Lupus

Systemic lupus erythematosus is a chronic autoimmune inflammatory disease characterized by multiple symptoms. The phenolic acids and other flavonoids in Nelumbo nucifera have anti-oxidants, anti-inflammatory, and immunomodulatory activities that are essential for managing SLE through natural sources. This study employs network pharmacology to unveil the multi-target and multi-pathway mechanisms of Nelumbo nucifera as a complementary therapy. The findings are validated through molecular modeling, which includes molecular docking followed by a molecular dynamics study.

Active compounds and targets of SLE were obtained from IMPPAT, KNApAcKFamily and SwissTargetPrediction databases. SLE-related targets were retrieved from GeneCards and OMIM databases. A protein–protein interaction (PPI) network was built to screen out the core targets using Cytoscape software. ShinyGO was used for GO and KEGG pathway enrichment analyses. Interactions between potential targets and active compounds were assessed by molecular docking and molecular dynamics simulation study.

In total, 12 active compounds and 1190 targets of N. nucifera’s were identified. A network analysis of the PPI network revealed 10 core targets. GO and KEGG pathway enrichment analyses indicated that the effects of N. nucifera are mediated mainly by AGE-RAGE and other associated signalling pathways. Molecular docking indicated favourable binding affinities, particularly leucocianidol exhibiting less than −4.5 kcal/mol for all 10 targets. Subsequent molecular dynamics simulations of the leucocianidol-ESR1 complex aimed to elucidate the optimal binding complex’s stability and flexibility.

Our study unveiled the potential therapeutic mechanism of N. nucifera in managing SLE. These findings provide insights for subsequent experimental validation and open up new avenues for further research in this field.

Physical inactivity, which is highly prevalent in patients with systemic lupus erythematosus (SLE), is an independent risk factor for cardiovascular events and causes many complications. This study aimed to investigate the effect of objective measurement and physical activity level on peripheral muscle strength, exercise capacity, pain, dyspnea, fatigue, anxiety, and depression in patients with SLE.

The present cross-sectional study analyzed 41 patients with SLE. Clinical and demographic characteristics of patients were recorded. Functional exercise capacity, peripheral muscle strength, dyspnea, pain, fatigue, anxiety, and depression were assessed. The physical activity level was assessed by a wearable activity tracker (Mi Band four smart band).

The number of steps measured by the activity tracker was 4384.43 ± 1558.21 steps per day in patients with SLE. Patients with physical activity levels below 5000 steps exhibited elevated levels of fatigue, along with diminished functional exercise capacity and knee muscle strength, in comparison to those who were above the 5000-step threshold. Physical activity levels correlated with functional exercise capacity (6MWT), physiological parameters (maximum heart rate, Δ heart rate, Δ dyspnea, QFM fatigue, Δ QFM fatigue), and knee extension muscle strength. The functional exercise capacity and knee extension were identified as significantly and dependently associated with physical activity levels in SLE patients.

Physical activity level is associated with functional exercise capacity and knee muscle strength in patients with SLE.

We aim to investigate the potential roles of key genes in the development of lupus nephritis (LN), screen key biomarkers, and construct the lncRNA XIST/miR-381-3P/STAT1 axis by using bioinformatic prediction combined with clinical validation, thereby providing new targets and insights for clinical research.

Gene expression microarrays GSE157293 and GSE112943 were downloaded from the GEO database to obtain differentially expressed genes (DEGs), followed by enrichment analyses on these DEGs, which were enriched and analyzed to construct a protein-protein interaction (PPI) network to screen core genes. The lncRNA-miRNA-mRNA regulatory network was predicted and constructed based on the miRNA database. 37 female patients with systemic lupus erythematosus (SLE) were recruited to validate the bioinformatics results by exploring the diagnostic value of the target ceRNA axis in LN by dual luciferase and real-time fluorescence quantitative PCR (RT-qPCR) and receiver operating characteristic (ROC).

The data represented that a total of 133 differential genes were screened in the GSE157293 dataset and 2869 differential genes in the GSE112943 dataset, yielding a total of 26 differentially co-expressed genes. Six core genes (STAT1, OAS2, OAS3, IFI44, DDX60, and IFI44L) were screened. Biological functional analysis identified key relevant pathways in LN. ROC curve analysis suggested that lncRNA XIST, miR-381-3P, and STAT1 could be used as potential molecular markers to assist in the diagnosis of LN.

STAT1 is a key gene in the development of LN. In conclusion, lncRNA XIST, miR-381-3P, and STAT1 can be used as new molecular markers to assist in the diagnosis of LN, and the lncRNA XIST/miR-381-3P/STAT1 axis may be a potential therapeutic target for LN.

To describe the uptake of anti-SARS-CoV2 vaccination in 2021 and investigate vaccine effectiveness in systemic lupus erythematosus (SLE) patients in Sweden.

The cumulative incidence of first anti-SARS-CoV2 vaccination was estimated among SLE patients from the Swedish National Patient Register and matched comparators living in Sweden on January 1, 2021. To assess vaccine effectiveness, we included the individuals who received two doses of anti-SARS-CoV2 mRNA vaccines before year 2022, with no COVID-19 diagnosis code before the 2nd vaccine dose. Hospitalization rates with COVID-19 as main diagnosis during the year after second dose were compared between SLE patients and comparators in multivariable-adjusted marginal Cox models, overall and stratified by immunosuppressive treatment received during the year before second vaccine dose.

Vaccination uptake was similar between SLE patients and comparators. By December 2021, 9% of both SLE and comparators had not received any vaccine doses. Among 5585 SLE patients and 37,102 comparators, 11 COVID-19 hospitalizations in the SLE group and 20 in the comparators occurred. SLE was associated with a higher risk of COVID-19 hospitalization (HR = 3.47, 95%CI 1.63-7.39). The HR was higher for immunosuppressive-treated SLE (7.03 95%CI 3.00-16.46) than for immunosuppressive-untreated (1.50 95%CI 0.34-6.60). Vaccination of immunosuppressive-untreated SLE patients had similar effectiveness as comparators.

Anti-SARS-CoV2 vaccination coverage was similar between SLE patients and the general population in Sweden. Even though the incidence of post-vaccination COVID-19 hospitalization was very low, vaccine effectiveness was diminished in SLE patients compared to the general population and lowest in those treated with immunosuppressants.

Systemic lupus erythematosus is a multisystemic rheumatic disease with different clinical features. Disturbance in apoptosis regulation seems to be a major factor in SLE development.

Survivin plays a key role in mitosis and inhibiting apoptosis. A study was conducted to examine the expression level of survivin and miRNAs that affect survivin transcript levels in patients with SLE.

We isolated peripheral blood mononuclear cells from 50 inactive SLE patients and 50 healthy controls. RNA is extracted and converted to cDNA. The quantitative real‐time polymerase chain reaction is conducted to assess the expression levels of survivin total and its variants with effective miRNAs in PBMCs.

Expression levels of miR-34a-5p (fold change = 1.5, p⁺⁺ = 0.027), and 218-5p (fold change = 1.5, p⁺⁺ = 0.020) were significantly increased. While miR-150-5p (fold change = 0.56, p⁺⁺ = 0.003) was significantly decreased. The mRNA expression of survivin-WT (fold change = 0.63, p+⁺ = 0.002) was significantly downregulated in SLE patients compared to the healthy controls. Survivin total and its two major variants (survivin-2B, and survivin-ΔEx3) did not differ significantly between SLE patients and controls.

Although survivin-TS and its two variants (survivin-2B, and survivin-ΔEx3) were not differently expressed in SLE patients, survivin-WT had altered expression. Despite aberrant miRNA expression in PBMCs from SLE patients, survivin and miRNA expression were not associated with leukopenia. The pathogenesis of SLE disorder might be linked to survivin’s other roles in the immune system aside from anti-apoptotic functions.

The exact cause of systemic lupus erythematosus (SLE) is still unknown. However, hormonal, genetic, and environmental factors may play significant roles in its development. Infection has been recognized as a crucial trigger for SLE development. Several studies have reported a higher prevalence of Toxoplasma gondii infections in patients with SLE than in healthy individuals. However, these results were inconsistent. Therefore, this study aimed to conduct a systematic review and meta-analysis of published studies to provide a definitive conclusion regarding the relationship between T. gondii infection and SLE.

We conducted a comprehensive search across diverse databases using an array of search tools to uncover pertinent literature. Following the stringent application of the inclusion and exclusion criteria, we carefully selected the appropriate reports for our meta-analysis. Using Comprehensive Meta-Analysis software v4, we analyzed the data and determined the prevalence of antibodies against T. gondii in patients affected with SLE. To investigate the correlation between T. gondii seropositivity and SLE, we computed the risk ratios (RRs) and 95% confidence intervals (CI).

Eleven studies were considered eligible for inclusion in the present study. The prevalence of anti-IgG and IgM antibodies against T. gondii was 33.9% and 7.7%, respectively. A significant association between T. gondii IgG seropositivity and SLE was observed when compared to the controls (risk ratio = 2.14, 95% CI = 1.42 to 3.22, p = .000). However, IgM seropositivity against T. gondii was comparable between patients with SLE and healthy controls.

In summary, this study suggests that T. gondii IgG is more prevalent in patients with SLE than in healthy individuals in areas where T. gondii infections are more frequent. However, an exact cause-and-effect relationship still needs to be established. Therefore, additional research is necessary to validate these findings and to investigate the underlying mechanisms.

Systemic Lupus Erythematosus (SLE) is an autoimmune disease having a variety of clinical symptoms because of multiple organs being affected at once or progressively over time. Cardiovascular system (CVS) involvement is the third most frequent cause of death in SLE, among other factors. The prognosis can be determined by looking at QT interval measurements, which have shown an elevated risk of mortality from cardiovascular causes.

A case-control study was conducted on 80 patients (40 SLE patients and 40 controls) for a duration of 16 months. SLE patients and controls were identified from the general medicine and rheumatology outpatient department (OPD) based on the inclusion criteria. A thorough clinical examination was performed after obtaining a detailed clinical history. Baseline blood tests were then performed on the SLE patients and ECG was taken from both cases and controls. The serum uric acid level was measured using an automated analyzer, and the ESR was computed using Westergren’s Method. The corrected QT interval (QTc) was estimated using Bazett’s method. All the collected data were compared and analyzed using IBM SPSS Statistics version 23.0.

The majority of age distribution among SLE patients and controls was 21–25 years (37.5%) (Mean - 15.7 ± 14.9 years). Duration of SLE was predominantly reported between 1 and 12 months (62.5%). Very high (40%) and high (40%) lupus disease activity was recorded in the majority as per the SELENA-SLEDAI score. There was a significant difference between QTc values among SLE patients and controls (t- 8.117) (p-.0005). Upon correlating SLEDAI with the QTc, QTd, ESR, and Uric acid parameters among the SLE patients, ESR parameters were found to be moderately correlated (r-0.460) with the SLEDAI which was statistically significant (p- .003).

QTc interval and ESR values can be a simple and potential method for early detection of cardiac involvement in SLE patients with active disease activity. This will not only facilitate early diagnosis of disease activity, but it will also provide an affordable and accessible avenue for low and middle-income countries to decrease the SLE burden.

Anti-neuronal antibodies target antigens produced by tumour cells and cells of nervous system. These antibodies are formed as a result of autoimmune response elicited by the underlying malignancy, when proteins restricted to immune privileged neurons are presented by the tumour. Previous studies have shown presence of anti-neuronal antibodies in systemic lupus erythematosus and neuropsychiatric lupus (NPSLE) but information on individual antibodies and their pathogenic role is lacking.

To assess the frequency of anti-neuronal antibodies in our neuropsychiatric lupus cohort and to assess any significant association with specific neurological syndrome and to see if the antibodies were more likely to occur in active rather than inactive neuropsychiatric lupus.

This cross-sectional study was conducted in our center from 2019 to 2022. Neuropsychiatric manifestations were defined according to 1999 American College of Rheumatology (ACR) nomenclature and case definitions for neuropsychiatric lupus. Samples were taken from active or inactive NPSLE patients with their informed consent. Testing was done on an anti-neuronal antigen panel which consisted of [Amphiphysin, CV2, GAD 65, PNMA2 (Ma-2/Ta), Ri, Yo, Hu, recoverin, SOX1, titin, Zic, Tr)] by semi-quantitative Line immune assay. Association between the categorical variables and antibody positivity group was established using chi-square/Fisher’s exact test as appropriate.

65 patients were recruited, of which 23 (35%) patients had active NPSLE at the time of sample collection. Anti-neuronal antibodies were positive in 13/65 (20%) patients with anti-Gad 65 antibodies having the highest frequency (6.2%) followed by anti CV 2 (3.1%), anti Sox1 (3.1%), anti Amphiphysin (3.1%) anti recoverin (1.5%), anti Yo (1.5%) and anti Zic (1.5%). The panel of anti-neuronal antibodies did not show any specific association with NPSLE features.

However, an interesting finding was that, patients with active disease had higher odds of having anti-neuronal antibodies with an OR = 10 (95% CI:2.38 -42) (p < 0.001) than inactive disease.

Anti-neuronal antibodies were more likely to be positive in active neuropsychiatric lupus patients, and these antibodies which are commonly used to diagnose paraneoplastic syndromes may have a potential role in the diagnosis of NPSLE.

Increased frequency of autoimmune thyroid disease, particularly Hashimoto’s thyroiditis (HT) was reported several studies in the literature, in individuals with childhood-onset systemic lupus erythematosus (cSLE). Our study aimed to investigate the prevalence and contributing factors of thyroid dysfunction and HT among cSLE patients.

Thyroid function tests were obtained cross-sectionally from cSLE patients. Demographic, clinical, and laboratory characteristics and activity scores were collected from medical records. Patients diagnosed with cSLE were compared to the healthy control group for the frequency of thyroid dysfunction. The Mann-Whitney U, independent samples t test, and the Chi-square or Fisher’s exact test were used to compare study groups. A p-value below 0.05 was considered statistically significant.

Out of 73 cSLE patients, 14 (19.1%) had subclinical hypothyroidism, 9 (12.3%) had clinical hypothyroidism, 12 (16.4%) were diagnosed with HT, and 12 (16.4%) had a family history of HT. Thyroid USG was performed in 5 euthyroid patients and 1 borderline subclinical hypothyroid patient with positive thyroid autoantibody and reported as diffuse heterogeneous echogenicity enlargement in the thyroid gland. There were no significant differences in clinical and laboratory data or medication used between the groups with and without HT; however, patients with HT had a higher frequency of clinical hypothyroidism and family history of HT. Cumulative prednisolone dose was significantly lower in patients diagnosed with HT. The frequency of HT was considerably higher in patients with cSLE compared to the healthy control group.

The results demonstrate an increased incidence of HT in cSLE patients, even if they are euthyroid, and recommend that cSLE patients be screened more frequently.

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease with multi organ involvement. One of the most common manifestations is pulmonary disease with a reported prevalence between 5%–90%.

Given this wide range of prevalence, there is a need to more closely define types of pulmonary disease in SLE and associated risk factors.

We sought to characterize the presentation of pulmonary manifestations in an established SLE cohort using electronic health record data.

All patients were >18 years of age and had confirmed SLE by a rheumatologist using SLICC or 2019 ACR/EULAR classification criteria. 220 patients with imaging were included in this study; average age was 42.5 years, 86.7% identified as female, 60.5% identified as white, 37.3% as Black, and 1.82% as Asian.

Generalized estimating equations were utilized to analyze the data, accounting for its repeated measured nature.

We found an association between smoking (present/prior smoker) and radiologist reported disease on computerized tomography (CT) scan, as well as an association between smoking (present/prior smoker), older age, and male sex with having pulmonary disease identified on chest X-ray. The most common findings on CT and X-ray were increased lung density (24%, 12%) and atelectasis (18%, 10%). The most common disease found on CT was pleural effusion (24%) and mediastinal/axillary lymphadenopathy (16%).

While our study is limited by the retrospective nature, our results show that certain factors, namely smoking, older age, or male sex should prompt clinicians to have a higher suspicion for lung disease in SLE patients.

Skin involvement is common in systemic lupus erythematosus (SLE), but may be resistant to conventional treatment. We sought to evaluate the efficacy of anifrolumab (ANI) in refractory cutaneous manifestations of SLE.

Case series of patients with refractory cutaneous SLE from three Rheumatology Departments in Greece. Outcome measures were improvement in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K), physician global assessment (PGA) and Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI). Clinically relevant improvement in skin was defined as decrease ≥50% (CLASI50) from baseline values.

Eighteen patients received ANI; all had active skin involvement at baseline. Mean (SD) SLEDAI and PGA at ANI initiation were 7.4 (2.7) and 1.4 (0.5), respectively, with a mean prednisone dose 4.9 (4.5) mg/day. Mean CLASI (Activity/Damage) at baseline was 13.9 (9.7)/2.9 (4.6). Patients were refractory to a mean 6.3 (1.5) immunomodulatory agents (including hydroxychloroquine and glucocorticoids) before the initiation of ANI. After a mean 8.5 (4.6) months, 89% (n = 16/18) of patients demonstrated significant improvement in general lupus and cutaneous disease activity, and glucocorticoid tapering. Mean SLEDAI and mean CLASI at last visit were 3.4 (1.9) and 2.1 (2.4)/1.4 (2.2), respectively, and mean daily prednisone dose decreased to 2.4 (2.2). Of note, in this group of highly refractory patients CLASI50 was achieved in 16/18 (89%) patients. One patient discontinued ANI after 4 infusions due to a varicella-zoster virus infection and one patient, who initially responded to treatment with ANI, experienced a skin flare due to temporary discontinuation due to Covid 19 infection. DORIS remission and LLDAS were attained in two (11.1%) and eleven (61.1%) patients, respectively.

Anifrolumab is highly effective in various skin manifestations of SLE, even after prior failure to multiple treatments.

Macrophage activation syndrome (MAS) is an acquired form of hemo phagocytic lymphohistiocytosis (HLH) and is usually associated with infections, autoimmune, auto inflammatory syndromes and malignancies.

A 14 year old girl presented with sub-acute onset of fever with lymphadenopathy, pancytopenia,high ferritin values and a falling erythrocyte sedimentation rate. She was evaluated with relevant laboratory tests that was suggestive of systemic Lupus erythematosus and associated macrophage activation syndrome She recovered with immunosuppressive therapy and other supportive care.

There is a need for a high index of suspicion of occult MAS and MAS in patients with systemic lupus erythematosus as it may be an initial presentation. Delay in diagnosis and initiation of treatment can lead to a higher mortality.

This study aims to explore the treatment pattern of systemic lupus erythematosus (SLE) in Aotearoa/New Zealand.

SLE patients were linked to the pharmaceutical dispensing data. The use of publicly funded anti-malarials, immunomodulators, biologics, glucocorticoids and bisphosphonates were compared by gender, ethnicity, age group, socioeconomic status and year of SLE identification. Adherence to hydroxychloroquine was examined using the medication possession ratio (MPR), with a MPR of ≥0.8 considered as high adherence.

Of the 2631 SLE patients, 73.8% used hydroxychloroquine, 64.1% used immunomodulators/biologics and 68.0% used 5 mg or more prednisone daily for at least 90 days. Women were more likely to use hydroxychloroquine than men. Asian patients had a different treatment pattern than other ethnic groups, and Māori were less likely to use hydroxychloroquine. The proportions of patients using different treatments decreased with age. Of the patients using hydroxychloroquine, 54.5% had high adherence. For patients over 40 years old and on long term prednisone, 47.3% had bisphosphonates and this figure was 17.8% for patients under the age of 40 years old. Patients with better socioeconomic status had a higher probability of using bisphosphonates than patients with lower socioeconomic status.

Adherence to hydroxychloroquine in these patients varied and was lower in men and in Māori. Prednisone is commonly prescribed and used long term. Half of those over the age of 40 years old co-administered bisphosphonate. Further research is needed to identify the reasons for these discrepancies on SLE treatments by gender, ethnicity, age and socioeconomic status.