Systemic Lupus Erythematosus Group Research Articles

Integrative analysis of systemic lupus erythematosus biomarkers: Role of fecal hsa-mir-223–3p and gut microbiota in transkingdom dynamics

Systemic lupus erythematosus (SLE) involves a florid set of clinical manifestations whose autoreactive origin is characterized by an overactivation of the immune system and the production of a large number of autoantibodies. Because it is a complex pathology with an inflammatory component, its pathogenesis is not yet fully understood, assuming both genetic and environmental predisposing factors. Currently, it is known that the role of the human microbiome is crucial in maintaining the transkingdom balance between commensal microorganisms and the immune system. In the present work we study the intestinal microbiota of Argentine patients with different stages of SLE receiving or not different treatments. Microbiota composition and fecal miRNAs were assessed by 16 S sequencing and qPCR. hsa-miR-223–3p, a miRNA involved in several inflammation regulation pathways, was found underexpressed in SLE patients without immunosuppressive treatment. In terms of microbiota there were clear differences in population structure (Weighted and Unweighted Unifrac distances, p-value <0.05) and core microbiome between cases and controls. In addition, Collinsella, Bifidobacterium, Streptococcus genera and aromatics degradation metabolisms were overrepresented in the SLE group. Medical treatment was also determinant as several microbial metabolic pathways were influenced by immunosuppressive therapy. Particularly, allantoin degradation metabolism was differentially expressed in the group of patients receiving immunosuppressants. Finally, we performed a logistic regression model (LASSO: least absolute shrinkage and selection operator) considering the expression levels of the fecal hsa-miR223–3p; the core microbiota; the differentially abundant bacterial taxa and the differentially abundant metabolic pathways (p<0.05). The model predicted that SLE patients could be associated with greater relative abundance of the formaldehyde oxidation pathway (RUMP_PWY). On the contrary, the preponderance of the ketodeoxyoctonate (Kdo) biosynthesis and activation route (PWY_1269) and the genera Lachnospiraceae_UCG_004, Lachnospira, Victivallis and UCG_003 (genus belonging to the family Oscillospiraceae of the class Clostridia) were associated with a control phenotype. Overall, the present work could contribute to the development of integral diagnostic tools for the comprehensive phenotyping of patients with SLE. In this sense, studying the commensal microbial profile and possible pathobionts associated with SLE in our population proposes more effective and precise strategies to explore possible treatments based on the microbiota of SLE patients.

#2074 Aberrant m6A modification pattern and m6A-related proteins expression in SLE

Abstract Background and Aims Systemic lupus erythematosus (SLE) is an autoimmune disease of unknown cause. N6-methyladenosine (m6A) is the most common mRNA modification and is involved in various immune processes leading to immune homeostasis disorders. However, the role of m6A in dysregulated immune response of SLE remains unknown. Here, we aim to explore the m6A pattern and expression of m6A-related proteins in the SLE. Method Peripheral blood mononuclear cells (PBMCs) from healthy controls and SLE patients were collected to compare the m6A modification profile by methylated RNA immunoprecipitation sequencing (MeRIP-seq). Expression of 3 m6A-related proteins, including methyltransferase 3 (METTL3), Alkb homologue 5 (ALKBH5), and Fat mass and obesity-associated protein (FTO) and in PBMCs of SLE patients were detected using western blotting (WB). Renal METTL3 expression was further examined in MRL/lpr mice using WB and immunofluorescence. Results SLE patients contained only 28.74% of the same m6A peaks as healthy controls, and 7.881% of the peaks were specific in SLE group (Fig. 1A). The m6A differential peaks were enriched in exon, intron and near 3’ UTR region (Fig. 1B). In addition, compared with healthy controls, m6A modified motifs were obviously aberrant in SLE patients (Fig. 1C). GO and KEGG enrichment analysis showed that some of the m6A peak differential genes were associated with regulation of cellular process, and cytokine-cytokine receptor interaction signaling pathway (Fig. 1D and 1E). Expression of METTL3 and ALKBH5 in SLE patients were significantly increased (METTL3, SLE-AP vs HC, p &amp;lt; 0.001; SLE-SP vs HC, p = 0.0042; ALKBH5, SLE-AP vs HC, p &amp;lt; 0.001; SLE-SP vs HC, p &amp;lt; 0.001; Fig. 1F). There were no significant differences in FTO expressions between the two groups (SLE-AP vs HC, p = 0.167; SLE-SP vs HC, p = 0.477; Fig. 1F). Compared with C57BL/6 mice, renal METTL3 in the MRL/lpr mice was distinctly elevated (p &amp;lt; 0.001; Fig. 1G), which co-localized with CD138 + plasma cells (Fig. 1H). Conclusion These results suggested a distinctly abnormal m6A modification features and m6A-related proteins in SLE patients, indicating the potential significant role of m6A in the pathogenesis of SLE.

Accuracy of Anti-SARS-CoV-2 Antibody in Comparison with Surrogate Viral Neutralization Test in Persons Living with HIV, Systemic Lupus Erythematosus, and Chronic Kidney Disease.

The presence of the anti-SARS-CoV-2-RBD antibody (anti-RBD) prevents severe COVID-19. We aimed to determine the accuracy of a point-of-care anti-RBD testing implemented in persons living with HIV (PLWH), systemic lupus erythematosus (SLE), and chronic kidney disease (CKD). We enrolled 182 non-comorbid subjects and 335 comorbid subjects (PLWH, SLE, CKD) to test the anti-RBD assay compared to the surrogate viral neutralization test (sVNT) as the reference test. We performed linear correlation analysis between anti-RBD and sVNT, along with an ROC analysis to ascertain the anti-RBD cutoff at 30%, 60%, and 90% inhibition of sVNT, to calculate accuracy. The correlations between anti-RBD and sVNT among all groups were excellent, with R = 0.7903, R = 0.7843, and R = 0.8153 among the non-comorbid, SLE, and CKD groups, respectively, and with significantly higher correlation among the PLWH group (R = 0.8877; p-value = 0.0072) compared to the non-comorbid group. The accuracy of the anti-RBD test among the PLWH and CKD groups was similar to that among the non-comorbid group but showed lower sensitivity in the SLE group (p = 0.000014). The specificity of the test remained high in all groups. In conclusion, the anti-RBD test had excellent correlation with the sVNT. The persistently high specificity in all groups suggests that this test can be reliably utilized to detect the presence of low neutralization capacity, prompting additional vaccination.

B- and T-Lymphocyte Attenuator in Systemic Lupus Erythematosus Disease Pathogenesis.

B- and T-lymphocyte attenuator (BTLA; CD272) is an immunoglobulin superfamily member and part of a family of checkpoint inhibitory receptors that negatively regulate immune cell activation. The natural ligand for BTLA is herpes virus entry mediator (HVEM; TNFRSF14), and binding of HVEM to BTLA leads to attenuation of lymphocyte activation. In this study, we evaluated the role of BTLA and HVEM expression in the pathogenesis of systemic lupus erythematosus (SLE), a multisystem autoimmune disease. Peripheral blood mononuclear cells from healthy volunteers (N = 7) were evaluated by mass cytometry by time-of-flight to establish baseline expression of BTLA and HVEM on human lymphocytes compared with patients with SLE during a self-reported flare (N = 5). High levels of BTLA protein were observed on B cells, CD4+, and CD8+ T cells, and plasmacytoid dendritic cells in healthy participants. HVEM protein levels were lower in patients with SLE compared with healthy participants, while BTLA levels were similar between SLE and healthy groups. Correlations of BTLA-HVEM hub genes' expression with patient and disease characteristics were also analyzed using whole blood gene expression data from patients with SLE (N = 1,760) and compared with healthy participants (N = 60). HVEM, being one of the SLE-associated genes, showed an exceptionally strong negative association with disease activity. Several other genes in the BTLA-HVEM signaling network were strongly (negative or positive) correlated, while BTLA had a low association with disease activity. Collectively, these data provide a clinical rationale for targeting BTLA with an agonist in SLE patients with low HVEM expression.

Two-dimensional speckle-tracking echocardiography in left ventricular systolic function in patients with systemic lupus erythematosus.

To investigate whether two-dimensional speckle-tracking echocardiography (2DSTE) can be considered a criterion for early left ventricular (LV) systolic impairment in patients with systemic lupus erythematosus (SLE) and to further explore the association with each other. We included 38 patients with SLE and assessed the degree of disease activity according to the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) 2000 scoring criteria, together with 38 healthy controls who were matched by sex and age. Routine LV systolic function evaluation parameters were obtained by echocardiography as well as 2DSTE measurement of LV strain parameters to obtain global longitudinal strain (GLS) values, respectively. (I) On routine LV function parameters such as ejection fractions (EF) and left ventricular end-diastolic internal diameter (LVIDd), the SLE group and the control group did not reflect differences. In contrast, on the LV strain parameter obtained from 2DSTE measurements, the GLS values in all cardiac planes were lower in the SLE group than in the control group and showed statistically significant differences. (II) Correlation analysis showed that there was a correlation between SLEDAI and GLS, especially a meaningful correlation with GLS Avg and GLS A4C, with correlation coefficients of 0.35 and 0.47, respectively. The use of 2DSTE can detect early impaired LV systolic function in SLE patients, and GLS is progressively gaining attention as an indicator of subclinical myocardial injury and LV function in SLE patients. The correlation that exists between GLS and SLEDAI might contribute to a better assessment of cardiac involvement in SLE patients. Key Points • Cardiac involvement has become one of the major factors in the poor prognosis of SLE patients, which directly affects the mortality of SLE patients. Traditional echocardiography is difficult to detect early left ventricular function impairment, thus affecting clinicians' judgment and diagnosis. • 2DSTE can recognize subclinical myocardial injury in SLE patients at an early stage, and its derived strain parameters may be used as an indicator to evaluate myocardial involvement and reflect disease activity in SLE patients.

Assessment of hematologic indices for diagnosis in juvenile systemic lupus erythematosus.

The aim was to present effective approaches utilizing novel hematological parameters for early diagnosis of juvenile-onset systemic lupus erythematosus (jSLE). Our study at Umraniye Training and Research Hospital involved a jSLE patient cohort from 2016 to 2022 and matched healthy controls aligning with sex and age. We use the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) for disease activity. Our approach was to analyze leukocyte, neutrophil, lymphocyte, monocyte, and platelet counts, along with ratios such as neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), and monocyte-to-platelet ratio (MPR). We also explored novel indices: the systemic inflammatory index (SII), systemic inflammation response index (SIRI), and aggregate index of systemic inflammation (AISI) to identify relationships between systemic indices and jSLE activity. Upon comparative analysis with the healthy control group, systemic lupus erythematosus (SLE) patients exhibited significantly elevated levels of the hematological parameters NLR, SII, and SIRI (p-values: 0.010, 0.048, 0.025, respectively). Among SLE patients, neutrophil, lymphocyte, and platelet distribution width (PDW) values were notably higher, while hemoglobin, red blood cell distribution width (RDW), and procalcitonin (PCT) values were significantly lower. In comparison, C-reactive protein (CRP) and sedimentation values were markedly elevated in the SLE group in contrast to the healthy control cohort. Patients with significantly elevated disease activity had notably higher values of NLR (p = 0.010) and SII (p = 0.048). Among patients with positive antinuclear antibodies (ANA), elevated levels of NLR, SII, and SIRI were noted (p-values: 0.018, 0.021, 0.035). In this study, the novel hematological markers SII, SIRI, and AISI were found to effectively reflect inflammation in SLE patients, exhibit associations with high disease activity, and demonstrate heightened sensitivity in detecting cases with high disease activity.

Serum long non-coding Ribonucleic Acid H19 serves as a biomarker for systemic lupus erythematosus and participates in the disease progression.

This study aimed to investigate the expression of H19 and its possible molecular mechanism in systemic lupus erythematosus (SLE). The expression of H19 and miR-19b in serum and peripheral blood mononuclear cells (PBMCs) were detected by reverse transcription quantitative polymerase chain reaction (RT-qPCR). Receiver operator characteristic (ROC) curve was constructed to evaluate the diagnostic value of serum H19 in SLE. Pearson correlation coefficient was used to analyze the correlation between serum levels of H19 and miR-19b. Flow cytometry and Cell counting kit-8 (CCK-8) assay were performed to detect cell apoptosis and viability. The levels of pro-inflammatory and anti-inflammatory factors were measured by enzyme-linked immunosorbent assay (ELISA). Luciferase reporter gene assay was conducted to verify the interaction between H19 and miR-19b. The expression of H19 and miR-19b in SLE group were up-regulated and down-regulated, respectively. Serum H19 has certain clinical diagnostic value in SLE. In in vitro studies, overexpression of H19 can significantly inhibit the viability of PBMCs and promote apoptosis and inflammatory response of PBMCs by interacting with miR-19b. The expression of H19 is upregulated in patients with SLE and plays a role in cell function and inflammation by targeting miR-19b in PBMCs, which may be one of the pathological mechanisms of SLE.

Accumulation of Microvascular Target Organ Damage in Systemic Lupus Erythematosus Patients Is Associated with Increased Cardiovascular Risk.

Background: Systemic lupus erythematosus (SLE) is a prototype autoimmune disease associated with increased cardiovascular (CV) burden. Besides increased arterial stiffness and subclinical atherosclerosis, microvascular dysfunction is considered an important component in the pathophysiology of CV disease. However, there is a lack of data regarding the effect of multiple target organ damage (TOD) on CV health. Objectives: This study aimed to evaluate (i) the presence of microvascular changes in SLE in various vascular beds, (ii) the possible associations between the accumulation of microvascular TOD and CV risk and (iii) whether Galectin-3 represents a predictor of combined microvascular TOD. Methods: Participants underwent (i) evaluation of skin microvascular perfusion (laser speckle contrast analysis), (ii) fundoscopy (non-mydriatic fundus camera), (iii) indirect assessment of myocardial perfusion (subendocardial viability ratio) and (iv) determination of urine albumin-to-creatinine ratio (UACR). CV risk was calculated using the QResearch Risk Estimator version 3 (QRISK3). Serum Galectin-3 levels were determined. Results: Forty-seven SLE patients and fifty controls were studied. SLE patients demonstrated impaired skin microvascular reactivity (160.2 ± 41.0 vs. 203.6 ± 40.1%), retinal arteriolar narrowing (88.1 ± 11.1 vs. 94.6 ± 13.5 μm) and higher UACR levels compared to controls. Furthermore, SLE individuals had significantly higher Galectin-3 levels [21.5(6.1) vs. 6.6(6.6) ng/dL], QRISK3 scores [7.0(8.6) vs. 1.3(3.6)%] and a greater chance for microvascular dysfunction. In the SLE group, patients with multiple TOD exhibited higher QRISK3. In the multivariate analysis, the accumulation of TOD correlated with disease activity and Galectin-3 (p < 0.05). Conclusions: Our study showed for the first time that SLE patients exhibit a greater number of cases of TOD. The accumulation of TOD was associated with increased CV risk. Clinicians dealing with SLE should be aware and seek microvascular alterations.

Patients with neuropsychiatric involvement systemic lupus erythematosus experience poorer health-related quality of life and more fatigue than systemic lupus erythematosus patients with no neuropsychiatric involvement, irrespective of neuropsychiatric activity.

Substantial proportions of patients with systemic lupus erythematosus (SLE) report poor health-related quality of life (HRQoL). Our objective was to investigate the impact of neuropsychiatric involvement (NP) in SLE on patient-reported outcomes. We analysed data from four phase III trials (BLISS-52, BLISS-76, BLISS-SC, EMBRACE; N = 2968). The neuropsychiatric SLE (NPSLE) group comprised individuals with NP-British Isles Lupus Assessment group (BILAG) A/B/C/D or score in any descriptor of the NP-SLEDAI-2K at baseline (N = 350), while the non-NPSLE group consisted of patients with NP-BILAG E (N = 2618). HRQoL was assessed with the SF-36, EQ-5D-3L, and FACIT-F. Full health state (FHS) was defined as "no problems" in all EQ-5D dimensions. NPSLE patients reported lower scores in the SF-36 physical and mental component summary compared with the non-NPSLE population (mean±s.d.: 35.7±9.1 versus 39.6±9.6; p<0.001 and 37.3±12.1 versus 41.4±11.0; p<0.001, respectively). NPSLE patients also exhibited impaired HRQoL in all EQ-5D dimensions compared with non-NPSLE patients (p<0.05 for all). A substantially lower proportion among NPSLE patients experienced FHS in comparison with the non-NPSLE group (3.3% versus 14.5%; p<0.001). NPSLE was associated with severe fatigue (23.8±12.2 versus 31.5±11.6; p<0.001). Notably, our findings revealed no discernible distinctions between active and inactive NPSLE patients with regard to SF-36, EQ-5D, FHS, and FACIT-F scores. Neuropsychiatric involvement in patients with SLE has a detrimental effect on HRQoL experience and is associated with severe fatigue, regardless of the degree of neuropsychiatric disease activity. Early intervention is warranted in NPSLE patients to enhance long-term HRQoL experience.

Pregnancies in patients with systemic lupus erythematosus during 2000–2018 in Finland: a case–control study

ObjectivesThe aim was to investigate, how pregnancies proceed in patients with systemic lupus erythematosus (SLE) compared to their individually matched population controls.Material and methodsAdult incident SLE patients were identified from the register of new special reimbursement decisions for SLE drugs in 2000–2014. For each patient, 1–3 randomly selected controls from the Population Register Centre were matched. Data regarding pregnancies were obtained from the Finnish Medical Birth Register, Care Register and Register of Congenital Malformations until 2018. The study utilized data from the Drug Purchase Register and educational information from Statistic Finland.ResultsA total of 163 deliveries for 103 mothers with SLE and 580 deliveries for 371 population controls were identified. The duration of pregnancies in SLE women was significantly shorter compared to controls (38.9 versus 39.6 weeks). There were more urgent Caesarean Sections. (15% versus 9%) and need for care at neonatal intensive care unit (NICU) (21% versus 11%) among deliveries in SLE mothers. No statistical difference was observed between SLE and control groups in the occurrence of preeclampsia or major congenital malformations. Gestational age was 2.5 weeks shorter when the mother experienced pre-eclampsia. Hydroxychloroquine was purchased by 30% of SLE mothers during pregnancy.ConclusionThe course of pregnancies in Finnish SLE patients seems to be quite moderate compared to controls, and no new safety issues were detected. The low utilization of hydroxychloroquine indicates that the benefits of the drug to pregnancy and disease course are not optimally recognized by specialists treating SLE mothers.

Assessment of Arterial Stiffness and Biochemical Markers in Systemic Lupus Erythematosus in the Diagnosis of Subclinical Atherosclerosis.

Patients with systemic lupus erythematosus (SLE) are 2-10 times more likely to develop cardiovascular disease (CVD) than the general population. The assessment of the risk of developing CVD is an important direction for further clinical management. The study was conducted retrospectively and included patients with SLE. The aim of the study was to assess the measurements of pulse wave velocity (PWV), carotid intima-media thickness (CIMT), ankle-brachial index (ABI) and biochemical parameters. Subclinical atherosclerosis was also assessed. The study included 98 patients with SLE with an age- and sex-matched control group of 68 healthy adults. Statistical significance was found in the SLE group and the controls for N-terminal fragment of pro-B-type natriuretic peptide (NT proBNP) (144.87 vs. 36.41 pg/mL, p = 0.0018), high-sensitivity cardiac troponin (hs-cTn) (25.43 vs. 6.38 ng/L, p = 0.0303) and D-Dimer levels (0.73 vs. 0.36 µg/mL, p = 0.0088), left CIMT (1.03 vs. 0.62 mm, p < 0.0001), right CIMT (0.93 vs. 0.63 mm, p < 0.0001) and PWV CF (9.74 vs. 7.98 m/s, p = 0.0294). A positive correlation was found between NT proBNP and PWV CF (r = 0.6880, p = 0.0498) and hs-cTn and PVW carotid-femoral (CF) (r = 0.8862, p = 0.0499) in SLE. A positive correlation was reported between PWV CF and systolic blood pressure (r = 0.5025, p = 0.0487). The measurement of carotid-femoral PWV is a simple, non-invasive, and reproducible method and may independently predict future CVD events and their cause. Further studies are warranted to establish the prognostic value of PWV in patients with SLE, as it may be superior to CIMT measurements in the early stages of vascular disorders.

Does stress response axis activation differ between patients with autoimmune disease and healthy people?

Many studies have shown that patients with autoimmune disease present a hypoactive hypothalamic-pituitary-adrenal (HPA) axis, but the results are controversial. Our objective was to study differences in stress response axis activity between patients with autoimmune disease and healthy people. The study sample consisted of 97 women divided into four groups: 37 healthy women (HW), 21 with systemic lupus erythematosus (SLE), 21 with Sjögren's syndrome (SS), and 18 with systemic sclerosis (SSc). After being exposed to a stress task, participants' skin conductance and salivary cortisol levels were measured in order to assess their response to psychological stress. Diurnal cortisol concentrations were assessed by measuring salivary cortisol in samples collected five times over one day. In addition, self-administered questionnaires were used to assess psychological variables. A time×group interaction effect was found (p=0.003) in salivary cortisol secretion in response to stressful challenge. The healthy group presented normal activation, the SS and SLE groups showed no activation, and the SSc group presented a similar activation pattern to the HW group, except at the time of recovery. Total cortisol production (AUCg) was higher in the SSc group than in the HW group (p=0.001). Differences were also observed in the cortisol AUCg collected over one day between healthy women and patients with SLE (p=0.004) as well as with SSc (p=0.001): women with SLE and SSc presented higher total hormone production than healthy women. Patients with autoimmune disease present a different HPA axis response, which may contribute to the harmful effects of stress in these diseases.

Main circulating CD8&lt;sup&gt;+&lt;/sup&gt; T cell subsets in patients with systemic lupus erythematosus

Relevance. Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by loss of immune tolerance and sustained production of autoantibodies.The aim of the study – to compare composition of peripheral blood cytotoxic CD8+ T lymphocytes (Tc) subsets and assess the clinical significance of them in systemic lupus erythematosus. Materials and methods. A total of 35 SLE patients and 49 healthy volunteers were included in the study. Phenotyping of peripheral blood T cell subpopulations was carried out by means of flow cytometry. T lymphocytes were determined using CD3+, CD4+, CD8+ antibodies. Tc were identified by using CD45RA and CD62L antibodies. Also the expression of chemokine receptors (CCR4, CCR6, CXCR3 and CXCR5) on Tc cells was assessed and the main Tc subpopulations were determined: Type 1 (Tc1), type 2 (Tc2), type 17 (Tc17), type 17/1 (Tc17.1), type 17/22 (Tc17.22) cytotoxic cells and T follicular cytotoxic cells (Tfc).Results. The absolute and relative number of Tc was significantly higher in the group of patients with SLE compared with the control group. Additionally, there was a significant decrease in the relative number of Tc1, Tc 17.1 and Tfc1 and a significant increase in the relative number of Tc2, Tfc 17 and Tfc17.1 within the SLE group when compared to the control group. There were significant positive correlationfor Tc1 and levels of C3 and C4 complement components (r=0.404, p&lt;0.05).Conclusions. The absolute and relative number of peripheral blood Tc subsets is altered in SLE patients compared with the control group. It was found that patients with SLE contained increased number of Tc2 cells, which seems to be associated with markers of disease activity. These results demonstrate a prominent pathological role of Tc2 in SLE. While Tc1, Tc17, Tc17.1, Tfc subsets probably have regulatory functions

Abstract 52: Predictors of Mortality in Patients With Various Rheumatological Conditions Admitted for Stroke: Findings From National Inpatient Sample 2020

Background/Purpose: Stroke imposes a substantial healthcare burden, with ischemic stroke (IS) mortality rising from 2.04 million (1990) to 3.29 million (2019) and projected to reach 4.90 million by 2030 according to the Global Burden of Disease Study. Autoimmune diseases are increasingly associated with chronic conditions and may modify risks by altering underlying pathophysiology. We aimed to compare in-hospital mortality and predictors in stroke patients with secondary rheumatological conditions. Methods: Using the National Inpatient Sample (NIS), we identified patients ≥18 admitted for stroke (Jan 2019 - Dec 2020), stratified into RA, SLE, scleroderma, or vasculitides groups using ICD-10-CM codes. We compared demographics, hospital traits, comorbidities, and outcomes. In-hospital mortality, our primary outcome, was analyzed through multivariate logistic regression using STATA 18. Results: Incorporating a cohort of 32,180 stroke patients, consisting of 23,439 with rheumatoid arthritis (RA), 7,080 with systemic lupus erythematosus (SLE), 960 with scleroderma, and 700 with vasculitides, the main findings are as follows: Mortality rates were 5.73% (n=1345) for RA, 6.28% (n=445) for SLE, 9.37% (n=90) for scleroderma, and 10.71% (n=75) for vasculitides, with no significant disparity between the latter three and RA. Age emerged as a significant mortality predictor (OR 1.01, p &lt;0.01, CI 1.00 to 1.02), while no associations were observed for gender, race, insurance, or hospital traits. Regarding comorbidities, congestive heart failure (OR 1.73, p &lt;0.01, CI 1.32 to 2.26) and liver disease (OR 2.20, p &lt; 0.01, CI 1.27 to 3.79) exhibited connections to higher mortality, while no significant associations were detected for hypertension, dyslipidemia, chronic obstructive pulmonary disease, kidney disease, coronary artery disease, diabetes, obesity, or peripheral vascular disease. Conclusions: Rheumatological diseases, inducing cytokine-mediated systemic inflammation, potentially modify risks in stroke-admitted patients. This study uniquely compares stroke mortality and predictors across distinct rheumatological diseases, revealing age, congestive heart failure, and liver disease as significant mortality predictors.

Systemic lupus erythematosus is associated with increased risk of mortality and acute kidney injury in patients with COVID-19 hospitalization: Insights from a National Inpatient Sample analysis.

The COVID-19 pandemic has significantly impacted global health, especially for patients with chronic diseases that may compromise the immune system. This study investigates the association between systemic lupus erythematosus (SLE) and COVID-19 outcomes. Data from the National Inpatient Sample (NIS) were analyzed to create a retrospective cohort of COVID-19 hospitalizations, comparing patients with and without SLE. Propensity-score matched analysis was conducted to assess the association between SLE and clinical outcomes in COVID-19 hospitalizations. The study included over a million COVID-19 hospitalizations, with approximately 0.5% having a secondary diagnosis of SLE. The SLE-COVID hospitalizations were predominantly female and younger, with a median age of 57.2, while the non-SLE-COVID group had a median age of 64.8 years. Comorbidities such as chronic obstructive pulmonary disease, renal failure, liver disease, and others were more prevalent in the SLE-COVID group. Patients with SLE and COVID-19 had a significantly higher incidence of acute kidney injury requiring dialysis than those without SLE. In-hospital mortality was higher in the SLE group, particularly in the 18-44 year age group (6.15% vs 2.47%, p = .022). COVID-19 patients with SLE are at an increased mortality risk, especially in the younger age group, and a higher incidence of acute kidney injury requiring dialysis. The elevated risk of adverse outcomes underscores the vulnerability of SLE patients to COVID-19. These findings emphasize the importance of special precautions and patient education for individuals with SLE to mitigate the risks associated with COVID-19.

Pro-inflammatory activation of monocytes in patients with immunoinflammatory rheumatic diseases

The pathogenesis of immunoinflammatory rheumatic diseases (IRDs) is based on chronic inflammation, one of the key mechanisms of which may be abnormal activation of macrophages, leading to further disruption of the immune system.The aim – to evaluate the pro-inflammatory activation of circulating monocytes in patients with IRDs.Material and methods. The study included 149 participants: 53 patients with rheumatoid arthritis (RA), 45 – with systemic lupus erythematosus (SLE), 34 – with systemic scleroderma (SSc) and 17 participants without IRD, aged 30 to 65 years. Basal and lipolysaccharide (LPS)-stimulated secretion of monocytes was studied in a primary culture of monocytes obtained by immunomagnetic separation from blood. Quantitative assessment of the cytokines tumor necrosis factor-α (TNF-α), interleukin 1β (IL-1β) and the monocyte chemoattractant protein-1 (MCP-1) was carried out in the culture fluid by ELISA. Pro-inflammatory activation of monocytes was calculated as the ratio of LPS-stimulated and basal secretions.Results. It was shown that the basal secretion of all studied cytokines was significantly increased in all groups of patients with IRDs, except for the secretion of IL-1β in the SLE group, compared with the control. LPS-stimulated secretion of TNF-α was increased and MCP-1 was decreased in patients with IRDs compared to the control group; LPS-stimulated IL-1β secretion only in the SSc group was significantly different from the control group. In the RA group, monocyte activation was reduced for all cytokines compared to the control, in the SLE group – for TNF-α and MCP-1, in the SSc group – for MCP-1.Conclusion. The decrease in pro-inflammatory activation of monocytes in patients with IRDs is due to a high level of basal secretion of cytokines, which can lead to disruption of the adequate immune response in these diseases and is an important link in the pathogenesis of chronic inflammation.

Platelet-to-lymphocyte ratio as a biomarker of systemic inflammation in systemic lupus erythematosus: A meta-analysis and systematic review.

The objective of this study was to evaluate the relationship between the platelet-to-lymphocyte ratio (PLR) and systemic lupus erythematosus (SLE). Additionally, the study aimed to establish an association between PLR and SLE disease activity, specifically lupus nephritis (LN). We conducted a comprehensive search across Medline, Embase, and Cochrane databases to identify relevant articles. Subsequently, we performed meta-analyses to compare PLR between SLE patients and controls, as well as active and inactive SLE cases, along with LN and non-LN groups. Furthermore, a meta-analysis was conducted on correlation coefficients between PLR and various parameters in SLE patients, including the SLE Disease Activity Index (SLEDAI), C3, C4, anti-dsDNA, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP). In total, fifteen studies comprising 1,522 SLE patients and 1,424 controls were eligible for inclusion. The meta-analysis demonstrated a significant elevation of PLR in the SLE group compared to the control group (Standardized Mean Difference [SMD] = 0.604, 95% Confidence Interval [CI] = 0.299-0.909, p < 0.001). Upon stratification by ethnicity, an elevated PLR was observed in the SLE group among both Asian and Arab populations. Subgroup analysis based on sample size revealed consistently higher PLR in both small (n < 200) and large sample (n ≥ 200) SLE groups. Moreover, when considering disease activity, there was a noteworthy trend of increased PLR in the active disease group compared to the inactive group (SMD = 0.553, 95% CI = 0.000-1.106, p = 0.050). However, the meta-analysis did not demonstrate a significant distinction in PLR between the LN and non-LN groups. Notably, a positive association was established between PLR and SLEDAI (correlation coefficient = 0.325, 95% CI = 0.176-0.459, p < 0.001). Furthermore, PLR exhibited positive correlations with ESR, CRP, proteinuria, C3, and anti-dsDNA antibody levels. The outcomes of this meta-analysis underscored the elevated PLR in SLE patients, suggesting its potential as a biomarker for gauging systemic inflammation in SLE. Additionally, PLR exhibited correlations with SLEDAI, as well as with key indicators such as ESR, CRP, proteinuria, C3, and anti-dsDNA antibody levels.

Changes in retinal and choroidal thickness and vascular density in patients with systemic lupus erythematosus: Assessed by optical coherence tomography angiography.

The aim was to investigate the changes in retinal and choroidal thickness and vascular density in patients with systemic lupus erythematosus (SLE) using optical coherence tomography angiography (OCTA). Twenty-nine patients with SLE (29 eyes) and 25 control subjects (25 eyes) were enrolled. SLE activity was assessed using the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). Retinal thickness (RT), inner retinal thickness (IRT), outer retinal thickness (ORT), choroidal thickness (ChT), retinal superficial vascular density (SVD), retinal deep vascular density (DVD), choriocapillary vascular density (CCVD), foveal avascular zone (FAZ), superficial FAZ (sFAZ), and deep FAZ (dFAZ) were measured using OCTA. The retinal and choroidal thickness and vascular density between the control group and SLE group were compared. The relationships between SLEDAI scores and the retinal and choroidal thickness and vascular density in SLE group were analyzed. The SVD was significantly increased, and the DVD and CCVD were significantly decreased in the SLE group compared to the control group (p < .05). The results of receiver operating characteristic (ROC) showed that the area under the curve (AUC) values of SVD, DVD, and CCVD were 0.873, 0.729, and 0.727, indicating a high accuracy in discriminating patients with SLE from controls. Correlation analysis showed that the SLEDAI scores were positively correlated with dFAZ (r = 0.589, p = .001) and FAZ (r = 0.451, p = .018), and negatively correlated with DVD (r = -0.491, p = .009) and CCVD (r = -0.521, p = .005). DVD and CCVD were decreased in the SLE and might be related to the disease activity. SVD, DVD, and CCVD may hold promise in the discovery of biomarkers for diagnosing SLE.

Using PROMIS-29 to determine symptom burdens in the context of the Type 1 and 2 systemic lupus erythematosus (SLE) model: a cross sectional study

ObjectiveTo account for heterogeneity in systemic lupus erythematosus (SLE) and bridge discrepancies between patient- and physician-perceived SLE activity, we developed the Type 1 and 2 SLE model. We examined PROMIS-29 scores, a composite patient-reported outcome (PRO) measure, through the lens of the model.MethodsPatients completed PROMIS-29 and the polysymptomatic distress scale (PSD). Rheumatologists completed the SLE disease activity index (SLEDAI), and physician’s global assessments (PGAs) for Type 1 and 2 SLE. We defined Type 1 SLE using SLEDAI, Type 1 PGA, and active nephritis, and Type 2 SLE using PSD and Type 2 PGA. We compared PROMIS-29 T-scores among Type 1 and 2 SLE groups and explored whether PROMIS-29 can predict Type 1 and 2 SLE activity.ResultsCompared to the general population, patients with isolated Type 1 SLE reported greater pain and physical dysfunction but less depression and improved social functions; patients with high Type 2 SLE (irrespective of Type 1 activity) reported high levels of pain, fatigue, and social and physical limitations. Patients with minimal Type 1 and 2 SLE had less depression and greater physical functioning with other domains similar to national norms. PROMIS-29 predicted Type 2 but not Type 1 SLE activity.ConclusionPROMIS-29 similarities in patients with high Type 2 SLE, with and without active Type 1 SLE, demonstrate the challenges of using PROs to assess SLE inflammation. In conjunction with the Type 1 and 2 SLE model, however, PROMIS-29 identified distinct symptom patterns, suggesting that the model may help clinicians interpret PROs.

Gut microbiota landscape and potential biomarker identification in female patients with systemic lupus erythematosus using machine learning.

Systemic Lupus Erythematosus (SLE) is a complex autoimmune disease that disproportionately affects women. Early diagnosis and prevention are crucial for women's health, and the gut microbiota has been found to be strongly associated with SLE. This study aimed to identify potential biomarkers for SLE by characterizing the gut microbiota landscape using feature selection and exploring the use of machine learning (ML) algorithms with significantly dysregulated microbiotas (SDMs) for early identification of SLE patients. Additionally, we used the SHapley Additive exPlanations (SHAP) interpretability framework to visualize the impact of SDMs on the risk of developing SLE in females. Stool samples were collected from 54 SLE patients and 55 Negative Controls (NC) for microbiota analysis using 16S rRNA sequencing. Feature selection was performed using Elastic Net and Boruta on species-level taxonomy. Subsequently, four ML algorithms, namely logistic regression (LR), Adaptive Boosting (AdaBoost), Random Forest (RF), and eXtreme gradient boosting (XGBoost), were used to achieve early identification of SLE with SDMs. Finally, the best-performing algorithm was combined with SHAP to explore how SDMs affect the risk of developing SLE in females. Both alpha and beta diversity were found to be different in SLE group. Following feature selection, 68 and 21 microbiota were retained in Elastic Net and Boruta, respectively, with 16 microbiota overlapping between the two, i.e., SDMs for SLE. The four ML algorithms with SDMs could effectively identify SLE patients, with XGBoost performing the best, achieving Accuracy, Sensitivity, Specificity, Positive Predictive Value, Negative Predictive Value, and AUC values of 0.844, 0.750, 0.938, 0.923, 0.790, and 0.930, respectively. The SHAP interpretability framework showed a complex non-linear relationship between the relative abundance of SDMs and the risk of SLE, with Escherichia_fergusonii having the largest SHAP value. This study revealed dysbiosis in the gut microbiota of female SLE patients. ML classifiers combined with SDMs can facilitate early identification of female patients with SLE, particularly XGBoost. The SHAP interpretability framework provides insight into the impact of SDMs on the risk of SLE and may inform future scientific treatment for SLE.