The involvement of T regulatory lymphocytes in a cohort of lupus nephritis patients: a pilot study

T regulator lymphocytes (Tregs) play a key role in the maintenance of immune tolerance and in the development of autoimmune diseases. Expression of Foxp3 is specific for Tregs, and can be used for the identification of these cells. This study investigated the variations of Tregs Foxp3? in the kidney biopsies inflammatory infiltrate of different lupus nephritis classes compared to that of ANCA glomerulonephritis, acute tubulointerstitial nephritis and nephroangiosclerosis. Sections of paraffin-embedded tissue have been stained by immunohistochemistry with anti-CD3 and anti-FoxP3 antibodies. We find that the ratio of FoxP3?/CD3? cells is significantly lower in patients with lupus nephritis class IV and in patients with vasculitides than in the course of nephroangiosclerosis, tubulointerstitial nephritis and lupus nephritis class V. The data presented herein demonstrate a decrease of FoxP3? Treg cells in the inflammatory infiltrate of lupus nephritis, particularly during the most active phases of lupus nephritis, as observed in the course of a IV class nephritis

Event reconstruction for KM3NeT/ORCA using convolutional neural networks

The KM3NeT research infrastructure is currently under construction at two locations in the Mediterranean Sea. The KM3NeT/ORCA water-Cherenkov neutrino detector off the French coast will instrument several megatons of seawater with photosensors. Its main objective is the determination of the neutrino mass ordering. This work aims at demonstrating the general applicability of deep convolutional neural networks to neutrino telescopes, using simulated datasets for the KM3NeT/ORCA detector as an example. To this end, the networks are employed to achieve reconstruction and classification tasks that constitute an alternative to the analysis pipeline presented for KM3NeT/ORCA in the KM3NeT Letter of Intent. They are used to infer event reconstruction estimates for the energy, the direction, and the interaction point of incident neutrinos. The spatial distribution of Cherenkov light generated by charged particles induced in neutrino interactions is classified as shower- or track-like, and the main background processes associated with the detection of atmospheric neutrinos are recognized. Performance comparisons to machine-learning classification and maximum-likelihood reconstruction algorithms previously developed for KM3NeT/ORCA are provided. It is shown that this application of deep convolutional neural networks to simulated datasets for a large-volume neutrino telescope yields competitive reconstruction results and performance improvements with respect to classical approaches

Event reconstruction for KM3NeT/ORCA using convolutional neural networks

The KM3NeT research infrastructure is currently under construction at two locations in the Mediterranean Sea. The KM3NeT/ORCA water-Cherenkov neutrino de tector off the French coast will instrument several megatons of seawater with photosensors. Its main objective is the determination of the neutrino mass ordering. This work aims at demonstrating the general applicability of deep convolutional neural networks to neutrino telescopes, using simulated datasets for the KM3NeT/ORCA detector as an example. To this end, the networks are employed to achieve reconstruction and classification tasks that constitute an alternative to the analysis pipeline presented for KM3NeT/ORCA in the KM3NeT Letter of Intent. They are used to infer event reconstruction estimates for the energy, the direction, and the interaction point of incident neutrinos. The spatial distribution of Cherenkov light generated by charged particles induced in neutrino interactions is classified as shower-or track-like, and the main background processes associated with the detection of atmospheric neutrinos are recognized. Performance comparisons to machine-learning classification and maximum-likelihood reconstruction algorithms previously developed for KM3NeT/ORCA are provided. It is shown that this application of deep convolutional neural networks to simulated datasets for a large-volume neutrino telescope yields competitive reconstruction results and performance improvements with respect to classical approaches

Belimumab and low-doses of mycophenolate mofetil as induction therapy of class IV lupus nephritis: case series and literature review

Abstract Background The treatment of Lupus Nephritis (LN) is an unmet need in the management of patients with Systemic Lupus Erythematosus (SLE). Case presentation We report two cases of women affected by Lupus Nephritis (LN) ISN/RNP Class IV with serological active disease, high disease activity and marked fatigue. In both cases, Mycophenolate mofetil (MMF), as induction therapy, was poorly tolerated because of gastrointestinal toxicity. Belimumab, together with low-doses of MMF, was effective as induction treatment leading to early achievement of complete renal response in these two selected cases of LN. Conclusions We also report a literature review concerning the efficacy and safety of Belimumab in Lupus Nephritis. Further studies are needed to evaluate the use of Belimumab to manage the renal involvement in patients with Systemic Lupus Erythematosus, waiting for the results of ongoing randomized clinical trials

The relation between, metabolic syndrome and quality of life in patients with Systemic Lupus Erythematosus.

Systemic Lupus Erythematosus (SLE) is associated to an increased prevalence of Metabolic Syndrome (MeS) and to a reduction of Quality of Life (QoL). The aim of this study is to evaluate the association between MeS and QoL in SLE.SLE patients were consecutively enrolled in a cross sectional study. MeS was defined according to IFD definition. Therapy with glucocorticoids (GC) and antimalarial was analyzed as cumulative years of exposure. We used a cut off of 7.5 mg of prednisone to define high daily dose of GC. QoL was quantified using SF-36. We used BDI and HAM-H to assess symptoms of mood disorders. Fatigue was evaluated using Facit-Fatigue, physical activity using IPAQ, sleep quality using PSQI and alexithymia using TAS-20.We enrolled 100 SLE patients. MeS prevalence was 34%. Patients with MeS presented reduced scores in SF-36 MCS and PCS compared to patients without MeS (p 0.03 and p 0.004). BDI and HAM-H score were significantly higher in patients meeting MeS criteria compared to subjects without MeS (p 0.004, p 0.02). These results were confirmed after adjustment for confounders. Compared to patients without MeS, those with MeS presented higher age, lower education level, higher recent SELENA-SLEDAI, higher number of flares, increased SDI, longer cumulative exposure to high dose GC and shorter duration of antimalarial therapy. In the multiple logistic regression model, the variable associated to the Odds Ratio of having MeS were: the average of recent SELENA-SLEDAI (OR 1.15 p 0.04), the years of exposure to high dose of GC (OR 1.18 p 0.004), the years of exposure to antimalarials (OR 0.82 p 0.03) and the BDI score (OR 1.1 p 0.005).A modern management of SLE should not miss to take all the possible measures to ensure an adequate QoL to SLE patients, with particular attention to those affected by MeS

Prolonged remission is associated with a reduced risk of cardiovascular disease in patients with systemic lupus erythematosus: a GIRRCS (Gruppo Italiano di Ricerca in Reumatologia Clinica e Sperimentale) study

Prolonged remission (PR), defined as a 5-year consecutive period of no disease activity based on SLEDAI-2K, has been reported to be associated with a lower damage accrual over time in patients with systemic lupus erythematosus (SLE), as the consequence of a lower activity burden. Since disease activity is considered to play a role in the incidence of cardiovascular disease (CVD), we investigated the relationship, if any, between PR and the occurrence of a subsequent first CV event in patients with SLE. Out of 488 patients consecutively admitted to two tertiary Italian centers from November 1, 2000, to December 31, 2016, the 294 patients, who had been followed at least for 5 years, had not experienced any CV event at admission, and had been visited biannually during follow-up, were considered for the present study. The incidence of a first CV in patients who had achieved PR was compared with that registered in those who had not. Moreover, it was compared among PR patients subdivided into three groups: complete remission, clinical off-corticosteroids (offCR), and clinical on-corticosteroids remission (onCR). Kaplan–Meier curves and the log-rank test were used to analyze differences in event-free survival among groups. Cox regression was used to investigate disease and therapeutic features associated with the development of a first CV event. During 9 years median follow-up time, 24 (8.1%) CV events occurred. Out of the 294 patients, 126 (42.8%) had achieved PR. Kaplan–Meier analysis revealed a greater overall CV event-free rate in these patients as compared to both those with a shorter lasting remission and those who had never remitted (log-rank test χ2 = 14.43; p = 0.0001). In addition, CV outcome did not differ among PR patients, irrespectively the type of remission achieved (p > 0.05). At multivariate analysis, hydroxychloroquine therapy and PR resulted to be protective (HR 0.19; HR 0.18), while arterial hypertension and antiphospholipid positivity increased the risk of a first CV event (HR 2.61; HR 2.47). The PR, whichever the subtype, is associated with a better CV outcome and should be considered as a treat-to-target goal in the CV risk management of the lupus patient

Clinical features of patients with systemic lupus erythematosus according to health-related quality of life, entity of pain, fatigue and depression: a cluster analysis

To identify the distribution of patients with systemic lupus erythematosus (SLE) in clusters according to the levels of health-related quality of life (HRQoL), entity of pain, fatigue and depression

Role of the Specialized Proresolving Mediator Resolvin D1 in Systemic Lupus Erythematosus: Preliminary Results

Objective. Systemic lupus erythematosus (SLE) is an autoimmune systemic disease and its pathogenesis has not yet been completely clarified. Patients with SLE show a deranged lipid metabolism, which can contribute to the immunopathogenesis of the disease and to the accelerated atherosclerosis. Resolvin D1 (RvD1), a product of the metabolism of the omega-3 polyunsaturated fatty acid docosahexaenoic acid (DHA), acts as a specialized proresolving mediator which can contribute in restoring the homeostasis in inflamed tissues. The aim of the present pilot study is to evaluate plasma levels of RvD1 in patients with SLE and healthy subjects, investigating its potential role as a biomarker of SLE and assessing its relationship with disease activity and laboratory parameters. Methods. Thirty patients with SLE and thirty age- and sex-matched healthy subjects (HSs) have been consecutively recruited at Campus Bio-Medico University Hospital. RvD1 plasma levels were measured by ELISA according to the manufacturer’s protocol (Cayman Chemical Co.). RvD1 levels were compared using Mann–Whitney test. Discriminatory ability for SLE has been evaluated by the area under the ROC curve. Results. Lower levels of RvD1, 45.6 (35.5–57.4) pg/ml, in patients with SLE have been found compared to HSs, 65.1 (39.43–87.95) pg/ml (p=0.0043). The area under the ROC curve (AUC) for RvD1 was 0.71 (95% CI: 0.578–0.82) and the threshold value of RvD1 for the classification of SLE was <58.4 pg/ml, sensitivity 80% (95% CI: 61.4–92.3), and specificity 63.3% (95% CI: 43.9–80.1), likelihood ratio 2.2 (95% CI: 1.3–3.6). Conclusions. The present preliminary study allows hypothesizing a dysregulation of RvD1 in patients with SLE, confirming the emerging role of bioactive lipids in this disease

Multiple logistic regression analysis investigating the effects of SLE-related parameters and QoL-related parameters on MeS.

<p>Multiple logistic regression analysis investigating the effects of SLE-related parameters and QoL-related parameters on MeS.</p

Multinomial regression model (dependent variable: quartiles of MCS and PCS values; upper quartile vs lower quartiles).

<p>Analysis of variables associated to MCS and PCS in SLE.</p