Frequency of sarcopenia in Turkish women with systemic lupus erythematosus.

OBJECTIVE: This study aimed to evaluate the prevalence of sarcopenia and its clinical significance in Turkish women with SLE, exploring the association between muscle mass, muscle strength and SLE disease activity. METHODS: A cross-sectional study was conducted at Gazi University Hospital's Department of Rheumatology from January to December 2020. It involved 82 patients with SLE, diagnosed according to the 2019 American College of Rheumatology/European Alliance of Associations for Rheumatology criteria, and 69 healthy controls. Sarcopenia was assessed using hand grip dynamometry (hand grip strength (HGS)) and bioelectrical impedance analysis for muscle mass, with sarcopenia defined according to the 2018 European Working Group on Sarcopenia in Older People criteria and specific cut-offs for the Turkish population. The main outcomes measured were the presence of sarcopenia and probable sarcopenia, HGS values, skeletal muscle mass index and SLE Disease Activity Index 2000 (SLEDAI-2K). RESULTS: Among the patients with SLE, 51.2% met the criteria for probable sarcopenia and 12.9% were diagnosed with sarcopenia. The mean HGS was significantly lower in the SLE group (21.7±4.9 kg) compared with controls, indicating reduced muscle strength. The prevalence of anti-double-stranded DNA (anti-dsDNA) antibodies was 82.9%. Multivariate regression analysis identified height and levels of anti-dsDNA antibodies as independent predictors for developing probable sarcopenia. No significant association was found between clinical parameters, including SLEDAI-2K scores, and sarcopenia status. CONCLUSIONS: Sarcopenia is prevalent among Turkish women with SLE, with a significant proportion showing reduced muscle strength. The study found no direct association between sarcopenia and SLE disease activity or clinical parameters. These findings underscore the importance of including muscle strength assessments in the routine clinical evaluation of patients with SLE to potentially improve management and quality of life.

Heterogeneity of right ventricular echocardiographic parameters in systemic lupus erythematosus among four clinical subgroups, as stratified by clinical organ involvement in observational cohort.

BACKGROUND: Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease. Cardiac involvement in SLE is rare but plays an important prognostic role. The degree of cardiac involvement according to SLE subsets defined by non-cardiac manifestations is unknown. The objective of this study was to identify differences in transthoracic echocardiography (TTE) parameters associated with different SLE subgroups. METHODS: One hundred eighty-one patients who fulfilled the 2019 American College of Rheumatology/EULAR classification criteria for SLE and underwent baseline TTE were included in this cross-sectional study. We defined four subsets of SLE based on the predominant clinical manifestations. A multivariate multinomial regression analysis was performed to determine whether TTE parameters differed between groups. RESULTS: Four clinical subsets were defined according to non-cardiac clinical manifestations: group A (n=37 patients) showed features of mixed connective tissue disease, group B (n=76 patients) had primarily cutaneous involvement, group C (n=18) exhibited prominent serositis and group D (n=50) had severe, multi-organ involvement, including notable renal disease. Forty TTE parameters were assessed between groups. Per multivariate multinomial regression analysis, there were statistically significant differences in early diastolic tricuspid annular velocity (RV-Ea, p<0.0001), RV S' wave (p=0.0031) and RV end-diastolic diameter (p=0.0419) between the groups. Group B (primarily cutaneous involvement) had the lowest degree of RV dysfunction. CONCLUSION: When defining clinical phenotypes of SLE based on organ involvement, we found four distinct subgroups which showed notable differences in RV function on TTE. Risk-stratifying patients by clinical phenotype could help better tailor cardiac follow-up in this population.

Pregnancy loss in women with systemic lupus erythematosus: Grounded Theory.

OBJECTIVE: to learn the meanings attributed to pregnancy loss by women with Lupus. METHOD: qualitative research, based on Symbolic Interactionism and Grounded Theory. Data collection took place between January and August 2022 through in-depth interviews. Data analysis went through the stages of initial and focused coding. RESULTS: seventeen women participated. The central phenomenon "The climb to motherhood: falls and overcoming" was constructed, consisting of three categories: "Falling to the ground during the climb: the experience of pregnancy loss"; "Getting up and following the path: new attempts to conceive"; and "Remembering the journey: meanings attributed to pregnancy losses". FINAL CONSIDERATIONS: experiencing pregnancy is, analogously, like climbing a mountain, where obstacles need to be overcome to reach the summit. The experience of pregnancy loss is seen as complex, especially when there is fragility in healthcare and a lack of awareness regarding feelings of loss and grief.

Patient and Physician Perspectives of Systemic Lupus Erythematosus Flare: A Qualitative Study.

OBJECTIVE: Systemic lupus erythematosus (SLE) flares are associated with increased damage and decreased health-related quality of life. We hypothesized that there is discordance between physicians' and patients' views of SLE flare. In this study, we aimed to explore patient and physician descriptions of SLE flares. METHODS: We conducted a qualitative descriptive study using in-depth interviews with a purposeful sample of patients with SLE (who met 1997 American College of Rheumatology or Systemic Lupus International Collaborating Clinics criteria) and practicing rheumatologists. Interviews were audio-recorded, transcribed, and analyzed using applied thematic analysis. RESULTS: Forty-two patient participants with SLE, representing a range of SLE activity, completed interviews. The majority described flare symptoms as joint pain, fatigue, and skin issues lasting several days. Few included objective signs or laboratory measures, when available, as features of flare. We interviewed 13 rheumatologists from 10 academic and 3 community settings. The majority defined flare as increased or worsening SLE disease activity, with slightly more than half requiring objective findings. Around half of the rheumatologists included fatigue, pain, or other patient-reported symptoms. CONCLUSION: Patients and physicians described flare differently. Participants with SLE perceived flares as several days of fatigue, pain, and skin issues. Providers defined flares as periods of increased clinical SLE activity. Our findings suggest the current definition of flare may be insufficient to integrate both perceptions. Further study is needed to understand the pathophysiology of patient flares and the best way to incorporate patients' perspectives into clinical assessments.

Temporal Daily Relationships Between Sleep and Pain in Adolescents With Systemic Lupus Erythematosus.

INTRODUCTION: Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder characterized by recurrent episodes of pain. This study aimed to describe the temporal daily relationships between sleep and pain in adolescents with SLE. METHOD: Twenty-three adolescents with SLE recruited from a pediatric hospital wore actigraphy and completed diaries. Generalized estimating equation models were used. RESULTS: On average, evening pain negatively predicted subsequent sleep quality that night, and, on average, sleep quality negatively predicted morning pain. Shorter total sleep time significantly predicted higher morning pain (95% confidence intervals [CI], -0.38 to -0.03, p = .02), whereas sleep efficiency and sleep quality were not significantly associated with morning pain (95% CI, -0.03 to 0.03; 95% CI, -0.08 to 0.06, respectively). Subsequent evening pain did not predict daily nighttime sleep DISCUSSION: Our findings suggest that sleep is a target for pain interventions to include among adolescents with SLE.

Dolor, uso de ortesis plantares, calzado y consejos de salud en personas con lupus eritematoso sistémico. Un estudio descriptivo / Pain, use of plantar orthoses, footwear and health advice in people with systemic lupus erythematosus. A descriptive study

Objetivos: Conocer la percepción de los pacientes sobre el dolor y localización en los pies debido al lupus eritematoso sistémico (LES). Identificar los consejos y cuidados recibidos sobre los problemas de sus pies y calzado, y qué profesional los proporcionó. Conocer si los pacientes usaban ortesis plantares o calzado ortopédico. Pacientes y métodos: Estudio observacional, descriptivo, transversal, realizado entre marzo y mayo de 2021 sobre 47 personas con LES. Cinco participantes se excluyeron por no completar el cuestionario, siendo 42 los participantes después de obtener su consentimiento informado. Se confeccionó una hoja de recogida de datos para alcanzar los objetivos. Resultados: El 47.6 % de los pacientes presentaba dolor en los pies atribuido al LES durante la entrevista, con un promedio de dolor de 4.4 (DE = 2.97). El dolor se localizó principalmente en el antepié y los dedos. El 31 % y el 21.4 % recibieron cuidados o consejos para sus problemas en los pies respectivamente, siendo podólogos y reumatólogos los principales prescriptores. El 31 % recibió consejos sobre el calzado adecuado, proporcionados principalmente por podólogos y reumatólogos. El 33.33 % utilizaba ortesis plantares, siendo mayormente prescritas por reumatólogos y podólogos. Solo un 4.8 % utilizaba calzado ortopédico o hecho a medida. Conclusiones: Se encontró una prevalencia significativa de dolor en los pies atribuido al LES, siendo el antepié y los dedos las áreas más afectadas. Un porcentaje limitado de pacientes recibió cuidados y consejos para sus problemas en los pies, y el uso de ortesis plantares y calzado ortopédico fue poco común (AU)

Objectives: To know the perception of patients about pain and location in the feet due to Systemic Lupus Erythematosus (SLE). Identify the advice and care received about the problems of your feet and footwear, and which professional provided it. To know if patients wore plantar orthoses or orthopedic shoes. Patients and methods: Observational, descriptive, cross-sectional study, conducted between March and May 2021 on 47 people with SLE. Five participants were excluded for not completing the questionnaire, with 42 participants after obtaining their informed consent. A data collection sheet was prepared to achieve the objectives. Results: A total of 47.6 % of patients had foot pain attributed to SLE during the interview, with an average pain of 4.4 (SD = 2.97). The pain was mainly localized to the forefoot and fingers. Thirtyone (31 %) and 21.4 % received care or advice for their foot problems respectively, with podiatrists and rheumatologists being the main prescribers. Also, 31 % received advice on proper footwear, provided mainly by podiatrists and rheumatologists. One third (33,33 %) used plantar orthoses, being mostly prescribed by rheumatologists and podiatrists. Only 4.8 % used orthopedic or custom-made shoes.Conclusions: A significant prevalence of foot pain attributed to SLE was found, with the forefoot and toes being the most affected areas. A limited percentage of patients received care and advice for their foot problems, and the use of plantar orthotics and orthopedic footwear was uncommon (AU)

Vitronectin, a Novel Urinary Proteomic Biomarker, Promotes Cell Pyroptosis in Juvenile Systemic Lupus Erythematosus.

Objective: Identifying new markers of juvenile systemic lupus erythematosus (JSLE) is critical event to predict patient stratification and prognosis. The aim of the present study is to analyze alteration of urinary protein expression and screen potential valuable biomarkers in juvenile systemic lupus erythematosus (JSLE). Methods: The urine was collected from the patients with or without JSLE and detected by mass spectrometry to analyze proteomic changes. ELISA was used to verify the Vitronectin (VTN) changes in a new set of patients. The clinical correlation was performed to analyze between VTN and clinical pathological parameters. WB and ELISA were used to analyze VTN-mediated cell pyroptosis. Results: Herein, we have identified a group of 105 differentially expressed proteins with ≥1.3-fold upregulation or ≤0.77-fold downregulation in JSLE patients. These proteins were involved in several important biological processes, including acute phase inflammatory responses, complement activation, hemostasis, and immune system regulation through Gene Ontology and functional enrichment analysis. Interestingly, urinary ephrin type-A receptor 4 (EPHA4) and VTN were significantly reduced in both inactive and active JSLE patients, and VTN treatment in THP-1 derived macrophages led to a significant increased cell pyroptosis by activation of Nod-like receptor family protein 3 (NLRP3) inflammasomes, resulting in caspase-1 activation, cleaved gasdermin D (GSDMD), and IL-18 secretion. Most importantly, the urinary VTN was also linearly correlated with clinical characteristics of JSLE, implying that VTN could be a specific diagnostic biomarker to distinguish inactive and active JSLE. Conclusion: This study provided a novel role of VTN in pyroptosis in JSLE through the urinary proteomic profile for JSLE, which could be a nonintrusive monitoring strategy in clinical diagnosis.

Long-term growth and final adult height outcome in childhood-onset systemic lupus erythematosus.

BACKGROUND: Growth impairment is the most common complication in patients with childhood-onset systemic lupus erythematosus (cSLE). There are limited data on risk factors affecting growth development in Asian patients with cSLE. This study aimed to determine the predictors of growth impairment in such patients. METHODS: All SLE patients aged < 15 years diagnosed in Ramathibodi Hospital between 2006 and 2016 were enrolled in a retrospective cohort study. Baseline characteristics, including height, weight, clinical manifestations, disease activity score, and medications, were reviewed from medical records from the time at diagnosis to achievement of final adult height (FAH). Age at menarche in girls, adult voice appearance in boys, and parental height were collected by interview. Parent-adjusted FAH (PaFAH) Z-score was calculated as the difference between FAH Z-score for chronological age of the patients and their mid parental height-Z score. The patients were classified into two groups: (1) normal growth (PaFAH Z-score ≥ - 1.5, 2) growth impairment (PaFAH Z-score < - 1.5). Descriptive statistics and logistic regression analysis were used to analyze the data. RESULTS: Of 106 cSLE patients, 19 (18%) were male and 87 (82%) were female. The mean age at study enrollment was 20.6 ± 3.0 years, mean age at diagnosis 12.1 ± 2.3 years, and mean age at achievement of FAH 17.5 ± 1.9 years. Growth impairment was found in 23.6% of patients (52.6% in boys and 17.2% in girls). Predictors of growth impairment were male sex, duration of disease before menarche in girls and adult voice appearance in boys, and cumulative corticosteroid dose (prednisolone equivalent) ≥230 mg/kg received before the late phase of puberty, with odds ratios of 7.07 (95%CI 2.11-23.74), 1.26 (95% CI 1.02-1.56), and 6.99 (95%CI 1.63-30.02), respectively. CONCLUSIONS: One-fourth of cSLE patients developed growth impairment, which mostly affected male patients. Longer duration of disease before the late phase of puberty and corticosteroid dose ≥230 mg/kg received before the late phase of puberty were factors predictive of growth impairment.

Timing of Childhood-Onset Systemic Lupus Erythematosus Diagnosis Relative to Menarche and the Impact on Final Adult Height.

OBJECTIVE: The aim of this study was to examine the impact of timing of a childhood-onset systemic lupus erythematosus (SLE) diagnosis relative to menarchal status, on final height, accounting for disease-associated factors. METHODS: We conducted a cohort study of female patients age <18 years at childhood-onset SLE diagnosis, followed at a tertiary care pediatric center from July 1982 to March 2016 and restricted to patients with documented age of menarche and final height. We compared final height between patients diagnosed pre- and postmenarche. We tested the association of the timing of childhood-onset SLE diagnosis with final height, adjusted for ethnicity, in linear regression models. We performed subgroup analyses of patients with growth during follow-up, additionally adjusting for average daily corticosteroid dose and disease activity. RESULTS: Of 401 female childhood-onset SLE patients in the study, 115 patients (29%) were diagnosed premenarche and 286 (71%) postmenarche. Patients diagnosed premenarche were older at menarche compared with patients diagnosed postmenarche (mean ± SD age 13.5 ± 1.4 versus 12.5 ± 1.3 years; P < 0.001). The mean ± SD final height for girls diagnosed postmenarche (161.4 ± 6.9 cm) was greater than for those diagnosed premenarche (158.8 ± 7.3 cm; P = 0.001). In regression analysis, those diagnosed postmenarche were significantly taller than those diagnosed premenarche, as adjusted for ethnicity and disease severity (mean ± SD ß = 2.6 ± 0.7 cm; P = 0.0006). CONCLUSION: In this large cohort study of girls with childhood-onset SLE, patients diagnosed postmenarche achieved a taller final height than those diagnosed premenarche, even after accounting for ethnicity and disease severity.

Evaluation of Immune Response and Disease Status in Systemic Lupus Erythematosus Patients Following SARS-CoV-2 Vaccination.

OBJECTIVE: To evaluate seroreactivity and disease flares after COVID-19 vaccination in a multiethnic/multiracial cohort of patients with systemic lupus erythematosus (SLE). METHODS: Ninety SLE patients and 20 healthy controls receiving a complete COVID-19 vaccine regimen were included. IgG seroreactivity to the SARS-CoV-2 spike receptor-binding domain (RBD) and SARS-CoV-2 microneutralization were used to evaluate B cell responses; interferon-γ (IFNγ) production was measured by enzyme-linked immunospot (ELISpot) assay in order to assess T cell responses. Disease activity was measured by the hybrid SLE Disease Activity Index (SLEDAI), and flares were identified according to the Safety of Estrogens in Lupus Erythematosus National Assessment-SLEDAI flare index. RESULTS: Overall, fully vaccinated SLE patients produced significantly lower IgG antibodies against SARS-CoV-2 spike RBD compared to fully vaccinated controls. Twenty-six SLE patients (28.8%) generated an IgG response below that of the lowest control (<100 units/ml). In logistic regression analyses, the use of any immunosuppressant or prednisone and a normal anti-double-stranded DNA antibody level prior to vaccination were associated with decreased vaccine responses. IgG seroreactivity to the SARS-CoV-2 spike RBD strongly correlated with the SARS-CoV-2 microneutralization titers and correlated with antigen-specific IFNγ production determined by ELISpot. In a subset of patients with poor antibody responses, IFNγ production was similarly diminished. Pre- and postvaccination SLEDAI scores were similar in both groups. Postvaccination flares occurred in 11.4% of patients; 1.3% of these were severe. CONCLUSION: In a multiethnic/multiracial study of SLE patients, 29% had a low response to the COVID-19 vaccine which was associated with receiving immunosuppressive therapy. Reassuringly, severe disease flares were rare. While minimal protective levels remain unknown, these data suggest that protocol development is needed to assess the efficacy of booster vaccination.

Association between depression and sleep quality in patients with systemic lupus erythematosus: a systematic review and meta-analysis.

BACKGROUND: Currently, there is no consistent understanding of the relationship between depression and sleep quality in patients with systemic lupus erythematosus (SLE). This study aimed to explore the correlation between depression and sleep quality in SLE patients. METHODS: Five English (PubMed, Web of Science, EMBASE, Cochrane Library, and CINAHL) databases were systematically searched from inception to January 12, 2021. Two authors independently screened publications and extracted data according to set inclusion and exclusion criteria. Statistical analyses were performed with STATA 16.0. Data were pooled using a random-effects model. RESULTS: A total of 9 identified studies matched the inclusion criteria, reporting on 514 patients with SLE in the analysis. A moderate correlation of depression with sleep quality was found (pooled r = 0.580 [0.473, 0.670]). Compared to good sleepers, patients with SLE and poor sleep quality had higher levels of depression (standardized mean difference = - 1.28 [- 1.87, - 0.69]). Depression was associated with subjective sleep quality (r = 0.332 [0.009, 0.592]), sleep latency (r = 0.412 [0.101, 0.649]), sleep disturbances (r = 0.405 [0.094, 0.645]), daytime dysfunction (r = 0.503 [0.214, 0.711]), the four dimensions of Pittsburgh Sleep Quality Index (PSQI), while no significant correlation was found in the other three PSQI dimensions. CONCLUSION: Depression had a moderate correlation with sleep quality in patients with SLE. Patients with poor sleep quality tended to have higher level of depression than that of good sleepers. Awareness of the correlation may help rheumatology physicians and nurses to assess and prevent depression and improve sleep quality in patients with SLE.

Predictive factors for concomitant pulmonary arterial hypertension at diagnosis of systemic lupus erythematosus in a Chinese population.

AIM: To investigate the predictive factors of pulmonary arterial hypertension (PAH) in systemic lupus erythematosus (SLE) patients. METHOD: This chart review study included 408 SLE patients. We defined PAH as 2 consecutive systolic pulmonary arterial pressure (PAP) values ≥40 mm Hg by echocardiography. Demographic characteristics, clinical symptoms, autoantibodies, and laboratory tests were studied. RESULTS: Thirty-four patients in the SLE/PAH+ group and 374 patients in the SLE/PAH- group were analyzed. The prevalence of PAH in SLE is 8.3% in this study. The occurrences of interstitial pneumonitis, polyserositis and myocardial damage were higher in the SLE/PAH+ group (P = .001, P = .033 and P < .001, respectively). The occurrence of anti-double-stranded DNA and anti-ribosomal RNA protein (anti-rRNP) antibodies were lower in the SLE/PAH+ group (P = .003, .010). Positive rates of anti-Sjögren's syndrome antigen A (anti-SSA)/Ro52 antibodies and anti-SSB antibodies were higher in the SLE/PAH+ group (P = .046, .021). C-reactive protein and immunoglobin G (IgG) were higher in the SLE/PAH+ group (P = .009, .005). Ejection fraction and SLE disease activity index between the 2 groups had no differences. Multivariable logistic regression indicated that interstitial pneumonitis, myocardial damage and high IgG are predictive factors for SLE-associated PAH patients. CONCLUSION: From this study, we found that interstitial pneumonitis, myocardial damage, and high IgG were predictive factors of PAH in SLE patients.

Autoimmune Connective Tissue Diseases: Systemic Lupus Erythematosus and Rheumatoid Arthritis.

Systemic lupus erythematosus and rheumatoid arthritis are just 2 of several autoimmune connective tissue diseases that are primarily chronic in nature but can present to the emergency department by virtue of an acute exacerbation of disease. Beyond an acute exacerbation of disease, their predilection for invading multiple organ systems lends itself to the potential for patients presenting to the emergency department with either a single or isolated symptom or a myriad of signs and/or symptoms indicative of a degree of disease complexity and severity that warrant timely recognition and resuscitation.

Physical Fitness Attenuates the Impact of Higher Body Mass and Adiposity on Inflammation in Women With Systemic Lupus Erythematosus.

Aims: Higher body mass and adiposity represent independent contributors to the systemic low-grade inflammatory state often observed in patients with systemic lupus erythematosus (SLE). This study assessed the role of physical fitness in the association of body mass and adiposity with inflammation in women with SLE. Methods: A total of 77 women with SLE were included in this cross-sectional study. We obtained body mass index, waist-to-height ratio, and body fat percentage as indicators of body mass and adiposity. Inflammation was assessed through Serum levels of C-reactive protein, interleukin 6, and leptin. Cardiorespiratory fitness was assessed with the 6-minute walk test, range of motion with the back-scratch test, and muscular strength with handgrip dynamometry. Results: Cardiorespiratory fitness attenuated the association of both body mass index and body fat percentage with interleukin 6 (all, P<0.05). Range of motion attenuated the association of body mass index with interleukin 6 (P<0.05) and the association of body fat percentage with C-reactive protein (P<0.05). These interactions indicated that higher fitness was associated with a lower increase in inflammation per unit increase of body mass or adiposity. Muscular strength showed a non-significant trend to attenuate the association of body fat percentage with interleukin 6 (P=0.057) but potentiated the association of body fat percentage with leptin (P<0.05). Conclusion: These findings suggest that higher levels of cardiorespiratory fitness and range of motion might attenuate the impact of higher body mass and adiposity on inflammation in women with SLE. The role of muscular strength requires further investigation.

Impact of menopause on women with systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by chronic and systemic inflammation affecting multiple organ systems, including an increased risk of cardiovascular disease due to the SLE-associated hyperinflammatory state. SLE shows a strong female predominance, suggesting a potential role of sex hormones in the pathogenesis of the disease. Evidence suggests an earlier age of menopause among women with SLE, despite mixed findings regarding other markers of ovarian aging. In healthy populations, the menopausal transition is associated with important physiologic changes resulting in increased cardiometabolic risk and risk of osteoporosis. Thus, women with SLE who experience the inflammatory effects of the autoimmune condition combined with the (potentially earlier) menopausal transition may represent a particularly vulnerable group of individuals during a particular window of time. Little is known, however, about strategies for cardiovascular risk or bone loss mitigation in women with SLE during the menopausal transition. Further, despite lack of knowledge regarding the burden of menopausal symptoms in women with SLE, existing recommendations provide only cautionary guidance for the use of hormone replacement therapy to address menopausal symptoms in this population. Importantly, the data regarding both SLE and menopause-associated cardiovascular and osteoporotic risk demonstrate the critical need for additional research to identify the type and timing of treatments or interventions needed to best mitigate this increased risk.

Myeloid-Derived Suppressive Cell Expansion Promotes Melanoma Growth and Autoimmunity by Inhibiting CD40/IL27 Regulation in Macrophages.

The relationship between cancer and autoimmunity is complex. However, the incidence of solid tumors such as melanoma has increased significantly among patients with previous or newly diagnosed systemic autoimmune disease (AID). At the same time, immune checkpoint blockade (ICB) therapy of cancer induces de novo autoinflammation and exacerbates underlying AID, even without evident antitumor responses. Recently, systemic lupus erythematosus (SLE) activity was found to drive myeloid-derived suppressor cell (MDSC) formation in patients, a known barrier to healthy immune surveillance and successful cancer immunotherapy. Cross-talk between MDSCs and macrophages generally drives immune suppressive activity in the tumor microenvironment. However, it remains unclear how peripheral pregenerated MDSC under chronic inflammatory conditions modulates global macrophage immune functions and the impact it could have on existing tumors and underlying lupus nephritis. Here we show that pathogenic expansion of SLE-generated MDSCs by melanoma drives global macrophage polarization and simultaneously impacts the severity of lupus nephritis and tumor progression in SLE-prone mice. Molecular and functional data showed that MDSCs interact with autoimmune macrophages and inhibit cell surface expression of CD40 and the production of IL27. Moreover, low CD40/IL27 signaling in tumors correlated with high tumor-associated macrophage infiltration and ICB therapy resistance both in murine and human melanoma exhibiting active IFNγ signatures. These results suggest that preventing global macrophage reprogramming induced by MDSC-mediated inhibition of CD40/IL27 signaling provides a precision melanoma immunotherapy strategy, supporting an original and advantageous approach to treat solid tumors within established autoimmune landscapes. SIGNIFICANCE: Myeloid-derived suppressor cells induce macrophage reprogramming by suppressing CD40/IL27 signaling to drive melanoma progression, simultaneously affecting underlying autoimmune disease and facilitating resistance to immunotherapy within preexisting autoimmune landscapes.

Thrombotic risk assessment in patients with systemic lupus erythematosus: Validation of the adjusted-Global Antiphospholipid Syndrome Score (aGAPSS) in Thai patients.

BACKGROUND: The adjusted-Global Antiphospholipid Syndrome Score (aGAPSS) has been validated and used to predict antiphospholipid antibodies (aPL) related to vascular thrombosis (VT). OBJECTIVE: To validate aGAPSS for predicted aPL-related VT and pregnancy complications (PC) in Thai systemic lupus erythematosus (SLE) patients. METHODS: A cross-sectional study was performed among Thai SLE patients with clinical manifestations; history of VT and PC, cardiovascular risk factors, and aPL profiles were collected. The aGAPSS was calculated from the sum of the risk factors (hyperlipidemia = 3.0, arterial hypertension = 1.0, anti-cardiolipin antibody = 5.0, anti-b2 glycoprotein I antibody = 4.0, and lupus anticoagulant = 4.0). RESULTS: Of 132 SLE patients, 12 (9.1%) had VT and 5 (4.1%) had PC. When comparing the aGAPSS (median; interquartile range [IQR]) of patients with events (VT and/or PC) (6.5; IQR 3.3-9.0), VT (8.0; IQR 4.0-9.0), arterial thrombosis (3.5; IQR 1.0-5.8), and PC (9.0; IQR 8.0-11.5), and the aGAPSS of patients without an event (3.0; IQR 0-4.0), aGAPSS of patients with events was significantly higher, except in patients with arterial thrombosis. An aGAPSS of 4.5 or more was associated with risk of aPL-related VT (sensitivity 71.4%, specificity 76.7%), and an aGAPSS of 6.0 or more was associated with risk of aPL-PC (sensitivity 100%, specificity 84.0%). CONCLUSION: The aGAPSS could predict the risk of aPL-PC and aPL-related VT in Thai SLE patients.

Anifrolumab: First Approval.

Anifrolumab (anifrolumab-fnia; Saphnelo™) is a monoclonal antibody antagonist of the type 1 interferon receptor (IFNAR). It is being developed by AstraZeneca (under license from Medarex, now Bristol-Myers Squibb) for the treatment of autoimmune disorders, including systemic lupus erythematosus (SLE) and lupus nephritis, the underlying pathogenesis of which involves type 1 interferon. In July 2021, intravenous anifrolumab was approved in the USA for the treatment of adult patients with moderate to severe SLE who are receiving standard therapy. Anifrolumab (intravenous or subcutaneous) continues to be assessed in clinical studies in SLE in various countries, and the intravenous formulation is under regulatory review in the EU and Japan. This article summarizes the milestones in the development of anifrolumab leading to this first approval for the treatment of moderate to severe SLE.

Defective oogenesis in mice with pristane-induced model of systemic lupus.

Systemic lupus erythematosus (SLE) is a chronic systemic autoimmune disease characterized by generation of autoantibodies and severe damage of various organs. The hormonal changes associated with pregnancy and especially estrogen might lead to damage of reproductive function and ovarian quality. We employed a pristane-induced lupus model of Balb/c mice which resembles human lupus in an attempt to follow oogenesis disruption during the disease progression. The integrity of cytoskeletal and chromatin structures was estimated in oocytes derived by hormonally stimulated ovulation in lupus mice and the results were compared with those from healthy mice. Chromatin, tubulin and actin structures in oocytes were detected by Hoechst 33258, anti-alpha-tubulin antibody and rhodamine-labeled phalloidin, respectively. All available meiotic spindles were analyzed - in immature (metaphase I) and mature oocytes (metaphase II). The total number of mature oocytes obtained from lupus mice was lower compared to healthy controls. The maturation rate was 9.8 % for lupus mice, 12.7 % for 7-month old controls, and 14.3 % for the young control mice (4 weeks old). Another major difference between the studied groups was the higher percentage of defective metaphase I spindles registered in oocytes derived from lupus mice (60 % normal spindles), while for the young and older controls this proportion was 86 % and 81 %, respectively. No such difference was registered for metaphase II spindles. For both metaphase I and metaphase II oocytes, the proportions of normal actin cap and chromosomal condensation were similar between the experimental groups.