Pathophysiology Of Systemic Lupus Erythematosus Research Articles

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.

Systemic lupus erythematosus with diffuse alveolar hemorrhage.

To the Editor: Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the production of various autoantibodies. Disease prevalence is 20 to 70 per 100,000 among adults, and 1.89 to 25.7 per 100,000 among children.[1,2] The pathogenesis of SLE is associated with immune disorders, especially involving the activation of B and T cells, which can lead to abnormal antibodies with nuclear and cytosolic antigens from apoptotic cells of the immune complexes (ICs) removing the damaged cells, and excessive activation of the complement system, thus causing damage to target organs,[3] such as the kidneys and lungs. With pulmonary involvement in SLE patients, various comorbidities may occur, including pleurisy and diffuse alveolar hemorrhage (DAH). DAH, first described in 1904, is a rare, serious, and potentially life-threatening complication of SLE.[1] DAH can also occur in other diseases, including antiphospholipid syndrome, connective tissue diseases, infective endocarditis, and other infections.[4] The prevalence of SLE-DAH in adults ranges from 0.5% to 5.7%, with a female-to-male ratio of approximately 6:1, and a higher prevalence in young females. Onset is at an average age of 27 years, approximately 35 months after SLE onset, with a mean reported mortality of 50%.[1] In children with SLE, DAH incidence is approximately 0.8%to 4.9%; however, the mortality rate is over 30%,[2,5] emphasizing the need for timely diagnosis and appropriate choice of treatment, and for simultaneously researching new potential treatments to reduce mortality, by clinicians. SLE-DAH pathogenesis is illustrated in Figure 1. Its development may be related to macrophage and neutrophil recruitment to the lungs at the early stage. Systemic inflammation involving the pulmonary vasculature, caused by overactive autoimmune responses and cytokine storms, is thought to be the main cause of DAH, which may be related to the overactivation of the complement pathway [Figure 1]. The pathological manifestations are mainly autoantibody-mediated pulmonary capillaritis, mild alveolar hemorrhage, and diffuse alveolar injury.[4] Mild bleeding may be related to mononuclear cell (Mc) infiltration of the alveolar wall. Additionally, the excessive complement pathway is closely related to the B cell activation, and can also activate neutrophils, forming neutrophil cell traps and secreting cytokines, also related to DAH [Figure 1].Figure 1: Pathogenesis of SLE-DAH. In SLE-DAH, increased alveolar wall cell apoptosis can lead to RBC infiltration into the alveolar space, which may lead to bleeding; however, the source of apoptotic cells is unclear and alveolar epithelial cells, Mc, and MQ may phagocytose apoptotic cells and RBCs. During inflammation, bone marrow-derived MQs are recruited to the alveoli and differentiate into proinflammatory M1-type MQs and IgM/C3-induced apoptotic cells, bind to C3b receptors 3 and 4 on MQs, accelerating the development of DAH. In SLE, excessive B cell activation can produce numerous autoantibodies in response to antigens (such as vascular endothelial cells of phospholipids, etc.), the formation of ICs, and excessive activation of complement, making up the immune response that can result in the endothelial cell damage, pulmonary capillary inflammation, increased permeability, and infiltration of RBC into alveolar cavities, causing DAH. Hyperactivation of pulmonary complement leads to the production of anaphylaxis toxins and effector cell activating mediators, particularly C5a. C5a attracts and activates NEs and releases inflammatory mediators, including proteolytic enzymes, chemokines (such as CXCL2), and cytokines (such as TNF-α), which worsen alveolar damage and capillary leakage. Also, C5a can bind to C5a receptors on NEs, activating them to form NETs. NETs are fibrous networks protruding from activated NE cell membranes that accelerate inflammatory processes by releasing histones, active lyases, and various cytokines into the extracellular space. Ab: Antibody; CXCL2: Chemokine ligand 2; DAH: Diffuse alveolar hemorrhage; ICs: Immune complexes; IFN: Interferon; Ig: Immunoglobulin; IL: Interleukin; Mc: Mononuclear cell; MQ: Macrophages; NE: Neutrophil; NET: Neutrophil extracellular trap; RBCs: Red blood cells; SLE: Systemic lupus erythematosus; TNF: Tumor necrosis factor.SLE-DAH diagnosis requires careful history, symptom assessment, and physical examination. A combination of laboratory tests, lung imaging, and bronchoalveolar lavage fluid analysis will provide evidence for diagnosis. It also needs to be differentiated from other diseases (including diastolic dysfunction, deep fungal infections, end-stage chronic kidney disease with uremia, etc.). The diagnostic flow is illustrated in Supplementary Figure 1, https://links.lww.com/CM9/B415. SLE-DAH has a high mortality rate, especially acute macroscopic bleeding requiring prompt treatment. Glucocorticoids (GCs) are the main treatment for SLE-DAH, and it is recommended to use large doses immediately after diagnosis to exclude infection, as well as to treat underlying diseases.[4] It can reduce acute inflammatory responses by inhibiting inflammatory cells and cytokines. However, it is often fatal in immunocompromised patients. Therefore, the effectiveness of high-dose GC for DAH treatment remains controversial. Treatment of SLE-DAH using cyclophosphamide (CTX) has been shown to improve survival.[6] In children with SLE-DAH, a regimen of high-dose methylprednisolone pulse combined with CTX is recommended.[7] B-cell activation is thought to play an important role in SLE pathophysiology. Rituximab (RTX) is a chimeric monoclonal antibody targeting cluster of differentiation 20 (CD20) that reduces the serum levels of antibodies, immune complexes (ICs), and cytokines by specifically targeting the elimination of CD20+ B cells. In one study, all SLE-DAH patients were treated with RTX, and the follow-up time was 12 to 58 months. All patients survived, with no recurrence in three patients having a history of DAH recurrence.[8] Therefore, RTX could be used as a drug for SLE-DAH. Intravenous immunoglobulin (IVIG) has immunomodulatory effects, including inhibition of B-cell proliferation, antibody production, growth factors, and cytokines, and can exert anti-inflammatory effects by inhibiting the complement system. In a recent literature review of treatment strategies for DAH patients, it was found that a patient with DAH and pulmonary infection had no recurrence of DAH after adding IVIG once a month to the treatment regimen of daily GC.[9] These results indicate that IVIG combined with other therapies is effective in SLE-DAH treatment. ICs and pathological antibodies may cause SLE-DAH capillaritis. Therapeutic plasma exchange (TPE) removes ICs, antibodies, and cytokines, and has been used as an adjunct therapy in patients who do not respond to high-dose GC and CTX therapy. The 1-year survival rate of DAH patients treated with TPE is higher than that of patients treated with GC pulse therapy, whether combined with immunosuppressive agents or not.[10] However, few studies have reported that TPE treatment increases mortality.[11] Recombinant hereditary factor VIIa (FVIIa) has a good hemostatic effect in patients with life-threatening intractable hemorrhage. FVIIa stops bleeding by forming the FVIIa-tissue factor complex, which activates factor X leading to thrombin production and clot formation. In a recent comprehensive review of 111 DAH cases, the patients were treated with systemic or intrapulmonary rFVIIa. In patients receiving systemic rFVIIa, single or repeated doses of 35 to 200 μg/kg were used, with an average of 250 μg/kg per episode. However, patients receiving intrapulmonary rFVIIa had almost complete hemostasis at 50 μg/kg per episode, which was not significantly different from systemic administration, and no thromboembolic events were reported.[4] In children, intrapulmonary FVIIa administration can successfully induce pulmonary hemostasis and reduce the risk of systemic complications,[4] indicating that it can be an effective treatment strategy for children and adults with DAH. Mesenchymal stem cells (MSCs) are pluripotent cells that differentiate into various mesenchymal lineages. MSCs exert immunomodulatory effects by inhibiting the proliferation and activation of T, B, and other immune cells. Human umbilical cord-derived MSCs have been used as a single-push intravenous infusion in a trial series, resulting in improved oxygen saturation and complete suppression of lung infiltration after 2 to 3 weeks.[1] Other studies have found that human umbilical cord MSC-exosomes reduce SLE-DAH-induced inflammation and alveolar hemorrhage by increasing the proportion of M2 macrophages.[12] Based on these results, MSCs and human umbilical cord MSC-exosomes may provide new prospects for DAH treatment. Currently, SLE-DAH pathogenesis remains unclear. For patients suspected to have DAH, it is necessary to undergo the relevant examination to confirm the diagnosis and exclude other diseases with similar manifestations. GC and CTX are the most commonly used treatment methods for SLE-DAH. In addition to treating the primary disease, hemostatic management is crucial. For non-responders, MSCs and human umbilical cord MSC-exosomes are new therapeutic strategies to consider. SLE-DAH treatment has mainly been reported in individual cases; therefore, individualized treatment is required. Conflicts of interest None.

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.

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.

The expression of Ets-1 and Fli-1 is associated with interferon-inducible genes in peripheral blood mononuclear cells from Japanese patients with systemic lupus erythematosus.

Transcription factors E26 transformation-specific-1 (Ets-1) and Friend leukemia insertion site-1 (Fli-1) and type I interferon (IFN) have been implicated in systemic lupus erythematosus (SLE). We examined the expression of these genes in peripheral blood mononuclear cells (PBMCs) from Japanese patients with SLE and analyzed their association with SLE. We enrolled 53 Japanese patients with SLE, 42 patients with rheumatoid arthritis (RA), and 30 healthy donors (HDs) (as controls) in this study. PBMCs were collected from all participants, and the expressions of Ets-1, Fli-1, and three interferon-inducible genes (IFIGs) (interferon-inducible protein with tetratricopeptide 1 [IFIT1], interferon-inducible protein 44 [IFI44], and eukaryotic translation initiation factor 2 alpha kinase 2 [EIF2AK2]) were measured using real-time polymerase chain reaction (PCR). The relationships of each molecule with clinical symptoms, laboratory data, and treatments were analyzed. The expression of Ets-1 and Fli-1 was significantly lower in the PBMCs from patients with SLE than that in the PBMCs from patients with RA and HDs. The expression of the three IFIGs was significantly higher in the PBMCs from patients with SLE than that in the PBMCs from patients with RA and HDs. For patients with SLE, significantly positive correlations were found between Ets-1 and three IFIGs; a similar trend was observed between Fli-1 and IFIGs. IFIG expression in the PBMCs was significantly higher in patients with SLE than that in other participants, and the expression of Ets-1 and Fli-1 was positively associated with IFN expression. Therefore, it was suggested that Ets-1 and Fli-1 were associated with the pathophysiology of SLE by regulating the type I IFN pathway.

Association of - 717 A > G (rs2794521) CRP polymorphism with high cardiovascular risk by C-reactive protein in systemic lupus erythematosus patients.

Systemic lupus erythematosus (SLE) is an autoimmune disease where genetic factors have been related to SLE susceptibility and disease severity. CRP polymorphisms have been associated with high C-reactive protein (CRP) serum levels, cardiovascular disease (CVD), and high clinical disease activity in SLE patients; however, the evidence is still inconclusive. This study was aimed to assess the association of the - 717 A > G, - 409 G > A, + 1444 C > T, and + 1846 C > T CRP polymorphisms with genetic susceptibility, clinical disease activity, and CVD risk in Mexican-mestizo SLE patients. A comparative cross-sectional study was conducted on 369 unrelated women: 183 with SLE according to the 1997 SLE-ACR criteria and 186 healthy subjects (HS). The clinical disease activity was assessed by the Mex-SLEDAI score; CRP and lipid profile were quantified by turbidimetry and colorimetric-enzymatic assays, respectively. The CRP polymorphisms genotyping was carried out by allelic discrimination. SLE patients with - 717 AA genotype had higher CRP serum levels than SLE carriers of AG and GG genotypes (AA = 5mg/L vs. AG = 3.2mg/L vs. GG = 2.4mg/L; p = 0.01), and the AA genotype was associated with high CVD risk by CRP in SLE patients (OR = 3; CI: 1.2-7.6; p < 0.01). The - 717 A > G CRP polymorphism is a risk factor for high CRP levels and high CVD risk in Mexican-mestizo SLE patients. Key Points • Cardiovascular disease is one of the major causes of death in SLE patients due to the higher prevalence of traditional and non-traditional cardiovascular risk factors. • C-reactive protein is a liver-derived acute-phase protein suggested as one powerful independent risk predictor factor for cardiovascular disease. • Single nucleotide polymorphisms in CRP have been suggested as genetic susceptibility factors that could modify the SLE pathophysiology outcomes. • Mexican-mestizo SLE patients carrying the -717 A>G CRP AA genotype had 3-fold high cardiovascular disease risk than SLE patients with AG or GG genotypes.

Low-dose interleukin-2 therapy in active systemic lupus erythematosus (LUPIL-2): a multicentre, double-blind, randomised and placebo-controlled phase II trial

ObjectivesA regulatory T cell (Treg) insufficiency due to shortage of interleukin-2 (IL-2) is central to the pathophysiology of systemic lupus erythematosus (SLE). We performed a multicentre, double-blinded, randomised, placebo-controlled phase...

Systematic lupus erythematous patients following COVID-19 vaccination: Its flares up and precautions

Systemic lupus erythematosus (SLE) is an autoimmune disease that can cause both direct and indirect inflammatory damage to multiple organs. Clinical symptoms in the skin, joints, kidneys, and central nervous system, as well as serological indicators such as antinuclear antibodies (ANA), notable antibodies to dsDNA, are used to diagnose SLE. mRNA SARS-CoV-2 vaccines have been shown to trigger SLE flares and the development of new rheumatic diseases. SARS-CoV-2 mRNA vaccinations increase type I interferon (INF), which is not only known to have a role in the antiviral response but is also a crucial cytokine in the pathophysiology of SLE. Furthermore, both the mRNA and adenovirus vaccines boost the production of type 1 interferons, which are required for the spread of SARS-CoV-2. The danger of not administering the COVID-19 vaccination to SLE patients is significantly larger than the likelihood of its adverse effects, which are most likely caused by intrinsic immune failure, demographic disease activity, medications, linked organ damage, and comorbidities. The adverse effects of COVID-19 vaccination in SLE patients are common (about 50%), although they do not interfere with daily functioning in the majority of cases. Several precautions can be taken to avoid the complications associated with COVID-19 vaccinations.