 Your new post is loading...
Your new post is loading...
|
Suggested by
LIGHTING
December 21, 2018 2:51 PM
|
Join Dr Furie and colleagues in a discussion of best practices in the multidisciplinary care of patients with SLE.
|
Scooped by
Gilbert C FAURE
December 17, 2018 2:19 PM
|
Images in Clinical Medicine from The New England Journal of Medicine — Neonatal Lupus...
|
|
Scooped by
Gilbert C FAURE
December 13, 2018 3:04 PM
|
The treatment of systemic lupus erythematosus involves a balance between control of disease activity and prevention of therapeutic harm that requires careful optimization. In this Review, the authors discuss available and emerging therapeutic strategies that exploit the current drug armamentarium.
|
|
Scooped by
Gilbert C FAURE
December 7, 2018 2:44 PM
|
|
|
Scooped by
Gilbert C FAURE
December 4, 2018 4:00 PM
|
Objectives No simple or standardized assay is available to quantify interferon‐α (IFNα) in routine clinical practice. Single‐molecule–array (Simoa) digital enzyme‐linked immunosorbent assay (ELISA) technology enables direct IFNα quantification at fg/mL concentrations. This study was undertaken to assess IFNα digital ELISA diagnostic performances to monitor systemic lupus erythematosus (SLE) activity. Methods IFNα concentrations in serum samples from 150 consecutive SLE patients in a cross‐sectional study were determined with digital ELISA and a functional biological activity assay (bioassay). According to their SELENA–SLEDAI flare composite, patients were divided into groups with inactive (SLEDAI <4 or clinical SLEDAI =0) or active SLE (SLEDAI ≥4 or clinical SLEDAI >0), and into groups with no flare or mild/moderate flare or severe flare. Results Based on healthy blood donors, the abnormal serum‐IFNα level threshold value was 136 fg/mL. Next, using receiver operating characteristics curves for an SLE‐patient series, widely heterogeneous for disease activity and organ involvement, the threshold IFNα value associated with active disease was determined to be 266 fg/mL. The digital ELISA‐assessed serum‐IFNα level was a better biomarker of disease activity than the Farr test: its specificity, likelihood ratio for positive results and positive‐predictive value better discerned active SLE or flare from inactive patients. The digital ELISA was more sensitive than the bioassay to detect low‐abnormal serum‐IFNα concentrations and patients with low disease activity. Conclusion Direct serum‐IFNα determination with a highly sensitive assay might improve monitoring of clinical SLE activity and selection of the best candidates for anti‐IFNα treatment. This article is protected by copyright. All rights reserved.
Systemic lupus erythematosus (SLE) is an autoimmune disease with a strong genetic component and etiology characterized by chronic inflammation and autoantibody production. The purpose of this study was to ascertain copy number variation (CNV) in SLE using a case-control design in an admixed...
Via Krishan Maggon
Biomarkers for pulmonary manifestations in systemic lupus erythematosus (SLE) are missing. Plasma samples of nine SLE patients with known pulmonary involvement ...
Via Krishan Maggon
|
|
Scooped by
Gilbert C FAURE
November 23, 2018 2:34 AM
|
Detection of antinuclear antibodies (ANAs) is of paramount importance for diagnosis and assessment of autoimmune diseases (ADs), but may vary depending on the method used. Therefore, we aimed to compare three different line immunoassays (LIAs) for ANAs testing in order to simultaneously evaluate their concordance with the results obtained by a well known and widely used ELISA. Sera from women with established systemic lupus erythematosus (SLE, n=62) and Sjogren’s syndrome (SS, n=28) were examined. Patients with SLE had an average age of 48.7 years (IQR 36.8–57.0) with a disease duration of 14.8 years (IQR 9.0–18.0). Patients with SS had an average age of 62.1 years (IQR 55.5–71.0) with a duration of disease of 13.1 years (IQR 8.3–17).
Table 1 shows the results from the two-by-two comparison for the four techniques. Different levels of agreement were observed among the assays. In general, they were deficient. The analysis showed only one ‘strong’ level of agreement between ELISA and IMTEC-ANA-LIA Maxx for anti-Ro measurement. Out of 39 comparisons, 14 did …
|
|
Scooped by
Gilbert C FAURE
November 14, 2018 1:50 PM
|
A genetic variant of the killer immunoglobulin‐like receptor 3DL1 (KIR3DL1) has been found in patients with systemic lupus erythematosus (SLE). Herein, we investigated the presence of autoantibodies to KIR3DL1 in a cohort of patients with SLE. We tested sera from 28 patients with SLE, 11 patients with rheumatoid arthritis (RA), and 17 healthy control subjects for anti‐KIR3DL1 activity by an enzyme‐linked immunosorbent assay (ELISA) using recombinant KIR3DL1‐EGFP and EGFP proteins. Anti‐KIR3DL1 antibodies were detected in 22 (79%) out of the 28 patients with SLE, whereas they were present only in three (27%) out of the 11 patients with RA examined. Notably, 10 (91%) out of the 11 samples from patients with SLE prior to therapy had anti‐KIR3DL1 antibodies. None of the samples from healthy donors were positive for the antibodies. Here, we report the presence of anti‐KIR3DL1 antibodies in the sera of patients with SLE for the first time. Anti‐KIR3DL1 autoantibodies may be involved in the pathogenesis of autoimmune diseases. This article is protected by copyright. All rights reserved.
|
|
Suggested by
LIGHTING
November 13, 2018 4:08 AM
|
I glanced up from Amanda Wolf’s chart as the emergency department nurse, followed by the lab technician (tech), followed by the electrocardiogram (ECG) tech flowed into cubicle No. 5. John Benner, MD, pulled up a chair to review the case with me at the nursing station. You Might Also Like Childhood-onset Lupus Brings Distinct Challenges... [Read More]
|
|
Scooped by
Gilbert C FAURE
November 2, 2018 7:41 AM
|
Monogenic lupus is a form of systemic lupus erythematosus (SLE) that occurs in patients with a single gene defect. This rare variant of lupus generally presents with early onset severe disease, especially affecting the kidneys and central nervous system. To date, a significant number of genes have been implicated in monogenic lupus, providing valuable insights into a very complex disease process. Throughout this review, we will summarize the genes reported to be associated with monogenic lupus or lupus-like diseases, and the pathogenic mechanisms affected by the mutations involved upon inducing autoimmunity.
|
|
Scooped by
Gilbert C FAURE
October 31, 2018 6:17 AM
|
The current management of antiphospholipid syndrome (APS) centres on attenuating the procoagulant state while balancing the haemorrhagic risks.1 This approach relies mainly on a thromboprophylaxis strategy rather than targeting pathogenic antiphospholipid antibodies (aPL)-mediated pathways.
|
|
Scooped by
Gilbert C FAURE
October 29, 2018 5:03 AM
|
Autoantibodies characteristic for antiphospholipid syndrome (APS) and systemic lupus erythematosus (SLE) are anti‐β2‐glycoprotein I (β2GPI) antibodies and anti‐DNA antibodies, respectively, and nearly half of APS cases occur in SLE. Anti‐β2GPI antibodies are recognized to play a pivotal role in inducing a prothrombotic state, but the precise mechanism has not been fully elucidated. In a widely‐accepted view, binding of anti‐β2GPI antibodies to cell surface β2GPI in monocytes and endothelial cells triggers the TLR4‐MyD88 signaling pathway which leads to activation of p38 MAPK, MEK‐1/ERK, and/or NF‐κB, and expression of tissue factor (TF). However resting cells do not express substantial amounts of TLR4. Previously, we generated a mouse monoclonal anti‐β2GPI antibody WB‐6 and showed that it induced a prothrombotic state‐including TF expression on circulating monocytes‐in normal mice. In the current study, we aimed to clarify the mechanism of interaction between WB‐6 and resting monocytes, and found that WB‐6 exhibits binding activity to DNA and enters living monocytes or a monocytic cell line, and to a lesser extent vascular endothelial cells. Treatment of the cells with DNase I reduced the internalization, suggesting the involvement of cell surface DNA in this phenomenon. Monocytes harboring internalized WB‐6 expressed TF and TNF‐α, which in turn stimulated endothelial cells to express ICAM‐I and VCAM‐I. These results suggest a possibility that a subset of anti‐β2GPI antibodies with dual reactivity to DNA possesses ability to stimulate DNA sensors in the cytoplasm, in addition to the cell surface receptor mediated pathways, leading to produce proinflammatory and prothrombotic states. This article is protected by copyright. All rights reserved.
|
Abstract
Sometimes new ideas come from old places. Complement's central role in lupus pathogenesis has been known for years, and a reduction in C3 and C4 levels is one of the strongest biomarkers for increased lupus disease activity. However, every rheumatologist knows that some patients with no symptoms of active lupus will present with low complement levels, whereas some patients with aggressive disease have levels that never budge from the “normal” range. How can we better utilize the biomarkers associated with the complement system to guide therapy in lupus – both to predict lupus flares so that damage from unwanted inflammation can be prevented and to allow withdrawal of therapy after inflammation has resolved so as to minimize harm from toxic immunosuppressants?
Via Krishan Maggon
Non‐classical monocytes infiltrate the kidney parenchyma and participate in tissue damage in patients with lupus nephritis (LN). Circulating microparticles (MPs) seem to play critical roles in the activation of monocytes in systemic lupus erythematosus (SLE) patients. This study aims to characterize the phenotypes of MPs and monocyte subsets in LN patients and to determine their potential to discriminate between SLE patients with and without LN. Blood and urine samples from SLE patients were collected. In monocyte subsets from whole blood samples several phenotypic markers were evaluated. MPs were isolated from platelet‐poor plasma and urine by centrifugation. This phenotypic marker characterization was performed using multiparametric flow cytometry. We observed that patients with active LN have lower counts of non‐classical monocytes than do those without renal involvement. All monocyte subsets exhibited lower expression of CX3CR1 and ICAM‐1 in LN than in patients without LN. High frequencies of MP‐HMGB1+ and MP‐HLA‐DR+ were detected in circulation and urine of LN patients. Although MP‐HMGB1+, MP‐HLA‐DR+, and MP‐CX3CR1+ from urine were able to discriminate between patients with and without LN, only urinary MP‐HMGB1+ were different between patients with active and inactive LN. Therefore, these vesicles may be useful as biomarkers of LN. This article is protected by copyright. All rights reserved
Via Krishan Maggon
|
|
Scooped by
Gilbert C FAURE
December 13, 2018 11:35 AM
|
Case study of 3 month old with bloody urine - investigation, diagnosis and treatment of Neonatal lupus Erythematosus plus the immunology of the disease.
|
|
Scooped by
Gilbert C FAURE
December 7, 2018 2:42 PM
|
Epitope mapping of anti-Ro52 antibodies (Abs) has been extensively studied in patients with Sjögren’s syndrome (SjS) and systemic lupus erythematosus (SLE). Comprehensive epitope mapping in systemic sclerosis (SSc), where anti-Ro52 antibodies are also frequently detected, has not been performed. The aim of the present study was to fully characterize Ro52 epitopes in anti-Ro52-positive SSc using Ro52 fragments spanning the full antigen. Further analysis was made according to anti-Ro60 status. Epitope mapping was performed in 43 anti-Ro52-positive SSc patients. Seventy eight anti-Ro52-positive pathological controls, including 20 patients with SjS, 28 patients with SLE, 15 patients with dermatomyositis (DM) and 15 patients with primary biliary cholangitis (PBC), and 20 anti-Ro52-negative healthy individuals as normal controls were also tested. Five recombinant Ro52 fragments [Ro52-1 (aa 1-127), Ro52-2 (aa 125-268), Ro52-3 (aa 268-475), Ro52-4 (aa 57-180), and Ro52-5 (aa 181-320) were used to test reactivity by line-immunoassay and in house ELISA. Anti-Ro60 reactivity was tested by ELISA. All anti-Ro52 positive sera reacted with Ro52-2; none recognized Ro52-3. Antibodies against Ro52-1 were less frequently found in SSc than in SjS/SLE (11.6% vs 41.7%, p=0.001); and antibodies against Ro52-4 were less frequently found in SSc than in SjS/SLE (27.9% vs 50%, p=0.03). In SSc patients, reactivity against Ro52-1 was more frequent in anti-Ro52+/anti-Ro60+ than i
|
|
Scooped by
Gilbert C FAURE
November 29, 2018 12:13 PM
|
The B cell survival cytokine BAFF has been linked with the pathogenesis of systemic lupus erythematosus (SLE). BAFF binds distinct BAFF-family surface receptors, including the BAFF-R and transmembrane activator and CAML interactor (TACI). Although originally characterized as a negative regulator of B cell activation, TACI signals are critical for class-switched autoantibody (autoAb) production in BAFF transgenic mice. Consistent with this finding, a subset of transitional splenic B cells upregulate surface TACI expression and contribute to BAFF-driven autoAb. In the current study, we interrogated the B cell signals required for transitional B cell TACI expression and Ab production. Surprisingly, despite established roles for dual BCR and TLR signals in autoAb production in SLE, signals downstream of these receptors exerted distinct impacts on transitional B cell TACI expression and autoAb titers. Whereas loss of BCR signals prevented transitional B cell TACI expression and resulted in loss of serum autoAb across all Ig isotypes, lack of TLR signals exerted a more limited impact restricted to autoAb class-switch recombination without altering transitional B cell TACI expression. Finally, in parallel with the protective effect of TACI deletion, loss of BAFF-R signaling also protected against BAFF-driven autoimmunity. Together, these findings highlight how multiple signaling pathways integrate to promote class-switched autoAb production by transitional B cells, events that likely impact the pathogenesis of SLE and other BAFF-dependent autoimmune diseases.
Objective to appraise the role of epitope spreading in established human systemic lupus erythematosus (SLE). Methods IgG‐autoantibody reactivity to 398 distinct recombinant proteins was measured in 69 SLE patients over 6 years and compared to 45 controls. Changes in mean fluorescence intensity (MFI), number of autoantibodies to distinct antigens, and reactivity to distinct clones of selected established antigenic targets U1‐RNP, Sm, and ribosomal P representing epitope fine mapping were assessed. Linear mixed modelling adjusted for age and sex with Bonferroni correction was applied. Results The total number of autoantibodies, mean MFI, and number of autoantibodies in epitope fine mapping were higher in SLE compared to controls (p<0.0001). The total number of antibodies to distinct autoantigens remained stable, while the mean MFI decreased over time in SLE (p<0.021). SLE patients showed variable recognition of epitopes in fine mapping over time. In particular, SLE patients recognized more clones of the U1‐RNP complex at the time of new organ involvement (+0.65, p =0.007). Patients with lupus nephritis had a higher mean MFI (p=0.047). Time‐averaged MFI of 22 individual autoantibodies were higher in SLE after Bonferroni correction including dsDNA (p<0.0001). DsDNA and histone cluster 2 H3c MFIs were associated to the SLAM (p<0.0001). Conclusion Longitudinal surveillance of the IgG‐autoantibody repertoire in established SLE reveals evidence for sustained breadth of autoantibody repertoire without significant expansion. Associations of disease activity are confirmed for dsDNA and histone H3 autoantibodies. This article is protected by copyright. All rights reserved.
Via Krishan Maggon
Abstract
Introduction: Multiple pathways are involved in the pathogenesis of systemic lupus erythematosus (SLE). The Janus kinase-signal transducers and activators of transcription (JAK-STAT) pathway mediates the intracellular signals of more than 60 cytokines, growth factors and hormones from the type I/II cytokine receptors. Dysregulation of the cytokines is a hallmark of SLE; inhibition of downstream signaling mediated by the JAKs is an attractive therapeutic option.
Areas covered: This article reviews the preliminary data concerning the efficacy of the JAK inhibitors (Jakinibs) in SLE. JAK inhibition has shown promise in murine lupus dermatitis and nephritis. Ex-vivo studies of human SLE have demonstrated the effect of JAK1/2 inhibition on the activation of the STAT proteins and autoantibody production from B cells. A phase II trial reported modest efficacy of baricitinib in improving synovitis in SLE patients.
Expert opinions: Inhibition of the JAK-STAT pathway is an attractive therapeutic option. The convenience of oral administration and lower production cost of the Jakinibs could replace the biological agents in the treatment hierarchy of autoimmune inflammatory diseases. Additional clinical data are needed; results of ongoing studies of the newer Jakinibs in cutaneous and non-life-threatening lupus are eagerly awaited.
Keywords: JAK, Jakinib, lupus, targeted, therapeutic, systemic lupus, SLE, autoimmune disease
Via Krishan Maggon
|
|
Scooped by
Gilbert C FAURE
November 18, 2018 1:40 PM
|
J Immunol. 2018 Oct 29. pii: ji1701487. doi: 10.4049/jimmunol.1701487.[Epub ahead of print]...
|
|
Scooped by
Gilbert C FAURE
November 14, 2018 8:35 AM
|
Aim The aim of this manuscript is to describe the development of the Asia Pacific Lupus Collaboration (APLC) cohort. Method The APLC cohort is an ongoing, prospective longitudinal cohort. Adult patients who meet either the American College of Rheumatology (ACR) Modified Classification Criteria for systemic lupus erythematosus (SLE), or the Systemic Lupus International Collaborating Clinics (SLICC) Classification Criteria, and provide informed consent are recruited into the cohort. Patients are routinely followed up at 3‐ to 6‐monthly intervals. Information on demographics, clinical manifestations, treatment, pathology results, outcomes, and patient‐reported quality of life (Short‐form 36 version 2) are collected using a standardized case report form. Each site is responsible for obtaining local ethics and governance approval, patient recruitment, data collection, and data transfer into a centralized APLC database. Results The latest APLC cohort comprises 2160 patients with >12 000 visits from Australia, China, Hong Kong, Indonesia, Japan, Malaysia, Philippines, Singapore, Taiwan and Thailand. The APLC has proposed the Lupus Low Disease Activity State (LLDAS) as a treat‐to‐target (T2T) endpoint, and reported several retrospective and cross‐sectional analyses consistent with the validity of LLDAS. Longitudinal validation of LLDAS as a T2T endpoint is currently underway. Conclusion The APLC cohort is one of the largest contemporary SLE patient cohorts in the world. It is the only cohort with substantial representation of Asian patients. This cohort represents a unique resource for future clinical research including evaluation of other endpoints and quality of care.
Background/Purpose: We showed previously that complement activation – cell-bound complement activation products (CB-CAPS) or multi-analyte assay panel (MAP) – is a sensitive and specific biomarker for the diagnosis of systemic lupus erythematosus (SLE).
Via Krishan Maggon
|
|
Scooped by
Gilbert C FAURE
October 31, 2018 3:29 PM
|
Objectives To examine the prevalence and associated factors related to the coexistence of antiphospholipid syndrome (APS) and systemic lupus erythematosus (SLE) in a cohort of Colombian patients with SLE, and to discuss the coexistence of APS with other autoimmune diseases (ADs).
|
|
Suggested by
LIGHTING
October 30, 2018 7:43 AM
|
Systemic lupus erythematosus (SLE), a complex and heterogeneous autoimmune disease, represents a significant challenge for both diagnosis and treatment. Patients with SLE in Latin America face special problems that should be considered when therapeutic guidelines are developed. The objective of the study is to develop clinical practice guidelines for Latin American patients with lupus. Two independent teams (rheumatologists with experience in lupus management and methodologists) had an initial meeting in Panama City, Panama, in April 2016. They selected a list of questions for the clinical problems most commonly seen in Latin American patients with SLE. These were addressed with the best available evidence and summarised in a standardised format following the Grading of Recommendations Assessment, Development and Evaluation approach. All preliminary findings were discussed in a second face-to-face meeting in Washington, DC, in November 2016. As a result, nine organ/system sections are presented with the main findings; an ‘overarching’ treatment approach was added. Special emphasis was made on regional implementation issues. Best pharmacologic options were examined for musculoskeletal, mucocutaneous, kidney, cardiac, pulmonary, neuropsychiatric, haematological manifestations and the antiphospholipid syndrome. The roles of main therapeutic options (ie, glucocorticoids, antimalarials, immunosuppressant agents, therapeutic plasma exchange, belimumab, rituximab, abatacept, low-dose aspirin and anticoagulants) were summarised in each section. In all cases, benefits and harms, certainty of the evidence, values and preferences, feasibility, acceptability and equity issues were considered to produce a recommendation with special focus on ethnic and socioeconomic aspects. Guidelines for Latin American patients with lupus have been developed and could be used in similar settings.
|
Scoop.it!
