Pathophysiology Of Systemic Lupus Erythematosus Research Articles

Potential role of bacterial extracellular vesicles in the pathophysiology of systemic lupus erythematosus

Systemic Lupus Erythematosus (SLE) is a rare autoimmune disorder influenced by various factors, including infections. Following bacterial or viral infections, there is an increase in IFN-I production, primarily by plasmacytoid dendritic cells (pDCs). Overproduction of IFN-I has been shown to drive the progression of SLE. Recent findings indicate that the gene expression signature of IFN-I in lupus nephritis patients does not co-occur with pDCs as expected; instead, it is localized in glomerular regions with anastomosing capillaries, suggesting a potential source from the blood. T cells, natural killer cells, and myeloid lineage cells may also secrete IFN in the bloodstream. Bacterial presence in the bloodstream challenges the concept of blood sterility, raising the possibility that cell-free microbial components, such as bacterial extracellular vesicles (BEVs), could trigger excessive IFN production through systemic circulation. While existing studies suggest a role for BEVs in human SLE, experimental evidence has yet to establish a direct association between the entire BEV nanoparticle and the disease. Research has primarily focused on (1) mammalian EVs and (2) purified eDNA and other specific cargoes as contributors to SLE progression. It remains unproven whether these bacterial molecules exert their effects while associated with vesicular membranes, i.e., BEVs. We hypothesize that BEVs, which carry diverse cargoes including nucleic acids, may enter systemic circulation, induce cellular responses leading to IFN overproduction, and exacerbate SLE severity. Clinical studies could investigate the association of BEVs with SLE progression by monitoring their presence and quantity in blood samples and correlating these factors with disease outcomes. Furthermore, understanding the involvement of BEVs may aid in identifying SLE biomarkers, inform infection prevention strategies, and inspire the development of BEV-neutralizing agents.

Dexamethasone and IFN-γ primed mesenchymal stem cells conditioned media immunomodulates aberrant NETosis in SLE via PGE2 and IDO.

Systemic Lupus Erythematosus (SLE) is characterized by dysregulated immune responses, with neutrophil extracellular traps (NETs) playing a significant role. NETs are recognized by autoantibodies in SLE patients, exacerbating pathology. Both excessive NET formation and impaired degradation contribute to SLE pathophysiology. To investigate the immunomodulatory effects of Dexamethasone-primed Wharton's jelly (WJ) derived MSCs CM (DW) and IFN-γ-primed WJ-MSCs-CM (IW) on NETosis and associated protein markers in SLE patients' LPS or ribonucleoprotein immune complexes (RNP ICs) induced neutrophils and in pristane induced lupus (PIL) model. And to elucidate the mechanism involved therein. We investigated the immunomodulatory effects of DW and IW on NETosis in SLE. Utilizing ex vivo and in vivo models, we assessed the impact of preconditioned media on NET formation and associated protein markers neutrophil elastase (NE), citrullinated histone (citH3), myeloperoxidase (MPO), cytoplasmic and mitochondrial ROS production. We also examined the involvement of key immunomodulatory factors present in DW and IW, including prostaglandin E2 (PGE2), indoleamine 2,3-dioxygenase (IDO), and transforming growth factor-beta (TGF-β). Preconditioned media effectively suppressed NETosis and reduced ROS generation in SLE neutrophils, indicating their immunomodulatory potential. Inhibition studies implicated IDO and PGE2 in mediating this effect. Combined treatment with DW or IW together with hydroxychloroquine (HCQ) demonstrated superior efficacy over HCQ alone, a standard SLE medication. In PIL mouse model, DW and IW treatments reduced NETosis, ROS generation, as evidenced by decreased NET-associated protein expression in vital organs. Our study highlights the multifaceted impact of IW and DW on NETosis, ROS dynamics, and lupus severity in SLE. These findings underscore the potential of preconditioned media for the development of targeted, personalized approaches for SLE treatment.

The Beneficial Effect of Exercise and Vitamin D Supplementation on Comorbidities Associated with Systemic Lupus Erythematosus

Objective: A multisystem chronic autoimmune illness with recurrent and relapsing episodes that can affect the locomotor system as well as the liver and kidneys is known as systemic lupus erythematosus (SLE). Vitamin D deficiency is thought to play a role in the pathogenesis of SLE. Therefore, our primary aim in this literature review is to determine the role of vitamin D deficiency on SLE symptoms. Our secondary aim is to explain the benefits of exercise on SLE-related comorbidities. Method: A comprehensive literature search on SLE symptoms, biochemistry, and pathophysiology was performed via Google Scholar. The effect of exercise on SLE comorbidities was investigated. Results: Some studies suggest that SLE is caused by environmental and genetic factors. The exact cause of the disease is still unknown, but there is evidence that vitamin D deficiency is associated with SLE symptoms. In addition to drug treatment for locomotor system involvement in SLE patients, physiotherapy applications are also included. In this study, the positive effects of exercise in SLE patients on pain, fatigue, and sleep problems caused by both disease-related and side effects of pharmacological applications used in treatment are reported. Information about the effects of vitamin D deficiency in SLE and how exercise contributes to the improvement of these symptoms is presented. Conclusion: Vitamin D deficiency in the symptoms seen in Systemic Lupus Erythematosus cannot be corrected by vitamin D supplementation alone. At this point, exercise provides possible benefits in correcting vitamin D deficiency. Therefore, exercise has positive effects on SLE comorbidities. Future studies should be planned with the aim of establishing a suitable exercise prescription for SLE.

#2996 Diffuse alveolar haemorrhage in antiphospholipid syndrome—a rare case

Abstract Background and Aims Diffuse alveolar haemorrhage (DAH) is a serious manifestation of diseases such as systemic lupus erythematosus (SLE) and, apparently in a paradoxical manner, antiphospholipid syndrome (APS). Inflammation resulting from the deposition of immune complexes in alveolar capillaries appears to contribute to the pathophysiology of DAH, SLE and APS. Symptoms include cough, dyspnoea, haemoptysis or fever. It is associated with a drop in haemoglobin, respiratory failure and diffuse infiltrates on imaging exams. Bronchoscopy is diagnostic. It is important to exclude infection as treatment includes high-dose corticosteroid therapy and other immunosuppressive drugs. We present a challenging case regarding the diagnostic and therapeutic approach to this pathology. Case report This is the case of a 52-year-old Caucasian female, with a history of SLE, APS, splenectomy due to thrombocytopenia, IgM Kappa monoclonal gammopathy and indolent non-Hodgkin lymphoma. She was medicated with prednisolone 5 mg and warfarin (target INR between 2 and 3). The patient was observed due to a 1-day history of fever, nasal obstruction and odynophagia, associated with progressively worsening fatigue. On examination, she was pale, eupnoeic, tachycardic, with bibasal rales and a hyperaemic oropharynx. Lab workup results were the following: haemoglobin 7 g/dL (11.7 g/dL 3 months before), VGM 71 fL, presence of schistocytes, leukocytes 13.7 G/L, neutrophils 11.1 G/L, PCR 4.6 mg/dL, platelets 170 G/L, INR 3.6, aPTT 45 sec, negative D-Dimers, urea 54 mg/dL, creatinine 1.4 mg/dL, LDH 431 IU/L, normal haptoglobin, negative Coombs test. In arterial blood gas analysis, pO2 was 61 mmHg and lactate was 5 mmol/L. Chest X-ray showed bilateral basal cotton-wool infiltrates and chest CT showed bilateral ground-glass pattern. The rest of the investigation included no complement consumption, negative anti-ds-DNA antibody, positive lupus anticoagulant, anticardiolipin and anti-beta2-glycoprotein antibodies, negative cryoglobulins and no evidence of progression of the lymphoproliferative disease. She was admitted to the intensive care unit due to suspicion of atypical/viral pneumonia vs. DAH. Oxygen therapy, empirical antibiotic therapy with ceftriaxone and clarithromycin and oral methylprednisolone 1 mg/Kg/day were started. She needed blood transfusion, although without visible blood loss. Bronchofibroscopy was performed, with bronchoalveolar lavage suggestive of DAH, so it was decided to start intravenous pulses of methylprednisolone, plasmapheresis, and intravenous immunoglobulin (IVIG). Warfarin was changed to unfractionated heparin. The patient had clinical, analytical and radiological improvement. Due to the lack of evidence of infection, antibiotics were stopped after 7 days. The patient was discharged under weaning corticosteroid therapy and monthly IVIG (during 5 months), without recurrence in the following year. Conclusion This is a rare case of oligosymptomatic DAH in a patient with SLE and APS. The literature currently available on DAH in the context of SLE or APS is scarce and its treatment is mainly dependent on the experience of each medical centre. Corticosteroid therapy is consensual, with greater variability in other corticosteroid-sparing therapies. In the case of patients with APS, anticoagulation is a challenge, and it is important to resume it as soon as the bleeding is controlled due to the risk of thrombotic events.

Expression of hsa-let-7f-5p and serum levels of interleukin-10, cystatin-C and transforming growth factor-beta in systemic lupus erythematosus patients with lupus nephritis

Aim of the workTo investigate the impact of mi-RNA (hsa-let-7f-5p) expression, levels of cystatin C, serum interleukin-10 (IL-10), and transforming-growth-factor-beta (TGF-β) in systemic lupus erythematosus (SLE) patients with and without lupus nephritis (LN). Patients and methodsThe work included 60 SLE patients: thirty with and thirty without LN, along with thirty matched controls. The SLE disease activity index (SLEDAI) was assessed. Enzyme-linked-immunosorbent-assay (ELISA) was used to evaluate serum levels of TGF-β, IL-10, and Cystatin-C and expression of mi-RNA Let-7f-5p quantified using real-time polymerized-chain-reaction (PCR). ResultsThe mean age of LN patients was 31.6 ± 8.4 years, twenty-eight females and 2 males. mi-RNA Let-7f-5p, serum TGFβ, IL10, and cystatin C were significantly higher in those with LN (4.4 ± 2, 357.6 ± 50.8 ng/mL, 173.1 ± 18 pg/mL and 8.03 ± 1.96 ng/mL) compared to case without (2.5 ± 0.92, 319.7 ± 44.4 ng/mL, 108.8 ± 22.8 pg/mL, and 3.43 ± 1.1 ng/mL) and control (1.03 ± 0.07, 210.3 ± 18.6 ng/mL, 56 ± 18.5 pg/mL and 2.53 ± 1.1 ng/ml)(p < 0.001). In LN, mi-RNA Let-7f-5p and IL10 were significantly different in those with oral ulcers (n = 8)(p = 0.03, and p = 0.01 respectively). mi-RNA Let-7f-5p and TGF-β were significantly lower in those with headache (n = 3)(p < 0.001, and p = 0.04 respectively). In patients without LN, TGF-β was significantly lower in those with malar rash (n = 10)(p = 0.04) and serum cystatin-C was lower in those with arthritis (n = 12)(p = 0.02). In LN, IL-10 significantly correlated with disease duration (r = 0.38,p = 0.04) and cystatin-C inversely with platelets (r = -0.42,p = 0.02), Cystatin-C correlated with mi-RNA Let-7f-5p (r = 0.45,p = 0.01) and inversely with SLEDAI (r = -0.44,p = 0.01). ConclusionThe potential role of mi-RNA Let-7f-5p on LN with the possible involvement of TGFβ, IL10, and cystatin-C in the pathophysiology of both SLE and LN.

Mendelian Causes of Autoimmunity: the Lupus Phenotype.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that is characterized by its large heterogeneity in terms of clinical presentation and severity. The pathophysiology of SLE involves an aberrant autoimmune response against various tissues, an excess of apoptotic bodies, and an overproduction of type-I interferon. The genetic contribution to the disease is supported by studies of monozygotic twins, familial clustering, and genome-wide association studies (GWAS) that have identified numerous risk loci. In the early 70s, complement deficiencies led to the description of familial forms of SLE caused by a single gene defect. High-throughput sequencing has recently identified an increasing number of monogenic defects associated with lupus, shaping the concept of monogenic lupus and enhancing our insights into immune tolerance mechanisms. Monogenic lupus(moSLE) should be suspected in patients with either early-onset lupus or syndromic lupus, in male, or in familial cases of lupus. This review discusses the genetic basis of monogenic SLE and proposes its classification based on disrupted pathways. These pathways include defects in the clearance of apoptotic cells or immune complexes, interferonopathies, JAK-STATopathies, TLRopathies, and T and B cell dysregulations.

Unraveling IFN-I response dynamics and TNF crosstalk in the pathophysiology of systemic lupus erythematosus.

The innate immune system serves the crucial first line of defense against a wide variety of potential threats, during which the production of pro-inflammatory cytokines IFN-I and TNFα are key. This astonishing power to fight invaders, however, comes at the cost of risking IFN-I-related pathologies, such as observed during autoimmune diseases, during which IFN-I and TNFα response dynamics are dysregulated. Therefore, these response dynamics must be tightly regulated, and precisely matched with the potential threat. This regulation is currently far from understood. Using droplet-based microfluidics and ODE modeling, we studied the fundamentals of single-cell decision-making upon TLR signaling in human primary immune cells (n = 23). Next, using biologicals used for treating autoimmune diseases [i.e., anti-TNFα, and JAK inhibitors], we unraveled the crosstalk between IFN-I and TNFα signaling dynamics. Finally, we studied primary immune cells isolated from SLE patients (n = 8) to provide insights into SLE pathophysiology. single-cell IFN-I and TNFα response dynamics display remarkable differences, yet both being highly heterogeneous. Blocking TNFα signaling increases the percentage of IFN-I-producing cells, while blocking IFN-I signaling decreases the percentage of TNFα-producing cells. Single-cell decision-making in SLE patients is dysregulated, pointing towards a dysregulated crosstalk between IFN-I and TNFα response dynamics. We provide a solid droplet-based microfluidic platform to study inherent immune secretory behaviors, substantiated by ODE modeling, which can challenge the conceptualization within and between different immune signaling systems. These insights will build towards an improved fundamental understanding on single-cell decision-making in health and disease.

T Cell Dysfunction in Systemic Lupus Erythematosus

Systemic lupus erythematosus (SLE) is a systemic autoimmune inflammatory disease that can affect many organs in the body with very diverse clinical appearances. The prevalence of SLE in each country varies. The Lupus Foundation of America estimates that around 1.5 million cases occur in America and at least 5 million cases occur worldwide. The pathophysiology of SLE is very complex. The involvement of innate and adaptive immunity in the initiation and pathophysiology of SLE disease shows that there are interactions between leukocytes, cytokines, chemokines and tissue cells. T cells are the main component of the adaptive immune system which can kill infected host cells, activate other immune cells, produce cytokines and regulate immune responses. T cell dysfunction in SLE includes triggering inflammation through the secretion of pro-inflammatory cytokines, helping B cells produce autoantibodies and the accumulation of autoreactive T cells. Aberrations in T cells could be a therapeutic target for development and a potential SLE therapy.

An Emerging Role for Anti-DNA Antibodies in Systemic Lupus Erythematosus.

Anti-DNA antibodies are hallmark autoantibodies produced in systemic lupus erythematosus (SLE), but their pathogenetic role is not fully understood. Accumulating evidence suggests that some anti-DNA antibodies enter different types of live cells and affect the pathophysiology of SLE by stimulating or impairing these cells. Circulating neutrophils in SLE are activated by a type I interferon or other stimuli and are primed to release neutrophil extracellular traps (NETs) on additional stimulation. Anti-DNA antibodies are also involved in this process and may induce NET release. Thereafter, they bind and protect extracellular DNA in the NETs from digestion by nucleases, resulting in increased NET immunogenicity. This review discusses the pathogenetic role of anti-DNA antibodies in SLE, mainly focusing on recent progress in the two research fields concerning antibody penetration into live cells and NETosis.

B Cell Tolerance and Targeted Therapies in SLE.

Systemic Lupus Erythematosus (SLE) is a chronic systemic autoimmune disease of high clinical and molecular heterogeneity, and a relapsing-remitting pattern. The disease is currently without cure and more prevalent in women. B cell tolerance and production of autoantibodies are critical mechanisms that drive SLE pathophysiology. However, how the balance of the immune system is broken and how the innate and adaptive immune systems are interacting during lupus-specific autoimmune responses are still largely unknown. Here, we review the latest knowledge on B cell development, maturation, and central versus peripheral tolerance in connection to SLE and treatment options. We also discuss the regulation of B cells by conventional T cells, granulocytes, and unconventional T cells, and how effector B cells exert their functions in SLE. We also discuss mechanisms of action of B cell-targeted therapies, as well as possible future directions based on current knowledge of B cell biology.

Evaluation of some immunological parameters for Staphylococcus xylosus infections in patients with Systemic lupus erythematosus

Purpose: Systemic lupus erythematosus (SLE) is a chronic, systemic autoimmune illness that manifests clinically as well as immunologically and in several lab tests abnormalities. Patients with SLE frequently get infections, which account for 30–50% of morbidity and death. The bacterial species Staphylococcus xylosus is a member of the Staphylococcus genus. This study's objective was to assess several immunological indicators of S.xylosus infections in individuals with systemic lupus erythematosus in the Najaf Governorate of Iraq. Subjects and Methods: Blood samples were taken from 60 SLE patients ranging in age from 16 to 56. Each patient has had a sample of 10 milliliters of blood taken. 5 ml were used to measure immunologic parameters, and another 5 ml were used to diagnose S. Xylosus by culturing a sample on blood agar and mannitol salt agar. culture on mannitol salt agar and blood agar. Results: According to the microbiological tests, 26 specimens (or 43.3%) had isolated bacteria, whereas 34 specimens (or 56.7%) had no sign of bacterial growth. Out of the 26 blood samples collected, S.xylosus was detected in 2 samples. normal amounts of ANA and anti ds-DNA despite SLE sufferers. The results of this study showed that serum levels of CD69, IL-21, and IL-35 significantly increased when compared with controls, despite a substantial drop in Hb, WBC, and platelet counts but an elevated ESR. Conclusions: xylosus produces normal autoantibody levels that are utilized to diagnose SLE. An important factor in the pathophysiology of SLE, which causes the disease to develop, is a high concentration of inflammatory cytokines.

Whole blood hydroxychloroquine: Does genetic polymorphism of cytochrome P450 enzymes have a role?

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with a wide range of clinical manifestations and multifactorial etiologies ranging from environmental to genetic. SLE is associated with dysregulated immunological reactions, with increased immune complex formation leading to end-organ damages such as lupus nephritis, cutaneous lupus, and musculoskeletal disorders. Lupus treatment aims to reduce disease activity, prevent organ damage, and improve long-term patient survival and quality of life. Antimalarial, hydroxychloroquine (HCQ) is used as a first-line systemic treatment for lupus. It has shown profound efficacy in lupus and its associated conditions. However, wide variation in terms of clinical response to this drug has been observed among this group of patients. This variability has limited the potential of HCQ to achieve absolute clinical benefits. Several factors, including genetic polymorphisms of cytochrome P450 enzymes, have been stipulated as key entities leading to this inter-individual variation. Thus, there is a need for more studies to understand the role of genetic polymorphisms in CYP450 enzymes in the clinical response to HCQ. Focusing on the role of genetic polymorphism on whole blood HCQ in lupus disorder, this review aims to highlight up-to-date pathophysiology of SLE, the mechanism of action of HCQ, and finally the role of genetic polymorphism of CYP450 enzymes on whole blood HCQ level as well as clinical response in lupus.

Whole-genome bisulfite sequencing identified the key role of the Src family tyrosine kinases and related genes in systemic lupus erythematosus.

As a multisystemic autoimmune illness, the basic mechanisms behind the pathophysiology of systemic lupus erythematosus (SLE) remain poorly understood. We aimed to investigate the possible significance of SLE's DNA methylation and gainfurtherinsightinto potential SLE-related biomarkers and therapeutic targets. We used whole genome bisulfite sequencing (WGBS) method to analyze DNA methylation in 4 SLE patients and 4 healthy people. 702 differentially methylated regions (DMRs) were identified, and 480 DMR-associated genes were annotated. We found the majority of the DMR-associated elements were enriched in repeat and gene bodies. The top 10 hub genes identified were LCK, FYB, PTK2B, LYN, CTNNB1, MAPK1, GNAQ, PRKCA, ABL1, and CD247. Compared to the control group, LCK and PTK2B had considerably decreased levels of mRNA expression in the SLE group. Receiver operating characteristic (ROC) curve suggested that LCK and PTK2B may be potential candidate biomarkers to predict SLE. Our study improved comprehension of the DNA methylation patterns of SLE and identified potential biomarkers and therapeutic targets for SLE.

Refractory alopecia in lupus treated with tofacitinib - a case-based review.

One of the common cutaneous symptoms of systemic lupus erythematosus (SLE) that may have major psychosocial effects in a female is diffuse alopecia. Although Janus kinase inhibitors have shown encouraging results in the treatment of SLE and of alopecia areata in recent studies, tofacitinib in treating refractory alopecia caused by SLE has been rarely documented. The Janus kinases (JAKs) are intracellular tyrosine kinases that play a significant role in the pathophysiology of SLE by participating in a wide range of inflammatory cascades. Here, we reported a 33-year-old SLE patient with long standing (3years) refractory alopecia who took tofacitinib and observed a substantial increase in hair growth. This was sustained at 2-years follow-up even after tapering off glucocorticoids completely. In addition, we reviewed the literature to look for further evidence to support the use of JAK inhibitors for alopecia in SLE.

Inflammation-based biomarkers for the prediction of nephritis in systemic lupus erythematosus

Background/Aim: Inflammation is a crucial component in the pathophysiology of systemic lupus erythematosus (SLE) nephritis. Immune-based scores, such as the neutrophil-lymphocyte and the platelet-lymphocyte ratios (NLR and PLR, respectively) have been suggested as predictors of inflammation and prognosis in SLE. This study aimed to investigate the value of the systemic immune-inflammation index (SII), inflammatory prognostic index (IPI), and systemic inflammatory response index (SIRI) in SLE and lupus nephritis (LN). Methods: This case-control study consisted of 108 newly diagnosed SLE patients (separated into two subgroups, which included 34 patients with biopsy-proven LN and 74 without nephritis) and 108 age- and gender-matched healthy controls who presented to our outpatient clinic between October 2015 and June 2020. Patients with malignancy, lymphoproliferative and hematologic disorders, active infection, and autoimmune diseases other than SLE were excluded. Inflammation-based biomarkers were calculated at the first presentation of the disease and before any medication was administered. SII was calculated as Neutrophil/Lymphocyte x Platelet, SIRI as Neutrophil x Monocyte/Lymphocyte, and IPI as CRP x NLR/serum albumin. The Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) was used to measure disease activity. The capability of SII, SIRI, NLR, PLR, and IPI to distinguish between SLE patients with or without nephritis was assessed using receiver operating characteristic (ROC) curves. Correlations of inflammation-based scores (SII, SIRI, IPI, NLR) with disease activity and laboratory data of SLE patients were analyzed. Results: SII, SIRI, and IPI were significantly higher in SLE patients than in healthy controls (P=0.003, P=0.019, and P&lt;0.001, respectively) and also significantly higher in patients with nephritis than in those without (P&lt;0.001, P=0.009, and P=0.007, respectively). The area under the curve (AUC) for SII, SIRI, and IPI in terms of differentiating SLE patients with or without nephritis was 0.748, 0.690, and 0.663, respectively. The cut-off value of SII, SIRI, and IPI to predict LN was 552.25 (sensitivity: 64.7%; specificity: 64.9%; P&lt;0.001), 1.08 (sensitivity: 61.8%; specificity: 62.2%; P=0.002), and 4.48 (sensitivity: 61.8%; specificity, 62.2%; P=0.007), respectively. Conclusion: SII, SIRI, and IPI may be valuable and promising inflammation-based biomarkers in SLE and for the presence of nephritis in SLE patients. SII was found to be the most reliable predictor of SLE among the inflammation-based biomarkers in our study.

Systemic lupus erythematosus with diffuse alveolar hemorrhage.

Systemic lupus erythematosus with diffuse alveolar hemorrhage.

Blood levels of brain-derived neurotrophic factor (BDNF) in systemic lupus erythematous (SLE): a systematic review and meta-analysis

ObjectivesBDNF has been implicated in the pathophysiology of systemic lupus erythematosus (SLE), especially its neuropsychiatric symptoms. The purpose of this study was to investigate the profile of blood BDNF levels in patients with SLE.MethodsWe searched PubMed, EMBASE, and the Cochrane Library for papers that compared BDNF levels in SLE patients and healthy controls (HCs). The Newcastle–Ottawa scale was used to assess the quality of the included publications, and statistical analyses were carried out using R 4.0.4.ResultsThe final analysis included eight studies totaling 323 healthy controls and 658 SLE patients. Meta-analysis did not show statistically significant differences in blood BDNF concentrations in SLE patients compared to HCs (SMD 0.08, 95% CI [ − 1.15; 1.32], P value = 0.89). After removing outliers, there was no significant change in the results: SMD -0.3868 (95% CI [ − 1.17; 0.39], P value = 0.33. Univariate meta-regression analysis revealed that sample size, number of males, NOS score, and mean age of the SLE participants accounted for the heterogeneity of the studies (R2 were 26.89%, 16.53%, 18.8%, and 49.96%, respectively).ConclusionIn conclusion, our meta-analysis found no significant association between blood BDNF levels and SLE. The potential role and relevance of BDNF in SLE need to be further examined in higher quality studies.

Toll-like receptors 7 and 9 regulate the proliferation and differentiation of B cells in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is an autoimmune illness marked by the loss of immune tolerance and the production of autoantibodies against nucleic acids and other nuclear antigens (Ags). B lymphocytes are important in the immunopathogenesis of SLE. Multiple receptors control abnormal B-cell activation in SLE patients, including intrinsic Toll-like receptors (TLRs), B-cell receptors (BCRs), and cytokine receptors. The role of TLRs, notably TLR7 and TLR9, in the pathophysiology of SLE has been extensively explored in recent years. When endogenous or exogenous nucleic acid ligands are recognized by BCRs and internalized into B cells, they bind TLR7 or TLR9 to activate related signalling pathways and thus govern the proliferation and differentiation of B cells. Surprisingly, TLR7 and TLR9 appear to play opposing roles in SLE B cells, and the interaction between them is still poorly understood. In addition, other cells can enhance TLR signalling in B cells of SLE patients by releasing cytokines that accelerate the differentiation of B cells into plasma cells. Therefore, the delineation of how TLR7 and TLR9 regulate the abnormal activation of B cells in SLE may aid the understanding of the mechanisms of SLE and provide directions for TLR-targeted therapies for SLE.

The emerging role of noncoding RNAs in systemic lupus erythematosus: new insights into the master regulators of disease pathogenesis.

Auto-immune diseases are a form of chronic disorders in which the immune system destroys the body's cells due to a loss of tolerance to self-antigens. Systemic lupus erythematosus (SLE), identified by the production of autoantibodies in different body parts, is one of the most well-known examples of these diseases. Although the etiology of SLE is unclear, the disease's progression may be affected by genetic and environmental factors. As studies in twins provide adequate evidence for genetic involvement in the SLE, other phenomena such as metallization, histone modifications, and alterations in the expression of noncoding RNAs (ncRNAs) also indicate the involvement of epigenetic factors in this disease. Among all the epigenetic alterations, ncRNAs appear to have the most crucial contribution to the pathogenesis of SLE. The ncRNAs' length and size are divided into three main classes: micro RNAs, long noncoding RNAs (LncRNA), and circular RNAs (circRNAs). Accumulating evidence suggests that dysregulations in these ncRNAs contributed to the pathogenesis of SLE. Hence, clarifying the function of these groups of ncRNAs in the pathophysiology of SLE provides a deeper understanding of the disease. It also opens up new opportunities to develop targeted therapies for this disease.

Immunological and translational key challenges in systemic lupus erythematosus: A symposium update

The first LBMR-Tim (Toulouse Referral Medical Laboratory of Immunology) symposium convened on December 16, 2022 in Toulouse, France to address challenging questions in systemic lupus erythematosus (SLE). Special focus was put on (i) the role played by genes, sex, TLR7, and platelets on SLE pathophysiology; (ii) autoantibodies, urinary proteins, and thrombocytopenia contribution at the time of diagnosis and during follow-up; (iii) neuropsychiatric involvement, vaccine response in the COVID-19 era, and lupus nephritis management at the clinical frontline; and (iv) therapeutic perspectives in patients with lupus nephritis and the unexpected adventure of the Lupuzor/P140 peptide. The multidisciplinary panel of experts further supports the concept that a global approach including basic sciences, translational research, clinical expertise, and therapeutic development have to be prioritized in order to better understand and then improve the management of this complex syndrome.