Exacerbation Of Systemic Lupus Erythematosus Research Articles

#2051 Long-term follow-up of Israeli patients with lupus nephritis

Abstract Background and Aims Systemic lupus erythematosus (SLE) often affects the kidneys, and is associated with morbidity and mortality. Ethnic variations in clinical response to treatment and outcomes have been described. Information on real-life, long-term cohorts of the Middle Eastern Israeli population is lacking. We aimed to characterize the prevalence and long-term outcomes of kidney involvement in SLE patients in Israel and to identify variables associated with lupus nephritis (LN) and end-stage kidney disease (ESKD). Method This retrospective study, conducted between 2014-2023, included adult patients with SLE diagnosed for at least 12 months. Kidney involvement was based on a diagnosis of LN on a kidney biopsy. SLE patients without LN served as controls. Associated variables were collected including socio-demographics, disease-related characteristics, kidney-related factors, comorbidities, and all-cause mortality. Results A total of 182 adult patients with SLE were included. Of them, 54 (29.6%) had LN. Mean follow-up since diagnosis was 16.2 ± 13.8 years. Compared to the control group, patients with LN were diagnosed with SLE at younger ages (26.8 ± 12.9 vs. 35.5 ± 15.4 years, p < 0.01). Patients with LN and controls had similar proportions of females/males and Jewish/Arab patients (Table 1), and had comparable baseline eGFR before LN diagnosis (110 ± 48 vs. 107 ± 39 ml/min/m2, p = 0.66). The LN group had lower complement C3 levels at diagnosis and higher dsDNA titers (p = 0.001, 0.023 respectively; Table 1). Patients with LN had more hospitalization for SLE exacerbations [38.4% vs. 24.5%, odds ratio (OR) 1.9, 95% confidence interval (CI) 1-3.9, p = 0.06]. Of 54 patients with LN, 45 had available treatment information. All patients were treated with hydroxychloroquine, 19 patients (42.2%) were treated with cyclophosphamide, and 36 (80%) were treated with mycophenolate mofetil or mycophenolic acid. During follow-up of the LN patients, 5 patients (9.3%) were diagnosed with diabetes, 21 patients (38.9%) were diagnosed with hypertension, 5 patients (9.3%) had a stroke and 6 patients (11.1%) had an acute coronary syndrome. Eight of the LN patients (14.8%) developed ESKD as compared with one patient (0.8%) of the controls (OR 22.1, 95% CI 2.7-181.5, p < 0.001). On univariate analysis, ESKD was significantly associated with LN, hypertension, heart failure, and non-employment status. No difference in the rate of ESKD was found between Jewish and Arab patients. On multivariate regression analysis, LN and hypertension were the most important predictors for developing ESKD. Mortality among patients with ESKD was 22% vs. 4.6% among non-ESKD patients (p = 0.02) )Fig. 1). Conclusion This long-term study on Israeli SLE patients reveals that despite advances in SLE treatments, LN is associated with significant morbidity and mortality. The elevated risk of ESKD, particularly associated with LN and hypertension, underscores the imperative for targeted interventions to improve outcomes.

#1720 Insights from sodium-glucose transport 2 (SGLT2) inhibitors treatment in patients with systemic lupus erythematosus

Abstract Background and Aims Kidney involvement is common among patients with systemic lupus erythematosus (SLE) and it is an important cause of morbidity and mortality among this population. Recently, the EULAR 2023 update of the recommendations for the management of SLE advised considering the use of sodium-glucose transport 2 inhibitors (SGLT2i) as kidney protective agents in patients with chronic kidney disease with reduced glomerular filtration rate (GFR). Aims: To assess clinical characteristics and outcomes of Israeli patients with SLE treated with SLGT2i. Method This retrospective study, conducted between 2014–2023, included adult patients with SLE diagnosed for at least 12 months. Patients receiving SGLT2i for a duration of three months or longer were compared with a control group consisting of patients who were not treated with these agents. Associated variables were assessed including disease-related characteristics, kidney-related factors, and comorbidities such as diabetes and heart failure. Clinical outcomes including severe infections, hospitalizations, and all-cause mortality were recorded. Repeated measures analysis model was applied to compare the estimated GFR (eGFR) at different time points (before diagnosis, at diagnosis, and at the last follow-up), among the SGLT2i-treated patients and controls. Protein to creatinine ratio was compared before starting treatment with SGLT2i and on treatment at the last follow-up. Results A total of 165 consecutive patients were included in this analysis, with a mean follow-up from SLE diagnosis of 15.6 ± 11.8 years. Of them, 7 were treated chronically with SGLT2i and had available data. While age at SLE diagnosis was comparable between the two groups (29.8 ± 12.2 years in the SGLT2i group and 32.6 ± 14.3 years in controls, p = 0.6), SGLT2i treated patients were significantly older at last follow-up (62.1 ± 13.5 years vs. 47.3 ± 16.3 years, p = 0.019), and as a consequence, the duration of follow-up since SLE diagnosis was longer among them (26.2 ± 11 years vs. 15.3 ± 11.7 years in the controls, p = 0.04). Diabetes was diagnosed in 16 out of 165 patients (9.7%), and 5 out of 7 patients treated with SGLTi were diabetic (71.4% vs. 7.0% in controls, p < 0.01). Heart failure was diagnosed in 7.3% of the cohort, and was more prevalent among the SGLTi group (28.6% vs 6.3% in controls, p = 0.03). Only 26.6% of patients with diabetes and 16.7% of patients with heart failure were treated with SGLTi. On repeated measures analysis, eGFR decreased significantly during the study period (p = 0.043, Fig. 1). The decline in eGFR throughout the study period was comparable between the groups. Protein to creatinine ratio decreased significantly in the SGLTi-treated patients after starting treatment (1516 ± 1685 mg/g before treatment vs. 611 ± 875 mg/g after treatment, p = 0.05). The prevalence of severe infections requiring hospitalization was comparable between groups (28.6% in SGLTi vs 29.9% in controls, p = 0.9). Hospitalizations for SLE exacerbations, as well as hospitalization for cardiovascular events, were similarly comparable between groups (28.6% vs, 28.5%, p = 0.9 and 14.3% vs. 15.3%, p = 0.9; respectively). During the study period, 10 patients developed end-stage kidney disease and 11 patients died, with no significant difference between groups. Conclusion While the SGLT2i-treated patients were older and had higher rates of comorbidities such as diabetes, chronic kidney disease, and heart failure, a similar rate of kidney function decline was observed in both SGLT2i-treated patients and controls. Additionally, a comparable rate of severe infections was found in both groups of patients. This relatively small cohort could support the use of these kidney and heart protective agents in patients with SLE and kidney involvement. A special consideration should be given to patients with comorbid diabetes and heart failure.

Long-term results of therapy with sequential use of rituximab and belimumab in patients with systemic lupus erythematosus

Objective: To evaluate the efficacy of combination therapy with rituximab (RTM) and belimumab (BLM) in patients with systemic lupus erythematosus (SLE) during long-term follow-up. Material and methods. Twelve patients with definite high- and moderate activity SLE were included in the study. Nine of them had skin and joint manifestations, and the others had renal, peripheral nervous system involvement, and vasculitis. Patients received RTM at a dose of 500–2000 mg with premedication with 6-methylprednisolone and then BLM according to the standard regimen of 10 mg/kg once a month. Patients were divided into two groups according to the timing of assessment of long-term outcomes. In the 1st group, data were evaluated after 7–9 years (n = 4), and in the 2nd group – after 2–4 years (n = 8) after the prescription of biologic disease-modifying antirheumatic drugs (bDMARDs). Efficacy and tolerability of therapy, SLE activity, and dose of oral glucocorticoids (GC) were evaluated. Results and discussion. Against the background of combination therapy, clinical and immunological response was achieved in 11 of 12 patients after one year (median SLEDAI-2K at baseline – 10 [9.5; 14.5] points, 6 and 12 months after administratrion of BLM – 4 [2; 6] points). When bDMARDs were prescribed in the first two years of the disease, patients responded better to therapy and showed more significant positive dynamics in clinical and laboratory parameters. Subsequently, BLM therapy was limited to an average of 2 years, during which a stable remission was achieved. Prescribing bDMARDs allowed GC to be used as initial therapy in an exacerbation of SLE in medium and low doses (subsequently further reduced). Clinical remission was achieved and maintained in 7 patients, exacerbation at different time points after discontinuation of bDMARDs occurred in 3 patients, efficacy waned in one patient, and no result was achieved with combination therapy in another patient. Conclusion. The most pronounced positive result can be expected when a bDMARDs are prescribed as early as possible after diagnosis of SLE (in the first 2 years of the disease). It is advisable to administer BLM infusions as recommended once a month without long breaks between injections for at least 2 years and to continue until a durable effect is achieved. The use of low-dose GC and its discontinuation is an achievable goal, but careful monitoring of patients is needed to detect early symptoms of exacerbation.

Efficacy and Safety of Anti-SARS-CoV-2 Antiviral Agents and Monoclonal Antibodies in Patients with SLE: A Case-Control Study.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related disease (COVID-19) has spread pandemically with high rates of morbidity and mortality. COVID-19 has also posed unprecedented challenges in terms of rapid development of pharmacological countermeasures to prevent or contrast SARS-CoV-2 pathogenicity. Anti-SARS-CoV-2 antiviral agents and monoclonal antibodies have been specifically designed to attenuate COVID-19 morbidity and prevent mortality in vulnerable subjects, such as patients with immune-mediated diseases, but evidence for the safe and effective use of these drugs in this latter population group is scarce. Therefore, we designed a retrospective, multicentre, observational, case-control study to analyse the impact of these treatments in COVID-19 patients with systemic lupus erythematosus (SLE), a paradigmatic, multi-organ autoimmune disease. We identified 21 subjects treated with antivirals and/or monoclonal antibodies who were matched with 42 untreated patients by age, sex, SLE extension and duration. Treated patients had higher baseline SLE disease activity index 2000 scores [SLEDAI-2K median (interquartile range) = 4 (1-5) vs. 0 (0-2); p = 0.009], higher prednisone doses [5 (0-10) mg vs. 0 (0-3) mg; p = 0.002], and more severe COVID-19 symptoms by a five-point World Health Organisation-endorsed analogue scale [1 (0-1) vs. 0 (0-1); p < 0.010] compared to untreated patients. There was no difference between groups in terms of COVID-19 outcomes and sequelae, nor in terms of post-COVID-19 SLE exacerbations. Three subjects reported mild adverse events (two with monoclonal antibodies, one with nirmatrelvir/ritonavir). These data suggest that anti-SARS-CoV-2 antivirals and monoclonal antibodies might be safely and effectively used in patients with SLE, especially with active disease and more severe COVID-19 symptoms at presentation.

Case of successful treatment of acute respiratory distress syndrome in the parturient woman with systemic lupus erythematosus and cerebral cyst of the third ventricular complicated by posterior reversible encephalopathy syndrome

Pregnancy and the postpartum period provoke an exacerbation of systemic lupus erythematosus (SLE), which requires aggressive cytostatic therapy that can cause life-threatening conditions for the fetus and complications for the mother, one of which is posterior reversible encephalopathy syndrome (PRES- syndrome). The article describes a clinical case of successful treatment of acute respiratory distress syndrome (ARDS) in a 22-year-old woman in labor with high activity of SLE during pregnancy complicated by the development of PRES syndrome. Also, for the first time in the postpartum period, the patient was diagnosed with occlusive periventricular hydrocephalus, a giant cyst of the third ventricle. An emergency endoscopic cyst ventriculocisternostomy was performed. In the future, the development of severe ARDS against the background of sepsis, which required the setting of extracorporeal membrane oxygenation (ECMO). A multidisciplinary approach and timely therapy saved the life of a young mother.

Systemic Lupus Erythematosus in a Patient with Liver Cirrhosis: Case Report and Literature Review

Background: There are no treatment guidelines for systemic lupus erythematosus (SLE) for the patients with decompensated cirrhosis, especially for those who have a history of hepatitis B virus (HBV) infection, gastrointestinal bleeding and gastric fundus ulceration. Case Presentation: A 50-year-old woman who had a six-year history of lupus was admitted to our hospital. One month prior, at the Department of Gastroenterology, she was diagnosed with decompensated liver cirrhosis with gastric fundal varicose bleeding, and HBV-related infection. During her visit to the hospital, gastroscopy showed esophageal varices and a large gastric fundus ulcer. Laboratory data indicated the rapid decrease of red blood cells, granulocytes and platelets and the persistent increase of serum globulin levels. According to the patient's medical history and existing laboratory examination, the patient experienced an exacerbation of SLE, which could be life-threatening.-While it remained uncertain whether the liver cirrhosis was caused by SLE or the HBV infection, immediate treatment was necessary. Consequently, she was treated with a low dose of methylprednisolone and mycophenolate mofetil (MMF). The treatment resulted in significant clinical improvement. Moreover, there was no indication of HBV reactivation, gastrointestinal bleeding, liver dysfunction or other drug-induced side effects. Conclusion: This case indicated that irrespective of the underlying causes of liver cirrhosis, the combination of a low dose of methylprednisolone and MMF is an effective treatment method to inhibit the disease process for patients with SLE and decompensated liver cirrhosis, a large gastric fundus ulcer and HBV infection.

Vaccination of pneumococcal infection in patients with systemic lupus erythe matosus and antiphospholipid syndrome: experience of 6 years of use

Infections remain one of the main causes of morbidity and mortality in patients with immuno-inflammatory rheumatic diseases. Objective – to study the efficacy, immunogenicity and safety of the 23-valent polysaccharide pneumococcal vaccine (PPV-23) in patients with systemic lupus erythematosus (SLE) and antiphospholipid syndrome (AРS). Materials and methods. 91 patients were included in the study: 78 with SLE, of which 18 (23 %) – with secondary AРS, 13 – with primary AРS. 85 patients received immunosuppressive therapy, including 30 – genetically engineered biological drugs (bDMARD); 23 – anticoagulants. PPV-23 was administered subcutaneously, patients were observed for a year after vaccination. Results. Local reactions were observed in 49% of patients with SLE and secondary AРS, in 23% of patients with primary AРS. General reactions were noted in isolated cases, were short-term and did not require additional prescriptions. During the follow-up period, no exacerbations of SLE, relapses of thrombosis and thromboembolism associated with vaccination were detected; no development of new autoimmune diseases was registered. 10 (13%) patients with SLE were immunized against the background of high activity of the disease, no adverse reactions were recorded. In some patients, a transient increase in a-DNA and ANF was observed during the year without signs of exacerbation of the disease. 56% of patients with SLE and secondary AРS, 15.4% with primary AРS were “responders” to the vaccine. There was no negative effect on the immune response of the dose of GC &gt;10 mg/day, age, duration and activity of the disease. With the treatment of bDMARD, a full-fledged vaccine response was recorded much less frequently than with standard therapy (38% and 67.4%, respectively; p=0.01). After vaccination, there was a significant decrease in the number of lower respiratory tract infections (LRTI) (p=0.0001), including community-acquired pneumonia (PN) (p=0.03) and acute bronchitis (p=0.04), ENT infections (p=0.001). In the treatment of rituximab (RTM), compared with belimumab (BLM), a greater number of LRTI was observed, mainly due to PN. After vaccination on RTM therapy, the number of INDP in general (p=0.008) and PN in particular (p=0.03) decreased, isolated cases of LRTI and ENT organs were recorded on BLM therapy. Within 4–6 years after vaccination, 30 patients with SLE retained the clinical effect of vaccination, while immunogenicity decreased to 18%. Conclusion. Safety, sufficient immunogenicity, and clinical efficacy of PPV-23 in patients with SLE and AРS have been shown. The use of bDMARD reduces the vaccine response. Immunization performed prior to or during treatment with bDMARD lasting &lt;1 year increases the number of vaccine responders.

New-onset acute psychosis as a manifestation of lupus cerebritis following concomitant COVID-19 infection and vaccination: a rare case report

BackgroundRare cases of COVID-19 infection- and vaccine-triggered autoimmune diseases have been separately reported in the literature. In this paper, we report the first and unique case of new onset acute psychosis as a manifestation of lupus cerebritis following concomitant COVID-19 infection and vaccination in a previously healthy 26-year-old Tunisian female.Case presentationA 26-years old female with a family history of a mother diagnosed with schizophrenia, and no personal medical or psychiatric history, was diagnosed with mild COVID-19 infection four days after receiving the second dose of Pfizer-BioNTech COVID-19 vaccine. One month after receiving the vaccine, she presented to the psychiatric emergency department with acute psychomotor agitation, incoherent speech and total insomnia evolving for five days. She was firstly diagnosed with a brief psychotic disorder according to the DSM-5, and was prescribed risperidone (2 mg/day). On the seventh day of admission, she reported the onset of severe asthenia with dysphagia. Physical examination found fever, tachycardia, and multiple mouth ulcers. Neurological evaluation revealed a dysarthria with left hemiparesis. On laboratory tests, she had severe acute kidney failure, proteinuria, high CRP values, and pancytopenia. Immune tests identified the presence of antinuclear antibodies. Brain magnetic resonance imaging (MRI) revealed hyperintense signals in the left fronto-parietal lobes and the cerebellum. The patient was diagnosed with systemic lupus erythematosus (SLE) and put on anti-SLE drugs and antipsychotics, with a favorable evolution.ConclusionsThe chronological relationship between COVID-19 infection, vaccination and the first lupus cerebritis manifestations is highly suggestive, albeit with no certainty, of the potential causal link. We suggest that precautionary measures should be taken to decrease the risk of SLE onset or exacerbation after COVID-19 vaccination, including a systematic COVID-19 testing before vaccination in individuals with specific predisposition.

B cell activation via immunometabolism in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is an inflammatory autoimmune disease involving multiple organs in which B cells perform important functions such as antibody and cytokine production and antigen presentation. B cells are activated and differentiated by the primary B cell receptor, co-stimulatory molecule signals-such as CD40/CD40L-, the Toll-like receptors 7,9, and various cytokine signals. The importance of immunometabolism in the activation, differentiation, and exerting functions of B cells and other immune cells has been widely reported in recent years. However, the regulatory mechanism of immunometabolism in B cells and its involvement in SLE pathogenesis remain elusive. Similarly, the importance of the PI3K-Akt-mTOR signaling pathway, glycolytic system, and oxidative phosphorylation has been demonstrated in the mechanisms of B cell immunometabolic activation, mainly in mouse studies. However, the activation of the mTOR pathway in B cells in patients with SLE, the induction of plasmablast differentiation through metabolic and transcription factor regulation by mTOR, and the involvement of this phenomenon in SLE pathogenesis are unclear. In our studies using activated B cells derived from healthy donors and from patients with SLE, we observed that methionine, an essential amino acid, is important for mTORC1 activation. Further, we observed that splenic tyrosine kinase and mTORC1 activation synergistically induce EZH2 expression and plasmablasts by suppressing BACH2 expression through epigenomic modification. Additionally, we identified another mechanism by which the glutaminolysis-induced enhancement of mitochondrial function promotes plasmablast differentiation in SLE. In this review, we focused on the SLE exacerbation mechanisms related to the activation of immune cells-especially B cells-and immunometabolism and reported the latest findings in the field.

Mendelian randomization analysis suggests no associations of herpes simplex virus infections with systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) characterized by immune dysfunction is possibly more vulnerable to herpes simplex virus (HSV) infection. The infection has been intensively considered a common onset and exacerbation of SLE. This study is aimed at elucidating the causal association between SLE and HSV. A bidirectional two-sample Mendelian Randomization (TSMR) analysis was systematically conducted to explore the causal effect of SLE and HSV on each other. The causality was estimated by inverse variance weighted (IVW), MR-Egger and weighted median methods based on the summary-level genome-wide association studies (GWAS) data from a publicly available database. Genetically proxied HSV infection exhibited no causal association with SLE in the forward MR analysis using IVW method (odds ratio [OR] = 0.987; 95% confidence interval [CI]: 0.891-1.093; p = 0.798), nor did HSV-1 IgG (OR = 1.241; 95% CI: 0.874-1.762; p = 0.227) and HSV-2 IgG (OR = 0.934; 95% CI: 0.821-1.062; p = 0.297). Similar null results with HSV infection (OR = 1.021; 95% CI: 0.986-1.057; p = 0.245), HSV-1 IgG (OR = 1.003; 95% CI: 0.982-1.024; p = 0.788) and HSV-2 IgG (OR = 1.034; 95% CI: 0.991-1.080; p = 0.121) were observed in the reverse MR where SLE served as the exposure. Our study demonstrated no causal association between the genetically predicted HSV and SLE.

Primena nivolumaba kod bolesnice sa mukozalnim melanomom i sistemskim lupusom - prikaz slučaja sa pregledom literature

Introduction. Systemic lupus erythematosus (SLE) represents a multisystemic disease characterized by antibody production, complement activation, and immune complexes deposition. Certain types of malignancies occur more often, and conversely, some of them occur less often in SLE patients. Mucosal melanoma of the anorectal region represents a rare form of melanoma occurring in 1.5% of all melanoma patients, predominantly female. The introduction of novel agents dramatically changed the outcome in melanoma patients and introduced different adverse events, diverse contraindications, and drug interactions. Immune checkpoint inhibitors have a role in the maintenance of immunologic homeostasis. Patients with underlying autoimmune diseases were often excluded from clinical trials, for fear of possible autoimmune disease exacerbation or high-grade immune-related adverse events. Due to that, data regarding this subgroup of patients is limited, with no clear recommendations. Given the fact that prevalence among the general population is high (5-10%), autoimmune diseases represent common comorbidity in cancer patients. Having that in mind, it is of utmost importance to personalize the approach and individualize the SLE treatment and enable the use of PD-1 antibody in the safest and most useful way while keeping the SLE in control. Case report. Herein we present a 79-year-old with primary mucosal melanoma of the anorectal region, with lung metastasis and preexisting SLE in remission. Hydroxychloroquine was the only treatment for SLE. Nivolumab treatment was initiated in the standard dosing schedule. After the first and second follow-up, no further progression of melanoma was detected, with no SLE exacerbation and immune-related adverse events. Conclusion. PD-1 treatment in a patient with an underlying autoimmune disease represents a viable choice with a necessity for a multidisciplinary approach and close monitoring.

A survey of systemic lupus erythematosus patients' attitudes toward influenza and pneumococcal vaccination in Southwest China.

Vaccination is the most effective measure for prevention against infectious diseases in patients with systemic lupus erythematosus (SLE). Therefore, it is important to know SLE patients' attitudes toward influenza and pneumococcal vaccination. This study aimed to investigate the attitude toward influenza and pneumococcal vaccination among SLE patients in Southwest China and its influencing factors. A web-based questionnaire was conducted to collect data regarding SLE patients' demographics, history of infections, medications, comorbidities, attitudes toward infection and vaccination, rates of influenza and pneumococcal vaccination, and role of health professionals in promoting vaccination. Univariate and multivariate logistic regression analyses were conducted to assess the vaccination willingness-associated factors. A total of 251 patients participated in the survey and 240 questionnaires were completed and statistically analyzed. The influenza and pneumococcal vaccination rates were 8.3 and 1.7%, respectively. The top three reasons for non-vaccination were worrying about the SLE exacerbation or flare resulting from the vaccine or its adjuvants, being concerned about adverse events, and the lack of awareness of vaccine availability. More than half of the participants were willing to be vaccinated against influenza (56.2%) and pneumococcus (52.9%). Factors associated to the willingness to receive the influenza vaccine and pneumococcal vaccine were being afraid of infection, believing in the efficacy of influenza vaccination, lower family income, less perceived care from family members, perceived susceptibility to pneumococcal infection, and perceiving influenza and pneumococcal vaccination as beneficial for health. The influenza and pneumococcal vaccination rates are low among SLE patients in Southwest China. The positive perspective of vaccination on health represented the most impacting factor on their willingness to undergo influenza and pneumococcal vaccination. Non-vaccinated patients were mainly concerned about exacerbation of the disease or adverse events caused by vaccines. It is important to improve the compliance with the guideline-recommended roles of health professionals and to promote the collaboration between rheumatology and primary care teams.

Enteric Toll-like receptor 7 stimulation causes acute exacerbation in lupus-susceptible mice.

Autoimmune diseases are often accompanied by acute exacerbation. However, the mechanism underlying systemic lupus erythematosus (SLE) flares remains unclear. We investigated whether short-term enteric Toll-like receptor 7 (TLR7) stimulation can exacerbate SLE using B6SKG mice, which spontaneously develop SLE due to a mutation in the zeta‒chain‒associated protein kinase 70 (Zap70) gene. Imiquimod (IMQ) or phosphate-buffered saline (PBS) were orally administered on B6WT and B6SKG mice every other day for 2weeks. SLE exacerbation was assessed via fluorescent immunohistochemical staining of glomeruli for IgG and C3, hematoxylin and eosin staining of kidneys, and enzyme-linked immunosorbent assay for antinuclear antibody (ANA). Flow cytometry was used to evaluate germinal center B cells (GCBs), plasma cells, follicular helper T cells (Tfhs), regulatory T cells (Tregs), effector T cells (Th1s and Th17s), plasmacytoid dendritic cells (pDCs), conventional dendritic cells (cDCs), and macrophages (Mφs) in spleens. Oral administration of IMQ every other day for 2weeks resulted in exacerbation of splenomegaly, increased IgG and C3 deposition in glomeruli, and increased ANA production in the B6SKG IMQ (SKG-IMQ) group compared to the B6SKG PBS (SKG-PBS) group; the percentages of GCBs, plasma cells, Tfhs, Th1s, pDCs, and Mφs were also increased in the SKG-IMQ group. Splenomegaly, IgG, and C3 deposition in glomeruli, and the percentages of GCBs, plasma cells, Tfhs, and Th1s were enhanced in SKG-IMQ mice compared with B6SKG mice topically treated with IMQ (SKG-ear-IMQ). Oral TLR7 stimulation in a Zap70 genetic mutation background can cause acute exacerbations of SLE. Key Points • The mechanism of SLE flares is not well understood. • We have created a model that causes short-term SLE exacerbations in mice with a genetic background. • IMQ administered orally causes more SLE in mice than transdermally.

Comparison of Maternal and Perinatal Outcomes of Pregnancy with Systemic Lupus Erythematosus in Planned Referrals Compared to Emergency Referrals Based on the Maternal Fetal Triage Index at Dr. Kariadi General Hospital, Semarang, Indonesia

Background: Systemic lupus erythematosus (SLE) is an autoimmune disease that attacks the skin and the musculoskeletal, kidney, neuropsychiatric, hematological, cardiovascular, pulmonary, and reproductive systems. In pregnancies with SLE, early referral to the hospital with the involvement of obstetricians and rheumatologists, and other specialists as needed, as well as individual management plans, regular reviews, and early recognition of flares and complications, are important. This study aimed to determine the differences in maternal and perinatal outcomes referred by planned referrals compared to emergency referrals, especially in pregnant patients with SLE.&#x0D; Methods: This study was an analytic observational study with a retrospective cohort approach. A total of 40 subjects participated in this study. Data analysis using SPSS software was carried out univariate and bivariate to examine the relationship between types of referrals and maternal and perinatal outcomes.&#x0D; Results: There were significant differences between the types of emergency referrals and planned referrals in the variable incidence of preeclampsia and SLE exacerbations. There were no significant differences between the types of emergency referrals and planned referrals on the variable incidence of lupus nephritis, maternal death, premature delivery, fetal growth restriction, fetal death, and the incidence of neonatal lupus syndrome.&#x0D; Conclusion: The incidence of severe preeclampsia and SLE exacerbation was lower in planned referrals compared to emergency referrals in pregnant patients with SLE at Dr. Kariadi General Hospital, Semarang, Indonesia.

Systemic lupus erythematosus following SARS-CoV-2 vaccination; a review of literature

From March 2020, the coronavirus disease 2019 (COVID-19) pandemic challenged public health and healthcare systems worldwide. Viral infection is one of the environmental factors that has been associated with the development, relapse, or exacerbation of systemic lupus erythematosus (SLE). SLE patients are at an increased risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) because of immune system dysfunction related to their disease as well as immunosuppression medications. So far, the most effective way to reduce SARS-CoV-2 infection-induced hospitalization and death is vaccination. On the other hand, SLE patients present distinct challenges related to the safety and effectiveness of SARS-CoV-2 vaccination. We have reviewed some reports on the onset or flare of SLE post-COVID-19 vaccination. Of note, the mRNA COVID-19 vaccines are associated with increased SLE disease activity, more frequently than the other types of COVID-19 vaccines.

Association of Viral Infection With the Development and Pathogenesis of Systemic Lupus Erythematosus.

Systemic lupus erythematosus (SLE) is an autoimmune disease that causes multiple organ damage in women of childbearing age and has a relapsing-remitting course. SLE is caused by the interaction between genetic and environmental factors, however, its underlying triggers remain unknown. Among the environmental factors, the involvement of infections as a trigger for SLE, especially those of viral etiology, has been widely reported. Human endogenous retroviruses (HERVs) may put patients at a genetic predisposition to SLE, while the Epstein-Barr virus (EBV) may play a role as an environmental factor that triggers the development of SLE. It has been suggested that EBV-infected B-cells may become resistant to apoptosis, resulting in the activation, proliferation, and antibody production of autoreactive B-cells, which cause tissue damage in SLE. However, the interaction between the virus and immune cells, as well as the impact of the virus on the differentiation and dysfunction of immune cells, remain unclear. In this review, we focus on the relationship between the development and pathogenesis of SLE and viral infections, as well as the mechanism of SLE exacerbation via activation of immune cells, such as B-cells, based on the latest findings.

Heart arrest due to systemic lupus erythematosus relapse: case report

Summary We report a case of a 36-year-old man who was admitted to the Vilnius University Hospital Santaros clinics emergency department suffering from acute chest pain and experienced cardiac arrest. Changes in the electrocardiogram, elevated troponin level, and clinical symptoms lead to ST-elevation myocardial infarction (MI) diagnosis. The patient was diagnosed with systemic lupus erythematosus (SLE). He was in a remission state of SLE and was not taking drugs for one year before MI happened. SLE may be associated with antiphospholipid syndrome, which can cause cardiovascular complications such as MI. Although it is a usual practice to stop treatment in remission, in some cases, clinicians should consider continuing SLE treatment to avoid cardiovascular complications. In this case, the exacerbation of SLE and myocardial infarction occurred almost simultaneously with no previous thrombotic or cardiovascular events.

POSC189 A Patient Registry-Based Cross-Sectional Study of the Burden and Management of Comorbid Psoriatic Arthritis (PsA) in Patients with Systemic Lupus Erythematosus (SLE)

Coexistence of PsA and SLE is considered rare. Given the potential for phototherapy or drug-induced exacerbation of SLE, or worsening psoriasis with some biologic treatments, this study sought to better understand the burden of real-world comorbidities critical to optimizing patient outcomes. The OM1 SLE Registry (OM1;Boston, MA) follows 46,900+ SLE patients in the U.S. managed by rheumatologists longitudinally w/deep clinical data, including laboratory, patient-reported and disease activity information, and linked claims, starting from 2013. Index date was set by the first encounter w/SLE diagnosis code and ≥18 months of baseline available. Comorbidities were defined by ≥2 outpatient diagnosis codes ≥30 days apart or one inpatient diagnosis code prior to index. Obesity was defined as BMI≥30 kg/m2. Medications were identified by prescriptions, administrations or fills. RAPID3 (Routine Assessment of Patient Index Data 3) at index was also explored. Study included 44,186 patients (92% female, mean age 51 years) from the OM1 SLE Registry, 703 (1.4%) of whom had documented PsA. Patients with co-morbid PsA were slightly older, with higher proportion male (12% vs. 8%), white (68% vs. 56%) and non-Hispanic (69% vs. 64%) patients. Patients with PsA were more likely to be obese (50% vs. 40%). Mean joint-related disease activity was moderate (mean RAPID-3=4) across patients. Proportion with other autoimmune conditions were similar. Recent treatment w/systemic steroids, methotrexate, leflunomide and TNFa and IL-17 or IL12/23 inhibitors was more common in SLE-PsA patients. Hydroxychloroquine was less commonly used in PsA patients (31% vs. 42%). Managing T-cell and B-cell-driven conditions simultaneously poses a clinical challenge, attempting to balance treating cutaneous and joint-related manifestations with exacerbating disease flares. Clinical development and availability of therapies with other mechanisms of action may provide important alternatives. Since clinical trials typically exclude many comorbid conditions, real-world data regarding these complex phenotypes provide important insights into tailored treatment strategies.

Deciphering the Molecular Mechanism of Flares in Patients with Systemic Lupus Erythematosus through Single-Cell Transcriptome Analysis of the Peripheral Blood.

A remarkable, yet poorly explained feature of Systemic Lupus Erythematosus (SLE) is the propensity to flare following a preceding period of disease inactivity. The clinical burden of lupus flares is substantial since they often tend to involve multiple or major organs, and carry a near two-fold increased risk for accrual of irreversible organ damage. The cellular and molecular mechanisms underlying the progression of SLE from inactive to active state remain ill-defined. Application of novel sequencing technologies together with cellular immunology assays, have illustrated the important role of multiple types of both innate and adaptive cells and associated pathways. We have previously described significant differences in the blood transcriptome of SLE patients at active versus inactive disease, and we have also defined genome regions (domains) with co-ordinated expression of genes implicated in the disease. In the present study, we aim to decipher the cellular and molecular basis of SLE exacerbations by utilising novel single-cell sequencing approaches, which allow us to characterise the transcriptional and epigenetic landscapes of thousands of cells in the peripheral blood of patients. The significance of the study lies in the detailed characterisation of the molecular and regulatory program of immune cell subpopulations that underlie progression from inactive to active SLE. Accordingly, our results may be exploited to identify biomarkers for disease monitoring and novel therapeutic targets.

Predictive factors of fetal and maternal pregnancy outcomes in Japanese patients with systemic lupus erythematosus.

The number of pregnant and delivery cases in systemic lupus erythematosus (SLE) patients are increasing due to the advances in therapies. However, there are many problems such as the exacerbation of SLE during pregnancy and the risk of fetal complications. We investigated the impact of both pregnancy on lupus and lupus on pregnancy in Japanese patients. We retrospectively analyzed 64 pregnancies in 39 cases of lupus patients at Kyushu University Hospital, Japan, from October 2002 to July 2018 and then assessed the clinical profiles and maternal and fetal outcomes. In terms of the impact of pregnancy on SLE, 29.7% of patients had lupus flare during pregnancy. Multivariate analysis showed that flare rates were significantly higher in patients who discontinued the immunosuppressants when pregnancy was detected or before pregnancy. Pregnancy results were 25.0% for preterm birth, 39.1% for low birth weight infants, and 31.3% for small-for-gestational-age infants. Regarding the effect of SLE on fetal death, the rates of stillbirth were significantly higher in cases whose C3 value at 12 weeks of gestation was lower than before conception. Preterm birth was associated with disease duration and lupus flare during pregnancy. Discontinuation of immunosuppressive drugs was a predictive factor for lupus flare during pregnancy. Further, the decrease of C3 levels at 12 weeks of gestation from baseline was a predictive factor for fetal loss. It is essential for lupus pregnant patients to prevent flares, even with the use of immunosuppressive medications.