Lupus Research Articles

Glycoxidation of mammalian whole histone generates highly immunogenic aggregates: Sera of SLE patients contain autoantibodies against aggregates.

Non-enzymatic glycation and oxidation of self-proteins, causing formation and accumulation of advanced glycation end products (AGEs), have been reported in an array of pathologies, including systemic lupus erythematosus (SLE). Such modifications may generate neo-epitopes, break immunological tolerance, and induce antibody response. In this study, we have first analysed the structural modifications of whole histone in the presence of deoxyribose followed by oxidation with hydroxyl radicals. Changes in the secondary and tertiary structure of the whole histone were determined by spectroscopic techniques and biochemical assays. Fluorescence spectroscopy and UPLC-MS showed the generation of AGEs such as carboxymethyl lysine and pentosidine, while DLS and TEM indicated the presence of amorphous AGE-aggregates. Moreover, rabbits immunized with these histone-AGEs exhibited enhanced immunogenicity and ELISA and western immunoblot of IgG antibodies from SLE patients' sera showed a significantly higher specificity towards modified histone-AGEs than the native histone.

51955 A patient’s view of switching from intravenous to subcutaneous immunoglobulin for the management of recalcitrant systemic lupus erythematosus

51955 A patient’s view of switching from intravenous to subcutaneous immunoglobulin for the management of recalcitrant systemic lupus erythematosus

Neonatal lupus erythematosus presenting with effusions: A 13-year retrospective study.

Neonatal systemic lupus erythematosus (NLE) is an acquired autoimmune disease. The presence of effusions, such as pleural effusion and pericardial effusion, is rare. The present study helped investigate the clinical characteristics and progression of children with NLE combined with effusions. Clinical data of patients diagnosed with NLE were retrospectively collected and analyzed from January 1, 2011, to December 31, 2023, at the Children's Hospital of Soochow University and Suzhou Municipal Hospital. Patients with NLE were divided into effusion and non-effusion groups based on the presence of effusion. Moreover, the clinical data of the newborns in both groups were compared and investigated. Eleven (11/45, 24.44%) NLE patients had effusions, such as pleural effusion, testicular hydrocele, peritoneal effusion, pericardial effusion, and hydrocephalus. Other organs involved in effusion patients were cutaneous, gastrointestinal, hematologic, cardiac, and neurological. Among the patients with effusion, five cases of SLE in pregnant mothers, two cases of Sjogren's syndrome, one case of photoallergic symptoms, and three of pregnant mothers with no history of antenatal autoimmune disease. Pregnant mother' autoimmune disease in remission prior to pregnancy, or stable low disease activity. Seven patients were positive for Anti-SSA, five of which were double positive for Anti-SSA and Anti-SSB. Compared with the non-effusion group, the effusion group patients had significantly higher lactate dehydrogenase, creatine kinase, and fibrinogen, significantly lower platelets, total protein, and albumin. These patients were likelier to have thrombocytopenia and coagulation abnormalities. Logistics regression analysis demonstrated that NLE patients with effusions are more likely to have decreased serum total protein levels. All NLE patients with effusion have self-resorption of the effusion. 24.44% of patients had effusions in our study. NLE patients with effusion are more likely to have hematologic involvement and a more inflammatory response. The effusion in NLE patients is usually self-resorption, severe cases can be treated with nonsteroidal anti-inflammatory drugs/steroids. Key Points • NLE patients combined with effusions and were self-limiting, with pleural effusion being the most common. • NLE patients combined with effusions have a more inflammatory response, significant abnormalities in the blood routine and biochemical-related indexes.

Lupus on the Mind: A Case of Psychosis in Uncontrolled Systemic Lupus Erythematosus.

Lupus on the Mind: A Case of Psychosis in Uncontrolled Systemic Lupus Erythematosus.

Serum IFN-γ Predicts the Therapeutic Effect of Belimumab in Refractory Lupus Nephritis Patients.

To evaluate belimumabf's efficacy in refractory lupus nephritis (LN) patients and identify predictive serum biomarkers for treatment response. In this single-arm retrospective study,we assessed clinical responses in LN patients at baseline and six months after initiating belimumab. Serum cytokines (IL-2, IL-4, IL-6, IL-10, TNF-α, IFN-γ) were quantified using multiplex magnetic bead flow immunoassay before and after treatment. Fourteen patients with various subtypes of refractory LN participated in the study: seven with class III and V LN, three with type V alone, two with class III, and two with class IV+V and V LN. Post six months of belimumab therapy, all participants exhibited a reduction in the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)-2K scores from their respective baseline values. Notably, most patients showed a decrease in the dosage of prednisone, levels of 24-hour urinary protein, immunoglobulins, erythrocyte sedimentation rate (ESR), and anti-double-stranded DNA antibody IgM, along with serum levels of IL-4, IL-6, IL-10, and IFN-γ. Meanwhile, levels of C3, C4, IL-2, and TNF-α were observed to increase. Of the participants, nine (64.29%) achieved a complete renal response, one (7.14%) showed a partial response, and four (28.57%) exhibited no response. Significantly, higher baseline serum IFN-γ levels were found in patients who did not achieve complete renal response (CR) compared to those who did (p = 0.009). Receiver operating characteristic (ROC) curve analysis demonstrated that baseline IFN-γ levels had an area under curve (AUC) of 0.96 (0.70-1.00), with a sensitivity of 0.89 and a specificity of 1.00 (p < 0.001). Belimumab shows potential efficacy in treating refractory LN. Baseline serum IFN-γ levels may predict response to belimumab therapy, potentially enabling more targeted treatment approaches for this challenging condition.

54463 A machine learning approach to predicting inpatient mortality of systemic lupus erythematosus in the United States

54463 A machine learning approach to predicting inpatient mortality of systemic lupus erythematosus in the United States

Immunodeficiency: Complement disorders.

The complement system is an important component of innate and adaptive immunity that consists of three activation pathways. The classic complement pathway plays a role in humoral immunity, whereas the alternative and lectin pathways augment the innate response. Impairment, deficiency, or overactivation of any of the known 50 complement proteins may lead to increased susceptibility to infection with encapsulated organisms, autoimmunity, hereditary angioedema, or thrombosis, depending on the affected protein. Classic pathway defects result from deficiencies of complement proteins C1q, C1r, C1s, C2, and C4, and typically manifest with features of systemic lupus erythematosus and infections with encapsulated organisms. Alternative pathway defects due to deficiencies of factor B, factor D, and properdin may present with increased susceptibility to Neisseria infections. Lectin pathway defects, including Mannose-binding protein-associated serine protease 2 (MASP2) and ficolin 3, may be asymptomatic or lead to pyogenic infections and autoimmunity. Complement protein C3 is common to all pathways, deficiency of which predisposes patients to severe frequent infections and glomerulonephritis. Deficiencies in factor H and factor I, which regulate the alternative pathway, may lead to hemolytic uremic syndrome. Disseminated Neisseria infections result from terminal pathway defects (i.e., C5, C6, C7, C8, and C9). Diagnosis of complement deficiencies involves screening with functional assays (i.e., total complement activity [CH50], alternative complement pathway activity [AH50], enzyme-linked immunosorbent assay [ELISA]) followed by measurement of individual complement factors by immunoassay. Management of complement deficiencies requires a comprehensive and individualized approach with special attention to vaccination against encapsulated bacteria, consideration of prophylactic antibiotics, treatment of comorbid autoimmunity, and close surveillance.

Correlation between neuropsychiatric systemic lupus erythematosus and immunological markers: a real-world retrospective study.

This study aimed to investigate disparities in clinical profiles and autoantibody patterns between patients with and without neuropsychiatric systemic lupus erythematosus (NPSLE) in a cohort and to identify risk factors associated with NPSLE in the Chinese population. SLE patients were retrospectively reviewed from two tertiary hospitals. The relationships between NPSLE and immunological biomarkers were explored. Among the 945 SLE patients, 75 (7.94%) were diagnosed with NPSLE. The most prevalent NP manifestations involved cognitive disorder (30.67%), headache (26.67%), seizure disorder (26.67%), and psychosis (26.67%).We observed significant associations between psychosis and anti-β2GPI antibodies (F = 6.092, p = 0.015), polyneuropathy and anti-Scl70 antibodies (F = 20.161, p < 0.001), demyelinating syndrome and anti-cardiolipin antibodies (F = 6.637, p = 0.011), myasthenia gravis and anti-RNP (F = 5.864, p = 0.017), and anti-Smith antibodies (F = 5.096, p = 0.026). Multivariate logistics analysis showed that anti-prothrombin (aPT) IgM antibodies (OR = 10.985, CI 1.279-94.343, p = 0.029), age (OR = 1.169, CI 1.032-1.325, p = 0.014), and serum creatinine (SCr) (OR = 1.014, CI 1.003-1.025, p = 0.009) were independent risk factors of NPSLE, while anti-Sjogren syndrome antigen B (SSB) antibodies (OR 0.023, CI 0.002-0.622, p = 0.023) and high complement C3 (OR = 0.001, CI 0-0.045, p < 0.001) indicated reduced risk of NPSLE. Various neuropsychiatric manifestations in SLE were found to be correlated with specific autoantibodies. Independent risk factors for NPSLE included aPT IgM antibodies, age, and elevated serum creatinine, while the absence of anti-SSB antibodies and low complement C3 levels were associated with increased risk. •Significant associations were found between specific autoantibodies and neuropsychiatric symptoms, shedding light on potential biomarkers for predicting and understanding NPSLE. •The study identifies independent risk factors for NPSLE in the Chinese population, including the presence of anti-prothrombin IgM antibodies, older age, elevated serum creatinine, and lower complement C3 levels.

Perioperative Surgical Recommendations in Patients with Lupus

Systemic lupus erythematosus (SLE) is a long-lasting autoimmune condition that affects the connective tissues and has a varied and diverse range of symptoms. The severity of the disease varies greatly, with the majority experiencing less severe versions. However, it may be life-threatening depending on the extent of organ involvement. The ailment was identified as early as the Middle Ages, with the 12th-century physician Rogerius being the first to use the name lupus to describe the characteristic malar rash. In 1872, Moric Kaposi was the first to acknowledge the systemic aspect of the disease. During the perioperative period, systemic lupus erythematosus (SLE) may provide significant difficulties for the anesthesiologist due to the presence of accumulated organ damage, coagulation abnormalities, and intricate care protocols. This article focuses on the signs and therapies of adult systemic lupus erythematosus (SLE) that are relevant to anesthesiologists. It also discusses the perioperative care of these patients, who present unique challenges due to the complexity of their condition.

A patient treated with ofatumumab for myasthenia gravis in conjunction with systemic lupus erythematosus and thyroid carcinoma.

Myasthenia gravis (MG) is an autoimmune disease mediated by B cells and is associated with acetylcholine receptor (AChR) and muscle-specific receptor tyrosine kinase (MuSK) antibodies in the postsynaptic membrane at the neuromuscular junction. Anti-CD20 monoclonal antibodies, such as ofatumumab demonstrated promising disease control in MG patients. We presented the rare case of a 34-year-old female with acetylcholine receptor-positive myasthenia gravis (AChR-MG), concomitant with systemic lupus erythematosus (SLE) and metastatic thyroid carcinoma, who was treated with ofatumumab and exhibited improvements during follow-up.

Polyglandular Syndrome type III in a young patient: case report

Introduction: Autoimmune polyglandular syndromes (APS) are rare diseases defined by the coexistence of at least two autoimmune endocrine diseases. Objective: To describe a case of type III polyglandular syndrome in a young patient. Case report: Female, 37 years old, with hypothyroidism, presented with a weight loss of 9 kg, daily vomiting, asthenia, fatigue, and postprandial fullness for 3 months. He also reported arthritis in his wrists, shoulders, and hips. In laboratory tests, macrocytic and hyperchromic anemia associated with leukopenia, as well as hypovitaminosis B12, was observed. Pernicious anemia was investigated as the cause of this deficiency. Upper digestive endoscopy showed moderate gastritis – histopathological with gastric atrophy, positive anti-intrinsic factor antibody. Due to inflammatory arthralgia, ANA was requested, with an associated positive anti-dsDNA result of 1:80. In the EULAR/2019 diagnostic criteria for Systemic Lupus Erythematosus (SLE), she presented 14 points, thus she was diagnosed with SLE, and hydroxychloroquine (HXC) was started. Conclusion: SPA is rare, mainly in association with non-glandular autoimmunity, following an early diagnosis.

Hepatic Manifestations in Systemic Lupus Erythematosus (SLE) and Cholestatic Hepatitis as Rare Initial Presentation: A Diagnostic Challenge

Hepatic Manifestations in Systemic Lupus Erythematosus (SLE) and Cholestatic Hepatitis as Rare Initial Presentation: A Diagnostic Challenge

Anti-vasodilator-stimulated phosphoprotein (VASP) antibodies are associated with neuropsychiatric disorders in systemic lupus erythematosus

BackgroundSystemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by multi-organ involvement and the presence of autoantibodies, pathogenic factors that can serve as diagnostic biomarkers. The current research has been focusing on exploring specific autoantigens with clinical relevance for SLE subtypes. In line with this objective, this study investigated potential antigenic targets associated with specific phenotypes in SLE by leveraging an omics-based approach combined with immunoassay techniques. MethodsA transcriptomic analysis was conducted in a cohort of 70 SLE patients to identify genes significantly correlated to the relevant phenotype. Epitope mapping and sequence analysis techniques were used to predict autoantigens, and the corresponding antibodies were subsequently quantified by enzyme-linked immunosorbent assay (ELISA) and validated by Western blot. ResultsTranscriptomic data analysis revealed a group of hub genes exhibiting a significant correlation with the neuropsychiatric phenotype and a positive relationship with platelets. Subsequent epitope prediction for the corresponding proteins highlighted vasodilator-stimulated phosphoprotein (VASP) as a potential autoantigen. Moreover, ELISA and immunoblotting confirmed that the anti-VASP antibody present in the serum was significantly elevated in SLE patients with neuropsychiatric involvement and positively associated with demyelination. ConclusionVASP harbors autoantigenic epitopes associated with neuropsychiatric phenotype, especially the demyelination symptom in SLE, and its antibodies may serve as promising biomarkers in this disease.

Decoding the Mysteries of Auto-Immune Disorders

An autoimmune disease (AI) happens when the immune system doesn’t recognise its cells. This leads to a problem with how it reacts to these cells. Some of these diseases can be due to your genes, the environment, or even certain infections. They can affect specific organs or the whole body. Examples of autoimmune diseases are insulin-dependent diabetes mellitus, rheumatoid arthritis, systemic lupus erythematosus, scleroderma, thyroiditis, and multiple sclerosis. But wait—there's more! Other conditions like arteriosclerosis, inflammatory bowel disease, schizophrenia, &amp; some types of infertility also fall into this category. Around 3% of people in North America &amp; Europe have autoimmune disorders. About three out of four people affected are women. How our immune system works and maintains tolerance is a wonder. The present paper aims to explore autoimmune diseases and what causes the immune system to react in a specific way

Gene profiling of Epstein-Barr Virus and human endogenous retrovirus in peripheral blood mononuclear cells of SLE patients: immune response implications

Systemic lupus erythematosus (SLE) is a multifactorial disease characterized by the convergence of genetic, immunological, and viral elements resulting in a complex interaction of both internal and external factors. The role of the Epstein-Barr virus (EBV) and human endogenous retroviruses (HERV-E) as triggers and maintenance elements in the pathogenesis of SLE has been widely recognized. Previous studies have independently evaluated the effects of EBV and HERV-E in this disease. In this work, for the first time, these viral factors are jointly investigated in SLE patients. This study aimed at assessing the differential expression of immune regulatory genes and the incidence of specific viral pathogens (EBV and HERV-E), alongside the detailed characterization of surface markers in T- and B-lymphocytes in patients with SLE and control participants. A comparative analysis between patients with SLE and control participants was performed, evaluating the expression of phenotypic markers and genes involved in the immune response (TNF-α, IL-2, IL-6, IL-10, IFNG, TLR3), as well as HERV-E gag and EBV viral genes (LMP1 and BZLF1).A significant association between SLE and EBV was found in this study. A notable increase in EBV LMP1 gene expression was observed in patients with SLE . Also, a significant overexpression of HERV-E was observed, in addition to a considerable increase in the distribution of the cell surface marker CD27 + on T- and B-lymphocytes, observed in individuals with SLE compared to the control group. This study provides evidence regarding the role that EBV virus plays in lymphocytes in the context of SLE, highlighting how both the virus and the host gene expression may influence disease pathogenesis by altering immune regulatory pathways mediated by TNF-α, IFN-γ, and IL-10, as well as parallel overexpression of HERV-E gag. The decrease in TLR3 could indicate a compromised antiviral response, which could facilitate viral reactivation and contribute to disease activity.

Expanded CD8+CD38+ T Cell Population in Patients With Systemic Lupus Erythematosus Is Linked to Increased Infection Rates: A Prospective Study.

One of the leading causes of morbidity and mortality among patients with systemic lupus erythematosus (SLE) is infections. The expression of the ectonucleotidase CD38 on the surface of CD8+ T cells has been linked to compromised cytotoxic function. The aim of this prospective study was to assess whether the presence of CD8+CD38+ in the peripheral blood of patients with SLE can serve as a biomarker for infectious complications. A cohort of 80 patients with SLE were recruited over 18 months. The rate of clinically significant infections and presence of CD8+CD38+ T cells in the peripheral blood were monitored at each clinic visit. The patients were classified into high CD38+ and low CD38+ CD8+ T cells using flow cytometry and a previously established cutoff rate of 28.4%. A total of 20 infections were registered over the study period. We observed that the patients with an expanded CD8+CD38+ T cell population in the peripheral blood had a higher rate of recurrent infections and a higher likelihood of infection compared with patients with a low CD8+CD38+ T cell population. The levels of CD38 in CD8+ T cells remained stable over time in the studied subjects. High levels of CD8+CD38+ T cells in the peripheral blood of patients with SLE identify a subgroup prone to infections for whom proper clinical measures should be applied.

Atypical Presentation of SLE

Systemic lupus erythematosus (SLE) presents with a wide array of cutaneous manifestations. The classical cutaneous features are malar rash, discoid rash, annular and papulosquamous lesions. There can also be some atypical manifestations. We present the case report of a patient, which satisfies the ACR/EULAR 2019 criteria for lupus and presented with unusual manifestation of a petechial rash.

CD9 and Aryl Hydrocarbon Receptor Are Markers of Human CD19+CD14+ Atypical B Cells and Are Dysregulated in Systemic Lupus Erythematous Disease.

Aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor whose expression regulates immune cell differentiation. Single-cell transcriptomic profiling was used to ascertain the heterogeneity of AHR expression in human B cell subpopulations. We identified a unique population of B cells marked by expression of AHR, CD9, and myeloid genes such as CD14 and CXCL8. Results were confirmed directly in human PBMCs and purified B cells at the protein level. TLR9 signaling induced CD14, CD9, and IL-8 protein expression in CD19+ B cells. CD14-expressing CD9+ B cells also highly expressed AHR and atypical B cell markers such as CD11c and TBET. In patients with active lupus disease, CD14+ and CD9+ B cells are dysregulated, with loss of CD9+ B cells strongly predicting disease severity and demonstrating the relevance of CD9+ B cells in systemic lupus erythematosus and autoimmune disease.

Clinical evaluation of skin lesions among patients with systemic lupus erythematosus: Experience from a tertiary care centre

Clinical evaluation of skin lesions among patients with systemic lupus erythematosus: Experience from a tertiary care centre

Integrative bioinformatics analysis of transcriptomic data from CD8+ T cells in Systemic Lupus Erythematosus

IntroductionSystemic Lupus Erythematosus (SLE) is a complex, multisystem autoimmune disorder characterized by extensive inflammation that affects nearly all organ systems in the body. It is primarily mediated by auto-antibodies and immune complexes, and it predominantly affects women more than men. This study employs an in-silico approach to identify key genes potentially involved in the pathogenesis of SLE. ObjectivesTo identify key genes potentially involved in SLE pathogenesis using in-silico approach. MethodsHigh-throughput sequencing dataset GSE97264, from the Gene Expression Omnibus (GEO) database, which contains RNA transcriptome data from CD8+ T-cells of 18 SLE patients and 14 healthy controls was utilized for the analysis. Differentially expressed genes (DEGs) were identified using the Bioconductor DESeq2 package in R platform. Gene Ontology (GO) and pathway enrichment analyses were performed using the ToppGene suite. Motif analysis of the genes’ promoter regions was conducted using HOMER software. Protein-protein interaction (PPI) and Reactome functional interaction (FI) networks were created using Cytoscape plugins StringApp and ReactomeFIViz, and analysed to identify hub genes. ResultsOur analysis identified 931 DEGs, with 577 upregulated and 354 downregulated. GO and pathway enrichment analyses indicated that upregulated genes were associated with immune responses, including cytokine production and receptor activation. Motif analysis identified key regulatory motifs linked to immune regulation in upregulated genes and T-cell activation in downregulated genes. PPI and FI networks analyses revealed 29 cell cycle-associated hub genes, with 10 genes—CDK1, TPX2, BIRC5, CCNA2, BUB1, BUB1B, AURKA, KIF2C, PLK1, and CDCA8—common to both biological networks, suggesting their crucial role in SLE pathogenesis. ConclusionThis study suggests that dysregulation of the identified 10 genes may impact immune responses and contribute to the autoimmune-like conditions observed in SLE. Several of these genes are also implicated in other autoimmune diseases, highlighting their potential as SLE biomarkers. Despite their known roles in other immune-related diseases involving CD8+ T cells, their direct association with SLE had not been previously established. This novel finding underscores the potential of these genes as therapeutic targets and may contribute to the development of diagnostic tools.