Effect Of Systemic Lupus Erythematosus Research Articles

Effects of systemic lupus erythematosus on the brain: a systematic review of structural MRI findings and their relationships with cognitive dysfunction

BackgroundCognitive dysfunction (CD) is highly prevalent in systemic lupus erythematosus (SLE), yet the underlying mechanisms are poorly understood. Neuroimaging utilising advanced MRI metrics may yield mechanistic insights. We conducted a...

NADPH oxidase in B cells and macrophages protects against murine lupus by regulation of TLR7.

Loss of NADPH oxidase (NOX2) exacerbates systemic lupus erythematosus (SLE) in mice and humans, but the mechanisms underlying this effect remain unclear. To identify the cell lineages in which NOX2 deficiency drives SLE, we employed conditional knockout (KO) and chimera approaches to delete Cybb in several hematopoietic cell lineages of MRL.Faslpr lupus-prone mice. Deletion of Cybb in macrophages/monocytes exacerbated lupus nephritis, though not to the degree observed in the Cybb global KOs. Unexpectedly, the absence of Cybb in B cells resulted in profound glomerulonephritis and interstitial nephritis, rivaling that seen with global deletion. Further, we identified that NOX2 is a key regulator of TLR7, a driver of SLE pathology, both globally and specifically in B cells. This is mediated in part through suppression of TLR7-mediated NF-kB signaling in B cells. Thus, NOX2's immunomodulatory effect in SLE is orchestrated not only by its function in the myeloid compartment, but through a pivotal role in B cells by selectively inhibiting TLR7 signaling.

P-210 A new insight into the effects of systemic lupus erythematosus on oocyte and embryo development and female fertility

Abstract Study question Does SLE affect oocyte and embryo development and female fertility in female patients? Summary answer Patients with SLE present worse outcomes in oocyte and embryonic development, thus yielding compromised female fertility and clinical pregnancy. What is known already Systemic lupus erythematosus (SLE) is often associated with adverse reproductive outcomes. However, it’s currently unclear regarding the role of SLE in oocyte and embryonic development. Also, it’s controversial whether SLE hurts fertility. There is a lack of comprehensive understanding and assessment of fertility in patients with SLE. Study design, size, duration This study retrospectively investigated oocyte and embryo development, ovarian reserve, and clinical outcomes in SLE patients who underwent in vitro fertilization (IVF) treatment from January 2013 to September 2022 at the University Hospital. Participants/materials, setting, methods In this study, we collected data from 34 SLE patients who were previously diagnosed and in remission for a total of 44 IVF cycles and matched 102 infertile women with a total of 148 IVF cycles by Propensity Score Matching (PSM) of 1:3 ratio. We then evaluated baseline characteristics, ovarian reserve, IVF laboratory outcomes, and clinical outcomes between the two groups. Main results and the role of chance After PSM matching, baseline characteristics including age, infertility types, and duration, as well as infertility causes overall coincided between the two groups. Anti-müllerian hormone (AMH) was significantly lower in the SLE group vs comparison (1.9 vs. 3.3 ng/mL, P=0.001). The SLE group performed a significant reduction in available embryo rate (76.6% vs. 86.0%, P=0.001), good-quality blastocyst formation rate (35.1% vs. 47.0%, P=0.003), and blastocyst formation rate (51.0% vs. 67.7%, P=0.001) compared to the comparison. As for clinical outcomes, the implantation rate in the SLE group was notably lower (37.9% vs. 54.9%, P=0.022). The CLBR following every embryo-transfer procedure was distinctly lower (41.2% vs 68.6%, P=0.016) in the SLE group vs comparison. Also, the conservative and optimal CLBRs following every complete cycle procedure were significantly reduced in the SLE group vs the comparison (P=0.001, both) Limitations, reasons for caution It’s a retrospective and single-center study, which is relevant to an inevitable risk of bias. Due to its special population selection, the sample size of this study is quite small. Wider implications of the findings This study provides data support to explore further the impact of SLE or other autoimmune diseases on female fertility, and it also calls for more attention to be given to these special patients by reproductive physicians. Comprehensive fertility assessment and individualized fertility guidance are recommended for patients with SLE. Trial registration number TJ-IRB20211280

Mendelian randomization reveals systemic lupus erythematosus and rheumatoid arthritis and risk of adverse pregnancy outcomes

BackgroundThe effect of systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) on adverse pregnancy outcomes is a controversial topic. This study aimed to use Mendelian randomization (MR) analysis to assess the causal relationship between SLE, RA and adverse pregnancy outcomes. MethodsGenetic variants for SLE and RA, as well as adverse pregnancy outcomes, were derived from pooled statistics from large public genome-wide association studies. Several methods, such as inverse variance weighting (IVW), MR-Egger, weighted median and MR-Pleiotropic Residuals Sum and Outliers, were employed to estimate two-sample causality. ResultsGenetic prediction of SLE was associated with higher odds of preterm labour [odds ratio (OR) 1.03, 95 % confidence interval (CI) 1.01–1.05; p = 0.008]. RA was associated with higher odds of preterm labour (OR 1.03, 95 % CI 1.01–1.06; p = 0.009), pre-eclampsia or eclampsia (OR 1.04, 95 % CI 1.01–1.07; p = 0.005), and poor fetal growth (OR 1.08, 95 % CI 1.04–1.12; p = 2.91 × 10−5). The results of bidirectional MR analysis did not indicate that SLE was associated with spontaneous abortion, pre-eclampsia or eclampsia, preterm rupture of membranes, or poor fetal growth (p-value for IVW 0.13–0.97). ConclusionsThis study found a genetic association between SLE and the risk of preterm labour, and highlights the importance of perinatal care and monitoring for patients with SLE. Furthermore, RA was found to be associated with a wide range of adverse outcomes, including preterm labour, pre-eclampsia or eclampsia, and poor fetal growth; as such, there is a need for more intensive therapeutic interventions and prenatal monitoring.

Causal effect of systemic lupus erythematosus on psychiatric disorders: A two-sample Mendelian randomization study

BackgroundThis study aims to investigate the association between systemic lupus erythematosus (SLE) and the risk of seven psychiatric disorders through the application of Mendelian randomization (MR) analysis due to previous observational studies that have suggested a potential link between SLE and psychiatric disorders. MethodsWe collected genetic instruments for SLE from a genome-wide association study (GWAS) involving 23,210 individuals. Seven psychiatric traits were enrolled from the recent largest GWAS, including major depression disorder (MDD), generalized anxiety disorder (GAD), schizophrenia (SCZ), bipolar disorder (BID), autism spectrum disorder (ASD), attention deficit/hyperactivity disorder (ADHD), and insomnia. Summary statistics for psychiatric disorders were obtained from different GWAS meta-analysis studies. The inverse variance weighted (IVW) method was used as the main MR analysis. ResultsThe IVW method indicated that SLE is associated with a higher risk of GAD (OR = 1.072, 95 % CI [1.017–1.129], P = 0.008) and SCZ (OR = 3.242, 95 % CI [1.578–6.660], P = 0.007). However, no evidence was found for the causal associations between SLE and other psychiatric disorders. Further analyses found no evidence of pleiotropy and heterogeneity. ConclusionsThis two-sample MR analysis provides evidence that genetically predicted SLE may increase the risk of GAD and SCZ in a European population. Future studies are needed to elucidate and investigate the mechanisms underlying these causal relationships. Considering the existence of racial genomic heterogeneity, our findings must be viewed with caution.

The effect of systemic lupus erythematosus (SLE) Disease Activity Score and SLE Disease Activity Index 2000-based remission states in patients with SLE on damage accrual.

This study aimed to compare the effect of the Systemic Lupus Erythematosus Disease Activity Score (SLE-DAS) with the SLE Disease Activity Index 2000 (SLEDAI-2K) remission state on damage accrual. This study classified SLE patients from the Lupus Clinic of the Royal Thai Army (LUCRA) cohort based on the SLE-DAS index, or Boolean-based, and SLEDAI-2K (Doria) remission state. Regression analysis models were constructed to identify predictors of the Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI) during follow-up. There were 197 patients identified; 97 patients met at least one definition of remission state, and 100 patients were in the non-remission group at enrollment. Of 97 patients, 97 achieved the SLE-DAS index-based definition, 74 achieved the SLE-DAS Boolean-based definition, and 55 achieved the Doria definition. The mean ± SD of follow-up was 4.77 ± 0.6 years. The changes in SDI over time were non-significantly lower in patients who met any definition of remission compared with those who did not. Multivariate analysis revealed that predictive factors for increased SDI were age and baseline SDI ≥ 1. SLE-DAS index, Boolean, and Doria-based definitions of remission at enrollment had no significant risk reduction on SDI compared with the non-remission group (HR 0.7, 95% CI 0.37-1.32, p = .27; HR 0.73, 95% CI 0.37-1.44, p = .37; HR 0.8, 95% CI 0.39-1.65, p = .55, respectively). Patients with SLE who achieved remission status according to the SLE-DAS index or SLEDAI-2K definitions did not show any significant difference in damage accrual compared to those who were not in remission.

Health-related quality of life in Chinese SLE patients: evidence from 1568 SLE patients and 2610 healthy controls.

To investigate the effects of systemic lupus erythematosus (SLE) on health-related quality of life (HRQOL), the relationship between disease activity and HRQOL, and potential factors affecting HRQOL in Chinese SLE patients. This study recruited 1568 patients and 2610 controls to explore the effects of SLE on HRQOL. The association between disease activity and HRQOL, and the influencing factors of HRQOL were determined in 1568 patients. Then, we prospectively followed 1096 patients to explore the association between reduced disease activity and improved HRQOL, and the influencing factors of improved HRQOL. The Short-Form 36 (SF-36) and SLE disease activity index (SLEDAI) were used to evaluate HRQOL and disease activity. Chinese SLE patients had lower HRQOL than controls in all domains (P < 0.001), especially in role-physical (RP) and role-emotional (RE). Compared with SLE patients from outside China, the HRQOL of Chinese patients appeared to be higher in mental component summary (MCS) but lower in RP and RE. SLEDAI was negatively correlated with HRQOL, which was validated using the results of a follow-up study, where SLEDAI reduction was positively associated with HRQOL improvements (P < 0.05). Furthermore, personality, life nervous and experiences of adverse life events may influence HRQOL and HRQOL improvements. SLE significantly affected the HRQOL of Chinese patients, especially in RP and RE. Disease activity was negatively correlated with HRQOL. We also found for the first time some factors affecting HRQOL, which can be regarded as the basis for improving the HRQOL of SLE patients.

DUSP2 inhibits the progression of lupus nephritis in mice by regulating the STAT3 pathway.

One of the most severe side effects of systemic lupus erythematosus (SLE) is lupus nephritis (LN). To search for potential therapeutic targets in SLE is crucial for the progression of SLE. In this study, we selected C57BL/6J mice as controls and MRL/lpr mice as an LN model and obtained dual specificity phosphatase 2 (DUSP2)-overexpressed mice by injecting AAV-DUSP2 plasmid into the tail vein. Then, proteinuria, urea nitrogen, dsDNA and TNF-α, IL-6, and IL-1β levels were measured in each group of mice. In addition, renal histopathological damage was assessed by hematoxylin-eosin. Finally, STAT3 phosphorylation levels were detected by Western blot assay. The results showed that DUSP2 could reduce proteinuria, urea nitrogen, dsDNA and TNF-α, IL-6, and IL-1β levels and improve renal tissue injury in mice with LN. Mechanistically, DUSP2 inhibited STAT3 phosphorylation. These results demonstrated that DUSP2 played a role in ameliorating LN, which provided potential targets for LN research.

Triptoquinone A and B exercise a therapeutic effect in systemic lupus erythematosus by regulating NLRC3.

The autoimmune disorder systemic lupus erythematosus (SLE) is multifaceted, with limited therapeutic alternatives and detrimental side effects, particularly on bones and joints. This research endeavors to examine the curative potential and underlying mechanisms of in addressing SLE-associated bone and joint complications. Triptoquinone A and triptoquinone B, constituents of Tripterygium wilfordii polyglycoside tablets (TGTs), exhibit antioxidant and anti-inflammatory attributes; nonetheless, its function in SLE therapy remains elusive. This investigation delves into the role of oxidative stress in systemic lupus erythematosus (SLE) and probes the prospective remedial effects of triptoquinone A and triptoquinone B on inflammation and cartilage deterioration in SLE-affected joints. Employing bioinformatics analyses, differentially expressed genes (DEGs) and protein-protein interactions were discerned in SLE, rheumatoid arthritis (RA), and osteoarthritis (OA) datasets. Enrichment analyses unveiled shared genes implicated in immune system regulation and toll-like receptor signaling pathways, among others. Subsequent examination of triptoquinone A and triptoquinone B revealed their capacity to diminish NLRC3 expression in chondrocytes, resulting in decreased pro-inflammatory cytokine levels and cartilage degradation enzyme expression. Suppression of NLRC3 augmented the protective effects of triptoquinone A and B, implying that targeting NLRC3 may constitute a potential therapeutic strategy for inflammation and cartilage degeneration-associated conditions in SLE patients. Our discoveries indicate that triptoquinone A and triptoquinone B may impede SLE progression via the NLRC3 axis, offering potential benefits for SLE-affected bone and joint health.

Systemic Lupus Erythematosus and Cardiovascular Diseases: A Systematic Review.

Systemic lupus erythematosus (SLE) is an autoimmune condition characterized by multi-organ involvement. The clinical presentation often varies from mild to moderate to severe. The cardiovascular system may also be affected, often portending a poor prognosis for patients. Although the relationship between SLE and cardiovascular disorders has been extensively explored through case reports and literature reviews, few systematic reviewsexplicitly focusing on this association have been conducted. In light of this, this systematic review aims to analyze the extent of the association between SLE and cardiovascular diseases (CVDs), by exploring therisk of developing CVDs, including myocardial infarction (MI), atherosclerosis, myocarditis, pericarditis and arrhythmias, in SLE patients vs. non-SLE patients. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to perform the systematic review. A detailed search was done covering the period from March 2003 to March 2023 using three databases: PubMed, Google Scholar, and Cochrane. The PubMed search identified 597 articles, while Google Scholar and Cochrane searches yielded 559 and three articles, respectively. Of the 1159 articles retrieved, we chose eight for final consideration, after excluding papers that did not discuss the role of SLE in CVDs, papers published earlier than 2003, and papers with incomplete data. The eight studies chosen included two narrative reviews, two systematic reviews, and four observational studies. In this systematic review, SLE was proven to have a strong relationship with diverse CVDs, including rare ones scarcely discussed in the literature, such as vasculitis and aortic dissection. All eight of the final papers indicated a connection between SLE and CVDs, based on the systematic analysis of thesearticles, which revealed that most recent research supports a higher risk of peripheral arterial occlusive disease (PAOD), MI, pericarditis, myocarditis, and other cardiovascular disorders in individuals with SLE. These associations may have certain gray areas, as patient characteristics and comorbidities often affect the extent of illness and long-term prognosis. Larger-scale studies are required to probe this relationship further and research the etiopathogenesis involved in order to improve patient outcomes. The effects of SLE on the heart are, however, unequivocal.

Effect of Systemic Lupus Erythematosus and Immunosuppressive Agents on COVID-19 Vaccination Antibody Response.

The risk of COVID-19 infection is increased in patients with systemic lupus erythematosus (SLE) versus those without SLE. Some immunosuppressive medications increase COVID-19 infection and decrease the efficacy of vaccination. Consensus documents have suggested management strategies for handling immunosuppressive medications to increase vaccine efficacy, but the benefit of such strategies has not been proven. The current study was undertaken to determine the effect of immunosuppressive drugs on vaccine response in SLE. We collected information on COVID-19 infection, vaccination history, and COVID-19 antibodies in the Hopkins Lupus Cohort. A cohort of health care workers was used for comparison. Outcome measures included SARS-CoV-2 antibody IgG levels after vaccination over time in both cohorts and effect of immunosuppressive medications on postvaccination IgG levels in SLE patients. The analysis was based on 365 observations from 334 different patients in the SLE cohort, and 2,235 observations from 1,887 different health care workers. SLE patients taking immunosuppressive medications had lower vaccine IgG levels than SLE patients who were not; but both groups had lower levels than health care workers. Holding mycophenolate for 1 week after vaccination increased postvaccine IgG levels significantly without leading to clinical flares. In multiple variable models, mycophenolate mofetil, tacrolimus, and belimumab all significantly reduced antibody response to vaccination. SLE patients, regardless of background immunosuppressive therapy, had lower vaccine IgG levels than health care workers. Mycophenolate, tacrolimus, and belimumab significantly reduced IgG response to vaccination. Holding mycophenolate for 1 week improved vaccine efficacy, providing clinical benefit on vaccine response without leading to clinical flares.

Therapeutic Effect of Systemic Lupus Erythematosus Traditional Chinese Medicine Based on the Deoxyribonucleic Acid Methylation of Interferon-Induced Genes

Systemic lupus erythematosus are all involved autoimmune illnesses with similar clinical, genetic and pathogenic characteristics. However, it is still uncertain what characteristics these disorder’s deoxyribonucleic acid methylation patterns have in common. To determine the typical methylation patterns of autoimmune illnesses, we undertook to analyze the methylation data for numerous inflammatory disorders in a unified manner, which included samples from systemic lupus erythematosus. In clusters of differentiation 4+ T cells, we discovered 15 289 locations that were differently methylated in patients with various autoimmune diseases compared to controls in medical imaging. In addition to this, the artificial intelligence plays a greater role in predicting the model of therapeutic effect of systemic lupus erythematosus. We determined that genes involved in the type I interferon pathway were significantly enriched at the regions that displayed the most substantial differential methylation. Interferon-induced protein 44-like is another interferon-related gene, but it is not annotated by gene ontology. The results showed that clusters of differentiation 4+ T cells from systemic lupus erythematosus patients often had hypo methylation of interferon-related genes; moreover interferon-related gene deoxyribonucleic acid methylation patterns may be useful diagnostic indicators for systemic lupus erythematosus.

Mendelian randomization study on the causal effects of systemic lupus erythematosus on major depressive disorder

The vast majority of epidemiological studies suggested a link between systemic lupus erythematosus (SLE) and major depressive disorder (MDD). However, the causality for SLE on the risk of MDD remained unknown due to confounding factors or reverse causality. Herein, we investigated the causality between SLE and MDD in those of European ancestry by a Mendelian randomization (MR) approach. Summary genetic data of cases with SLE/MDD were derived from independent largest public genome-wide association study. Forty-six single nucleotide polymorphisms associated with SLE were used as instrumental variables. The main causal inference was carried out using the MRE-IVW method. Additional, reverse-direction MR and multivariable MR analyses were further performed. Result indicated that SLE was causally associated with a lower risk of MDD (using the MRE-IVW method, odds ratio [OR] = 0.983, 95% confidence interval [CI] = 0.974–0.991, p = 1.18 × 10−4). Complementary analysis found no heterogeneity or horizontal pleiotropy. Multivariate MR analysis yielded consistent results (OR = 0.981; 95% CI = 0.969–0.993; p = 2.75 × 10−3). Reverse-direction MR analysis suggested non-causal relationship of MDD on the risk of SLE (using the IVW method, OR = 0.846, 95% CI = 0.345–2.072; p = 0.714). Thus, this is the first study providing evidence of potential causal links between SLE and MDD and further related research is needed.

Causal effects of systemic lupus erythematosus on endometrial cancer: A univariable and multivariable Mendelian randomization study.

ObjectiveSystemic lupus erythematosus (SLE) has been observationally associated with endometrial cancer, but the causality remains unclear. Here, we investigated for the first time the causal links between SLE and endometrial cancer risk.MethodsUnivariable and multivariable Mendelian randomization (MR) analyses were conducted to disentangle the causality of SLE with endometrial cancer. Apart from the inverse-variance weighted (IVW) method as the primary MR estimate, three complementary MR techniques including weighted median, weighted mode, and MR-Egger regression in univariable MR were conducted to clarify the robustness of the causal estimate and mediation effects of the body mass index (BMI) and were investigated within multivariable MR-IVW and MR-Egger analyses.ResultsAll univariable MR analyses consistently suggested that SLE has a protective effect on the risk of overall endometrial cancer (IVW: OR = 0.956, 95% CI = 0.932-0.981, P = 0.001) and endometrioid endometrial cancer (IVW: OR = 0.965, 95% CI = 0.933-0.999, P = 0.043). More compelling, after adjustment for BMI within the multivariable MR setting, the association between SLE and decreased risk of overall endometrial cancer was significantly stronger (IVW: OR = 0.952, 95% CI = 0.931-0.973, P = 9.58E-06).ConclusionsOur findings provide evidence of a significant causal relationship between SLE and decreased endometrial cancer risk. Further understanding of the underlying mechanisms linking SLE with endometrial cancer is therefore needed.

Is Vitamin D Deficiency the Cause or the Effect of Systemic Lupus Erythematosus: Evidence from Bidirectional Mendelian Randomization Analysis.

Background Vitamin D deficiency is common in patients with systemic lupus erythematosus (SLE). Observational studies have reported that it is associated with SLE. In this bidirectional Mendelian randomization (MR) study, we explored the genetic association between serum vitamin D (VD) levels and SLE using two models. Methods Genetic variants associated with vitamin D (n = 304,181), 25-hydroxyvitamin D levels (n = 401,460), and SLE (n = 213,683) at genome-wide significance (P < 5∗10−8) derived from large-scale publicly available GWAS data were used as instrumental variables. Bidirectional two-sample MR analyses were performed using the inverse variance weighted method (IVW, random, or fixed effect model). Sensitivity analyses including maximum likelihood, MR-Egger method, penalized weighted median method, MR-PRESSO, MR-RAPS, and MR-radial method were conducted. Results The findings showed that genetically predicted SLE using the IVW method had a negative effect on the vitamin D and 25-hydroxyvitamin D levels in the two models. The results of sensitivity analyses of different analytical approaches were consistent. Conclusions These findings indicated that genetically determined SLE had a negative effect on the vitamin D and 25-hydroxyvitamin D levels. Future studies, including random controlled clinical trials, should evaluate the association and mechanisms between serum VD levels and SLE.

Effects of Systemic Lupus Erythematosus on Clinical Outcomes and In-Patient Mortality Among Hospitalized Patients With Diverticulitis

PurposeThough there are studies on other autoimmune diseases, the literature is deficient on the associations between systemic lupus erythematosus (SLE) and diverticulitis. This study aims to evaluate the effects of SLE on clinical outcomes and in-patient mortality in patients with diverticulitis.MethodsThe National Inpatient Sample (NIS) database was used to identify adult patients with diverticulitis-related hospitalizations from 2012 to 2014 using the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes. Primary outcomes were mortality, hospital charges, and length of stay (LOS). Secondary outcomes were effects on the complications associated with diverticulitis. Chi-squared tests and independent t-tests were used. Multivariate analysis was performed to assess the primary outcomes after adjusting for confounding variables.ResultsThere were 2,553,320 diverticulitis-related hospitalizations from 2012 to 2014, of which 13,600 patients had SLE. The average LOS was 5.2 days, mortality rate was 0.8%, and total hospital charges per patient were $43,970. SLE was associated with a statistically significant longer LOS and higher hospital costs. SLE was statistically significant for having higher perforation rates but lower rates for morality, abscesses, and fistula formation. Differences in complications such as sepsis, gastrointestinal bleeding, and surgical intervention requirement were non-significant.ConclusionSince SLE causes a high inflammatory state, one would expect higher rates of complications and possibly higher mortality rates in those with concomitant diverticulitis. However, although there was a higher LOS and hospital cost, the mortality rate was lower and only a complication of perforation was found to be higher in SLE patients.

The effect of systemic lupus erythematosus on sexual function in women: an updated meta-analysis based on cross-sectional studies

BackgroundSystemic lupus erythematosus (SLE), a chronic systemic autoimmune disease, often affects different organs and tissues. It can be effectively managed using drugs; however, attention should be paid to the patient’s quality of life. This study aimed to evaluate the effect of SLE on female sexual function based on current literature.MethodsThe PubMed, Embase, and Cochrane Library databases were searched for eligible studies published up to November 9, 2021. This review included all English studies that compared the sexual function between women with SLE and healthy women. A meta-analysis was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.ResultsA total of 367 records were retrieved from 3 electronic databases. Five studies that involved 710 women with SLE and 2059 healthy women were finally included in this meta-analysis. The result indicated a significant decrease (mean difference = − 1.74, 95% confidence interval − 3.14 to − 0.34, p = 0.02) in the total scores of the Female Sexual Function Index in women with SLE, implying that healthy women had better sexual function than those with SLE.ConclusionThe results of our study indicated that SLE could negatively affect the quality of sexual life in terms of desire, arousal, and pain. Thus, close attention should be paid to the sexual function of women with SLE.Trial registration: This study was registered in the International Prospective Register of Systematic Reviews (registration number: CRD42021290439).

Mesenchymal Stem Cells-derived Exosomes Ameliorate Lupus by Inducing M2 Macrophage Polarization and Regulatory T Cell Expansion in MRL/lpr Mice

ABSTRACT Previous studies have implicated that the transplantation of human umbilical cord mesenchymal stem cells (hUC-MSCs) effectively alleviates systemic lupus erythematosus (SLE) primarily due to immunomodulatory effects. However, little is known about the role of hUC-MSC-derived exosomes in SLE. This study is carried out to investigate the modifying effects of hUC-MSC-exosomes on the differentiation and function of immune cells in SLE. hUC-MSC-derived exosomes were extracted from the cultural supernatant of hUC-MSCs by ultrahigh speed centrifugation. Quantitative real-time polymerase chain reaction, western blot, enzyme-linked immunosorbent assay, and flow cytometry were performed to estimate the effect of hUC-MSC-derived exosomes on macrophage and regulatory T cell (Treg) polarization. In vivo, hUC-MSC-exosomes were injected intravenously into 28-week-old MRL/lpr mice. We had found that exosomes derived from hUC-MSC restrained the proliferation and inflammation of macrophages in vitro. Besides, MSC-exosomes inhibited CD68+M1 and HLA-DR+M1 but promoted CD206+M2 and CD163+M2 in vitro. Moreover, MRL/lpr mice administrated by intravenous injection of MSC-exosomes had less infiltration of CD14+CD11c+M1 cells but more CD14+CD163+M2 cells as well as Tregs in spleens compared with those in MRL/lpr mice treated by PBS. Additionally, MSC-exosomes could alleviate nephritis, liver and lung injuries of MRL/lpr mice. The survival of lupus mice could be improved after MSC-exosome treatment. This study has suggested that MSC-derived exosomes exert anti-inflammatory and immunomodulatory effects in SLE. MSC-exosomes ameliorate nephritis and other key organ injuries by inducing M2 macrophages and Tregs polarization. As natural nanocarriers, MSC-exosomes may serve as a promising cell-free therapeutic strategy for SLE. Abbreviations: SLE: Systemic lupus erythematosus; hUC-MSCs: Human umbilical cord mesenchymal stem cells; MSCs: Mesenchymal stem cells; qRT-PCR: Quantitative real-time polymerase chain reaction; ELISA: Enzyme-linked immunosorbent assay; Tregs: Regulatory cells; TNF-α: Tumor necrosis factor alfa; IL: Interleukin; COVID-19: Coronavirus disease 2019; pTHP-1: PMA-induced THP-1 macrophages; TEM: Transmission electron microscopy; LPS: Lipopolysaccharide; EVs: Extracellular vesicles; TRAF1: Tumor necrosis factor receptor-associated factor 1; IRAK1: Interferon-α-interleukin-1 receptor-associated kinase 1; NF-κB: Nuclear factor-κB; BLyS: B lymphocyte stimulator; APRIL: A proliferation-inducing ligand

Investigation of the causal relationships between human IgG N-glycosylation and 12 common diseases associated with changes in the IgG N-glycome.

Changes in the N-glycosylation of immunoglobulin G (IgG) are often observed in pathological states, such as autoimmune, inflammatory, neurodegenerative, cardiovascular diseases and some types of cancer. However, in most cases, it is not clear if the disease onset causes these changes, or if the changes in IgG N-glycosylation are among the risk factors for the diseases. The aim of this study was to investigate the casual relationships between IgG N-glycosylation traits and 12 diseases, in which the alterations of IgG N-glycome were previously reported, using two sample Mendelian randomization (MR) approach. We have performed two sample MR using publicly available summary statistics of genome-wide association studies of IgG N-glycosylation and disease risks. Our results indicate positive causal effect of systemic lupus erythematosus (SLE) on the abundance of N-glycans with bisecting N-acetylglucosamine in the total IgG N-glycome. Therefore, we suggest regarding this IgG glycosylation trait as a biomarker of SLE. We also emphasize the need for more powerful GWAS studies of IgG N-glycosylation to further elucidate the causal effect of IgG N-glycome on the diseases.

Mindfulness-Based Stress Reduction for Systemic Lupus Erythematosus: A Mixed-Methods Pilot Randomized Controlled Trial of an Adapted Protocol.

Background: The psychological effects of systemic lupus erythematosus (SLE) are tremendous. This pilot mixed-methods randomized controlled trial aimed to evaluate the effects of a mindfulness-based stress reduction (MBSR) adapted protocol on psychological distress among SLE patients. Methods: 26 SLE patients were randomly assigned to MBSR group therapy (n = 15) or a waitlist (WL) group (n = 11). An adapted MBSR protocol for SLE was employed. Three measurements were conducted: pre-intervention, post-intervention and 6-months follow up. A sub-sample (n = 12) also underwent qualitative interviews to assess their subjective experience of MBSR. Results: Compared to the WL, the MBSR group showed greater improvements in quality of life, psychological inflexibility in pain and SLE-related shame. Analysis among MBSR participants showed additional improvements in SLE symptoms and illness perception. Improvements in psychological inflexibility in pain and SLE-related shame remained stable over six months, and depression levels declined steadily from pre-treatment to follow-up. Qualitative analysis showed improvements in mindfulness components (e.g., less impulsivity, higher acceptance), as well as reduced stress following MBSR. Conclusions: These results reveal the significant therapeutic potential of MBSR for SLE patients. With its emphasis on acceptance of negative physical and emotional states, mindfulness practice is a promising treatment option for SLE, which needs to be further applied and studied.