Biomarkers for systemic lupus erythematosus: A scoping review.

BACKGROUND: In recent years, newly discovered potential biomarkers have great research potential in the diagnosis, disease activity prediction, and treatment of systemic lupus erythematosus (SLE). OBJECTIVE: In this study, a scoping review of potential biomarkers for SLE over several years has identified the extent to which studies on biomarkers for SLE have been conducted, the specificity, sensitivity, and diagnostic value of potential biomarkers of SLE, the research potential of these biomarkers in disease diagnosis, and activity detection is discussed. METHODS: In PubMed and Google Scholar databases, "SLE," "biomarkers," "predictor," "autoimmune diseases," "lupus nephritis," "neuropsychiatric SLE," "diagnosis," "monitoring," and "disease activity" were used as keywords to systematically search for SLE molecular biomarkers published from 2020 to 2024. Analyze and summarize the literature that can guide the article. CONCLUSIONS: Recent findings suggest that some potential biomarkers may have clinical application prospects. However, to date, many of these biomarkers have not been subjected to repeated clinical validation. And no single biomarker has sufficient sensitivity and specificity for SLE. It is not scientific to choose only one or several biomarkers to judge the complex disease of SLE. It may be a good direction to carry out a meta-analysis of various biomarkers to find SLE biomarkers suitable for clinical use, or to evaluate SLE by combining multiple biomarkers through mathematical models. At the same time, advanced computational methods are needed to analyze large data sets and discover new biomarkers, and strive to find biomarkers that are sensitive and specific enough to SLE and can be used in clinical practice, rather than only staying in experimental research and data analysis.

Circulating extracellular vesicles as novel biomarkers for pulmonary arterial hypertension in patients with systemic lupus erythematosus.

Introduction: Pulmonary arterial hypertension (PAH) is a serious complication of systemic lupus erythematosus (SLE) with increased mortality. A prothrombotic state may contribute to pathogenesis of SLE-PAH. Extracellular vesicles (EVs) are known to be associated with thrombosis. Here, we investigated circulating EVs and their associations with SLE-PAH. Methods: Eighteen SLE-PAH patients, 36 SLE-non-PAH patients, and 36 healthy controls (HCs) were enrolled. Flow cytometry was used to analyze circulating EVs from leukocytes (LEVs), red blood cells (REVs), platelets (PEVs), endothelial cells (EEVs), and Annexin V+ EVs with membrane phosphatidylserine (PS) exposure. Results: Plasma levels of all EV subgroups were elevated in SLE patients with or without PAH compared to HCs. Furthermore, plasma Annexin V+ EVs, LEVs, PEVs, REVs, EEVs, and Annexin V+ REVs were significantly elevated in SLE-PAH patients compared to SLE-non-PAH patients. Additionally, PAH patients with moderate/high SLE showed a significant increase in LEVs, PEVs, REVs, Annexin V+ EVs, and Annexin V+ REVs compared to SLE-non-PAH patients. However, PAH patients with inactive/mild SLE only exhibited elevations in Annexin V+ EVs, REVs, and Annexin V+ REVs. In the SLE-PAH patients, EEVs were positively correlated with pulmonary arterial systolic pressure, while PEVs and EEVs were positively correlated with right ventricular diameter. Moreover, the receiver operating characteristic curve indicated that Annexin V+ EVs, LEVs, PEVs, REVs, EEVs and Annexin V+ REVs could predict the presence of PAH in SLE patients. Importantly, multivariate logistic regression analysis showed that circulating levels of LEVs or REVs, anti-nRNP antibody, and serositis were independent risk factors for PAH in SLE patients. Discussion: Findings reveal that specific subgroups of circulating EVs contribute to the hypercoagulation state and the severity of SLE-PAH. Higher plasma levels of LEVs or REVs may serve as biomarkers for SLE-PAH.

Clinical Profile and Outcomes of Patients With Systemic Lupus Erythematosus.

Background Systemic lupus erythematosus (SLE) is a complex autoimmune disorder characterized by relapsing-remitting immune system activation, affecting multiple organ systems. Despite significant advances in understanding SLE's pathogenesis, there remains a need for comprehensive clinical profiling at the time of diagnosis to improve early detection and management. This study addresses this gap by providing a detailed analysis of the clinical presentation, disease activity, and patient outcomes using the Systemic Lupus International Collaborating Clinics (SLICC) criteria and Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) index. Methodology This cross-sectional observational study included 80 patients diagnosed with SLE using the 2012 SLICC criteria. Patients were recruited from the Rheumatology department and other wards of Byramjee Jeejeebhoy Government Medical College and Sassoon General Hospital, Pune, India. All participants provided informed consent and institutional ethical approval was obtained. Data were collected through detailed clinical history, physical examinations, and standard tests such as chest X-rays, CBC, RFT, LFT, urine microscopy, creatine phosphokinase, ANA, AntiDsDNA, complement consumption, and Coombs' tests, with 2D echocardiography performed as needed. Follow-ups every three months over 1.5 years assessed disease activity using SLEDAI criteria. Patients aged 12 and above who met the SLICC criteria were included and those with other connective tissue disorders were excluded. Associations between clinical symptoms and organ involvement were analyzed using the chi-square test with a p-value of <0.05 considered significant. Results The study evaluated 80 patients with SLE, revealing a predominantly female cohort (80%) with a mean age of 29.4 years and a standard deviation of 8.3 years, skewed towards younger age groups. Clinical manifestations were diverse; the most common symptoms were (83.75%), oral ulcers (98.75%), and alopecia (95%). Anemia (66.25%) was the most prevalent abnormality, followed by albuminuria and renal abnormalities. Organ involvement was highest in the renal system (50%) and mucocutaneous features, with lower incidences in cardiac, gastrointestinal, and vascular systems. Gender-specific analyses indicated significant differences in SLE nephritis (p=0.048) and autoimmune hemolytic anemia (p=0.046). Autoantibody profiles showed high positivity for ANA (98.8%) and DsDNA (61.3%). Clinical outcomes demonstrated that 68.8% of patients achieved remission and 16.3% experienced organ damage. The SLEDAI scores significantly improved over time, with substantial reductions from baseline to nine months (p<0.001). Conclusion In conclusion, this study provides a detailed examination of SLE, revealing that it predominantly affects young adults and is characterized by diverse manifestations including mucocutaneous symptoms, significant renal involvement, and notable autoantibody profiles. The high prevalence of anti-nucleosome and anti-dsDNA antibodies underscores their diagnostic and prognostic value. Clinically, the findings highlight the necessity for early detection and targeted management of SLE, particularly in addressing renal and mucocutaneous symptoms. Future research should focus on longitudinal studies to track disease progression, explore genetic and environmental influences, and investigate regional variations to enhance treatment strategies and patient outcomes.

Relationship between type 1 diabetes and autoimmune diseases in european populations: A two-sample Mendelian randomization study.

Background: Previous studies have suggested an association between Type 1 diabetes (T1D) and autoimmune diseases (AIDs), but the causal relationship remains unclear. Therefore, this study utilizes publicly available Genome-Wide Association Studies (GWAS) databases and employs a two-sample Mendelian Randomization (MR) approach to explore the causal relationships between T1D and systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and inflammatory bowel disease (IBD). Methods: Summary GWAS data for T1D, SLE, RA, and IBD were downloaded from open GWAS databases and the International Inflammatory Bowel Disease Genetics Consortium (IIBDGC). We employed a series of methods to select instrumental variables closely related to T1D. To enhance the reliability of our conclusions, we applied multiple robust analytical methods, with the inverse variance weighted (IVW) method as the primary approach. Validation and meta-analysis were conducted using the FinnGen consortium. Additionally, we assessed heterogeneity, pleiotropy, and sensitivity to ensure the robustness of our conclusions. Results: A potential causal association was found between T1D and SLE (OR = 1.37, 95% CI = 1.26 - 1.49, P < 0.001), which was further confirmed by meta-analysis. Similarly, a potential causal association was found between T1D and RA (OR = 1.32, 95% CI = 1.17 - 1.50, P < 0.001), and this was also confirmed by meta-analysis. Although the association between T1D and IBD showed P < 0.05, the leave-one-out test did not pass, and further meta-analysis indicated no significant statistical association between them. Conclusion: Our study reveals the relationships between T1D and three clinically common autoimmune diseases (SLE, RA, and IBD). This research supplements previous studies and provides a reference for future clinical work.

Unusual presentations in systemic lupus erythematosus with concurrent IgA nephropathy lesion: a rare case report from Eastern Nepal.

Introduction: Systemic lupus erythematosus (SLE) is an autoimmune disease involving multiple organs. While lupus nephritis (LN) is seen in SLE, concurrent IgA nephropathy lesion is rare. Uncommon manifestations like cutaneous ulcers and orbital involvement present diagnostic challenges, and this case from Nepal emphasizes careful diagnostic approach in such cases. Case presentation: A 42-year-old female presented with bilateral lower limb swelling, gum bleeding, and epistaxis. Initial evaluation revealed pancytopenia and suspected renal involvement. Renal biopsy showed IgA nephropathy lesions, but clinical and laboratory findings favored lupus nephritis. Treatment with immunosuppressive agents was initiated. Despite therapy, the patient developed cutaneous ulcers and orbital cellulitis. Decreasing anti-ds DNA levels were noted during the course of treatment. Discussion: The diagnosis of lupus nephritis in the presence of IgA nephropathy lesions emphasizes the complexity of SLE diagnosis. Treatment with immunosuppressive agents targeting the underlying autoimmune process, yet the development of cutaneous ulcers and orbital cellulitis highlights the importance of timely intervention in managing SLE complications. In resource-limited settings, clinicians should initiate interventions based on clinical and lab findings while awaiting detailed biopsy results. Conclusion: This case highlights diagnostic challenges in SLE and emphasizes the necessity for careful monitoring and timely intervention in managing complications. The interplay between SLE and IgA Nephropathy (IgAN) suggests that SLE may trigger or exacerbate it, complicating disease management. Further exploration is needed to enhance the understanding and management of complex autoimmune disorders like SLE.

Unraveling the Complexity: A Rare Case of Systemic Sclerosis, Rheumatoid Arthritis, and Systemic Lupus Erythematosus Overlap Syndrome.

Overlap syndromes involving systemic sclerosis (SSc), rheumatoid arthritis (RA), and systemic lupus erythematosus (SLE) are rare and present significant diagnostic and therapeutic challenges. This case report details a 54-year-old female who presented with a constellation of clinical and serological features suggestive of both SSc, RA, and SLE. The patient's clinical course, diagnostic findings, and response to treatment are discussed highlighting the need for a multidisciplinary approach in managing such complex cases.

Recognition of differently expressed genes and DNA methylation markers in patients with Lupus nephritis.

Background and Objectives: Systemic lupus erythematosus (SLE) is distinguished by dysregulated immune system activity, resulting in a spectrum of clinical manifestations, with lupus nephritis being particularly prominent. This study endeavors to discern novel targets as potential therapeutic markers for this condition. Methods: Weighted correlation network analysis (WGCNA) was used to construct the network and select the key hub genes in the co-expression module based on the gene expression dataset GSE81622. Subsequently, functional enrichment and pathway analysis were performed for SLE and lupus nephritis. In addition, also identify genes and differences in SLE with lupus nephritis and methylation site. Finally, qRT-PCR and western blot were used to verify the up-regulated expression levels of the selected key genes. Results: Within the co-expression modules constructed by WGCNA, the MElightcyan module exhibited the strongest positive correlation with lupus nephritis (0.4, P = 0.003), while showing a weaker correlation with the control group SLE (0.058) and a negative correlation with the control group (-0.41, P = 0.002). Additionally, the MEgreenyellow module displayed the highest positive correlation with SLE (0.25), but its P value was 0.06, which did not reach statistical significance(P > 0.05). Furthermore, it had a negative correlation with the control group was (-0.38, P = 0.004). The module associated with lupus nephritis was characterized by processes such as neutrophil activation (neutrophil_activation), neutrophil degranulation (neutrophil_degranulation), neutrophil activation involved in immune response (neutrophil_activation_involved_in_immune_response), neutrophils mediated immune (neutrophil_mediated_immunity) and white blood cells degranulation (leukocyte_degranulation) and so on the adjustment of the process. Secondly, in the analysis of SLE samples, the identification of differentially expressed genes revealed 125 genes, with 49 being up-regulated and 76 down-regulated. In the case of lupus nephritis samples, 156 differentially expressed genes were discerned, include in 70 up-regulated and 86 down-regulated genes. When examining differential methylation sites, we observed 12432 such sites in the SLE sample analysis, encompassing 2260 hypermethylation sites and 10172 hypomethylation sites. In the lupus nephritis samples analysis, 9613 differential methylation sites were identified, comprising 4542 hypermethylation sites and 5071 hypomethylation sites. Substantiating our findings, experimental validation of the up-regulated genes in lupus nephritis confirmed increased levels of gene expression and protein expression for CEACAM1 and SLC2A5. Conclusions: We have identified several genes, notably CEACAM1 and SLC2A5, as potential markers for lupus nephritis. Their elevated expression levels and reduced DNA methylation in lupus nephritis contribute to a more comprehensive understanding of the aberrant epigenetic regulation of expression in this condition. These findings hold significant implications for the diagnosis and therapeutic strategies of lupus nephritis.

Assessment of renal response in Tunisian patients with proliferative lupus nephritis under three different induction immunosuppressive agents: A prognostic retrospective study.

OBJECTIVE: The aim of our study was to evaluate the renal response (RR) of three immunosuppressive protocols in the induction treatment of proliferative lupus nephritis (PLN) in a Tunisian population. METHODS: We performed a retrospective prognostic cohort study in the Internal Medicine Department of the Habib Thameur University Hospital in Tunis from January 2000 to December 2023, and included kidney biopsy proven proliferative lupus nephritis patients. Three induction treatments were compared: High CYP regimen: glucocorticoids (GC) + IV cyclophosphamide (CYP) in monthly pulses of 0.7 g/m2 for 6 months; Low CYP regimen: GC + IV CYP in biweekly pulses of 500 mg for 3 months; and MMF regimen: GC + oral MMF 1.5 g twice daily for 6 months. The primary endpoint was the incidence of RR (complete and partial remission) at one year post-diagnosis. The additional outcomes were end-stage kidney disease (ESKD), severe adverse events (AEs) and death. RESULTS: Our study included 78 PLN patients (High CYP: 17, Low CYP: 40, MMF: 21). The study found that 94.1% of patients receiving High CYP achieved the primary endpoint, RR, compared to 67.5% of those receiving Low CYP and 61.9% in the MMF group. For the additional outcomes, there were 3 cases of ESKD, all in the Low CYP group, 5 cases of death (4 in the Low CYP group and 1 in the MMF group), and 20 cases of severe AEs, all of which were severe infections (5 in the High CYP group, 12 in the Low CYP group, and 3 in the MMF group). Multivariate analysis showed that the High CYP regimen was more associated with RR than the MMF regimen, with an adjusted OR of 9.846 (95% CI: 1.087-98.210); p = 0.042. Multivariate analysis did not show statistically significant differences between the High CYP regimen and the Low CYP regimen in terms of RR. CONCLUSION: As an induction treatment for PLN, the High CYP regimen was strongly associated with a higher rate of RR than the MMF regimen. There were no statistically significant differences between the High CYP regimen and the Low CYP regimen in terms of RR.

Exploring genetic and immune cell dynamics in systemic lupus erythematosus patients with Epstein-Barr virus infection via machine learning.

OBJECTIVES: Epstein-Barr Virus (EBV) is a widespread virus implicated in various diseases, including Systemic Lupus Erythematosus (SLE). However, the specific genes and pathways altered in SLE patients with EBV infection remain unclear. We aimed to identify key genes and immune cells in SLE patients with EBV infection. METHODS: The datasets of SLE (GSE50772 and GSE81622) or EBV infection (GSE85599 and GSE45918) were obtained from the Gene Expression Omnibus (GEO) database. Next, differential gene expression (DEGs) analysis were conducted to identify overlapping DEGs and then enrichment analysis was performed. Machine learning was applied to identify key genes. Validation was conducted using ROC curve analysis and expression level verification in test datasets and single-cell RNA sequencing. Immune cell infiltration patterns were analyzed using CIBERSORTx, and clinical data were reviewed for SLE patients. RESULTS: We identified 58 overlapping DEGs enriched in interferon-related pathways. Five overlapping DEGs (IFI27, TXK, RAPGEF6, PIK3IP1, PSENEN) were selected as key genes by machine learning algorithms, with IFI27 showing the highest diagnostic performance. The expression level of IFI27 was found higher in CD4 CTL, CD8 naïve and various B cell subsets of SLE patients with EBV infection. IFI27 showed significant correlation with B intermediate and CD4 CT. Clinical data showed lower CD4 T cell proportions in SLE patients with EBV infection. CONCLUSION: This study identifies IFI27 as a key gene for SLE patients with EBV infection, influencing CD4 CTL and B cell subtypes. These findings enhance the understanding of the molecular mechanisms linking SLE and EBV infection, providing potential targets for diagnostic and therapeutic strategies.

Identification of RNA uridylation subtypes, and the prognostic and therapeutic value of RNA uridylation in systemic lupus erythematosus.

The uridylation of 3'-RNA-a major process in epitranscriptomics- is catalyzed by terminal uridylyl transferases (TUTases), which are involved in multiple diseases and the immune response. Nonetheless, the role of TUTases in systemic lupus erythematosus (SLE) remains unknown. Here we identified increased level of MTPAP and ZCCHC6 and decreased level of PAPD5 and ZCCHC11 in SLE patients from Gene Expression Omnibus (GEO) GSE50772, GSE65391, and GSE121239. The random forest model was applied to screen 4 TUTase candidates (MTPAP, ZCCHC6, PAPD5, and ZCCHC11) to predict the susceptibility of SLE. A nomogram was constructed based on the 4 selected TUTase regulators. Decision curve analysis indicated that patients could benefit from the nomogram. Moreover, based on the 4 differentially expressed genes, individuals with SLE were divided into three patterns (Cluster A-C) using the consensus clustering method. Cluster B was enriched in adaptive immune cells, with the lowest TCE signature expression, manifesting a higher Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) than that in Cluster A and C. whereas, Cluster C was enriched in innate immune cells, with the highest T-cell exhaustion (TCE) signature expression, manifesting lower SLEDAI than that in Cluster B. Clinically, lupus nephritis (LN) patients manifested increased expression of MTPAP and ZCCHC6 and decreased expression of PAPD5 and ZCCHC11 in PBMCs using Quantitative Polymerase Chain Reaction (q-PCR). Immunohistochemistry (IHC) illustrated higher level of ZCCHC6 in the kidneys of LN patients than that in NC. In summary, TUTases could predict the occurrence of SLE and stratify patients based on their immune characteristics, eventually predicting the disease activity and guiding immune therapy.

Role of Interleukin-17 in Predicting Activity of Rheumatoid Arthritis and Systemic Lupus Erythematosus.

Background: Although high serum levels of interleukin (IL)-17 and its producing cells have been found in rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) in earlier research, it is still unclear how these findings relate to disease activity. Objectives: This study examines the link between serum levels of IL-17 and the activity of both RA and SLE. Design: This pilot case-control study included 100 patients with RA, 100 with SLE, and 100 healthy controls. Methods: The Disease Activity Score-28 (DAS28) scores assessed the activity of RA, whereas the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) scores assessed SLE activity. All participants' data were compared and correlated. Results: Serum levels of IL-17 were significantly higher in RA and SLE patients compared with the controls (P < .001) and showed significantly positive correlations (P < .001) with rheumatoid factor titer, anti-cyclic citrullinated peptide (anti-CCP) and DAS28 score among the RA patients. Although among SLE patients, they were significantly positively correlated (P < .001) with anti-double-stranded DNA (anti-ds DNA) levels and the SLEDAI-2K scores, the best cut-off value of IL-17 for predicting moderate and high disease activity was > 175 pg/mL among RA patients and > 95 pg/mL among SLE patients. Conclusions: There is a significant correlation between RA and SLE activity and serum levels of IL-17. This discovery emphasizes IL-17 as a potential therapeutic target.

Impact of connective tissue diseases on complications following aesthetic surgery: A matched cohort study.

BACKGROUND: The association between connective tissue diseases (CTDs), including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and scleroderma, and complications following aesthetic surgery is under-investigated. We hypothesized that the risk of complications following aesthetic surgery was higher in patients with these connective tissue disorders compared to matched non-CTD patients. METHODS: All patients diagnosed with RA, SLE, and scleroderma who underwent aesthetic surgery at our institution from 2003-2022 were reviewed. Demographic data, comorbidities, medications, procedures, and postoperative complications were collected. Non-CTD controls were identified for each procedure and matched 1:1 based on propensity scores derived from race, sex, body mass index, smoking status, and comorbidities. RESULTS: Six hundred 38 patients were included, comprising 319 (50%) patients diagnosed with CTD and 319 (50%) controls. The average age at surgery was 56.3 years. There were 129 complications. There were no differences between the CTD and non-CTD patients in number of total complications (69 versus 60, p = 0.38), major complications (23 versus 16, p = 0.25), or minor complications (46 versus 44, p = 0.73). Complications were not significantly different between CTD patients and controls who underwent blepharoplasty (p = 0.38), breast reduction (p = 0.91), abdominoplasty (p = 0.46), or rhytidectomy (p = 0.50). CTD patients who underwent breast augmentation had significantly more complications than matched non-CTD patients in bivariate analysis (7 versus 0, p = 0.018*) and multivariable logistic regression (OR: 10.2, 95% CI: 1.21 to 93.3, p = 0.039*). CONCLUSIONS: Most aesthetic surgeries can safely be performed in patients with CTDs. Patients seeking breast augmentation should be counseled on a potentially increased risk of postoperative complications.

Longitudinally Extensive Transverse Myelitis in a Patient With Systemic Lupus Erythematosus: A Case Report and Literature Review.

Longitudinally extensive transverse myelitis (LETM) is a rare but severe neurological complication of systemic lupus erythematosus (SLE). The existing literature contains only limited information about this condition. We present a case of a 38-year-old female with SLE who presented with quadriparesis. Magnetic resonance imaging (MRI) of the brain and spinal cord showed T2-weighted high signal intensity involving the brainstem, bilateral middle and inferior cerebellar peduncles, and C1-C7 spinal cord segments. Early intervention with high-dose methylprednisolone and cyclophosphamide was initiated, resulting in partial clinical recovery. A comprehensive literature review highlights the importance of early diagnosis and treatment, discusses the potential etiologies, and explores the prognostic factors influencing patient outcomes. This case report underscores the need for a high level of clinical suspicion and prompt therapeutic intervention to improve prognosis in SLE patients presenting with LETM.

Early human migration determines the risk of being attacked by wolves: ethnic gene diversity on the development of systemic lupus erythematosus.

The prevalence of systemic lupus erythematosus (SLE) varies significantly based on ethnicity rather than geographic distribution; thus, the prevalence is higher in Asian, Hispanic, and Black African populations than in European populations. The risk of developing lupus nephritis (LN) is the highest among Asian populations. Therefore, we hypothesize that human genetic diversity between races has occurred through the early human migration and human genetic adaptation to various environments, with a particular focus on pathogens. Additionally, we compile the currently available evidence on the ethnic gene diversity of SLE and how it relates to disease severity. The human leukocyte antigen (HLA) locus is well established as associated with susceptibility to SLE; specific allele distributions have been observed across diverse populations. Notably, specific amino acid residues within these HLA loci demonstrate significant associations with SLE risk. The non-HLA genetic loci associated with SLE risk also varies across diverse ancestries, implicating distinct immunological pathways, such as the type-I interferon and janus kinase-signal transducers and activators of transcription (JAK-STAT) pathways in Asians, the type-II interferon signaling pathway in Europeans, and B cell activation pathway in Africans. Furthermore, assessing individual genetic susceptibility using genetic risk scores (GRS) for SLE helps to reveal the diverse prevalence, age of onset, and clinical phenotypes across different ethnicities. A higher GRS increases the risk of LN and the severity of SLE. Therefore, understanding ethnic gene diversity is crucial for elucidating disease mechanisms and SLE severity, which could enable the development of novel drugs specific to each race.

Improved diagnosis of systemic lupus erythematosus with human-derived double-stranded DNA antigen.

Anti-double-stranded DNA antibodies (anti-dsDNA) serve as a crucial serological indicator for systemic lupus erythematosus (SLE). Chemiluminescent immunoassay (CIA) is mainly used in clinical diagnosis of SLE, but suffers from low specificity, partially because the use of dsDNA antigens of varied sources in current CIA kits that sometimes led to controversial results. On the basis that anti-dsDNA in healthy individuals tend to selectively bind with dsDNA originating from pathogens, whereas pathogenic anti-dsDNA in SLE patients bind all forms of dsDNA, here we proposed the use of dsDNA fragment derived from human genome as antigen (synthesized via PCR using the human genomic DNA as the template). A magnetic bead-based immunofluorescence assay (IFA) was thus developed for SLE diagnosis, which exhibited improved sensitivity and specificity over CIA using the WHO reference reagent (15/174) as standard. For clinical serum sample analysis (n = 590), IFA exhibited an accuracy of 71.9% that was higher than CIA (65.3%). Crucially, the IFA results exhibited stronger correlations with the activity of SLE, renal involvement, and its prognosis. Besides the improved clinical diagnosis, the proposed IFA also holds great promise in assay standardization due to the high homogeneity of the synthetic dsDNA.

Blood-dominant disease in late-and-early-onset lupus: A systematic review and meta-analysis.

OBJECTIVES: Numerous studies have explored hematological manifestations in early-onset systemic lupus erythematosus (erSLE) (age ≤ 50) and late-onset SLE (ltSLE) patients (age > 50), yielding diverse results. This study employs a meta-analysis to examine differences in hematologic manifestations between ltSLE and erSLE. METHODS: Studies investigating the frequency of hematological manifestations in ltSLE patients were included. The frequencies of autoimmune hemolytic anemia (AIHA), thrombocytopenia (TP), lymphopenia, leukopenia, lymphadenopathy, and thrombosis were compared between erSLE and ltSLE groups. Two authors independently reviewed and assessed data consistency among abstracts, tables, and text to mitigate bias. Forest plots were utilized to compare odds ratios (95 % CI) of hematological manifestations by age groups, and study heterogeneity was evaluated using I2. RESULTS: The analysis included 39 eligible studies with 19,103 SLE patients (16,314 erSLE, 2789 ltSLE). Among these studies, 28 reported AIHA which was found to be more frequent in erSLE (OR = 1.29, 95 %CI = 1.11-1.39, p = 0.0008). Twenty studies provided data on lymphopenia which was found to be more frequent in erSLE (OR = 1.184, 95 %CI = 1.063-1.318, p = 0.0021). 32 studies included data on leukopenia and the frequency was higher in erSLE (OR: 1.338, 95 %CI: 1.22-1.47, p < 0.0001). Lymphadenopathy was more prevalent in erSLE (OR = 2.32, 95 % CI = 1.61-3.34, p < 0.0001). No significant difference was observed in thrombosis and TP frequency between the two groups. CONCLUSION: Attributing hematological findings to SLE in late-onset patients presents challenges due to comorbidities and polypharmacy. Overall, the frequencies of AIHA, lymphopenia, leukopenia, and lymphadenopathy were more common in erSLE patients compared to ltSLE in this study.

Systemic Lupus Erythematosus Presenting as Isolated Thrombocytopenia: A Case Report and Review of the Literature.

Immune thrombocytopenic purpura (ITP) is an autoimmune disorder characterized by a low platelet count, which can lead to increased bleeding and bruising. Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that can affect multiple organ systems and often presents with various hematologic abnormalities, including thrombocytopenia. A 32-year-old woman presented to the emergency department with petechiae, extensive ecchymosis, rectal bleeding, generalized body aches, anorexia, and weakness. Despite showing no clinical features of SLE, laboratory findings revealed severe thrombocytopenia and anemia. Initial treatment with low-dose steroids showed no improvement, but a high-dose steroid regimen significantly increased her platelet count. Further investigations revealed elevated ANA and positive anti-dsDNA, leading to a diagnosis of isolated thrombocytopenia as the initial manifestation of SLE. The subsequent findings of elevated ANA and positive anti-dsDNA confirmed the diagnosis of SLE, with ITP as its initial manifestation. This case underscores the importance of considering underlying autoimmune diseases in patients presenting with isolated thrombocytopenia after ruling out other causes. Early recognition and appropriate treatment of autoimmune conditions like SLE can significantly improve patient outcomes, even when initial presentations are atypical.

Urinary biomarkers for active Lupus Nephritis that have survived independent validation across cohorts.

Most reported biomarkers for lupus nephritis (LN) have not been independently validated across cohorts. Moreover, many of the documented biomarker candidates have been reported to be elevated in LN compared to healthy controls. However, biomarkers that distinguish patients with active LN (ALN) from inactive systemic lupus erythematosus (iSLE) hold significant clinical utility. Hence, our review attempts to identify urine protein biomarkers for LN that have been independently validated across two or more cohorts and exhibit good diagnostic potential for distinguishing ALN from iSLE. PubMed and OVID were screened for studies assessing the diagnostic value of urinary biomarkers in patients with ALN compared to iSLE. Forty peer-reviewed articles were evaluated, encompassing urine biomarker data from 3,411 distinct patients. Of the 32 candidate biomarkers identified, fourteen were repeatedly reported/tested in four or more papers each, namely ALCAM, CCL2 (MCP1), CD163, HAVCR1 (KIM-1), HPGDS, ICAM-1 (CD54), ICAM-2 (CD102), IGFBP-2, LCN2, NCAM-1 (CD56), SELE (E-Selectin), SELL (L-Selectin), TNFSF12 (TWEAK), and VCAM-1, with most exhibiting C-statistics of 0.80 or more across multiple studies when discriminating patients with ALN from iSLE. The 32 reproducibly elevated biomarkers for active LN mapped to nine functional categories. The urinary proteins reported here promise to serve as a liquid biopsy for ALN. Besides representing potential candidates for diagnostic, monitoring, predictive, and prognostic biomarkers in LN, they also provide a window into potential molecular processes within the kidney that may be driving LN. Thus, ongoing advances in proteomics, which offer wider proteome coverage at increased sensitivity, are likely to further reshape our perspective of urinary biomarkers for LN.

The Intersection of Autoimmunity and Neurology: Insights From a Case of Striatal Lupus Encephalitis.

Systemic lupus erythematosus (SLE) is a multifactorial autoimmune disorder predominantly affecting women, characterized by the production of autoantibodies against various nuclear antigens, leading to widespread immune dysregulation and multisystem involvement. Among its complex manifestations, neuropsychiatric systemic lupus erythematosus (NPSLE) represents a particularly challenging aspect of the disease due to its wide spectrum of neurological and psychiatric symptoms. This case report presents a rare instance of striatal lupus encephalitis, a severe subtype of NPSLE, in a 32-year-old woman, highlighting its distinct clinical and radiological features. The patient initially developed bilateral ocular occlusive vasculitis and later presented with acute right-sided hemiparesis and facial asymmetry. Magnetic resonance imaging (MRI) revealed bilateral symmetrical T2-weighted and fluid-attenuated inversion recovery (FLAIR) hyperintense signals in the basal ganglia, consistent with striatal lupus encephalitis. No white matter hyperintensity or vasculitis changes were seen. Cerebrospinal fluid analysis revealed markedly elevated protein levels, though no infectious organism was identified. The patient was treated with high-dose prednisolone, alongside empirical antibiotic and antiviral therapy to address potential meningoencephalitis. Remarkably, she made a full recovery from her stroke-like symptoms. Despite its rarity, the identification of striatal lupus encephalitis is critical due to the severe and potentially irreversible nature of the neurological damage. This case underscores the importance of a comprehensive diagnostic approach, integrating clinical, serological, and neuroimaging findings to differentiate striatal lupus encephalitis from other neuropsychiatric conditions associated with SLE. Its management typically involves aggressive immunosuppressive therapy, with intravenous methylprednisolone being the first-line treatment. The case also illustrates the potential for recovery with prompt and appropriate treatment, as evidenced by the complete resolution of neurological symptoms and MRI findings at follow-up.

Treatment of discoid lupus with lenalidomide and anifrolumab: Case report and review of the literature.

Discoid lupus erythematosus (DLE) is a devastating autoimmune disease with few therapies available. For patients with little to no symptom improvement with initial treatment, the literature surrounding further treatment options and their efficacy remains limited. Here we report a 46-year-old patient with lupus and refractory DLE, who failed numerous medications since her initial diagnosis in 2014. She had a robust response to lenalidomide with further improvement after adding anifrolumab (ANI), in conjunction with the standard of care hydroxychloroquine. Furthermore, she was able to taper off steroids without interval flares. The patient has not experienced any major infections since the initiation of treatment. No previous case reports describing outcomes of lenalidomide and ANI have been reported, yet the combinational approach has potential. Future clinical trials are needed to investigate the safety of the combination of lenalidomide and ANI in lupus patients with refractory DLE.