Active Systemic Lupus Erythematosus Research Articles

Urine L-selectin reflects clinical and histological renal disease activity and treatment response in lupus nephritis across multi-ethnicity.

There is an urgent need for novel biomarkers in lupus nephritis (LN). We report a non-invasive urinary biomarker, L-selectin, in two independent multi-ethnic cohorts. uL-selectin was tested cross-sectionally in a Chinese cohort (n=255) and a US cohort (n=219) of SLE patients and controls using ELISA. A longitudinal cohort includes 20 active Chinese LN patients. uL-selectin was significantly increased in active LN patients compared to active non-renal SLE, inactive LN, inactive non-renal SLE, chronic kidney disease patients, and healthy controls. uL-selectin positively correlated with global and renal disease activities as well as histological activity index and chronicity index (CI). Low uL-selectin was an independent predictor for high CI. During follow-up, uL-selectin levels decreased significantly in the complete renal remission group. uL-selectin is a novel biomarker of disease activity and renal histopathology in LN across multiple ethnicities. It also reflects treatment response in LN patients during follow up.

55 Association between autoantibodies and complement activation in systemic lupus erythematosus

55 Association between autoantibodies and complement activation in systemic lupus erythematosus

Obesity is associated with pain and impaired mobility despite therapy in systemic lupus erythematosus.

To investigate whether abnormal BMI is associated with health-related quality of life (HRQoL) impairments, defined as patient-reported problems within the different dimensions of the three-level EQ-5D (EQ-5D-3L), before and after treatment for active systemic lupus erythematosus (SLE). We conducted a post-hoc analysis of data from two phase III clinical trials of belimumab in SLE, i.e., BLISS-52 (n = 865) and BLISS-76 (n = 819). Underweight was defined as BMI <18.5 kg/m2, normal weight as BMI ≥18.5 but <25 kg/m2, pre-obesity as BMI ≥25 but <30 kg/m2, and obesity as BMI ≥30 kg/m2. We investigated associations between BMI groups and problems (level 2 or 3) within each one of the five EQ-5D dimensions before treatment initiation and at week 52, using logistic regression analysis adjusting for age, ethnicity, disease activity, and glucocorticoid dose, and for the post-treatment analysis also for belimumab treatment and baseline EQ-5D-3L responses. Of 1,684 patients included, 73 (4%) were classified as underweight, 850 (50%) as normal weight, 438 (26%) as pre-obese, and 323 (19%) as obese. At baseline, obesity was associated with mild to severe problems in all EQ-5D dimensions (p < 0.05 for all), yielding the strongest association with problems in mobility (adjusted odds ratio, aOR: 2.1; 95% confidence interval, CI: 1.6-2.8; p < 0.001). Pre-obesity was also associated with problems in mobility (aOR: 1.4; 95% CI: 1.1-1.8; p = 0.005). Post-intervention, obesity was associated with problems in mobility and pain/discomfort, and pre-obesity with problems in mobility and self-care (p < 0.05 for all). Our study adds to the evidence that high BMI negatively affects SLE patients' HRQoL, with obesity being associated with pain and impaired mobility despite therapy.

OCULAR COMPLICATIONS IN CUTANEOUS LUPUS ERYTHEMATOSUS : A SYSTEMATIC REVIEW

Introduction: Dry eye disease (DED) is a multifactorial disorder of the ocular surface characterized by disruption of tear film homeostasis, instability of the tear film, and inflammation of the ocular surface. Although the precise mechanism of action is still inadequately understood, numerous studies have demonstrated that IPL has the potential to alleviate both the signs and symptoms of dry eye.&#x0D; &#x0D; The aim: This article showed ocular complications in cutaneous lupus erythematosus.&#x0D; &#x0D; Methods: By comparing itself to the standards set by the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) 2020, this study was able to show that it met all of the requirements. So, the experts were able to make sure that the study was as up-to-date as it was possible to be. For this search approach, publications that came out between 2013 and 2023 were taken into account. Several different online reference sources, like Pubmed and SagePub, were used to do this. It was decided not to take into account review pieces, works that had already been published, or works that were only half done.&#x0D; &#x0D; Result: In the PubMed database, the results of our search brought up 115 articles, whereas the results of our search on SagePub brought up 97 articles. The results of the search conducted for the last year of 2013 yielded a total 32 articles for PubMed and 26 articles for SagePub. In the end, we compiled a total of 27 papers, 14 of which came from PubMed and 13 of which came from SagePub. We included nine research that met the criteria.&#x0D; &#x0D; Conclusion: SLE ocular symptoms can indicate active SLE. In daily ophthalmology, SLE should be considered a differential diagnosis, especially for symptoms. Systemic treatment is based on ophthalmology. SLE management requires division and medical field collaboration. Systemic treatment includes antimalarials, corticosteroids, immunomodulators, and biologics.

Case of successful treatment of acute respiratory distress syndrome in the parturient woman with systemic lupus erythematosus and cerebral cyst of the third ventricular complicated by posterior reversible encephalopathy syndrome

Pregnancy and the postpartum period provoke an exacerbation of systemic lupus erythematosus (SLE), which requires aggressive cytostatic therapy that can cause life-threatening conditions for the fetus and complications for the mother, one of which is posterior reversible encephalopathy syndrome (PRES- syndrome). The article describes a clinical case of successful treatment of acute respiratory distress syndrome (ARDS) in a 22-year-old woman in labor with high activity of SLE during pregnancy complicated by the development of PRES syndrome. Also, for the first time in the postpartum period, the patient was diagnosed with occlusive periventricular hydrocephalus, a giant cyst of the third ventricle. An emergency endoscopic cyst ventriculocisternostomy was performed. In the future, the development of severe ARDS against the background of sepsis, which required the setting of extracorporeal membrane oxygenation (ECMO). A multidisciplinary approach and timely therapy saved the life of a young mother.

Musculoskeletal symptoms in juvenile onset systemic lupus erythematosus

In juvenile onset systemic lupus erythematosus (SLE), musculoskeletal involvement is one of the most common manifestations. Musculoskeletal symptoms may be due to disease activity itself, organ damage due to SLE activity, drug exposure, or comorbidities. Although they are not life-threatening, they still have a significant impact on disability severity and social exclusion. This article discusses the clinical features of various causes of musculoskeletal manifestations in SLE with onset in childhood and adolescence, the adequate interpretation of which is important for diagnosing and evaluating SLE activity and for correcting the treatment of the disease, thereby improving the long-term prognosis and quality of life of patients.

Citrullinated histone H3 in systemic lupus erythematosus and antiphospholipid syndrome (preliminary results)

Citrullinated histone H3 (CitH3) is a specific marker for NETosis; its role in determining the clinical and laboratory manifestations of systemic lupus erythematosus (SLE) remains to be elucidated.Objective: To evaluate the role of CitH3 in the development of clinical and laboratory manifestations in patients with SLE with and without an-tiphospholipid syndrome (APS).Material and methods. The study included 30 patients with SLE and 39 with SLE+APS, including 51 (73.9%) women and 18 (26.1%) men. The median age of the patients was 36 [32; 46.5] years. The control group consisted of 26 healthy individuals.SLE activity was assessed by the SLEDAI-2K index. Patients were divided into two groups: 41 patients with moderate and high SLE activity (SLEDAI-2K ≥6) were included in the first group, and 28 patients with low activity or remission (SLEDAI-2K &lt;6) were included in the second group.CitH3 content in blood serum was determined by enzyme immunoassay using a set of reagents for the assay of CitH3 (BlueGene Biotech, China) according to the manufacturer's instructions.Results and discussion. CitH3 content in blood serum was significantly higher in SLE than in the control group (p=0.048). High blood serum CitH3 content was associated with moderate and high SLE activity (p=0.039). CitH3 concentration was inversely correlated with lymphocyte count but was not related to immunological parameters. Increased CitH3 levels were associated with photosensitivity, while lower levels were associated with a history of serositis. There were no significant differences between blood serum CitH3 levels in patients with SLE and SLE+APS (p=0.39).Conclusion. The concentration of a specific marker for NETosis, CitH3, is increased in patients with SLE, and this increase is associated with moderate and high disease activity.

CD4 T lymphocyte subsets display heterogeneous susceptibility to apoptosis induced by serum from patients with systemic lupus erythematosus

BackgroundSerum from systemic lupus erythematosus (SLE) patients has been shown to induce T-lymphocyte (TL) apoptosis. Given that different cells of the immune system display different sensitivity to apoptosis, we set to evaluate the in vitro effect of SLE serum on regulatory T-cells (Treg), Th17, Th1 and Th2 from SLE patients and healthy controls.MethodsPeripheral blood mononuclear cells from SLE patients or normal controls were exposed to a pool of sera from SLE patients or normal controls. Annexin V was used to label cells in apoptosis or necrosis. Annexin V-labeled Treg, Th17, Th1 and Th2 cells were determined using flow cytometry.ResultsTotal CD3 + and CD4 + cells from SLE patients showed higher frequency of spontaneous apoptosis/necrosis, whereas Th1 cells from SLE patients presented reduced spontaneous apoptosis/necrosis rate as compared with cells from controls. Incubation with SLE serum induced increased frequency of apoptotic/necrotic CD3 + , CD4 + and Th2 cells from normal controls or from SLE patients as compared with cultures incubated with normal human serum (NHS) or without human serum at all. Incubation with SLE serum did not increase the apoptosis/necrosis rate in Th1 or Th17 cells. Treg cells from SLE patients were more prone to apoptosis/necrosis induced by SLE serum than Treg cells from normal individuals. Th1, Th2, and Th17 cells presented increased apoptosis rates in cultures without human serum.ConclusionOur findings indicate that the serum of patients with active SLE stimulates apoptosis of CD4 + T cells in general and exhibit differentiated effects on CD4 + T-cell subsets.

Does baricitinib reduce disease activity in patients with systemic lupus erythematosus? A systematic review and meta-analysis of randomized controlled trials.

Baricitinib is a selective Janus kinase inhibitor that has recently been approved for treating certain autoimmune disorders. This meta-analysis pooled the conflicting results from all published randomized controlled trials (RCTs) about the efficacy and safety of baricitinib in patients with systemic lupus erythematosus (SLE). We systemically searched four electronic databases. RCTs comparing baricitinib versus placebo were included. Our outcomes were pooled as the risk ratio (RR) in the random effects model. Our primary outcome was the proportion of patients who achieved a SLE Responder Index-4 (SRI-4) response. A total of three RCTs, comprising 1849 patients, were included. Baricitinib 4 mg was associated with a significantly higher proportion of patients who attained SRI-4 response at week 24 (RR = 1.19, 95% CI [1.05, 1.35], P < 0.01). However, this did not reach statistical significance with baricitinib 4 mg at week 52 and baricitinib 2 mg at both week 24 and week 52 (RR = 1.13, 95% CI [0.96, 1.34], P = 0.15; RR = 1.09, 95% CI [0.96, 1.24], P = 0.20; RR = 1.05, 95% CI [0.92, 1.19], P = 0.50, respectively). The risk for serious infections was higher in the baricitinib 4 mg group (RR = 2.23, 95% CI [1.13, 4.37], P = 0.02). Baricitinib 2 mg did not show any clinical benefit. In contrast, baricitinib 4 mg might have the potential to reduce SLE disease activity; however, further research is required to evaluate its long-term efficacy. Until higher-quality evidence is developed, the benefits and risks of baricitinib should be considered before initiating its therapy. Key Points • Baricitinib is a selective Janus kinase inhibitor that has recently been approved for treating certain autoimmune disorders; however, its efficacy in patients with systemic lupus erythematosus (SLE) is still inconclusive. • In our meta-analysis, baricitinib 2 mg did not show any clinical benefit. In contrast, baricitinib 4 mg significantly reduced SLE activity in terms of SRI-4 response at week 24. However, this did not reach statistical significance at week 52. • Further studies are required to investigate the long-term efficacy of baricitinib 4 mg in patients with SLE.

IL-33 Orchestrated the Interaction and Immunoregulatory Functions of Alternatively Activated Macrophages and Regulatory T Cells InVitro.

Our group has previously demonstrated elevated serum-soluble ST2 in patients with active systemic lupus erythematosus, suggesting a role of IL-33 in the underlying pathogenesis. However, inconsistent results have been reported on the effect of exogenous IL-33 on murine lupus activity, which may be mediated by concerted actions of various immune cells invivo. This study aimed to examine the function of IL-33 on macrophage polarization and regulatory T cells (Treg) and their interactive effects in the lupus setting by invitro coculture experiments of macrophages and T cells that were performed in the presence or absence of IL-33-containing medium. Compared to IL-4-polarized bone marrow-derived macrophages (BMDM) from MRL/MpJ mice, adding IL-33 enhanced mRNA expression of markers of alternatively activated macrophages, including CD206 and Arg1. IL-33 and IL-4 copolarized BMDM produced higher TGF-β but not IL-6 upon inflammatory challenge. These BMDM induced an increase in the Foxp3+CD25+ Treg population in cocultured allogeneic T cells from MRL/MpJ and predisease MRL/lpr mice. These copolarized BMDM also showed an enhanced suppressive effect on T cell proliferation with reduced IFN-γ and IL-17 release but increased TGF-β production. In the presence of TGF-β and IL-2, IL-33 also directly promoted inducible Treg that expressed a high level of CD25 and more sustained Foxp3. Unpolarized BMDM cocultured with these Treg displayed higher phagocytosis. In conclusion, TGF-β was identified as a key cytokine produced by IL-4 and IL-33 copolarized alternatively activated macrophages and the induced Treg, which may contribute to a positive feedback loop potentiating the immunoregulatory functions of IL-33.

E32 Intra cranial hypertension in juvenile neurolupus

Abstract Introduction Neurolupus is one of the two key prognostic parameters of lupus. Its manifestation can be central or peripheral, revealing the disease or occurring during the course of evolution. It’s important to not consider all neurological manifestations during SLE as related to lupus, ruling out Central nervous system (CNS) infection and anti-phospholipid syndrome (APS) is primordial. Objectives To share 3 rare observations of neurolupus with intracranial hypertension syndrome and discuss their therapeutic modalities. To highlight the lack of evidence in the treatment of such cases. Method A retrospective analysis of data from medical records. Results We report three observations of Intracranial hypertension syndrome involving three girls, ranging from 9 to 14 years. Clinical symptomatology was dominated by headache, vomiting and visual disturbances. Examination found papillary oedema stage 3 in all the three patients, convergent strabismus in two patients and elevated intracranial pressure measurement in all the three girls ranged from 95 mm to 57 mm of H2O. Brain MRI performed in all three-patients was normal. Data from laboratory tests showed, thrombocytopenia in one patient, pancytopenia in one patient, positive antinuclear antibodies in all patients, positive anti-DNA antibody in one patient, C3, C4 consumption in two patients, positive proteinuria in two patients and positive anti phospholipid antibodies in one patient. All patients had active SLE at the time of admission with a Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) at least at 17. Symptomatic treatment with carbonic anhydrase inhibitor was initiated, followed by methylprednisolone pulse therapy then oral corticosteroids and hydroxychloroquine in all the three patients. Immunosuppressive therapy with Rituximab 1 g at two-week intervals was administrated in two patients, the third one did not receive any suppressive treatment in addition to corticosteroids due to the favorable outcome. The course was favorable in all patients with regression of clinical symptoms of intracranial hypertension and papillary oedema immediately after cerebro spinal fluid (CSF) subtraction. Discussion and Conclusion Neurolupus presents with heterogeneous symptoms that make its diagnosis difficult. Intracranial hypertension syndrome is a rare manifestation resulting from a disorder of CSF resorption, its pathogenesis is poorly understood with an inflammatory hypothesis based on immune deposits. There are no therapeutic recommendations to date. This isolated syndrome without other neurological signs of severity responds very well to symptomatic treatment with carbonic anhydrase inhibitors and to CSF withdrawal, as was the case in our patients. The use of immunosuppressive therapy (rituximab in our patients) was indicated due to the severity of the clinical picture with severe renal involvement. In addition, other immunosuppressive drugs can be an alternative option therapy. Ethics The study was performed according to the principles of the Declaration of Helsinki.

Acute pancreatitis caused by Systemic Lupus Erythematosus activity: A case report and literature review.

A 32-year-old woman with systemic lupus erythematosus came to the rheumatology outpatient clinic reporting abdominal pain for a week, along with fever, arthralgias, myalgias, alopecia, asthenia and dyspnea on exertion over the last two months. She was hypotensive and tachycardic, requiring admission to the intensive care unit. She was diagnosed with lupus-related acute pancreatitis, an unusual complication occurring in less than 1% of cases. Most cases are mild and self-limited; however, severe and life-threatening events with multiple organ failure are possible. This article is a case report of lupus-related critical acute pancreatitis, and a literature review.

Mitochondrial Lon protease promotes CD4+ T cell activation by activating the cGAS-STING-TBK1 axis in systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is an autoimmune disease in which autoreactive CD4+ T cells play an essential role. We extracted CD4+ T cells from SLE-prone Fcgr2b-/- mice to elaborate the mechanism of mitochondrial Lon protease in CD4+ T cell activation in SLE. Transcriptome sequencing was performed in SLE-prone Fcgr2b-/- mice, and the stimulator of interferon gene (STING) related to SLE was obtained. It was demonstrated that STING expression was elevated in CD4+ T cells in SLE-prone Fcgr2b-/- mice. The downstream genes and pathways of STING were predicted by GO and KEGG approaches. The data indicated that STING regulated IFN signaling to promote CD4+ T cell activation in SLE-prone Fcgr2b-/- mice. Next, the interaction of cGAS, STING, TBK1, and IFN-I was verified by Co-IP assay. Moreover, the roles of cGAS, STING, and TBK1 in activating CD4+ T cells from SLE-prone Fcgr2b-/- mice were evaluated using gain- or loss-of-function experiments. Mechanistically, cGAS upregulated the IFN-I signaling pathway by directly interacting with STING and TBK1, contributing to CD4+ T cell activation. Besides, cytosolic mtDNA could activate CD4+ T cell activation in SLE-prone Fcgr2b-/- mice by upregulating the cGAS-STING-TBK1 axis. The function of mitochondrial Lon protease in oxidative damage and mtDNA release in CD4+ T cells of SLE-prone Fcgr2b-/- mice were explored. Mitochondrial Lon protease enhanced mtDNA release into the cytoplasm under oxidative stress. Collectively, our work indicates that mitochondrial Lon protease enhances CD4+ T cell activation by inducing mtDNA leakage and offers new candidate targets for developing diagnostic and therapeutic strategies.

Real-world efficacy ofbelimumab inachieving remission or low-disease activity insystemic lupus erythematosus: A retrospective study.

We investigated the effect of belimumab (BEL) on achieving low disease activity (LDA) and remission as an additive molecular-targeting agent to standard of care (SoC) in patients with systemic lupus erythematosus (SLE). Clinical information was retrospectively collected from patients with SLE who received BEL additive to SoC (BEL + SoC), and from patients treated with SoC alone as a control arm. Disease activity was measured by SLE-disease activity score (SLE-DAS). The proportion of patients in LDA and remission at 12 months was compared after propensity score matching. The factors contributing to LDA and remission achievement were identified by Cox proportional hazard model. BEL + SoC significantly reduced SLE-DAS at 6 months, with a significantly higher proportion of patients achieving LDA and remission at 12 months compared to SoC alone. The presence of arthritis at baseline was significantly associated with achieving LDA and remission. Additionally, both treatment groups experienced a significant reduction in daily glucocorticoid dose. Adding BEL to SoC was beneficial for patients with arthritis, leading to higher proportion of achieving LDA and remission, while also reducing their glucocorticoid dose. Our results indicate the utility of BEL in a treat-to-target approach for SLE patients in a real-world setting.

Proteomic analysis identifies subgroups of patients with active systemic lupus erythematosus

ObjectiveSystemic lupus erythematosus (SLE) is a clinically and biologically heterogenous autoimmune disease. We aimed to investigate the plasma proteome of patients with active SLE to identify novel subgroups, or endotypes, of patients.MethodPlasma was collected from patients with active SLE who were enrolled in the British Isles Lupus Assessment Group Biologics Registry (BILAG-BR). The plasma proteome was analysed using a data-independent acquisition method, Sequential Window Acquisition of All theoretical mass spectra mass spectrometry (SWATH-MS). Unsupervised, data-driven clustering algorithms were used to delineate groups of patients with a shared proteomic profile.ResultsIn 223 patients, six clusters were identified based on quantification of 581 proteins. Between the clusters, there were significant differences in age (p = 0.012) and ethnicity (p = 0.003). There was increased musculoskeletal disease activity in cluster 1 (C1), 19/27 (70.4%) (p = 0.002) and renal activity in cluster 6 (C6) 15/24 (62.5%) (p = 0.051). Anti-SSa/Ro was the only autoantibody that significantly differed between clusters (p = 0.017). C1 was associated with p21-activated kinases (PAK) and Phospholipase C (PLC) signalling. Within C1 there were two sub-clusters (C1A and C1B) defined by 49 proteins related to cytoskeletal protein binding. C2 and C6 demonstrated opposite Rho family GTPase and Rho GDI signalling. Three proteins (MZB1, SND1 and AGL) identified in C6 increased the classification of active renal disease although this did not reach statistical significance (p = 0.0617).ConclusionsUnsupervised proteomic analysis identifies clusters of patients with active SLE, that are associated with clinical and serological features, which may facilitate biomarker discovery. The observed proteomic heterogeneity further supports the need for a personalised approach to treatment in SLE.

Kharakter i chastota komorbidnykh urazhen sertsia u khvorykh na systemnyi chervonyi vovchak, shcho yikh diahnostovano za dopomohoiu ekhokardiohrafii, vyiavlennia i kharakterystyka yikhnikh syntropichnykh variantiv

Introduction. Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by damage of different organs and systems. It has been proven that cardiovascular events are proportionally more frequent in SLE affected persons in comparison with general population of corresponding age and sex. Echocardiography is most oftenly used due to its wide availability, ease of implementation, non-invasiveness, safety for visualization of anatomical features, assessment of structure and function of the heart and main vessels. Syntropic comorbid lesions are the non-random combination of two or more syndromes or nosological units with common genetic and/or etiological and pathogenetic mechanisms in a person, which may under certain circumstances influence each other's course. The aim of the study. To investigate nature and frequency of comorbid heart lesions in patients with systemic lupus erythematosus, diagnosed by echocardiography, to identify and characterize their syntropic variants. Materials and methods. 125 patients were included in the study after signing the voluntary Consent to participate, in accordance with the requirements of the Helsinki Declaration of Human Rights, the Council of Europe Convention on Human Rights and Biomedicine, in a randomized manner with preliminary stratification based on the presence of SLE, as well as heart lesions detected by echocardiography. The study included 110 women (88.00 %) and 15 men (12.00 %) aged 18 to 74 years (mean age 42.48 ±1.12 years). All patients with SLE were stratified into five groups based on the evaluation of SLE activity (Systemic Lupus Erythematosus Disease Activity Index scale - SLEDAI). All participants were patients of the Rheumatology Department of Lviv Regional Clinical Hospital. The study included two phases, during which the nature and frequency of comorbid heart lesions, detected by echocardiography, followed by elimination and characterization of syntropic lesions were determined. Results. About half of SLE patients with comorbid heart lesions have mitral valve (MV) insufficiency, and about 1/3 of patients have mitral valve stenosis with left ventricle (LV) diastolic dysfunction. With decreasing frequency we recorded thickening of the aortic valve (AV) leaflets, increased thickness of the interventricular septum (IS), pericardial effusion, enlargement of the left atrial (LA) cavity, enlargement of the right ventricle (RV), increased thickness of the posterior wall of LV in diastole, prolapse of MV, pulmonary hypertension, insufficiency of the tricuspid valve (TV), increase in the diameter of the ascending aorta, AV insufficiency, systolic dysfunction of the LV, enlargement of the LV cavity in diastole. Mitral stenosis and aortic stenosis were found in one case only. Having studied comorbid heart lesions in SLE affected patients, we found that some of them depend statistically reliable on the activity of disease. Therefore, we consider heart valve thickening, pulmonary hypertension, pericardial effusion, and heart failure to be syntropic heart lesions in patients with SLE. Other lesions, the frequency of detection of which does not depend on the activity of SLE, was related to its accompanying diseases. Conclusions. In patients with SLE, mitral valve insufficiency, thickening of the mitral valve leaflets, diastolic dysfunction of the left ventricle, thickening of the aortic valve leaflets, increased thickness of the interventricular septum, and pericardial effusion dominate among the comorbid heart lesions diagnosed by echocardiography. Syntropic heart lesions in patients with SLE included thickening of the mitral valve leaflets, pulmonary hypertension, pericardial effusion, and mitral valve insufficiency. Keywords: systemic lupus erythematosus, comorbid lesions of the circulatory system, syntropic lesions, heart valve lesions, diagnosis, echocardiography.

Risk Assessment Model for Postpartum Venous Thromboembolism Prevention in Patients with Systemic Lupus Erythematosus.

This article assesses the application of the Royal College of Obstetricians and Gynaecologists (RCOG) venous thromboembolism (VTE) risk model on a cohort of postpartum patients with a history of systemic lupus erythematosus (SLE). This is a secondary analysis of an ongoing patient registry of women with SLE from 2016 to 2022. There were 49 SLE patients with 55 pregnancies using the Definitions of Remission in SLE (DORIS) criteria to determine SLE disease activity. RCOG risk assessment model scoring was calculated for each patient prior to and after delivery. The primary outcome was the qualification of "active SLE" by standard rheumatologic criteria and assessment of recommendations for VTE prophylaxis based on RCOG VTE risk assessment scoring. Data were analyzed using Fisher's exact test, chi-square test, and Mann-Whitney U test with significance defined as p < 0.05. In the study cohort, 34 pregnancies (61.8%) were in DORIS remission at delivery. Twenty-one pregnancies (38.2%) were not and scored 3 points on the RCOG VTE risk model. Of these pregnancies, only 19% (n = 4) were recommended for VTE prophylaxis by the obstetrical provider despite RCOG score ≥3. Only 35.7% (n = 5) of pregnancies in DORIS remission, but with 3 points for non-SLE-related VTE risk factors (n = 14), were recommended for VTE prophylaxis. Of the 20 pregnancies in remission with an RCOG score < 3 after assessing all risk factors, 15% (n = 3) were nevertheless recommended for VTE prophylaxis. No patients had a postpartum VTE regardless of therapy. These data reveal a need to improve upon providing postpartum VTE prophylaxis to SLE patients not in remission while also recognizing a diagnosis of SLE alone should not equate with active disease. Moreover, SLE patients in remission may still warrant VTE prophylaxis if other non-SLE-related risk factors are present. · Those with SLE are at increased risk for VTE postpartum.. · VTE prophylaxis should be instituted when clinically appropriate.. · Caution should be exercised in broadly assigning disease activity for SLE diagnosis only.. · This study supports VTE prophylaxis use in postpartum patients with SLE..

Multimodal repertoire analysis unveils B cell biology in immune-mediated diseases

ObjectivesDespite the involvement of B cells in the pathogenesis of immune-mediated diseases (IMDs), biological mechanisms underlying their function are scarcely understood. To overcome this gap, here we constructed and investigated...

Decreased TAX1BP1 participates in systemic lupus erythematosus by regulating monocyte/macrophage function.

Systemic lupus erythematosus (SLE) involves disorders of innate and adaptive immune pathways. Tax1-binding protein 1 (TAX1BP1) modulates the production of antibodies in B cells and the T-cell cycle by regulating the NF-κB signaling pathway. However, the potential association of TAX1BP1 with SLE and its role in monocytes/macrophages have not been fully elucidated. In this study, we utilized whole-exome sequencing (WES) in combination with Sanger sequencing and identified 16 gene mutations, including in TAX1BP1, in an SLE family. TAX1BP1 protein expression with western blotting detection was reduced in SLE patients and correlated with disease activity negatively. Furthermore, RNA sequencing and 4D Label-Free Phosphoproteomic analysis were employed to characterize the transcriptome and phosphoproteome profiles in THP-1 and THP-1-differentiated M1 macrophages with TAX1BP1 knockdown. Silencing of TAX1BP1 in THP-1 and THP-1-differentiated M1 macrophages led to an increase in cluster of differentiation 80 (CD80) expression and differential changes in CD14 and CD16 expression, as assessed by flow cytometry. Additionally, western blot analysis showed that knockdown of TAX1BP1 led to a reduction in TRAF6 and p-p65 in THP-1-differentiated macrophages, with or without lipopolysaccharide (LPS) or tumor necrosis factor (TNF)-α stimulation. Taken together, our findings suggest that TAX1BP1 participates in SLE activity by regulating antigen presentation in monocytes and inflammatory responses in M1 macrophages.

The ratio of neutrophil to lymphocyte as a potential marker of clinicopathological activity for lupus nephritis.

The ratio of neutrophil to lymphocyte (NLR) is a novel inflammatory factor that is elevated in systemic lupus erythematosus (SLE). However, the relationship between NLR and renal pathological manifestations in patients with lupus nephritis (LN) has not been investigated. A retrospective study included 240 SLE patients, in which 186 patients with renal involvement and 124 LN patients underwent renal biopsy, 125 healthy volunteers and 125 chronic kidney disease (CKD) controls. Patients with SLE disease activity 2000 (SLEDAI-2K) > 9 and ≤ 9 were defined as severely active and mildly active, respectively. Clinical parameters and renal pathological data were collected from medical records. The correlations between NLR and clinicopathological features were analyzed. The NLR of SLE group was significantly higher than that of the sex-age matched control groups. Patients with nephritis had higher NLR levels than those without nephritis (P = 0.044). Increased NLR was observed in severely active group compared to mildly active group (P = 0.020). NLR was significantly positively related with SLEDAI score, Renal SLEDAI score, C-reactive protein (CRP), 24-h urine protein, renal activity index (AI), cellular crescents and tubular atrophy, and negatively correlated with serum albumin. NLR was significantly decreased after treatment. Based on the receiver operating characteristic (ROC) curve, the best NLR cut-off value to predict severe activity of SLE and cellular crescents in renal pathology was 2.19 and 3.16, respectively. NLR may be a non-invasive and potential inflammatory marker in evaluating clinical and renal pathological activity in LN patients.