Systemic Lupus Erythematosus In Remission Research Articles

BCMA-CD19 compound CAR T cells for systemic lupus erythematosus: a phase 1 open-label clinical trial

ObjectivesThis study aims to evaluate the safety and efficacy of BCMA-CD19 compound chimeric antigen receptor T cells (cCAR) to dual reset the humoral and B cell immune system in patients...

Molecular characterisation of lupus low disease activity state (LLDAS) and DORIS remission by whole-blood transcriptome-based pathways in a pan-European systemic lupus erythematosus cohort

ObjectivesTo unveil biological milieus underlying low disease activity (LDA) and remission versus active systemic lupus erythematosus (SLE).MethodsWe determined differentially expressed pathways (DEPs) in SLE patients from the PRECISESADS project (NTC02890121)...

Recent findings about antimalarials in cutaneous lupus erythematosus: What dermatologists should know.

Antimalarials (AMs), particularly hydroxychloroquine (HCQ) and chloroquine (CQ), are the cornerstone of the treatment for both systemic lupus erythematosus (SLE) and cutaneous lupus erythematosus (CLE). HCQ and CQ are recommended as first-line oral agents in all CLE guidelines. Initially thought to have potential therapeutic effects against COVID-19, HCQ has drawn significant attention in recent years, highlighting concerns over its potential toxicity among patients and physicians. This review aims to consolidate current evidence on the efficacy of AMs in CLE. Our focus will be on optimizing therapeutic strategies, such as switching from HCQ to CQ, adding quinacrine to either HCQ or CQ, or adjusting HCQ dose based on blood concentration. Additionally, we will explore the potential for HCQ dose reduction or discontinuation in cases of CLE or SLE remission. Our review will focus on the existing evidence regarding adverse events linked to AM usage, with a specific emphasis on severe events and those of particular interest to dermatologists. Last, we will discuss the optimal HCQ dose and the balance between preventing CLE or SLE flares and minimizing toxicity.

Sex-specific differences in ICOS+ T helper cell differentiation in systemic lupus erythematosus patients with low disease activity

Systemic lupus erythematosus (SLE) is a sex biased chronic autoimmune disease affecting predominantly females during reproductive ages. Changes in the ratio of inducible costimulatory molecule (ICOS)+ regulatory (Treg) and non-regulatory responder (Tresp) CD4+ T cells proved to be crucial for the occurrence of high disease activity. Here, we investigated how the differentiation of ICOS+CD45RA+CD31+ recent thymic emigrant (RTE) Tresps into CD45RA−CD31− memory Tresps affects the percentages of ICOS+ Tresps within total CD4+ T cells. Three different pathways (pathway 1 via CD45RA−CD31+ memory Tresps, pathway 2 via direct proliferation and pathway 3 via resting mature naïve CD45RA+CD31− (MN) cells) were examined in healthy controls and SLE remission patients separated by sex. In female SLE remission patients, immunosuppressive therapy inhibited the ICOS+ RTE differentiation via CD45RA−CD31+ memory Tresps and direct proliferation, leaving an age-independently increased differentiation into CD45RA−CD31− memory Tresps by conversion of resting MN Tresps compared with healthy controls. Due to exhaustion of this pathway with age, no age-dependent change in the percentages of ICOS+ Tresps within total CD4+ T cells could be found. In contrast, no age-independently increased differentiation could be detected in men due to sufficient immunosuppression of all three pathways. This allowed an age-dependent differentiation of ICOS+ RTE Tresps into CD45RA−CD31− memory Tresps by conversion of resting MN Tresps, resulting in age-dependently increasing percentages of ICOS+ Tresps within total CD4+ T cells. We hypothesize that the sex-specific differential effect of immunosuppression on the differentiation of ICOS+ Tresps may explain the sex- and age-dependent occurrence of high disease activity.

CD19 CAR T-Cell Therapy in Autoimmune Disease — A Case Series with Follow-up

BackgroundTreatment for autoimmune diseases such as systemic lupus erythematosus (SLE), idiopathic inflammatory myositis, and systemic sclerosis often involves long-term immune suppression. Resetting aberrant autoimmunity in these diseases through deep depletion of B cells is a potential strategy for achieving sustained drug-free remission.MethodsWe evaluated 15 patients with severe SLE (8 patients), idiopathic inflammatory myositis (3 patients), or systemic sclerosis (4 patients) who received a single infusion of CD19 chimeric antigen receptor (CAR) T cells after preconditioning with fludarabine and cyclophosphamide. Efficacy up to 2 years after CAR T-cell infusion was assessed by means of Definition of Remission in SLE (DORIS) remission criteria, American College of Rheumatology–European League against Rheumatism (ACR–EULAR) major clinical response, and the score on the European Scleroderma Trials and Research Group (EUSTAR) activity index (with higher scores indicating greater disease activity), among others. Safety variables, including cytokine release syndrome and infections, were recorded.ResultsThe median follow-up was 15 months (range, 4 to 29). The mean (±SD) duration of B-cell aplasia was 112±47 days. All the patients with SLE had DORIS remission, all the patients with idiopathic inflammatory myositis had an ACR–EULAR major clinical response, and all the patients with systemic sclerosis had a decrease in the score on the EUSTAR activity index. Immunosuppressive therapy was completely stopped in all the patients. Grade 1 cytokine release syndrome occurred in 10 patients. One patient each had grade 2 cytokine release syndrome, grade 1 immune effector cell–associated neurotoxicity syndrome, and pneumonia that resulted in hospitalization.ConclusionsIn this case series, CD19 CAR T-cell transfer appeared to be feasible, safe, and efficacious in three different autoimmune diseases, providing rationale for further controlled clinical trials. (Funded by Deutsche Forschungsgemeinschaft and others.)

Neuromodulation with aerobic exercise reduces fatigue in systemic lupus erythematosus: a randomised, sham-controlled, double-blind study.

Transcranial direct current stimulation (tDCS) combined with aerobic exercise (tDCS-AE) effectively reduces fatigue in patients with fibromyalgia. However, no study has assessed this method in systemic lupus erythematosus (SLE) patients with significant fatigue. Therefore, we evaluated the safety and efficacy of tDCS-AE for significant fatigue symptoms in adult female SLE patients. This randomised, sham-controlled, double-blind study included 25 patients with SLE in remission or low disease activity (SLEDAI-2K £4) and with significant fatigue [≥36 points on the Fatigue Severity Scale (FSS) or ≥38 points on the Modified Fatigue Scale (MFIS)]. The patients received sham or tDCS for five consecutive days. The anode and cathode were positioned at M1 and Fp2, respectively (international 10-20 EEG system). tDCS was applied at an intensity of 2mA, and density of 0.057mA/cm2 in the tDCS-AE group. Both groups underwent combined low-intensity treadmill exercise. FSS, MFIS, pain visual analogue scale, physical activity, and sleep quality were evaluated at baseline and on days 7, 30, and 60. Adherence and safety were assessed using a standardised questionnaire. Improvement in fatigue levels was observed in both groups. However, a sustained reduction in fatigue levels on days 30 and 60 occurred only with tDCS-AEs (p<0.05). No significant differences were observed in pain level, sleep quality, or physical activity. No disease flares occurred and the adverse effects were mild and transient. Finally, the patient's adherence to the treatment was satisfactory. Despite isolated AEs, there was an improvement in fatigue, however, only tDCS-AE maintained significant and sustained improvement.

Identification and Characterization of CD8+ CD27+ CXCR3- T Cell Dysregulation and Progression-Associated Biomarkers in Systemic Lupus Erythematosus.

Systemic Lupus Erythematosus (SLE) etiopathogenesis highlights the contributions of overproduction of CD4+ T cells and loss of immune tolerance. However, the involvement of CD8+ T cells in SLE pathology and disease progression remains unclear. Here, the comprehensive immune cell dysregulation in total 263 clinical peripheral blood samples composed of active SLE (aSLE), remission SLE (rSLE) and healthy controls (HCs) is investigated via mass cytometry, flow cytometry and single-cell RNA sequencing. This is observed that CD8+ CD27+ CXCR3- T cells are increased in rSLE compare to aSLE. Meanwhile, the effector function of CD8+ CD27+ CXCR3- T cells are overactive in aSLE compare to HCs and rSLE, and are positively associated with clinical SLE activity. In addition, the response of peripheral blood mononuclear cells (PBMCs) is monitored to interleukin-2 stimulation in aSLE and rSLE to construct dynamic network biomarker (DNB) model. It is demonstrated that DNB score-related parameters can faithfully predict the remission of aSLE and the flares of rSLE. The abundance and functional dysregulation of CD8+ CD27+ CXCR3- T cells can be potential biomarkers for SLE prognosis and concomitant diagnosis. The DNB score with accurate prediction to SLE disease progression can provide clinical treatment suggestions especially for drug dosage determination.

Impact of low disease activity, remission, and complete remission on flares following tapering of corticosteroids and immunosuppressive therapy in patients with systemic lupus erythematous: a multinational cohort study.

Targets of treatment for systemic lupus erythematosus (SLE) include the Lupus Low Disease Activity State (LLDAS), remission, and complete remission. Whether treatment can be tapered after attaining these targets and whether tapering is safer in patients in complete remission compared with LLDAS are unknown. We aimed to assess the odds of disease flares after treatment tapering in stable disease, versus continuing the same therapy. We also aimed to examine whether tapering in complete remission resulted in fewer flares or longer time to flare compared with tapering in LLDAS or remission. This multinational cohort study was conducted at 25 sites across 13 Asia-Pacific countries. We included adult patients aged 18 years or older with stable SLE who were receiving routine clinical care, had two or more visits and had attained stable disease at one or more visits. We categorised stable disease into: LLDAS (Systemic Lupus Erythematosus Disease Activity Index 2000 [SLEDAI-2K] score ≤4, Physician Global Assessment [PGA] ≤1, and prednisolone ≤7·5 mg/day); Definitions of Remission in SLE (DORIS) remission (clinical SLEDAI-2K score 0, PGA <0·5, and prednisolone ≤5 mg/day); or complete remission on therapy (SLEDAI-2K score 0, PGA <0·5, and prednisolone ≤5 mg/day). Stable disease categories were mutually exclusive. Tapering was defined as any decrease in dose of corticosteroids or immunosuppressive therapy (mycophenolate mofetil, calcineurin inhibitors, azathioprine, leflunomide, or methotrexate). Using multivariable generalised estimating equations, we compared flares (SELENA-SLEDAI Flare Index) at the subsequent visit after drug tapering. We used generalised estimating equations and Cox proportional hazard models to compare tapering attempts that had begun in LLDAS, remission, and complete remission. Between May 1, 2013, and Dec 31, 2020, 4106 patients were recruited to the cohort, 3002 (73·1%) of whom were included in our analysis. 2769 (92·2%) participants were female, 233 (7·8%) were male, and 2636 (88·1%) of 2993 with ethnicity data available were Asian. The median age was 39·5 years (IQR 29·0-50·0). There were 14 808 patient visits for patients in LLDAS, or remission or complete remission, of which 13 140 (88·7%) entered the final multivariable model after excluding missing data. Among the 9863 visits at which patients continued the same therapy, 1121 (11·4%) flared at the next visit, of which 221 (19·7%) were severe flares. Of the 3277 visits at which a patient received a tapering of therapy, 557 (17·0%) flared at the next visit, of which 120 (21·5%) were severe flares. Tapering was associated with higher odds of flare compared with continuing the same therapy (odds ratio [OR] 1·24 [95% CI 1·10-1·39]; p=0·0005). Of 2095 continuous tapering attempts, 860 (41·1%) were initiated in LLDAS, 596 (28·4%) in remission, and 639 (30·5%) in complete remission. Tapering initiated in LLDAS (OR 1·37 [95% CI 1·03-1·81]; p=0·029) or remission (1·45 [1·08-1·94]; p=0·013) had higher odds of flare in 1 year compared with complete remission. Tapering in LLDAS (hazard ratio 1·24 [95% CI 1·04-1·48]; p=0·016) or remission (1·30 [1·08-1·56]; p=0·0054) had a significantly shorter time to first flare than tapering initiated in complete remission. Attaining sustained LLDAS, remission, or complete remission for at least 6 months just before the time of taper was associated with lower odds of flare at next visit, flares in 1 year, and longer time to flare. Tapering of corticosteroids or immunosuppressive therapy in patients with stable SLE was associated with excess flares. Our findings suggest that drug tapering should be carefully considered, weighing the risks and benefits, and is best exercised in complete (clinical and serological) remission and after maintaining stable disease for at least 6 months. AstraZeneca, BMS, Eli Lily, Janssen, Merck Serono, GSK, and UCB.

A rare case of autoimmune dysglycemia syndrome associated with systemic lupus erythematosus and dermatomyositis

Autoimmune dysglycemia syndrome (ADS) is a rare condition that presents as episodes of hypoglycemia as well as hyperglycemia and is classified as insulin autoimmune syndrome (IAS) and type B insulin resistance (TBIR). Autoimmunity plays a key role in the pathogenesis of this disorder, as evidenced by the presence of autoantibodies against endogenous insulin or the insulin receptor, and by its association with rheumatologic disorders. Treatment usually includes glycemic control and immunomodulatory agents. We report a case of a 31-year-old woman who was admitted for severe hypoglycemia. Further workup revealed underlying systemic lupus erythematosus (SLE) with renal involvement. During hospitalization, she continued to experience episodes of fasting hypoglycemia, as well as episodes of postprandial hyperglycemia. Hypoglycemia associated with a high serum insulin concentration and positive anti-insulin antibodies were consistent with IAS. Likewise, hyperglycemia and hypoglycemia in association with weight loss, acanthosis nigricans, polycystic ovarian syndrome, and normotriglyceridemia strongly suggested TBIR, although testing for antibodies against the insulin receptor was not available in Peru. Immunosuppressive therapy and metformin were indicated, resulting in remission of SLE and ADS. Years later, the patient exhibited features of dermatomyositis, such as Raynaud’s phenomenon, muscular weakness, heliotrope exanthema, and elevated muscle enzymes. Once again, the patient received immunosuppressive therapy. ADS is an infrequent cause of hypoglycemia, and the coexistence of its two pathophysiological mechanisms in a patient with SLE and subsequent development of dermatomyositis is even more rare. Our case is the first one reported describing this association.

Increase in Double Negative B Lymphocytes in Patients with Systemic Lupus Erythematosus in Remission and Their Correlation with Early Differentiated T Lymphocyte Subpopulations.

B and T lymphocytes demonstrate important alterations in patients with systemic lupus erythematous (SLE), with a significant upregulation of double negative (DN) B cells. The aim of this study was to evaluate the correlation of T cell immunity changes with the distinct B-cell-pattern SLE. In the present study, flow cytometry was performed in 30 patients in remission of SLE and 31 healthy controls to detect DN B cells (CD19+IgD-CD27-) and a wide range of T lymphocyte subpopulations based on the presence of CD45RA, CCR7, CD31, CD28, and CD57, defined as naive, memory, and advanced differentiated/senescent T cells. Both B and T lymphocytes were significantly reduced in SLE patients. However, the percentage of DN B cells were increased compared to HC (12.9 (2.3-74.2) vs. 8 (1.7-35), p = 0.04). The distribution of CD4 and CD8 lymphocytes demonstrated a shift to advanced differentiated subsets. The population of DN B cells had a significant positive correlation with most of the early differentiated T lymphocytes, CD4CD31+, CD4CD45RA+CD28+, CD4CD45RA+CD57-, CD4CD45RA-CD57-, CD4CD28+CD57-, CD4CD28+CD57+, CD4 CM, CD8 CD31+, CD8 NAÏVE, CD8CD45RA-CD57-, CD8CD28+CD57-, and CD8CD28+CD57+. Multiple regression analysis revealed CD4CD31+, CD8CD45RA-CD57-, and CD8CD28+CD57- cells as independent parameters contributing to DN B cells, with adjusted R2 = 0.534 and p < 0.0001. The predominance of DN B cells in patients with SLE is closely associated with early differentiated T lymphocyte subsets, indicating a potential causality role of DN B cells in T lymphocyte activation.

Epstein-Barr Virus Reactivation as a New Predictor of Achieving Remission or Lupus Low Disease Activity State in Patients with Systemic Lupus Erythematosus with Cutaneous Involvement.

Although Epstein-Barr virus (EBV) reactivation has long been associated with the pathogenesis of systemic lupus erythematosus (SLE), many aspects of this relationship remain unclear. Our objective was to investigate the association between EBV reactivation and the achievement of SLE remission and lupus low disease activity state (LLDAS) over a six-month period. Clinical, laboratory, and virological tests (anti-EBV antibodies and EBV DNA) were performed among 51 patients with the active form of SLE on two occasions six months apart. SLE remission and LLDAS achievement were assessed at the end of the follow-up period. Active EBV infection was detected in 45% of active SLE patients at baseline, and 77% transitioned to latent EBV infection at six months (p < 0.001). Multivariate regression revealed a higher titer of anti-EA(D) IgM-Abs and the presence of anti-EA(D) IgM-Abs as independent predictors of remission and LLDAS in SLE patients with mucocutaneous manifestations (p = 0.042) and rash only (p = 0.023), respectively. Since a higher C3 level was an independent predictor of transition to latent EBV infection (p = 0.027), the estimated cut-off value that could identify active SLE patients who will transition to latent EBV infection after six months was ≥0.780 g/L with a sensitivity of 70.6% and a specificity of 75.0% (AUC = 0.756, p = 0.003). EBV reactivation is common in patients with active SLE, and most of them transition to latent EBV infection after six months. Achieving remission and LLDAS in SLE patients with mucocutaneous manifestations can be predicted by a higher titer, whereas in SLE patients who have only a rash, the presence of anti-EA (D) IgM-Abs was a predictor of remission and LLDAS.

Lupus low disease activity state attainment in the phase 3 TULIP trials of anifrolumab in active systemic lupus erythematosus

ObjectivesIn patients with systemic lupus erythematosus (SLE), lupus low disease activity state (LLDAS) attainment is associated with improved outcomes. We investigated LLDAS attainment in anifrolumab-treated patients.MethodsWe performed post hoc analysis...

Primena nivolumaba kod bolesnice sa mukozalnim melanomom i sistemskim lupusom - prikaz slučaja sa pregledom literature

Introduction. Systemic lupus erythematosus (SLE) represents a multisystemic disease characterized by antibody production, complement activation, and immune complexes deposition. Certain types of malignancies occur more often, and conversely, some of them occur less often in SLE patients. Mucosal melanoma of the anorectal region represents a rare form of melanoma occurring in 1.5% of all melanoma patients, predominantly female. The introduction of novel agents dramatically changed the outcome in melanoma patients and introduced different adverse events, diverse contraindications, and drug interactions. Immune checkpoint inhibitors have a role in the maintenance of immunologic homeostasis. Patients with underlying autoimmune diseases were often excluded from clinical trials, for fear of possible autoimmune disease exacerbation or high-grade immune-related adverse events. Due to that, data regarding this subgroup of patients is limited, with no clear recommendations. Given the fact that prevalence among the general population is high (5-10%), autoimmune diseases represent common comorbidity in cancer patients. Having that in mind, it is of utmost importance to personalize the approach and individualize the SLE treatment and enable the use of PD-1 antibody in the safest and most useful way while keeping the SLE in control. Case report. Herein we present a 79-year-old with primary mucosal melanoma of the anorectal region, with lung metastasis and preexisting SLE in remission. Hydroxychloroquine was the only treatment for SLE. Nivolumab treatment was initiated in the standard dosing schedule. After the first and second follow-up, no further progression of melanoma was detected, with no SLE exacerbation and immune-related adverse events. Conclusion. PD-1 treatment in a patient with an underlying autoimmune disease represents a viable choice with a necessity for a multidisciplinary approach and close monitoring.

CD19-Targeted CAR-T Cells in Refractory Systemic Lupus Erythematosus: Safety, Efficacy, and Mechanistic Insights from the First Five Patients

Background: Systemic lupus erythematosus (SLE) is an auto-immune disease that is based on dysregulation of the adaptive immune system, autoantibody production and immune complex-mediated tissue damage. While treatment of SLE has substantially improved, a subset of patients experiences severe progressive disease despite T- and B-cell targeted therapy. Aim: For patients with refractory SLE, we aimed to achieve deep depletion of B cells using autologous CD19-CAR T cells with the goal of achieving an immunological reset and drug free remission. Methods: Five patients (4 women, 1 men) with SLE refractory to several immune-suppressive drugs including pulsed steroids, hydroxychloroquine, mycophenolate, cyclophosphamide, intravenous immunoglobulins, rituximab, and belimumab were treated with CD19 CAR T cells in a compassionate use program. Mean patient age was 21.8 ± 2.3 years, mean disease duration was 4.6 ± 3.0 years and mean SLE disease activity index (SLEDAI) was 11.8±3.8. Autologous T cells were transduced with a lentiviral anti-CD19 CAR vector composed of the FMC63 scFv, a CD8-derived hinge region, TNFRSF19-derived transmembrane domain, CD3ζ intracellular domain, and 4-1BB co-stimulatory domain and expanded within the local GMP facility utilizing the closed automated CliniMACS Prodigy® system (Miltenyi Biotec, Bergisch Gladbach, Germany). CAR T cells were re-infused at a dose of 1x106 CAR T cells/kg body weight after lymphodepletion with fludarabine/ cyclophosphamide. All SLE treatments with the exception of low dose prednisolone was stopped before CAR-T cell administration. After CAR-T cell treatment, no other immune-modulatory or immune-suppressive treatment was given. Tolerability was assessed following international guidelines. Results: Despite long-lasting high dose steroid treatment, sufficient numbers of CD19 CAR-T cells could be generated from 5/5 SLE patients. Lymphodepletion led to expected reduction of white blood cells. Following lymphodepletion, CAR T cells expanded in vivo with a peak on day 9 and a deep depletion of B cells was achieved in all patients. Bone marrow toxicity towards non-B cells was short and all patients recovered neutrophils (>500/nL) before day 14 post CAR T cells. Only mild CRS of °I occurred in all five patients. One patient received a single dose of tocilizumab due to persisting fever >24 hours. There were no ICANS, no CRS of any organ, and no infections. Remission of SLE according to DORIS criteria was achieved in all 5 patients after 3 months and the mean (±SD) SLEDAI score after 3 months was 0.4±0.9. Laboratory parameters normalized in all SLE patients after CAR-T transfer including seroconversion of anti-dsDNA antibodies and all patients were free of immune-suppressive drugs by month 3. One patient presented with proteinuria at month 4. Kidney biopsy as well as serum diagnostics showed no signs of SLE. After a steroid pulse, proteinuria went back to normal. Despite reconstitution of B cells no relapse of SLE was observed in the follow up of any of the patients which are now 17, 12, 8, 7, and 5 months after CAR T cell therapy. Reappearing B cells were naïve and showed non-class switched B cell receptors. While pre-existing vaccine-specific antibodies towards measles or VZV persisted, several auto-reactive antibodies were abrogated. Quality of life was poor at decision to treatment and improved substantially at month three. Improvement was mostly driven by abrogation of joint pain and of fatigue. Conclusions: Taken together, the preliminary data from this pilot study show that CD19 CAR T-cell therapy is very well tolerated in patients with a non-malignant B cell derived autoimmune disease and induce rapid remission of severe refractory SLE. Longer follow-up and higher patient numbers from controlled clinical trials are needed to confirm these promising results.

Anti-CD19 CAR T cell therapy for refractory systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a life-threatening autoimmune disease characterized by adaptive immune system activation, formation of double-stranded DNA autoantibodies and organ inflammation. Five patients with SLE (four women and one man) with a median (range) age of 22 (6) years, median (range) disease duration of 4 (8) years and active disease (median (range) SLE disease activity index Systemic Lupus Erythematosus Disease Activity Index: 16 (8)) refractory to several immunosuppressive drug treatments were enrolled in a compassionate-use chimeric antigen receptor (CAR) T cell program. Autologous T cells from patients with SLE were transduced with a lentiviral anti-CD19 CAR vector, expanded and reinfused at a dose of 1 × 106 CAR T cells per kg body weight into the patients after lymphodepletion with fludarabine and cyclophosphamide. CAR T cells expanded in vivo, led to deep depletion of B cells, improvement of clinical symptoms and normalization of laboratory parameters including seroconversion of anti-double-stranded DNA antibodies. Remission of SLE according to DORIS criteria was achieved in all five patients after 3 months and the median (range) Systemic Lupus Erythematosus Disease Activity Index score after 3 months was 0 (2). Drug-free remission was maintained during longer follow-up (median (range) of 8 (12) months after CAR T cell administration) and even after the reappearance of B cells, which was observed after a mean (±s.d.) of 110 ± 32 d after CAR T cell treatment. Reappearing B cells were naïve and showed non-class-switched B cell receptors. CAR T cell treatment was well tolerated with only mild cytokine-release syndrome. These data suggest that CD19 CAR T cell transfer is feasible, tolerable and highly effective in SLE.

Systemic lupus erythematosus and secondary antiphospholipid syndrome in native sisters with reduced fertility.

Systemic lupus erythematosus (SLE) and secondary anti-phospholipid syndrome (APS II) can cause increased morbidity and mortality of the fetus. We followed the course of fertility of two sisters with these two basic diseases. In the Center for Immunology of Reproduction, we confi rmed both sisters had increased levels of some selected anti-phospholipid antibodies (against phosphatidylserine, phosphatidylethanolamine, phosphatidylinositol, DL-glycerole, anexin V, phoshatidic acid, cardiolipin, beta2-glycoprotein I), anti-nuclear, and anti-DNA antibodies. During the established immunosuppressive and hormonal therapy at the time of SLE remission, both sisters became pregnant. There was a physiological progression of pregnancy until the 19th week. At the 20th week of pregnancy, the older sister miscarried again, and the younger sister developed hypertension in the 31st week of pregnancy which was terminated by caesarean section. In our causal evaluation, we addressed two serious autoimmune diseases (SLE, APS II) in two sisters and described their course of pregnancy. However, only one of them became a happy mother.

Activity of Protein S-C4b Binding Protein and Total TFPI Levels in Egyptian SLE Patients: A Cross-Sectional Study

BACKGROUND: Systemic lupus erythematosus (SLE) is an immune disorder with alternating active and remission phases. Cardiovascular diseases and thrombosis are the major causes of mortality in SLE. The anticoagulant activity of Protein S (PS) is complemented by C4 binding protein (C4BP) and tissue factor pathway inhibitor (TFPI). AIM: This study aims to determine the extent of change in the levels of PS activity, C4BP, and total TFPI in active SLE in comparison to the SLE remission phase and their association with thrombosis during SLE flare. METHODS: The study included 180 Egyptian SLE patients who were classified into two groups: 100 SLE cases as the active group and 80 SLE cases as the remission group. The PS activity levels were processed on automated coagulation analyzers, whereas the C4BP and total TFPI levels were measured via enzyme-linked immunosorbent assay. RESULTS: The PS activity and C4BP levels were lower in the active SLE cases than in the remitted ones (p &lt; 0.05). The levels of PS activity and C4BP were revealed to be independent predictors of SELENA-SLEDAI flare scores. In active SLE cases, the PS activity and C4BP levels were rated as excellent and fair classifiers of thrombotic risk in SLE flare, respectively. The total TFPI levels showed no association with SLE activity or its thrombotic consequences. CONCLUSIONS: The levels of PS activity and C4BP act as important biomarkers for SLE activity. Both can be implanted as predictive tools for thrombosis during activity.

Эндопротезирование суставов у пациентов с системной красной волчанкой

This article describes a case series of total joint replacement in 4 patients with systemic lupus erythematosus affecting the hip and knee joints. The average age of patients at the time of arthroplasty was 34 years. All patients were female and all received glucocorticosteroid therapy at varying doses of 5 to 10 mg per day. At the debut of the lupus erythematosus system, median activity index was 10 points. In one patient, remission of systemic lupus erythematosus was induced by mycophenolate mofetil, in another, by azathioprine. In total, three total arthroplasty were performed for aseptic necrosis of the head of the hip joint and one more arthroplasty due to severe osteoarthritis of the knee joint. At the time of arthroplasty in one clinical case a complete remission of systemic lupus erythematosus was observed, in three patients there was an incomplete remission. All components of the endoprostheses were stable, with no signs of osteolysis.In all cases, as a result of arthroplasty, a good effect was noted with increase in the functional activity of the hip and knee joints and decrease in pain. None of the patients had a recurrence of systemic lupus erythematosus and development of postoperative complications (except for the need for blood transfusion).Our own experience indicates the potentially high efficiency and relative safety of total hip and knee arthroplasty in patients with systemic lupus erythematosus, including in cases of severe disease with unfavorable prognostic factors. To reduce the risk of postoperative complications (primarily thromboembolism, infections, late delayed neutropenia), total arthroplasty should be performed during the period of remission of systemic lupus erythematosus in conditions of control of comorbid conditions and close cooperation between rheumatologists and orthopedic surgeons.Key words: systemic lupus erythematosus, total arthroplasty, hip joint, knee joint, aseptic necrosis, mycophenolate mofetil, azathioprine.

Системная красная волчанка: эпидемиология, отдаленные исходы и бремя болезни

The estimates of incidence and prevalence of systemic lupus erythematosus (SLE) in Europe are 1.5-4.9 per 100 000 persons-years and 30-70 per 100 000 people, respectively. Over the last 50 years, survival in SLE patients has improved significantly. Moreover, immunosuppressive treatment resulted in a decreased risk of death from active disease, whereas infections and cardiovascular disease have become the main causes of death in SLE populations. Almost 70% of SLE patients have recurrent course of disease, although long-term remissions or persistent disease activity also occur in a proportion of patients. Annually, every third SLE patient develops moderately severe or severe flares. Recurrent flares, complications of immunosuppressive treatment and comorbidity are associated with accrual of organ damage that increases the risk of death. SLE patients have impaired health-related quality of life correlating with both disease activity and organ damage. Being on remission of SLE or on low disease activity is associated with better outcomes, including lower mortality and risk of damage or flares, improved quality of life, lower hospitalisation rates and costs. Glucocorticoids remain the mainstay of SLE treatment, although their use should be limited, e.g. by proper administration of immunosuppressive or antiinflammatory agents that have steroid-sparing activity. Treatment and prevention of infections and cardiovascular outcomes are also essential for further improvement of survival of SLE patients.

SCANCell reveals diverse inter-cluster interaction patterns in systemic lupus erythematosus across the disease spectrum.

High-dimensional mass cytometry (CyTOF), which provides both cellular signatures and inter-cluster interactions like the antagonism between immune activation and suppression, and the pro-inflammatory synergy, sheds light on the cellular and molecular basis of disease pathogenesis. However, revealing the aberrance of inter-cluster communication networks in CyTOF datasets remains a significant challenge. Here, we developed Sample Classification and direct Association Network among Cell clusters (SCANCell) that quantifies the direct association (DA) network of cell clusters. SCANCell was applied to profile inter-cluster interaction patterns of a well-recruited systemic lupus erythematosus (SLE) cohort, including 8 healthy controls, 10 active SLE patients (APs) and 8 remission SLE patients (RPs). SCANCell identified decreased inter-cluster interactions of CD8+ T cells in APs compared with RPs, and enhanced DA of CD8+ T cells after stimulation with immunostimulatory cytokine interleukin-2 in vitro. These discoveries prove that SCANCell can uncover pathology- and drug stimulation-associated inter-cluster interactions, which potentially benefits understanding of pathogenesis and novel therapeutic strategies. The main processing scripts of SCNACell are available at https://github.com/Lxc417/SCANCell. Other codes for the following data statistics are available from the corresponding author upon request. Supplementary data are available at Bioinformatics online.