Cause Of Systemic Lupus Erythematosus Research Articles

Seroprevalence of Toxoplasma gondii immunoglobulins and its association with systemic lupus erythematosus: A systematic review and meta-analysis.

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.

Biochemical study of ZNF76 rs10947540 and SCUBE3 rs1888822 single nucleotide polymorphisms in the Egyptian patients with systemic lupus Erythematosus

ABSTRACT Systemic lupus erythematosus (SLE) is a common autoimmune disease marked by the formation of apoptotic debris and the presence of autoantibodies that target nuclear components. At this moment, the actual cause of SLE is uncertain. Genetic variables have been well proven to have a significant role in the propensity of SLE. This study aimed to investigate the effect of (ZNF76) rs (10947540) and (SCUBE) rs (1888822) gene polymorphism in patients with systemic lupus erythematosus. A case control study has been carried out at Medical Biochemistry & Molecular biology and Rheumatology unit of Internal Medicine Departments, Faculty of Medicine, Menoufia University, Egypt, for 1-year duration between 1 June 2022 and 1 June 2023. Sixty patients were females (75%) and twenty patients were males (25%). Their ages ranged from 19 to 53 years. Their disease durations ranged from 7 months to 20 years. The findings indicated that the TC genotype of the ZNF76 rs10947540 gene increases the risk of SLE by 2.274-fold, while the dominant TC + CC increases the risk by 2.472-fold, and the C allele increases the risk by 2.115-fold. Additionally, the results showed that the TT genotype of the SCUBE3 rs1888822 gene increases the risk of SLE by 3.702-fold, the dominant GT + TT increases the risk by 2.304-fold, and the T allele increases the risk by 2.089-fold, while the GT genotype increases the risk by 1.918-fold. The study revealed significant associations between the genotypes of these polymorphisms and certain clinical parameters in SLE patients. These findings highlight the potential genetic contributions to SLE susceptibility and its clinical manifestations, providing valuable insights for future research and potential personalized approaches to the management of this complex autoimmune disease.

Study of Serum Complement 3 Split Product iC3b /C3 Ratio in a Cohort of Systemic Lupus Erythematosus Patients

Abstract Background Systemic lupus erythematosus (SLE) is a chronic autoimmune systemic disease that causes widespread multi organ inflammation. The exact cause of SLE remains unclear; however, genetic, hormonal, and environmental factors contribute to the development of the disease. Aim of the Work The aim of this study is to measure the ratio of complement split product iC3b to C3 and its relation to disease activity and lupus nephritis in a cohort of SLE patients. Patients and Methods This study is a Cross sectional case control study conducted in internal medicine and Rheumatology unit, Ain Shams university hospital and Rheumatology unit, Maadi military hospital. Our study included. Results The present study shows that female were (76%) in active group of SLE patients and (60%) in inactive group while male were (24%) and (40%) respectively. with no significant difference. The mean of Disease Duration was (5.66 ± 1.97) with a range from 3 and 10 years in active group of SLE patients and (5.08 ± 1.54) with a range from 3 and 9 years in inactive group. with no significant difference. Regarding clinical manifestations of SLE the present study shows that active group of SLE patients had statistically highly significant increase in incidence of lupus nephritis, arthritis, serositis, oral ulcers, malar rash (p < 0.001) with significant increase in incidence of alopecia and neurological manifestations (p < 0.05). The current study shows that active group of SLE patients had statistically significantly higher mean ESR, anti-DNA titre, 24hr urinary proteins, serum creatinine, serum urea, and GFR levels (p = 0.000) than inactive group, Also active group had significant leucopenia, anemia (p = 0.000, 0.005 respectively) and C3 was significantly more consumed than inactive group (p < 0.05) Conclusion The ratio of complement split product iC3b to C3 concentrations correlates with the extent of SLE disease activity more than C3 alone. Furthermore, the iC3b:C3 ratio may discriminate between patients with lupus nephritis and patients without lupus nephritis. Detection of SLE disease activity and lupus nephritis by iC3b/C3 ratio help to make a proper decision in management to induce remission.

Mechanism and target treatment of primary immunodeficiency diseases with systemic lupus erythematosus‐like phenotype

AbstractPrimary immunodeficiency diseases (PIDs) present a heterogeneous group of diseases with aberrant immune response caused by monogenic mutations. Due to the immune dysfunction and dysregulation, PIDs have a wide clinical spectrum such as infections, autoimmunity, autoinflammation, allergy, and malignancies. Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized with multiple autoantibodies and multiple organ damage, which could be the predominant phenotype in patients with PIDs. In recent years, the increasing identification of monogenic causes of SLE and PIDs discloses the partially shared genetic background and common pathogenic process. The study of PIDs with SLE‐like phenotype paves the way for the exploration of lupus pathogenesis and new perspectives in targeted therapies concurrently.

Detection of genetic mutations underlying early-onset systemic lupus erythematosus.

We aimed to investigate the presence of monogenic causes of systemic lupus erythematosus (SLE) in our early-onset SLE patients. Fifteen pediatric SLE cases who had early disease onset (≤6 years) were enrolled in this study. All patients fulfilled the Systemic Lupus International Collaborating Clinics (SLICC) criteria. Genomic DNA was used for whole exome sequencing (WES). Pathogenic variants were confirmed by Sanger sequencing. The median age at diagnosis of 15 early-onset SLE patients included in the study was 4 (2-6) years (F/M = 12/3). Significant gene mutations were detected in five of these patients (33.3%). Patients 1 and 2 with homozygous DNASE1L3 mutations [c.320+4_320+7del and G188A (c.563G>C) variants] had skin involvement and oral ulcers. One of them (patient 1) had arthritis and nephritis, and another (patient 2) had nonscarring alopecia and thrombocytopenia. They are currently clinically inactive but have positive serological findings. Patient 3 with homozygous pathogenic ACP5 mutation [G109R (c.325G>A) variant] had arthritis, nephritis, short stature, and skeletal dysplasia. Patient 4 with a heterozygote novel IFIH1 mutation [L809F (c.2425C>T) variant] had skin findings and leukopenia. Patient 5 with novel C1S variant [homozygous C147W (c.441C>G) variant] had marked skin findings, oral ulcers, nonscarring alopecia, pancytopenia, and low total hemolytic complement CH50 level. All patients have responded to the treatments and have low Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) scores, on therapy. Genetic causes should be investigated in early-onset SLE, for better management and genetic counseling. On the other hand, multicenter studies may help to further define genotype-phenotype associations.

A Scoping Review of the Positive and Negative Bacteria Associated With the Gut Microbiomes of Systemic Lupus Erythematosus Patients.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that affects multiple systems of the body. Recent research on the gut microbiota dysbiosis associated with SLE patients has gained traction and warranted further exploration. It has not been determined whether the change in the gut microbiota is a cause of SLE or a symptom of SLE. However, based on the physiological and pathophysiological role of the bacteria in the gut microbiome, as levels of the bacteria rise or fall, symptomatology in SLE patients could be affected. This review analyzes the recent studies that examined the changes in the gut microbiota of SLE patients and highlights the correlations between gut dysbiosis and the clinical manifestations of SLE. A systematic search strategy was developed by combining the terms "SLE," "systemic lupus erythematosus," and "gut microbiome." Biomedical Reference Collection, CINAHL, Medline ProQuest, and PubMed Central databases were searched by combining the appropriate keywords with "AND." Only full-text, English-language articles were searched. The articles were restricted from 2013 to 2023. Only peer-reviewed controlled studies with both human and animal trials were included in this scoping review. Review articles, non-English articles, editorials, case studies, and duplicate articles from the four databases were excluded. Various species of bacteria were found to be positively or negatively associated with SLE gut microbiomes. Among the bacterial species increased were Clostridium, Lactobacilli, Streptococcus, Enterobacter, and Klebsiella. The bacterial species that decreased were Bifidobacteria, Prevotella, and the Firmicutes/Bacteroidetes ratio. Literature shows that Clostridium is one of several bacteria found in abundance, from pre-disease to the diseased state of SLE. Lachnospiraceae and Ruminococcaceae are both part of the family of butyrate-producing anaerobes that are known for their role in strengthening the skin barrier function and, therefore, may explain the cutaneous manifestations of SLE patients. Studies have also shown that the Firmicutes/Bacteroidetes ratio is significantly depressed, which may lead to appetite changes and weight loss seen in SLE patients. Based on the established role of these bacteria within the gut microbiome, the disruption in the gut ecosystem could explain the symptomatology common in SLE patients. By addressing these changes, our scoping review encourages further research to establish a true causal relationship between the bacterial changes in SLE patients as well as furthering the scope of microbiota changes in other systems and autoimmune diseases.

علاقة الانترلوكينات 37 و40 مع داء الذئبة الحمامية الجهازية في نساء مرضى عراقيات

The primary cause of systemic lupus erythematosus (SLE) is autoantibodies to self-antigens. Interleukin 37 (IL-37) and Interleukin 40 (IL-40) are important cytokines which may play a role in regulating inflammation and involved in pathogenesis of autoimmune diseases like SLE. This study was aimed the interleukin levels (IL-37 and IL-40) during systemic lupus erythematous (SLE) development in Iraqi female patients. The present study was conducted on 100 female SLE patients and 100 healthy female controls, with mean ages of patients and controls )32.85 ± 0.99 and 32.05 ± 0.91)years, respectively. Erythrocytes Sedimentation Rate (ESR) and C-reactive protein (CRP) were investigated in this study. Enzyme-linked immune sorbent assay(ELISA) kits examined levels of interleukins in the serum of patients and healthy controls. The results found that IL-37 levels in SLE patients were lower than in controls(23.39 ±0.92ng/mL vs48.02 ±0.46ng/mL), respectively, with a statistically significant. While serum IL-40 levels appeared to have a higher significant in patients compared with the healthy control (9.98 ±0.32ng/mL vs4.16 ±0.05ng/mL) respectively. Also, ESR and CRP was high significant in patients compared with healthy controls. In conclusion, these findings suggest that IL-40 and IL-37 could be used as a biomarker for SLE.

Phenotypic Variability in PRKCD: a Review of the Literature.

Protein kinase C δ (PKCδ) deficiency is a rare genetic disorder identified as a monogenic cause of systemic lupus erythematosus in 2013. Since the first cases were described, the phenotype has expanded to include children presenting with autoimmune lymphoproliferative syndrome-related syndromes and infection susceptibility similar to chronic granulomatous disease or combined immunodeficiency. We review the current published data regarding the pathophysiology, clinical presentation, investigation and management of PKCδ deficiency. Literature review was performed using MEDLINE. Twenty cases have been described in the literature with significant heterogeneity. The variation in clinical presentation delineates the broad and critical role of PKCδ in immune tolerance and effector functions against pathogens.

An early-onset SLE patient with a novel paternal inherited BACH2 mutation.

BACH2-related immunodeficiency and autoimmunity (BRIDA) is an inborn error of immunity, newly reported in 2017, presenting with symptoms of immunoglobulin deficiency and ongoing colitis. Studies using a mouse model have demonstrated that BACH2 deficiency predisposes individuals to systemic lupus erythematosus (SLE); however, no BACH2 deficiency has been reported in SLE patients. Here we describe a patient with BRIDA presenting with early-onset SLE, juvenile dermatomyositis, and IgA deficiency. Whole exome sequencing analysis of the patient and her parents revealed a novel heterozygous point mutation in BACH2, c.G1727T, resulting in substitution of a highly conserved arginine with leucine (R576L), which is predicted to be deleterious, in the patient and her father. Reduced BACH2 expression and deficient transcriptional repression of the BACH2 target, BLIMP1, were detected in PBMCs or lymphoblastoid cell lines of our patient. Notably, extreme reduction of memory B cells was detected in the patient's father, although he had no obvious symptoms. SLE symptoms and recurrent fever were relieved by treatment with prednisone combined with tofacitinib. Thus, we present the second report of BRIDA and demonstrate that BACH2 may be a monogenic cause of SLE.

MTOR Activation Underlies Enhanced B Cell Proliferation and Autoimmunity in PrkcdG510S/G510S Mice.

Autosomal recessive PRKCD deficiency has previously been associated with the development of systemic lupus erythematosus in human patients, but the mechanisms underlying autoimmunity remain poorly understood. We introduced the Prkcd G510S mutation that we previously associated to a Mendelian cause of systemic lupus erythematosus in the mouse genome, using CRISPR-Cas9 gene editing. PrkcdG510S/G510S mice recapitulated the human phenotype and had reduced lifespan. We demonstrate that this phenotype is linked to a B cell-autonomous role of Prkcd. A detailed analysis of B cell activation in PrkcdG510S/G510S mice shows an upregulation of the PI3K/mTOR pathway after the engagement of the BCR in these cells, leading to lymphoproliferation. Treatment of mice with rapamycin, an mTORC1 inhibitor, significantly improves autoimmune symptoms, demonstrating invivo the deleterious effect of mTOR pathway activation in PrkcdG510S/G510S mice. Additional defects in PrkcdG510S/G510S mice include a decrease in peripheral mature NK cells that might contribute to the known susceptibility to viral infections of patients with PRKCD mutations.

A cross-sectional study to know the prevalence of thyroid dysfunction in systemic lupus erythematosus

Background: Systemic lupus erythematosus (SLE) is a persistent autoimmune disease, the pathogenesis of which remains elusive. Autoimmune factors may be a cause of SLE and thyroid dysfunction. Many studies have revealed that the prevalence of thyroid disorder is higher in SLE patients than in the general population. SLE is a multisystem and hypothyroidism is an organ specific autoimmune disorder and can occur successively or simultaneously. Aims and Objectives: The aim of the study was to study the prevalence of thyroid disorder in patients with SLE. Materials and Methods: Patients admitted with definite clinical features of SLE and Antinuclear Antibodies positive, in medicine ward and healthy blood donors are taken as control. Sample was tested by fully automated analyzer. Results: Subclinical hypothyroidism was found in 24% of study group and 8% of control group which is statistically significant. Central and secondary hyperthyroidism was found in 10% of study group and 12% of control group but it was statistically insignificant. Several studies have documented an association between SLE and other autoimmune diseases such as Sjogren’s syndrome, autoimmune hemolytic anemia, and antiphospholipid syndrome. Subclinical hypothyroidism was higher than another thyroid dysfunction such as primary, central, and subclinical hypothyroidism was found to be higher in frequency, probably depicting the slow destructive process which is pathognomic of autoimmune thyroiditis. Conclusion: Subclinical hypothyroidism was more prevalent in SLE than that of overt hypothyroidism as compared with general population.

A study of CD11b rs1143679 gene polymorphism in Egyptian systemic lupus erythematosus patients

Background/aim The exact cause of systemic lupus erythematosus (SLE), an autoimmune disorder, is still vague. However, it is believed that its pathogenesis could be a result of the interplay between genetics and the environment. One such genetic factor is a single-nucleotide polymorphism in the CD11b gene (rs1143679) that has been shown to potentially increase a person’s susceptibility to SLE. This study aims to investigate the possible link of CD11b rs1143679 gene polymorphism to the risk of developing SLE, as well as the different manifestations and the disease severity in the studied group of Egyptian SLE patients. Patients and methods The present study enrolled 50 patients with SLE from Benha University Hospitals, Egypt. In addition to 30 apparently healthy individuals served as control, the CD11b gene (rs1143679) genetic variant was investigated by real-time PCR. The individuals with SLE were based on the Systemic Lupus International Collaborating Clinics criteria. Results A significant association of GA genotype (odds ratio=1.908, 95% confidence interval=1.021–3.568, P<0.05) with the risk to develop SLE and A allele was also linked to an elevated risk for SLE in comparison to the G allele (odds ratio=1.881, 95% confidence interval=1.038–3.408, P<0.05). Conclusion The CD11b rs1143679 gene polymorphism might be a potential risk factor for SLE in Egyptians.

Staphylococcus aureus skin colonization promotes SLE-like autoimmune inflammation via neutrophil activation and the IL-23/IL-17 axis.

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by inflammation of various organs such as skin, kidneys, bones, and brain and the presence of autoantibodies. Although the cause of SLE is not completely understood, environmental factors, genetic susceptibility, hormone factors, and environmental factors are thought to play essential roles in the pathogenesis of SLE. Among environmental factors, the microbiota are linked to the development of different autoimmune diseases. The microbiota in the nasal cavity and gut are involved in SLE development, but the influence of skin microbiota is still unclear. Here, we demonstrated that epithelial cell-specific IκBζ-deficient (NfkbizΔK5) mice showed spontaneous skin inflammation with increased abundance of Staphylococcus aureus on the skin. When S. aureus was epicutaneously applied on NfkbizΔK5 mice, NfkbizΔK5 mice developed SLE-associated autoantibodies, anti-dsDNA antibodies, anti-Sm antibodies, and glomerulonephritis with IgG deposition. Epicutaneous S. aureus application significantly increased staphylococcal colonization on the skin of NfkbizΔK5 mice with reduced expression of several antimicrobial peptides in the skin. This staphylococcal skin colonization promoted caspase-mediated keratinocyte apoptosis and neutrophil activation, inducing the interleukin-23 (IL-23)/IL-17 immune response by activating dendritic cells and T cells. Furthermore, the subcutaneous administration of anti-IL-23p19 and anti-IL-17A antibodies alleviated the systemic autoimmune response. Together, these findings underscore epithelial-immune cross-talk disturbances caused by skin dysbiosis as an essential mediator inducing autoimmune diseases.

Identification of a novel mutation in complement receptor 2 in Chinese familial systemic lupus erythematosus.

This study aims to analyze the relationship between complement receptor 2 (CR2) gene mutation and the clinical phenotype in Chinese familial systemic lupus erythematosus (SLE). A total of one Chinese familial SLE patients (median age: 30.25 years; range, 22 to 49 years) were included between January 2017 and December 2018. The clinical features and diagnoses of familial SLE patients were analyzed using whole-exome sequencing (WES) of genomic deoxyribonucleic acid (DNA) samples. Sanger sequencing was used to verify candidate mutations detected in the examined family. The mother and her three daughters were diagnosed with SLE. The clinical characteristics showed that the patient and her mother were diagnosed with lupus nephritis. The eldest daughter had decreased renal function and lower serum albumin levels. Immunological index analysis showed that all four patients were positive for anti-SSA and antinuclear antibody (ANA), but that only the second daughter was positive for anti-double-stranded DNA (dsDNA). Complement 3 (C3) was significantly decreased in all patients, while evaluation of the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) showed that the second and third daughters had mild active SLE. The mother and eldest daughter were treated with prednisolone combined with cyclophosphamide, while the other two daughters were treated with prednisolone alone. The WES and Sanger sequencing analyses revealed an unreported missense T>C mutation c.2804 in the 15th exon of the CR gene in all four patients. We identified a novel c.2804 (exon 15) T>C mutation in the CR gene of Chinese familial SLE. This mutation was previously reported, suggesting that the CR gene c.2804 (exon 15) T>C mutation is the probable cause of SLE in this family.

Systemic lupus erythematosus with trisomy X: a case report and review of the literature

BackgroundThe cause of systemic lupus erythematosus is not completely clear so far, but the prevalence of systemic lupus erythematosus is significantly increased in people with additional X chromosomes.Case presentationWe report a 17-year-old Chinese female patient with systemic lupus erythematosus complicated with trisomy X, accompanied by lupus nephritis, pancytopenia, hemolytic anemia, and multiserous effusion. The patient recovered well after treatment and returned regularly. We review the previously reported cases to summarize the clinical characteristics of these patients.ConclusionThe additional X chromosome is related to the development of systemic lupus erythematosus. Whether it is a subtype of systemic lupus erythematosus remains to be further confirmed.

The Role of Belimumab in Systemic Lupus Erythematosis: A Systematic Review.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease involving multiple systems with a range of clinical presentations caused by the production of antibodies, activation of complements, and deposition of immune complexes. The exact cause of SLE is still unknown. The effectiveness of traditional treatment methods for SLE is very little. Nowadays, resistance to conventional therapy, steroids, and immunosuppressants is common among SLE patients. Patients with refractory disease and nephritis generally have severe drug-induced toxicity which contributes to organ dysfunction, despite available therapies. Different biologic agents and therapeutic antibodies have become an alternative and have been under experiment in clinical trials, enrolling patients whose disease is inadequately controlled by conventional treatment. Belimumab is the only targeted therapy approved for SLE treatment. This systematic review discusses one such biological agent for treating systemic lupus erythematosus, namely, belimumab.The systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Studies included randomized clinical trials (RCTs) from 2005 to 2021 on adult SLE. patients treated with monoclonal antibodies to assess the efficacy and safety. Methodological quality was assessed using PubMed, PMC, the Cochrane Risk of Bias tool, and the QUality In Prognosis Studies Tool (QUIPS) for RCTs. Two independent reviewers performed an electronic search on MEDLINE, Cochrane Library, SCIELO, Scopus, and ResearchGate.Based on a systematic review of articles we found that belimumab appears to be efficacious and generally well-tolerated in the treatment of SLE as compared to other drugs. The long-term use of belimumab combined with standard therapy showed a low incidence of organ damage. A lower incidence of organ damage was seen after initiating treatment in patients with a high risk for organ dysfunction. Patients who test for antinuclear antibody or anti-dsDNA-positive SLE, with moderate symptoms in the skin and musculoskeletal systems despite immunosuppressants, are treated with belimumab as an adjunct therapy. Patients with severe lupus nephritis or active CNS lupus cannot be treated with belimumab. Belimumab is effective in most races, as a clinical trial done in North-East Asia showed improvement in SLE symptoms and decreased dependence on prednisone. Belimumab also decreased disease activity and severe flares. Belimumab had greater efficacy in children.

Lactobacillus: Friend or Foe for Systemic Lupus Erythematosus?

The cause of Systemic Lupus Erythematosus (SLE) remains largely unknown, despite the fact that it is well understood that a complex interaction between genes and environment is required for disease development. Microbiota serve as activators and are essential to immune homeostasis. Lactobacillus is thought to be an environmental agent affecting the development of SLE. However, beneficial therapeutic and anti-inflammatory effects of Lactobacillus on SLE were also explored. The discovery of Lactobacillus involvement in SLE will shed light on how SLE develops, as well as finding microbiota-targeted biomarkers and novel therapies. In this review, we attempt to describe the two sides of Lactobacillus in the occurrence, development, treatment and prognosis of SLE. We also discuss the effect of different strains Lactobacillus on immune cells, murine lupus, and patients. Finally, we try to illustrate the potential immunological mechanisms of Lactobacillus on SLE and provide evidence for further microbiota-targeted therapies.

Blocking GSDME-mediated pyroptosis in renal tubular epithelial cells alleviates disease activity in lupus mice

An increase in apoptosis and/or defects in the clearance of apoptotic cells resulting in massive secondary necrosis have been recognized as the main causes of systemic lupus erythematosus (SLE). Recent findings have revealed that gasdermin E (GSDME)-mediated pyroptosis is a mechanism associated with secondary necrosis. We aimed to investigate the effects of GSDME-mediated pyroptosis on disease activity in lupus mice. In vivo, high levels of GSDME expression were observed in the renal tubules of pristane-induced lupus (PIL) mice and SLE patients. In lupus mice, GSDME knockout or SP600125 administration effectively ameliorated lupus-like features by inhibiting GSDME-mediated renal tubular epithelial cell pyroptosis. In vitro, treatment with tumour necrosis factor-α (TNF-α) plus cycloheximide (CHX) or SLE sera induced HK2 cells to undergo pyroptosis in a caspase-3- and GSDME-dependent manner. Likewise, SP600125 significantly reduced GSDME expression and decreased pyroptosis in HK2 cells. GSDME-mediated pyroptosis may be associated with SLE pathogenesis, and targeting GSDME may be a potential strategy for treating SLE.

The Microbiota in Systemic Lupus Erythematosus: An Update on the Potential Function of Probiotics.

Systemic lupus erythematosus (SLE) is a kind of chronic diffuse connective tissue illness characterized by multisystem and multiorgan involvement, repeated recurrence and remission, and the presence of a large pool of autoantibodies in the body. Although the exact cause of SLE is not thoroughly revealed, accumulating evidence has manifested that intake of probiotics alters the composition of the gut microbiome, regulating the immunomodulatory and inflammatory response, which may be linked to the disease pathogenesis. Particularly, documented experiments demonstrated that SLE patients have remarkable changes in gut microbiota compared to healthy controls, indicating that the alteration of microbiota may be implicated in different phases of SLE. In this review, the alteration of microbiota in the development of SLE is summarized, and the mechanism of intestinal microbiota on the progression of immune and inflammatory responses in SLE is also discussed. Due to limited reports on the effects of probiotics supplementation in SLE patients, we emphasize advancements made in the last few years on the function and mechanisms of probiotics in the development of SLE animal models. Besides, we follow through literature to survey whether probiotics supplements can be an adjuvant therapy for comprehensive treatment of SLE. Research has indicated that intake of probiotics alters the composition of the gut microbiome, contributing to prevent the progression of SLE. Adjustment of the gut microbiome through probiotics supplementation seems to alleviate SLE symptoms and their cardiovascular and renal complications in animal models, marking this treatment as a potentially novel approach.

Assessment of Systemic Lupus Erythematosus in Term of Serum Anti-nucleosome and Interleukin 12 Markers in Relation to Epstein–Barr virus and Cytomegalovirus

Background: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease, more dominant in female, associated with high risk of life threating complication and increase morbidity and mortality. the exact cause of SLE is not yet known with many suggestions about a possible role of viral infection in the development of the disease. Epstein –Barr virus is the most commonly studied virus in an attempt to prove its presumed association with development of SLE.The objectives of this study are the measurement of the effect of CMV and EBV seropositivity in the auto immune status and severity of disease SLE measured by estimating the level of immunological markers anti-nucleosome and IL-12 with viral marker. Materials and Method: Forty newly diagnosed female with SLE were randomly selected from patient attended rheumatology clinic at medical city in Baghdad during the period between December 2018 to May In addition, with 40 apparently healthy females, as, a control groups. Both group were investigated for IL12, anti-nucleosome, EA, VCA, EBNA and CMV by ELISA and the results were statistically evaluated. Results: The studied viral markers in the current study which included EBV markers EA, VCA, EBNA, have shown significantly higher level compared to the control group. Similarly, anti-nucleosome and IL12 have shown significantly higher level compared to the control group. Conclusions: The possible defect in controlling viral infection and increased number of latent infected cell in SLE may enhance production of auto-antibodies