by a risk factor-integrated inflammatory score in Sorafenib treated hepatocellular carcinoma

2017

Background and aims Inflammation affects progression of hepatocellular carcinoma (HCC). We therefore postulate that systemic inflammatory markers could help to predict prognosis in HCC patients receiving sorafenib therapy. Methods Overall survival (OS) of HCC patients receiving palliative sorafenib treatment was correlated with the neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), C-reactive protein to albumin ratio (CAR), Glasgow prognostic score (GPS) and the modified GPS (mGPS) along with clinicopathological parameters. Predictors of OS were assessed by multivariable Cox regression and receiver operating characteristics and area under the curve (ROC-AUC) analyses.…

Knockout of the KH-Type Splicing Regulatory Protein Drives Glomerulonephritis in MRL-Faslpr Mice

2021

KH-type splicing regulatory protein (KSRP) is an RNA-binding protein that promotes mRNA decay and thereby negatively regulates cytokine expression at the post-transcriptional level. Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by dysregulated cytokine expression causing multiple organ manifestations

COVID-19—Importance for Patients on the Waiting List and after Kidney Transplantation—A Single Center Evaluation in 2020–2021

2021

(1) Background: Dialysis patients and recipients of a kidney allograft are at high risk for infection with SARS-CoV-2. It has been shown that the development of potent neutralizing humoral immunity against SARS CoV-2 leads to an increased probability of survival. However, the question of whether immunocompromised patients develop antibodies has not yet been sufficiently investigated; (2) Methods: SARS-CoV-2 antibodies were examined in hemodialysis patients on the waiting list for kidney transplantation as well as patients after kidney transplantation. Patients were interviewed about symptoms and comorbidities, BMI, and smoking history; (3) Results: SARS-CoV-2 antibodies were found in 16 out…

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

2021

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 a…

2017

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…

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

2018

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…

THU0248 GLOMERULAR AND TUBULOINTERSTITIAL LESIONS IN PER-PROTOCOL REPEAT BUT NOT BASELINE KIDNEY BIOPSY PORTEND RELAPSE AND LONG-TERM RENAL FUNCTION …

2020

Background:In patients with lupus nephritis (LN), clinical response to treatment and renal histopathology have been shown to be discordant. No clinical or laboratory markers have to date been shown to reliably portend renal prognosis, in particular renal function impairment.Objectives:To investigate whether per-protocol repeat renal biopsies are predictive of LN relapses and long-term impairment of renal function.Methods:Forty-two patients with an incident biopsy-proven active proliferative (class III/IV ± V) LN from the LN database of the Université catholique de Louvain were included in the present retrospective study. Per-protocol repeat kidney biopsies were performed in all patients aft…

Lipid presentation by the protein C receptor links coagulation with autoimmunity.

2021

A lipid-protein autoimmunity target Several autoimmune diseases, including systemic lupus erythematosus and primary antiphospholipid syndrome, are characterized by the presence of antiphospholipid antibodies (aPLs). These molecules can activate the complement and coagulation cascades, which contributes to pathologies such as thrombosis, stroke, and pregnancy complications. Müller-Calleja et al. found that endothelial protein C receptor (EPCR) in complex with lysobisphosphatidic acid (LBPA) is the cell-surface target for aPL and mediates its internalization (see the Perspective by Kaplan). aPL binding to EPCR-LBPA resulted in the activation of tissue factor–mediated coagulation and interfero…

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

2020

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…

sj-docx-1-tan-10.1177_17562864211051497 – Supplemental material for Association of serum neurofilament light chain levels and neuropsychiatric manife…

2021

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

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

2018

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 …

Applicability and safety of discontinuous ADVanced Organ Support (ADVOS) in the treatment of patients with acute-on-chronic liver failure (ACLF) outs…

2021

Background ADVanced Organ Support (ADVOS) is a novel type of extracorporeal albumin dialysis and holds promise to sustain liver function and recovery of patients with acute-on-chronic liver failure (ACLF). Previously, ADVOS was tested as continuous treatment for intensive care patients with liver failure. Data related to the applicability and safety as discontinuous treatment outside of ICU is not available. Aim Evaluation of ADVOS as discontinuous treatment for patients with ACLF outside intensive care unit and comparison with a matched historic cohort. Methods and results In this retrospective study, 26 patients with ACLF and the indication for renal replacement therapy related to HRS-AK…

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

2020

Non-bacterial thrombotic endocarditis in a patient with pancreatic carcinoma

2021

Repeated kidney re-transplantation—the Eurotransplant experience: a retrospective multicenter outcome analysis

2020

Transplant international (2020). doi:10.1111/tri.13569

Bleeding in Uremia

2021

Progressive deterioration of renal function eventually leads to uremia, which is associated with impaired function of platelets and a disturbed platelet–vessel wall interaction thus increasing the risk of bleeding in patients with renal failure. Furthermore, also anemia and anticoagulants/antiplatelet drugs contribute to the increased risk of bleeding in patients with end stage renal disease. Management of bleeding episodes in uremic patients includes an adequate dialysis, the correction of anemia with erythropoietin or erythropoetin stimulating agents, the administration of estrogens, desmopressin, fresh frozen plasma, cryoprecipitate, factor VIIa, or tranexamic acid. In severe bleeding ep…

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

2020

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…

Tryptophan immunoadsorption during pregnancy and breastfeeding in patients with acute relapse of multiple sclerosis and neuromyelitis optica.

2017

Background: Up to every fourth woman with multiple sclerosis (MS) or neuromyelitis optica spectrum disorder (NMOSD) suffers a clinically relevant relapse during pregnancy. High doses of steroids bear some serious risks, especially within the first trimester of pregnancy. Immunoadsorption (IA) is an effective and more selective treatment option in disabling MS relapse than plasma exchange. Data on the use of IA during pregnancy and breastfeeding are scarce. Methods: In this retrospective multicenter study, we analyzed the safety and efficacy of IA treatment in acute relapses during pregnancy or breastfeeding. The primary outcome parameter - change of acute relapse-related disability after IA…

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

2018

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…