Onset Of Systemic Lupus Erythematosus Research Articles

Lymphadenopathy in systemic lupus erythematosus: no microbial trigger found by shotgun metagenomics in a retrospective study on 38 patients.

Lymphadenopathy is a classical manifestation of systemic lupus erythematosus (SLE) flare, occurring in approximately half of patients during the course of the disease. Lymphadenopathy in SLE is frequently associated with fever. Microbial infection may play a role in SLE onset and flares. Objectives of this study were to describe lymphadenopathy in the course of SLE and identify potential infectious triggers using microbial metagenomic analysis. We performed a retrospective monocentric study of 38 patients with SLE who had lymph node biopsy at baseline or during follow-up. Shotgun metagenomics were performed in patient's lymph node biopsy to look for microbial RNA and/or DNA. Lymph node pathological analyses revealed follicular and/or paracortical hyperplasia 73.7% of patients and histiocytic necrotizing lymphadenitis 23.7%. At the time of biopsy, SLE patients exhibited fever in 29%, splenomegaly in 10%, cutaneous manifestations in 47%, polyarthritis in 32%, seritis in 13% and lupus nephritis in 18%. Half of patients (50%) had increased CRP level, 35% had low C3, 65% had hypergammaglobulinemia. Microbial metagenomic analysis of lymph node biopsy did not reveal the presence of microbial DNA in 92% of patients, the presence of CMV in very small quantities in 2 patients, and the presence of HHV-7 in low quantities in a single patient. Despite suggestion that certain microorganisms may play a role in the pathogenesis and flares of SLE, our microbial metagenomic analysis study did not highlight possible infectious triggering factors. Further and better-designed studies are needed to confirm these results.

Клинико-эпидемиологические особенности системной красной волчанки у детей: данные наблюдений ГБУЗ “Морозовская ДГКБ ДЗМ”

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease of unknown etiology characterized by hyperproduction of autoantibodies. The problems of timely diagnosis and identification of predictors of an unfavorable outcome of SLE are relevant due to the variable clinical picture and a high risk of 5-year mortality in the absence of treatment. The purposes of this research were to assess the frequency of various variants of SLE onset, to identify trigger factors contributing to the development of the disease and to analyze the degree of disease activity in children. Materials and methods used: a single-center cohort retrospective study was conducted involving patients aged 9 to 17 y/o who had undergone inpatient treatment at the rheumatological department of the Morozov Children’s City Clinical Hospital (Moscow, Russia) in 2020-2023, specifying age, gender, assessing the frequency of observed symptoms of SLE onset, disease activity according to the SLEDAI scale, laboratory parameters and drug treatment. Results: total of 45 records were analyzed: 75.5% (34) girls/24.5% (11) boys; median age 15 [13; 15] y/o; most frequent clinical syndrome was cutaneous (75.5%); kidney damage was noted in 40% of cases. 86.6% had hematological disorders as follows: thrombocytopenia and leukopenia (48.9%), anemia (46.6%): Coombs-positive anemia (71.4%), lymphopenia (37.7%) and increased ESR (66.6%). Antinuclear factor (ANF Hep2) was detected in all cases. According to the SLEDAI-2K scale, the median disease activity was 11 [7; 16] points. Low disease activity (less than 6 points) was observed in 4.4% (2), average (6 to 10 points) in 44.4% (20), high (11 to 19 points) in 37.7% (17), above average (over 20 points) in 13.3% (6). Moreover, disease activity was higher in girls (p=0.940) and a relationship was found between the time required for diagnosis and disease activity according to the SLEDAI-2K scale (p=0.206). Drug therapy: glucocorticoids (GCS) orally in all cases, intravenous pulse GCS therapy in 71.0%. Hydroxychloroquine therapy was prescribed in 100.0%, mycophenolate mofetil in 57.7%, intravenous immunoglobulin in 37.7%, cyclophosphamide in 13.3%, methotrexate in 6.6%, biological therapy in 31.0%, the drug of choice was rituximab. Conclusion: updating the data on the frequency of various variants of SLE debut as well as identifying the new trigger factors contributing to the development of the disease are necessary steps aiming to increasing the awareness of the SLE course with its debut in childhood, optimizing the diagnosis process and reducing the risk for complications.

Progranulin mediates the onset of pristane induced systemic lupus erythematosus

BackgroundsProgranulin (PGRN) is a growth factor-like molecule with diverse roles in homeostatic and pathogenic processes including the control of immune and inflammatory responses. Pathogenic inflammation is a hallmark of systemic lupus erythematosus (SLE) and elevated serum levels of PGRN has been evaluated as a biomarker of disease activity in SLE. However, the role of PGRN in SLE has not been fully investigated. This study is aimed to determine the potential involvements of PGRN in SLE.MethodsWild type (WT) and PGRN knockout (PGRN-/-) C57BL/6 mice received intraperitoneal injection of pristane for induction of a murine model of SLE. Sera were collected every biweekly and levels of anti-dsDNA antibody, IgG, and inflammatory factors were measured. Mice were sacrificed 5 months later and the renal lesions, as well as the proportions of T cell subtypes in the spleen were analyzed.ResultsFollowing exposure to pristane, PGRN-/- mice generated significantly lower levels of anti-dsDNA antibody and IgG relative to WT mice. PGRN-/- mouse kidneys had less IgG and collagen deposition compared with WT mice after pristane injection.ConclusionThe results indicate that PGRN participates in inflammatory response and renal damage in pristane induced SLE models, suggesting that PGRN mediates the onset of SLE.

Predicting the risk of cardiovascular and cerebrovascular event in systemic lupus erythematosus: a Chinese SLE treatment and research group study XXVI

ObjectivePatients with systemic lupus erythematosus (SLE) have an increased risk of cardiovascular and cerebrovascular events (CCEs). Furthermore, CCE was a significant factor contributing to mortality in patients with SLE. However,...

Exploring gastrointestinal manifestations in childhood onset systemic lupus erythematosus - Insights from a multicenter study.

Systemic lupus erythematosus (SLE) constitutes an autoimmune disorder with potential involvement of the gastrointestinal system (GIS). Our objective was to assess the gastrointestinal (GI) manifestations in patients diagnosed with childhood onset SLE. The study cohort consisted of 123 patients with childhood onset-SLE and GIS involvement from 16 referral departments of pediatric rheumatology. All participants met the Systemic Lupus International Collaborating Clinics criteria. Out of 123 patients, 78 (63.4%) exhibited GIS involvement at the initial SLE diagnosis, whereas the remaining 45 (36.6%) developed GI symptoms after a median duration of 12 (3-140) months. Eighty-two (66.7%) individuals experienced symptoms related to the GI tract, whereas the remaining patients received a diagnosis of GI involvement through laboratory assessments. The predominant initial GIS involvement symptom was abdominal pain, observed in 77 (62.6%) patients, followed by elevated hepatic transaminases in 70 (56.9%), hepatomegaly in 40 (32.5%), diarrhea in 26 (21.1%), and jaundice in 11 (8.9%) patients. The GIS involvement was associated with SLE in 82 (78.6%), while it resulted from drug-related adverse events in 35 (28.5%) patients or comorbidities in 6 (0.5%) patients. GIS involvement should be considered in all childhood onset-SLE patients, especially in the presence of suggestive symptoms or elevated hepatic transaminases. It is also crucial to consider SLE in the differential diagnosis of GIS manifestations in children. Apart from GIS involvement directly associated with SLE, adverse events of drugs should be kept in mind.

IL-17B alleviates the pathogenesis of systemic lupus erythematosus by inhibiting FASN-mediated differentiation of B cells.

The interleukin 17 (IL-17) family of cytokines has emerged as a critical player in autoimmune disease, including systemic lupus erythematosus (SLE). However, the role of IL-17B, a poorly understood cytokine, in the pathogenesis of SLE is still not known. In this study, we investigated the role of IL-17B in the activation and differentiation of B cells, and the pathogenesis of SLE. Intriguingly, IL-17B deficiency aggravated disease in lupus-prone mice and promoted the activation of B cells and the differentiation of germinal center B cells and plasma cells, while recombinant mouse IL-17B (rmIL-17B) significantly alleviated disease in lupus-prone mice. Mechanistically, rmIL-17B inhibited the activation of the Toll-like receptor and interferon pathways in B cells by downregulating fatty acid synthase-mediated (FASN-mediated) lipid metabolism. Loss of FASN significantly alleviated the disease in lupus-prone mice and inhibited the activation and differentiation of B cells. In addition, B cells had greater FASN expression and lower IL-17RB levels in patients with SLE than in healthy controls. Our study describes the role of IL-17B in regulating B cell activation and differentiation, and alleviating the onset of SLE. These findings will lay a theoretical foundation for further understanding of the pathogenesis of SLE.

Hydroxychloroquine and Cardiovascular Events in Patients With Systemic Lupus Erythematosus

Systemic lupus erythematosus (SLE) predisposes individuals to early cardiovascular (CV) events. While hydroxychloroquine is thought to mitigate CV risk factors, its protective role against CV events, particularly arterial ones, remains to be confirmed. To evaluate the association between hydroxychloroquine and the risk of myocardial infarction (MI), stroke, and other thromboembolic events (OTEs) in patients with SLE. This cohort study using a nested case-control design was conducted within the National French Healthcare Database (SNDS), which represents 99% of the French population, from 2010 to 2020. Participants were the cohort of all patients with SLE recorded in the SNDS. Patients with SLE experiencing CV events during the study period were the case group; those without CV events were controls. The analysis period was from February 2022 to September 2023. Hydroxychloroquine use within 365 days prior to the index date, defined as current (within 90 days), remote (91-365 days), or no exposure within the previous 365 days. Outcomes of interest were MI, stroke, and OTE, analyzed individually and as a composite outcome (primary analysis). Controls were matched to patients with CV events by age, sex, time since SLE onset and entry into the SNDS database, index date, prior antithrombotic and CV medication, chronic kidney disease, and hospitalization. Multivariable conditional logistic regression was performed using hydroxychloroquine exposure as the main independent variable. The SLE cohort included 52 883 patients (mean [SD] age, 44.23 [16.09] years; 45 255 [86.6%] female; mean [SD] follow-up, 9.01 [2.51] years), including 1981 patients with eligible CV events and 16 892 matched control patients. There were 669 MI events, 916 stroke events, and 696 OTEs in the individual outcome studies. For current exposure to hydroxychloroquine, the adjusted odds were lower for composite CV events (odds ratio [OR], 0.63; 95% CI, 0.57-0.69) as well as for MI (OR, 0.72; 95% CI, 0.60-0.85), stroke (OR, 0.69; 95% CI, 0.60-0.81), and OTEs (OR, 0.58; 95% CI, 0.49-0.69) individually compared with no hydroxychloroquine exposure within 365 days. In this nationwide cohort study of patients with SLE, a protective association was found between the current use of hydroxychloroquine and the occurrence of CV events, but not between remote use of hydroxychloroquine and CV outcomes, highlighting the value of continuous hydroxychloroquine treatment in patients with SLE.

SPATS2L is a positive feedback regulator of the type I interferon signaling pathway and plays a vital role in lupus.

Through genome-wide association studies (GWAS) and integrated expression quantitative trait locus (eQTL) analyses, numerous susceptibility genes ("eGenes", whose expressions are significantly associated with common variants) associated with systemic lupus erythematosus (SLE) have been identified. Notably, a subset of these eGenes is correlated with disease activity. However, the precise mechanisms through which these genes contribute to the initiation and progression of the disease remain to be fully elucidated. In this investigation, we initially identify SPATS2L as an SLE eGene correlated with disease activity. eSignaling and transcriptomic analyses suggest its involvement in the type I interferon (IFN) pathway. We observe a significant increase in SPATS2L expression following type I IFN stimulation, and the expression levels are dependent on both the concentration and duration of stimulation. Furthermore, through dual-luciferase reporter assays, western blot analysis, and imaging flow cytometry, we confirm that SPATS2L positively modulates the type I IFN pathway, acting as a positive feedback regulator. Notably, siRNA-mediated intervention targeting SPATS2L, an interferon-inducible gene, in peripheral blood mononuclear cells (PBMCs) from patients with SLE reverses the activation of the interferon pathway. In conclusion, our research highlights the pivotal role of SPATS2L as a positive-feedback regulatory molecule within the type I IFN pathway. Our findings suggest that SPATS2L plays a critical role in the onset and progression of SLE and may serve as a promising target for disease activity assessment and intervention strategies.

Comparison of Clinical and Laboratory Characteristics in Lupus Nephritis vs. Non-Lupus Nephritis Patients-A Comprehensive Retrospective Analysis Based on 921 Patients.

Background: Lupus nephritis (LN) is an inflammation of the kidneys that is related to systemic lupus erythematosus (SLE). This study aimed to evaluate the differences in clinical and laboratory characteristics between LN and non-LN SLE patients. Methods: We conducted a retrospective analysis of medical records collected from SLE patients treated at the University Hospital in Kraków, Poland, from 2012 to 2022. All patients met the 2019 European League Against Rheumatism and the American College of Rheumatology (EULAR/ACR) criteria for SLE. Results: Among 921 SLE patients, LN was documented in 331 (35.94%). LN patients were younger at SLE diagnosis (29 vs. 37 years; p < 0.001) and had a male proportion that was 2.09 times higher than the non-LN group (16.62% vs. 7.97%; p < 0.001). They were more often diagnosed with serositis and hematological or neurological involvement (p < 0.001 for all). Hypertension and hypercholesterolemia occurred more frequently in these patients (p < 0.001 for both). LN patients exhibited a higher frequency of anti-dsDNA, anti-histone, and anti-nucleosome antibodies (p < 0.001 for all). Conversely, the non-LN group had a 1.24-fold (95% CI: 1.03-1.50; p = 0.021) increase in the odds ratio of having positive anti-cardiolipin IgM antibody results. LN patients were more frequently treated with immunosuppressants. The risk factors for experiencing at least three LN flares included female sex, younger age at the onset of LN or SLE, LN occurring later than SLE onset, the presence of anti-nucleosome or anti-dsDNA antibodies, and certain SLE manifestations such as myalgia, arthritis, proteinuria > 3.5 g/day, and pathological urinary casts in the urine sediment. Conclusions: LN patients differ from non-LN patients in the age of SLE diagnosis, treatment modalities, and autoantibody profile and have more frequent, severe manifestations of SLE. However, we still need more prospective studies to understand the diversity of LN and its progression in SLE patients.

Pregnancy outcomes and risk factors analysis in patients with systemic lupus erythematous

BackgroundThe management of systemic lupus erythematosus (SLE) during pregnancy remains a challenge currently. Identifying early predictors of adverse pregnancy outcomes in SLE patients can help to develop treatment plan and improve prognosis. The aim of this study is to explore the clinical and laboratory variables in the early pregnancy that can predict adverse neonatal and maternal outcomes, thereby facilitating the grading management of SLE.MethodsA retrospective analysis was conducted on 126 pregnant women with SLE who were admitted to Zhongnan Hospital of Wuhan University between January 2017 and December 2022. All enrolled patients were diagnosed (including newly diagnosed and previously diagnosed) during first trimester of pregnancy and their clinical records, laboratory results and pregnancy outcomes were reviewed. The association between the clinical and laboratory characteristics of patients at 12 gestational age and the adverse neonatal (ANOs) as well as maternal outcomes (AMOs) were analyzed.ResultsA total of 117 live births (92.8%) were recorded in the study. ANOs occurred in 59 (46.8%) cases, including fetal loss in 9 cases (7.1%), preterm birth in 40 cases (31.7%), small for gestational (SGA) in 15 cases (11.9%), and complete heart block in 2 cases (1.5%). Univariate analysis showed that disease activity index (P < 0.0001), lupus nephritis (P = 0.0195), anti-SSB positivity (P = 0.0074) and hypocomplementemia (P = 0.0466) were related to ANOs. However, multivariate analysis showed that only disease activity during early pregnancy was an independent predictor for ANOs (OR = 7.053, 95% CI: 1.882 to 26.291, P = 0.004). In addition, 48 patients experienced AMOs during subsequent trimester, including 24 (19.0%) patients with disease flare and 23 (18.3%) patients with pre-eclampsia. Unplanned pregnancy (P = 0.010), active disease (P = 0.0004), new onset SLE (P = 0.0044) and lupus nephritis (P = 0.0009) were associated with AMOs in univariate analysis, while disease activity was identified as an independent risk factor for AMOs (OR = 2.553, 95% CI: 1.012–6.440, P = 0.047).ConclusionActive disease in early pregnancy is associated with adverse pregnancy outcomes. For patients with high risk factor for ANOs and AMOs, more intensive treatment and follow-up should be a wise measure. Especially for those who suffer from active disease, they should be fully informed and given the option to terminate or continue their pregnancy.

Late Onset Systemic Lupus Erythematosus: Different Clinical, Serological Presentations and Damage Compared to Adult Lupus in Egypt

Abstract Background Comparing cases of adult onset and late onset systemic lupus erythematous (SLE) reveals significant differences in clinical, serological, disease activity, and damage score. Objective This study aimed to analyze clinical manifestations, laboratory data, serological markers, and prognosis of late-onset SLE (L-SLE) and for comparing with adult- onset SLE. Patients and Methods One hundred fifty individuals with SLE were included in a cross-sectional study conducted at Ain Shams University Hospital divide into Group 1: 100 cases with adult-onset (age of onset ≥ 19 years and below 50 years). Group 2: 50 Patients with L-SLE (age of onset ≥ 50 years). All patients were subjected to medical history, physical examination, disease activity measured by the SLE disease activity index (SLEDAI-2K) and a damage score. Laboratory investigations as complete blood count (CBC), serum creatinine, anticardiolipin antibodies, lupus anticoagulant, protein creatinine ratio, serum complement (C3, C4), anti-dsDNA antibody, and antinuclear antibodies (ANA). Results Mucocutaneous manifestations, frequency of hematuria, proteinuria, urinary cast, consumed C3, positive anti-dsDNA antibodies, anti-cardiolipin antibody and lupus anticoagulant titers had considerably greater rates in-group 1 compared to group 2 (P-value &amp;lt;0.05) while group 2 had significantly more musculoskeletal symptoms (P-value &amp;lt;0.05). The SLEDAI scores of the two groups were equivalent, however the damage index was greater in group 2 (P-value 0.00). Neuropsychiatric, cutaneous, renal, and skin damage were more frequent in group 1, while musculoskeletal, endocrinal, pulmonary, cardiovascular and ocular damage were more frequent in- group 2. Conclusion L-SLE is different from adult onset SLE with more frequent damage.

#1602 Lupus nephritis multidisciplinary consultation: a new strategy for increasingly complex patients

Abstract Background and Aims Lupus nephritis (LN) is a major course of morbidity and mortality in patients with systemic lupus erythematosus (SLE), best managed by a multidisciplinary group. Recent management advances require greater collaboration between specialists and individualized treatments in severe cases. Method We conducted a retrospective, single-center study of a cohort of incident patients which were diagnosed with LN between 2015 and 2022 and began follow-up in the multidisciplinary rheumatology and nephrology consultation of our institution. Clinical and analytical characteristics at diagnosis and during follow-up were studied. The primary endpoint was complete remission rate at follow-up end, according to GLOSEN (Grupo de Estudio de Enfermedades Glomerulares de la SEN) [1] criteria. Changes in immunosuppression schemes over time were studied. Results 26 patients (92.3% women) were included. Median age at SLE diagnosis was 30.5 years [Interquartile range (IQR) 23.7 – 44.2]. Most patients were Hispanic (14 patients, 53.8%). Median time between SLE and LN diagnosis was 21 months (IQR 0-129 months). In 9 patients (34.6%), SLE and LN onset happened simultaneously. Most common renal manifestation was hematuria, which appeared in 19 patients (73.1%). Median proteinuria was 1.83 g/d (IQR 0.88-2.92) and serum creatinine level, 0.69 (IQR 0.51-1.18). Hypocomplementemia (88.5%) and positivity to anti-DNA (69.2%) were common. Most frequent classes found in renal biopsies were IV (30.8%) and V (23.1%). At LN debut, SLEDAI score, which assesses SLE manifestations, had a median value of 16 (IQR 12-20). Mycophenolate mofetil (96.2%) was the main induction agent. Intravenous steroids were administered in 14 patients (53.8%) and the rest received steroids at a dose of 0.5 mg/kg/day. Addition of another therapy, mainly tacrolimus (6 patients, 23.1%) and belimumab (4 patients, 15.4%), was needed to achieve remission in 12 patients (46.2%). In 8 of them (66.6%), treatments were added within the first 6 months. These 12 patients had less chronicity in the biopsy (median chronicity index: 0 vs. 2; p 0.004) and had higher proteinuria (median 1.41 g/day vs. 0.4 g/day; p 0.001). Likewise, SLEDAI score at 3 months was significantly higher in these 12 patients than in the standard of care group (median SLEDAI score 13 vs. 8; p 0.016). No differences were found in 3 month serum creatinine (p 0.181) or 3 month hematuria (p 0.496) After a median follow-up of 47 months, 15 (57.7%) and 9 patients (34.6%) achieved complete and partial remission, respectively. No differences in percentages of remission were observed between the 2 groups. Steroids were withdrawn in 12 patients (46.2%). Median steroid dose at the end of follow-up was 5 mg (IQR 3-5). Conclusion In our LN cohort, higher SLEDAI and proteinuria indicated the need for an individualized approach. Collaboration between Rheumatology and Nephrology specialists is essential to identify patients with these needs.

Interplay between the Chaperone System and Gut Microbiota Dysbiosis in Systemic Lupus Erythematosus Pathogenesis: Is Molecular Mimicry the Missing Link between Those Two Factors?

Systemic lupus erythematosus (SLE) is a multifactorial autoimmune disease characterized by self-immune tolerance breakdown and the production of autoantibodies, causing the deposition of immune complexes and triggering inflammation and immune-mediated damage. SLE pathogenesis involves genetic predisposition and a combination of environmental factors. Clinical manifestations are variable, making an early diagnosis challenging. Heat shock proteins (Hsps), belonging to the chaperone system, interact with the immune system, acting as pro-inflammatory factors, autoantigens, as well as immune tolerance promoters. Increased levels of some Hsps and the production of autoantibodies against them are correlated with SLE onset and progression. The production of these autoantibodies has been attributed to molecular mimicry, occurring upon viral and bacterial infections, since they are evolutionary highly conserved. Gut microbiota dysbiosis has been associated with the occurrence and severity of SLE. Numerous findings suggest that proteins and metabolites of commensal bacteria can mimic autoantigens, inducing autoimmunity, because of molecular mimicry. Here, we propose that shared epitopes between human Hsps and those of gut commensal bacteria cause the production of anti-Hsp autoantibodies that cross-react with human molecules, contributing to SLE pathogenesis. Thus, the involvement of the chaperone system, gut microbiota dysbiosis, and molecular mimicry in SLE ought to be coordinately studied.

Clinical profile, laboratory parameters and management outcomes in an eight-year-old female with childhood lupus nephritis

Systemic lupus erythematosus (SLE) is a chronic, multisystem, autoimmune disorder characterized by widespread inflammation of connective tissues affecting the skin, joints, kidneys, heart, lungs and nervous system. SLE is most often diagnosed in women during the second to fourth decades of life, but 15-20% cases are found in childhood. Renal involvement occurs in the majority of childhood onset SLE (cSLE) patients and is often fatal and hence constitutes an important determinant of prognosis. Multidisciplinary care is necessary for children with lupus nephritis in terms of immunosuppressive regimes with a common goal of achieving and maintaining renal remission. Despite a low prevalence rate of cSLE, it manifests with fatal complications like lupus nephritis in majority of cases. Renal biopsy is gold standard for staging of lupus nephritis, thus, deciding the modality of management and prognostication of cSLE.

Immune thrombocytopenia in systemic lupus erythematosus: Prevalence, risk factors, and a novel predictive model for risk assessment

IntroductionImmune thrombocytopenia (ITP) is a potentially severe manifestation of systemic lupus erythematosus (SLE) reported in 7–40% of SLE patients. ITP has been associated with a higher risk of organ damage and mortality. ObjectivesTo describe which factors are associated with the presence of ITP in SLE patients. MethodsRetrospective case–control study. Cases were defined as SLE patients who had ever developed ITP and were sex- and age-matched with two controls. A predictive model was constructed to identify SLE patients who were at risk of developing ITP. ResultsITP prevalence in our SLE cohort was 8.35%. Cases had a higher frequency of hemolytic anemia, while controls had a higher prevalence of arthritis at SLE diagnosis. During SLE progression, cases tested positive for anticardiolipin, anti-β2-glycoprotein 1, and lupus anticoagulant antibodies more frequently. Cases received mycophenolic acid and azathioprine more often than controls and had a higher SLICC/ACR score. The model demonstrated a sensitivity of 87.53%, a positive predictive value of 81.92%, a specificity of 80.50%, area under the curve of 83.92%, a F1 of 83% and an overall accuracy of 83.68%. The variables that best explain the model were hemolytic anemia, arthritis, oral ulcers, Raynaud's phenomenon, low C4, low CH50, anticardiolipin and anti-β2GP1 antibodies. ConclusionSLE patients who develop ITP have a distinct phenotype characterized by more hemolytic anemia and less arthritis at SLE onset, and higher prevalence of antiphospholipid syndrome antibodies during SLE progression. This phenotype is associated with heightened organ damage and the need for more intensive therapies and stricter follow-up. Our predictive model has demonstrated an impressive ability to identify SLE patients at risk of developing ITP.

Hematological manifestation of Pediatric Systemic Lupus Erythematosus (SLE) - A single centered cross-sectional study.

Systemic lupus erythematosus (SLE), the commonest type of lupus, is an autoimmune multisystemic disorder that can affect any organ system of the body, especially blood vessels and connective tissues, causing widespread inflammation. Pediatric onset of SLE is a rare condition with more hematological involvement. This study was undertaken to observe various hematological abnormalities and their association with various autoantibodies present in pediatric SLE in Eastern India. It was a single-centered, cross-sectional, observational, hospital-based study conducted in the Department of Pediatric Medicine in collaboration with the Department of Rheumatology in IPGME and R and SSKM Hospital, Kolkata. The duration of the study was 1.5 years, and a total of 30 children up to 12 years of age of either gender were enrolled. Study participants were evaluated for various parameters like demographic, hematological (anemia, neutropenia, leucopenia, lymphopenia, and thrombocytopenia), biochemical (CRP, Lactate dehydrogenase (LDH), and bilirubin), autoantibodies (anti-dsDNA, anti-Ro 52, and anti-Ribonucleoprotein [RNP]), and SLE related pathologies (Cutaneous, nephritis, serositis). In the present study, most of the participants had arthritis, muscle pain (86.66%), and hematological involvement (80%). Among cytopenias, anemia was the commonest. dsDNA autoantibody was positive in most of the patients (83%), and about one-third suffered from autoimmune hemolytic anemia (AIHA). No association was observed between autoantibodies and various hematological manifestations. It can be concluded from the present study that anemia is the most common cytopenia in pediatric SLE, but there is no association between autoantibodies and these cytopenias. However, study on larger population may give better results.

Cardiovascular risk in young people with childhood onset systemic lupus erythematosus

Cardiovascular risk in young people with childhood onset systemic lupus erythematosus

Aberrant phenotypes of circulating γδ-T cells may be involved in the onset of systemic lupus erythematosus.

Human gamma-delta T cells (γδ-T cells) play crucial roles in both innate and adaptive immune responses. However, much less is known about the immune status of γδT cells in systemic lupus erythematosus (SLE) patients. The objective of this study was to explore potential relationships between the frequency of γδ-T-cell subpopulations and disease activity, autoantibody titres and renal involvement in patients with SLE. Circulating γδ-T cells and their subsets (Vδ1+ T cells, Vδ2+ T cells and γδ-T-cell subpopulations defined by expression of surface receptors, including NKG2D, NKp30, NKp46 and PD-1), were identified via flow cytometry. Sixty active SLE patients were selected, including 41 new-onset and 19 relapsing cases. One hundred healthy controls (HCs) were enrolled as the control group. Percentages of these cell subsets in SLE patients and HCs and their relationships with disease activity were analysed. Twenty-two of the 41 new-onset SLE patients were assessed before and after treatment. Changes in the frequencies of these cell subsets and their relationships with renal involvement were also analysed. Compared with that in HCs, the percentage of total γδ-T cells among CD3+ T cells in SLE patients was significantly lower. An imbalance in the proportions of Vδ1+ and Vδ2+ T cells among γδ-T cells was observed. The proportion of Vδ1+ T cells among γδ-T cells was significantly greater in SLE patients than in HCs, while the proportion of Vδ2+ T cells was significantly lower. Expression levels of PD-1, NKG2D, NKp30 and NKp46 in Vδ1+ T cells and Vδ2+ T cells from SLE patients were generally significantly increased, except for expression of NKG2D in Vδ2+ T cells. Moreover, Vδ2+ T cells, Vδ1+ T cells and Vδ1+PD-1+ T cells were associated with disease activity, and an increase in Vδ2+ T-cell frequency and a decrease in PD-1 expression by γδ-T cells might be associated with effective treatment. Interestingly, our results indicated that Vδ2+ T cells and their Vδ2+NKp30+ T-cell subpopulation might be associated with renal involvement in SLE. A broad range of anomalies in the proportions of γδ-T-cell subsets and γδ-T cells in SLE patients may be involved in the pathogenesis of SLE. There is a strong association between Vδ2+ T cells and their Vδ2+NKp30+ T-cell subpopulation and LN occurrence. Our results indicate that γδ-T cells and their subpopulations might be key players in disease immunopathology and renal involvement in SLE.

Environmental exposure to polycyclic aromatic hydrocarbons: An underestimated risk factor for systemic lupus erythematosus onset and progression

ObjectiveTo investigate the link between systemic lupus erythematosus (SLE) incidence and exposure to environmental polycyclic aromatic hydrocarbons (PAH). MethodsA case-control study (ChiCTR2000038187) involving 316 SLE patients and 851 healthy controls (HCs) was executed. Environmental exposure was assessed via a questionnaire, stratified by gender and age (females <35 and ≥35 years, males). Blood samples collected from 89 HCs, 85 inactive, and 95 active SLE patients were used to measure serum benzo[a]pyrene diol epoxide -albumin (BPDE-Alb) adducts and PAH concentrations, indicating long-term and short-term exposure respectively. Intergroup comparisons and statistical analyses were conducted using R version 4.3.1. ResultsDiverse patterns were found in how environmental factors affect SLE onset across different demographics. Lifestyle exposure factors were found to be a stronger determinant of SLE onset than occupational exposure factors in women under 35. Indoor air pollution had a significant impact on SLE incidence, potentially comparable to outdoor air pollution. Lifestyle-related PAH exposure had a greater impact on SLE than occupational PAH exposure. PAH exposure levels progressively increase from HCs to inactive and active SLE patients. Active SLE patients show markedly higher BPDE-Alb levels than HCs. ConclusionsEnvironmental PAH, particularly lifestyle-related, are significant, yet under-recognized, risk factors for SLE. Statement of environmental implicationWe examined the relationship between exposure to environmental polycyclic aromatic hydrocarbons (PAH) and the incidence of systemic lupus erythematosus (SLE). PAH, prevalent in sources such as cigarette smoke, air pollution, and charred food, pose significant health hazards. This study is the first to investigate specific PAH exposure levels in SLE patients. We determined actual PAH exposure levels in both SLE patients and healthy individuals and indicated that long-term PAH exposure biomarker is more reliable for evaluating exposure in non-occupationally exposed groups like SLE, compared to short-term markers. These findings provide valuable insights for future research on similar non-occupationally exposed populations.

Comparison of Attainment and Protective Effects of Lupus Low Disease Activity State in Patients With Newly Diagnosed Versus Established Systemic Lupus Erythematosus.

To assess whether Lupus Low Disease Activity State (LLDAS) attainment is associated with favorable outcomes in patients with recent onset systemic lupus erythematosus (SLE). Data from a 13-country longitudinal SLE cohort were collected prospectively between 2013 and 2020. An inception cohort was defined based on disease duration < 1 year at enrollment. Patient characteristics between inception and noninception cohorts were compared. Survival analyses were performed to examine the association between LLDAS attainment and damage accrual and flare. Of the total 4106 patients, 680 (16.6%) were recruited within 1 year of SLE diagnosis (inception cohort). Compared to the noninception cohort, inception cohort patients were significantly younger, had higher disease activity, and used more glucocorticoids, but had less organ damage at enrollment. Significantly fewer inception cohort patients were in LLDAS at enrollment than the noninception cohort (29.6% vs 52.3%, P < 0.001), but three-quarters of both groups achieved LLDAS at least once during follow-up. Limiting analysis only to patients not in LLDAS at enrollment, inception cohort patients were 60% more likely to attain LLDAS (hazard ratio 1.37, 95% CI 1.16-1.61, P < 0.001) than noninception cohort patients and attained LLDAS significantly faster. LLDAS attainment was significantly protective against flare in both the inception and noninception cohorts. A total of 88 (13.6%) inception cohort patients accrued organ damage during a median 2.2 years of follow-up. LLDAS attainment is protective from flare in recent onset SLE. Significant protection from damage accrual was not observed because of low rates of damage accrual in the first years after SLE diagnosis. (ClinicalTrials.gov: NCT03138941).