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Vitamin D deficiency is increasingly common in systemic lupus erythematosus (SLE) patients and is associated with the disease activity and proteinuria. Recently, alterations in metabolism have been recognized as key regulators of SLE pathogenesis. Our objective was to identify differential metabolites in the serum metabolome of SLE with vitamin D deficiency. In this study, serum samples from 31 SLE patients were collected. Levels of 25(OH)D3 were assayed by ELISA. Patients were divided into two groups according to their vitamin D level (20 ng/ml). Untargeted metabolomics were used to study the metabolite profiles in serum by high-performance liquid chromatography-tandem mass spectrometry. Subsequently, we performed metabolomics profiling analysis to identify 52 significantly altered metabolites in vitamin D deficient SLE patients. The area under the curve (AUC) from ROC analyses was calculated to assess the diagnostic potential of each candidate metabolite biomarker. Lipids accounted for 66.67% of the differential metabolites in the serum, highlighted the disruption of lipid metabolism. The 52 differential metabolites were mapped to 27 metabolic pathways, with fat digestion and absorption, as well as lipid metabolism, emerging as the most significant pathways. The AUC of (S)-Oleuropeic acid and 2-Hydroxylinolenic acid during ROC analysis were 0.867 and 0.833, respectively, indicating their promising diagnostic potential. In conclusion, our results revealed vitamin D deficiency alters SLE metabolome, impacting lipid metabolism, and thrown insights into the pathogenesis and diagnosis of SLE.
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Biomarcadores , Lupus Eritematoso Sistémico , Metabolómica , Deficiencia de Vitamina D , Humanos , Lupus Eritematoso Sistémico/sangre , Lupus Eritematoso Sistémico/metabolismo , Deficiencia de Vitamina D/sangre , Deficiencia de Vitamina D/complicaciones , Femenino , Adulto , Masculino , Metabolómica/métodos , Biomarcadores/sangre , Metaboloma , Persona de Mediana Edad , Vitamina D/sangre , Vitamina D/análogos & derivados , Cromatografía Líquida de Alta Presión , Metabolismo de los Lípidos , Espectrometría de Masas en Tándem , Curva ROCRESUMEN
Lupus nephritis (LN) occurs in 50% of cases of systemic lupus erythematosus (SLE) and is one of the most serious complications that can occur during lupus progression. Mesangial cells (MCs) are intrinsic cells in the kidney that can regulate capillary blood flow, phagocytose apoptotic cells, and secrete vasoactive substances and growth factors. Previous studies have shown that various types of inflammatory cells can activate MCs for hyperproliferation, leading to disruption of the filtration barrier and impairment of renal function in LN. Here, we characterized the heterogeneity of kidney cells of LN mice by single-nucleus RNA sequencing (snRNA-seq) and revealed the interaction between macrophages and MCs through the CXC motif chemokine ligand 12 (CXCL12)/dipeptidyl peptidase 4 (DPP4) axis. In culture, macrophages modulated the proliferation and migration of MCs through this ligand-receptor interaction. In LN mice, treatment with linagliptin, a DPP4 inhibitor, effectively inhibited MC proliferation and reduced urinary protein levels. Together, our findings indicated that targeting the CXCL12/DPP4 axis with linagliptin treatment may serve as a novel strategy for the treatment of LN via the CXCL12/DPP4 axis.
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Proliferación Celular , Quimiocina CXCL12 , Dipeptidil Peptidasa 4 , Nefritis Lúpica , Macrófagos , Células Mesangiales , Nefritis Lúpica/patología , Nefritis Lúpica/metabolismo , Animales , Dipeptidil Peptidasa 4/metabolismo , Quimiocina CXCL12/metabolismo , Células Mesangiales/metabolismo , Células Mesangiales/patología , Células Mesangiales/efectos de los fármacos , Ratones , Macrófagos/metabolismo , Proliferación Celular/efectos de los fármacos , Humanos , Femenino , Movimiento Celular/efectos de los fármacos , Comunicación Celular/efectos de los fármacos , Linagliptina/farmacología , Transducción de Señal , Inhibidores de la Dipeptidil-Peptidasa IV/farmacología , Ratones Endogámicos C57BLRESUMEN
OBJECTIVES: To identify the effectiveness and safety of inactivated SARS-CoV-2 vaccines in rheumatic and musculoskeletal diseases (RMDs) patients. METHODS: RMD patients with COVID-19 in Jiangsu Province were polled between December 8, 2022, and February 1, 2023. Information on demographics, disease characteristics, antirheumatic drug use, vaccination status and survival state were collected. COVID-19-associated pneumonia was the primary outcome. The effect of COVID-19 immunization on RMD patients was assessed using multivariate logistic regression, and the adverse events (AEs) following vaccination were evaluated. RESULTS: Among 592 RMD patients with COVID-19, 276 (46.6%) individuals experienced COVID-19-associated pneumonia, and 290 (49.0%) patients were injected with inactivated vaccines. In multivariate logistic regression analysis, vaccines reduced the incidence of COVID-19-associated pneumonia, and receiving booster vaccine was an independent protective factor for COVID-19-associated pneumonia in RMD patients (OR 0.64, 95% CI 0.41-0.98, p = .034). In particular, inactivated vaccines have a protective impact on RMD patients with a high risk of developing pneumonia, including those aged 45 years and older (OR 0.53, 95% CI 0.34-0.83), and who have lung involvement (OR 0.43, 95% CI 0.23-0.82). The total AEs rate of vaccines was 13.9% (40/290), only 11 (3.8%) experienced the recurrence or deterioration of RMDs, and no serious AEs occurred. CONCLUSION: Inactivated COVID-19 vaccines were safe and effective in reducing the risk of COVID-19-associated pneumonia of RMD patients in China.
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Vacunas contra la COVID-19 , COVID-19 , Enfermedades Musculoesqueléticas , Enfermedades Reumáticas , Vacunas de Productos Inactivados , Humanos , COVID-19/prevención & control , COVID-19/epidemiología , Enfermedades Reumáticas/inmunología , Enfermedades Reumáticas/tratamiento farmacológico , Enfermedades Reumáticas/epidemiología , Masculino , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Vacunas contra la COVID-19/efectos adversos , Vacunas contra la COVID-19/administración & dosificación , Enfermedades Musculoesqueléticas/diagnóstico , Enfermedades Musculoesqueléticas/epidemiología , Vacunas de Productos Inactivados/efectos adversos , Anciano , Adulto , SARS-CoV-2/inmunología , China/epidemiología , Eficacia de las Vacunas , Resultado del Tratamiento , Factores de RiesgoRESUMEN
INTRODUCTION: This study aimed to analyze the risk factors associated with isoniazid-resistant and rifampicin-susceptible tuberculosis (Hr-TB) in adults. METHOD: The clinical data of 1,844 adult inpatients diagnosed with culture-positive pulmonary tuberculosis (PTB) in Nanjing Second Hospital from January 2019 and December 2021 were collected. All culture positive strain from the patient specimens underwent drug susceptibility testing (DST). Among them, 166 patients with Hr-TB were categorized as the Hr-TB group, while the remaining 1,678 patients were classified as having drug-susceptible tuberculosis (DS-TB). Hierarchical logistic regression was employed for multivariate analysis to identify variables associated with Hr-TB. RESULTS: Multivariate logistic regression analysis revealed that individuals with diabetes mellitus (DM) (OR 1.472, 95% CI 1.037-2.088, p = 0.030) and a history of previous tuberculosis treatment (OR 2.913, 95% CI 1.971-4.306, p = 0.000) were at higher risk of developing adult Hr-TB, with this risk being more pronounced in male patients. Within the cohort, 1,640 patients were newly treated, and among them, DM (OR 1.662, 95% CI 1.123-2.461, p = 0.011) was identified as risk factors for Hr-TB. CONCLUSIONS: Diabetes mellitus is a risk factor for Hr-TB in adults, and the contribution of diabetes as a risk factor was more pronounced in the newly treatment or male subgroup. And previous TB treatment history is also a risk factor for Hr-TB in adults.
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Antituberculosos , Isoniazida , Mycobacterium tuberculosis , Rifampin , Tuberculosis Pulmonar , Humanos , Masculino , Femenino , Factores de Riesgo , Isoniazida/uso terapéutico , Isoniazida/farmacología , Rifampin/uso terapéutico , Rifampin/farmacología , Persona de Mediana Edad , Adulto , China/epidemiología , Antituberculosos/uso terapéutico , Antituberculosos/farmacología , Mycobacterium tuberculosis/efectos de los fármacos , Mycobacterium tuberculosis/aislamiento & purificación , Tuberculosis Pulmonar/epidemiología , Tuberculosis Pulmonar/tratamiento farmacológico , Tuberculosis Pulmonar/microbiología , Tuberculosis Resistente a Múltiples Medicamentos/epidemiología , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Tuberculosis Resistente a Múltiples Medicamentos/microbiología , Pruebas de Sensibilidad Microbiana , Anciano , Adulto Joven , Estudios Retrospectivos , Diabetes Mellitus/epidemiología , Diabetes Mellitus/microbiologíaRESUMEN
Dry eye disease (DED) is a complex disorder driven by several factors like reduced tear production, increased evaporation, or poor tear quality. Oxidative stress plays a key role by exacerbating the inflammatory cycle. Previous studies explored antioxidants for DED treatment due to the link between oxidative damage and inflammation. Biochanin A (BCA) is a bioisoflavone from red clover with potent anti-inflammatory effects. This study investigated BCA's therapeutic potential for DED. Human corneal epithelial cells were cultured under hyperosmotic conditions to mimic DED. BCA treatment increased cell viability and decreased apoptosis and inflammatory cytokine expression. A DED mouse model was developed using female C57BL/6 mice in a controlled low-humidity environment combined with scopolamine injections. Mice received eye drops containing phosphate-buffered saline, low-dose BCA, or high-dose BCA. The effectiveness was evaluated by measuring tear volume, fluorescein staining, eye-closing ratio, corneal sensitivity and PAS staining. The levels of inflammatory components in corneas and conjunctiva were measured to assess DED severity. Maturation of antigen-presenting cells in cervical lymph nodes was analyzed by flow cytometry. BCA eye drops effectively reduced inflammation associated with DED in mice. BCA also decreased oxidative stress levels by reducing reactive oxygen species and enhancing the nuclear translocation of nuclear factor erythroid-2-related factor 2 (Nrf2). These findings demonstrate that BCA ameliorates oxidative stress and ocular surface inflammation, indicating potential as a DED treatment by relieving oxidative damage and mitigating inflammation.
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Síndromes de Ojo Seco , Genisteína , Ratones Endogámicos C57BL , Factor 2 Relacionado con NF-E2 , Estrés Oxidativo , Animales , Síndromes de Ojo Seco/tratamiento farmacológico , Síndromes de Ojo Seco/metabolismo , Síndromes de Ojo Seco/patología , Genisteína/farmacología , Genisteína/uso terapéutico , Femenino , Humanos , Estrés Oxidativo/efectos de los fármacos , Ratones , Factor 2 Relacionado con NF-E2/metabolismo , Modelos Animales de Enfermedad , Especies Reactivas de Oxígeno/metabolismo , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Citocinas/metabolismo , Apoptosis/efectos de los fármacos , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Inflamación/patología , Soluciones Oftálmicas/farmacología , Supervivencia Celular/efectos de los fármacos , Antioxidantes/farmacología , Células Epiteliales/efectos de los fármacos , Células Epiteliales/metabolismo , Línea Celular , Córnea/efectos de los fármacos , Córnea/metabolismo , Córnea/patologíaRESUMEN
OBJECTIVE: To evaluate the incidence and associated factors of initial and recurrent severe infections in hospitalized patients with systemic lupus erythematosus (SLE). METHODS: SLE patients that first hospitalized between 2010 and 2021 were studied retrospectively and divided into SLE with and without baseline severe infection groups. The primary outcome was the occurrence of severe infection during follow-up. Cox regression models were used to calculate the hazard ratio (HR) and 95% confidence interval (CI) for initial and recurrent severe infections. RESULTS: Among 1051 first hospitalized SLE patients, 164 (15.6%) had severe infection on admission. During a median follow-up of 4.1 years, 113 (10.8%) patients reached severe infection outcomes, including 27 with reinfection and 86 with initial severe infection (16.5% vs. 9.7%, p = .010). Patients with baseline severe infection had a higher cumulative incidence of reinfection (p = .007). After adjusting for confounding factors, renal involvement, elevated serum creatinine, hypoalbuminemia, cyclophosphamide, and mycophenolate mofetil treatment were associated with an increased risk of severe infection, especially initial severe infection. Low immunoglobulin, anti-dsDNA antibody positivity, and cyclophosphamide use significantly increased the risk of recurrent severe infection, with adjusted HR (95% CI) of 3.15 (1.22, 8.14), 3.60 (1.56, 8.28), and 2.14 (1.01, 5.76), respectively. Moreover, baseline severe infection and low immunoglobulin had a multiplicative interaction on reinfection, with adjusted RHR (95% CI) of 3.91 (1.27, 12.09). CONCLUSION: In this cohort of SLE, patients with severe infection had a higher risk of reinfection, and low immunoglobulin, anti-dsDNA antibody positivity, and cyclophosphamide use were independent risk factors for recurrent severe infection.
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Lupus Eritematoso Sistémico , Reinfección , Humanos , Estudios Retrospectivos , Ciclofosfamida/efectos adversos , Lupus Eritematoso Sistémico/diagnóstico , Lupus Eritematoso Sistémico/tratamiento farmacológico , Lupus Eritematoso Sistémico/epidemiología , Factores de Riesgo , Inmunoglobulinas , China/epidemiologíaRESUMEN
OBJECTIVE: The goal was to investigate the role and intracellular regulatory mechanisms of double-negative T (DNT) cells in the pathogenesis of systemic lupus erythematosus (SLE). METHODS: DNT cells were assessed in murine models, patients with SLE, and controls using flow cytometry (FCM). DNT cells from either resiquimod (R848) or vehicle-treated C57BL/6 (B6) mice were cultured with B cells from R848-treated mice to explore functions. Differential mechanistic target of rapamycin (mTOR) pathway signaling in DNT cells measured using FCM and quantitative polymerase chain reaction was validated by rapamycin inhibition. Candidate lipid metabolites detected using liquid chromatography with electrospray ionization mass spectrometry/mass spectrometry were functionally assessed in DNT cell cultures. RESULTS: DNT cells were markedly increased in both spontaneous and induced mouse lupus models and in patients with SLE. Expanded DNT cells from R848-treated B6 mice produced elevated interleukin (IL)-17A and IgG with increased germinal center B (GCB) cells. Expansion of DNT cells associated with activation of mTORC1 pathway that both IL-17A levels and the number of DNT cells exhibited dose-dependent reduction with rapamycin treatment. Lipidomics studies revealed differential patterns of lipid metabolites in T cells of R848-treated mice. Among candidate metabolites, elevated phosphatidic acid (PA) that was partially controlled by phospholipase D2 increased the expression of the mTORC1 downstream target p-S6 and positively expanded IL-17A-producing DNT cells. Similarly, elevated proportions of circulating DNT cells in patients with SLE correlated with disease activity and proteinuria, and IL-17A secretion was elevated after in vitro PA stimulation. CONCLUSION: The accumulation of PA in T cells could activate the mTORC1 pathway, promoting DNT cell expansion and IL-17A secretion, resulting in GCB cell abnormalities in lupus.
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Interleucina-17 , Lupus Eritematoso Sistémico , Diana Mecanicista del Complejo 1 de la Rapamicina , Ácidos Fosfatidicos , Transducción de Señal , Animales , Lupus Eritematoso Sistémico/inmunología , Lupus Eritematoso Sistémico/metabolismo , Interleucina-17/metabolismo , Ácidos Fosfatidicos/farmacología , Diana Mecanicista del Complejo 1 de la Rapamicina/metabolismo , Ratones , Humanos , Ratones Endogámicos C57BL , Femenino , Modelos Animales de Enfermedad , Linfocitos T/metabolismo , Linfocitos T/inmunologíaRESUMEN
OBJECTIVE: To construct a molecular immune map of patients with systemic sclerosis (SSc) by mass flow cytometry, and compare the number and molecular expression of double-negative T (DNT) cell subsets between patients and healthy controls (HC). METHODS: Peripheral blood mononuclear cells (PBMCs) were extracted from the peripheral blood of 17 SSc patients and 9 HC. A 42-channel panel was set up to perform mass cytometry by time of flight (CyTOF) analysis for DNT subgroups. Flow cytometry was used to validate subpopulation functions. The clinical data of patients were collected for correlation analysis. RESULTS: Compared with HC, the number of total DNT cells decreased in SSc patients. Six DNT subsets were obtained from CyTOF analysis, in which the proportion of cluster1 increased, while the proportion of cluster3 decreased. Further analysis revealed that cluster1 was characterized by high expression of CD28 and CCR7, and cluster3 was characterized by high expression of CD28 and CCR5. After in vitro stimulation, cluster1 secreted more IL-4 and cluster3 secreted more IL-10 in SSc patients compared to HC. Clinical correlation analysis suggested that cluster1 may play a pathogenic role while cluster3 may play a protective role in SSc. ROC curve analysis further revealed that cluster3 may be a potential indicator for determining disease activity in SSc patients. CONCLUSION: We found a new CCR5+CD28+ DNT cell subset, which played a protective role in the pathogenesis of SSc. Key Points ⢠The number of DNT cells decreased in SSc patients' peripheral blood. ⢠DNT cells do not infiltrate in the skin but secrete cytokines to participate in the pathogenesis of SSc. ⢠A CCR5+CD28+ DNT cell population may play a protective role in SSc.
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Leucocitos Mononucleares , Esclerodermia Sistémica , Humanos , Leucocitos Mononucleares/metabolismo , Antígenos CD28 , Citocinas/metabolismo , Subgrupos de Linfocitos TRESUMEN
BACKGROUND: Glibenclamide has garnered attention due to its multifaceted neuroprotective effects in cases of acute central nervous system injury. We initiated a trial to explore the effectiveness and safety of a high dose of glibenclamide in the management of cerebral oedema following aneurysmal subarachnoid haemorrhage (aSAH). METHODS: This trial constituted a single-centre, randomised clinical study. Half of the 56 patients assigned to the glibenclamide group received 15 mg of glibenclamide tablets daily for 10 days (5 mg, three times/day). The primary outcome was the proportion of patients achieving the subarachnoid haemorrhage early brain oedema score dichotomy (defined as Subarachnoid Haemorrhage Early Brain Oedema Score 0-2) at the 10-day postmedication. The secondary outcome of cerebral oedema was the concentration of sulfonylurea receptor 1-transient receptor potential melastatin 4 (SUR1-TRPM4) in the plasma and cerebrospinal fluid. RESULTS: We enrolled 56 patients diagnosed with aSAH, who were admitted to the neurosurgery intensive care unit between 22 August 2021 and 25 April 2023. The primary outcome revealed that the glibenclamide group exhibited a notably higher proportion of mild cerebral oedema in comparison to the placebo group (60.7% vs 42.9%, adjusted OR: 4.66, 95% CI 1.14 to 19.10, p=0.032). Furthermore, the concentration of SUR1-TRPM4 in the cerebrospinal fluid of the glibenclamide group was significantly higher than the placebo group (p=0.0002; p=0.026), while the plasma TRPM4 concentration in the glibenclamide group was significantly lower than the placebo group (p=0.001). CONCLUSION: Oral administration of high-dose glibenclamide notably reduced radiological assessment of cerebral oedema after 10 days of medication. Significant alterations were also observed in the concentration of SUR1-TRPM4 in plasma and cerebrospinal fluid. However, it is worth noting that glibenclamide was associated with a higher incidence of hypoglycaemia. Larger trials are warranted to evaluate the potential benefits of glibenclamide in mitigating swelling and then improving neurological function. TRIAL REGISTRATION NUMBER: ChiCTR2100049908.
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OBJECTIVE: To assess the long-term safety and efficacy of umbilical cord mesenchymal stem cells transplantation (UMSCT) in patients with systemic sclerosis (SSc). METHODS: Forty-one patients with moderate to severe SSc underwent UMSCT at the Affiliated Drum Tower Hospital of Nanjing University Medical School from 2009 to 2017. In this study, we conducted a longitudinal and retrospective analysis and compared the clinical and laboratory manifestations before and after UMSCT. The main outcome of the study was overall survival. We evaluated changes in the modified Rodnan Skin Score (mRSS), as well as the changes in the pulmonary examination by using high-resolution computed tomography (HRCT) and ultrasound cardiogram (UCG). Additionally, we assessed the Health Assessment Questionnaire-Disability Index (HAQ-DI) and the severity of peripheral vascular involvement during the first year after treatment. RESULTS: The overall 5-year survival rate was 92.7% (38 out of 41 patients). Following UMSCT, the mean mRSS significantly decreased from 18.68 (SD = 7.26, n = 41) at baseline to 13.95 (SD = 8.49, n = 41), 13.29 (SD = 7.67, n = 38), and 12.39 (SD = 8.49, n = 38) at 1, 3, and 5 years, respectively. Improvement or stability in HRCT images was observed in 72.0% of interstitial lung disease (ILD) patients. Pulmonary arterial hypertension (PAH) remained stable in 5 out of 8 patients at the 5-year follow-up. No adverse events related to UMSCT were observed in any of the patients during the follow-up period. CONCLUSION: UMSCT may provide a safe and feasible treatment option for patients with moderate to severe SSc based on long-term follow-up data. The randomized controlled study will further confirm the clinical efficacy of UMSCT in SSc. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00962923. Key Point ⢠UMSCT is safe and effective for SSc patients.
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Células Madre Mesenquimatosas , Esclerodermia Sistémica , Humanos , Estudios de Seguimiento , Pulmón , Estudios Retrospectivos , Esclerodermia Sistémica/diagnóstico por imagen , Esclerodermia Sistémica/terapiaRESUMEN
Abnormal mitochondrial function has been implicated in the progression of systemic lupus erythematosus (SLE), the prototypical autoimmune disease, yet the underlying cause remains unclear. In this study, mitochondrial-encoded NADH dehydrogenase 6 gene (MT-ND6) was identified as having increased m6A methylation and decreased expression in peripheral blood mononuclear cells of SLE patients by MeRIP-seq analysis. MT-ND6 expression was negatively correlated with SLE disease activity index score and 24-h urine protein level, and lower in patients with positive anti-Sm or anti-dsDNA antibodies. With the reduction of MT-ND6 levels, CD4+ T cells in SLE patients exhibited mitochondrial dysfunction, as evidenced by increased levels of reactive oxygen species (ROS) and mitochondrial ROS and insufficient ATP production. Accordingly, in vitro MT-ND6 silencing induced abnormalities in the above mitochondrial indicators in CD4+ T cells, and promoted the development of both transcription and inflammatory factors in these cells. In contrast, treatment with targeted mitochondrial antioxidants largely counteracted the silencing effect of MT-MD6. Thus, reduced MT-ND6 in SLE patients may lead to mitochondrial dysfunction through ROS overproduction, thereby promoting inflammatory CD4+ T cells.
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Lupus Eritematoso Sistémico , Enfermedades Mitocondriales , Humanos , Expresión Génica , Leucocitos Mononucleares , Lupus Eritematoso Sistémico/genética , NADH Deshidrogenasa/genética , Especies Reactivas de Oxígeno , Linfocitos TRESUMEN
OBJECTIVE: Patients with systemic lupus erythematosus (SLE) have an increased risk of venous thromboembolism (VTE). We conducted this study to develop a risk score algorithm for VTE in patients with SLE that provides individualised risk estimates. METHODS: We developed a clinical prediction model of VTE in 4502 patients with SLE based on the Chinese SLE Treatment and Research group cohort (CSTAR) from January 2009 to January 2020 and externally validated in 3780 patients with SLE in CSTAR from January 2020 to January 2022. Baseline data were obtained and VTE events were recorded during the follow-up. The prediction model was developed to predict VTE risk within 6 months in patients with SLE, using multivariate logistic regression and least absolute shrinkage and selection operator. SLE-VTE score and nomogram were established according to the model. RESULTS: A total of 4502 patients included in the development cohort, 135 had VTE events. The final prediction model (SLE-VTE score) included 11 variables: gender, age, body mass index, hyperlipidaemia, hypoalbuminaemia, C reactive protein, anti-ß2GPI antibodies, lupus anticoagulant, renal involvement, nervous system involvement and hydroxychloroquine, with area under the curve of 0.947 and 0.808 in the development (n=4502) and external validation cohort (n=3780), respectively. According to the net benefit and predicted probability thresholds, we recommend annual screening of VTE in high risk (≥1.03%) patients with SLE. CONCLUSION: Various factors are related to the occurrence of VTE in patients with SLE. The proposed SLE-VTE risk score can accurately predict the risk of VTE and help identify patients with SLE with a high risk of VTE who may benefit from thromboprophylaxis.
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Lupus Eritematoso Sistémico , Tromboembolia Venosa , Trombosis de la Vena , Humanos , Tromboembolia Venosa/diagnóstico , Tromboembolia Venosa/epidemiología , Tromboembolia Venosa/etiología , Trombosis de la Vena/epidemiología , Trombosis de la Vena/etiología , Anticoagulantes , Modelos Estadísticos , Pronóstico , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/epidemiologíaRESUMEN
We aimed to investigate the factors associated with vitamin D deficiency and changes in 25 (OH)D levels, as well as the impact of those changes on disease activity and renal function among SLE patients. This retrospective cohort study was based on the medical records of SLE patients hospitalized between 2010 and 2021. We collected relevant information from this patient population. Logistic regression analysis was employed to determine the factors associated with vitamin D deficiency and increased 25 (OH)D levels, and we calculated the odds ratios (ORs) and 95% confidence intervals (CIs) accordingly. At baseline, among the 1257 SLE patients, the median and interquartile range of 25 (OH)D levels were 14 (9, 20) ng/ml, with 953 (75.8%) patients exhibiting 25 (OH)D deficiency (< 20 ng/ml). The presence of 25 (OH)D deficiency was found to be associated with renal involvement and a high glucocorticoid (GC) maintenance dose. Among the 383 patients who were followed up for an average of 18 months, an increase of at least 100% in 25 (OH)D levels was positively associated with a decreased GC maintenance dose and vitamin D3 supplementation, with adjusted odds ratios(OR) (95% confidence interval [CI]) of 2.16 (1.02, 4.59) and 1300 (70, 22300), respectively. Furthermore, an increased level of 25 (OH)D was significantly associated with a decrease in the Disease Activity Index 2000 score and the urinary protein/creatinine ratio. Patients with SLE have low vitamin D levels, especially those with impaired kidney function. Increased 25 (OH)D levels can be achieved through supplementation with high doses of vitamin D3 and are associated with improvements in disease activity and the urinary protein/creatinine ratio.
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INTRODUCTION: The association between mycophenolate mofetil (MMF) and infection in patients with systemic lupus erythematosus (SLE) has not been clarified. This study evaluated the degree and factors in effect of MMF use on infection in patients with SLE. METHODS: A hospitalized-based observational study was conducted to collect medical records on patients with SLE during 2010-2021. A nested case-control study was performed among 3339 patients with SLE, including 1577 cases and 1762 controls by whether they developed any type of infection. The exposure of MMF use was determined within 1 year before diagnosed infection or the end of follow-up. Logistic regression was used to estimate the odds ratio (OR) and 95% confidence interval (CI) for association between MMF and subsequent infection. RESULTS: MMF was significantly associated with the risk of overall infection (adjusted OR 1.90, 95% CI 1.48-2.44) and different types of infections, including bacterial infection (adjusted OR 2.07, 95% CI 1.55-2.75), viral infection (adjusted OR 1.92, 95% CI 1.23-3.01), and opportunistic infection (adjusted OR 2.13, 95% CI 1.31-3.46). The top three risks of specific types of infections were bacteremia/septicemia, urinary tract infection/pyelonephritis, and herpes zoster. Stratification analysis showed risk of overall infection increased especially in MMF users with age over 55 years, diabetes, central nervous system involvement, and thrombocytopenia. Moreover, the risk of infection increased with increasing dosage and duration of MMF use. Additionally, the combination of MMF with CYC and other immunosuppressants significantly increases the risk of infections compared to using a single one. CONCLUSIONS: MMF use is associated with various type of infections in patients with SLE, particularly in those with longer use, older age, complications with comorbidities, and concomitant use of CYC or other immunosuppressants.
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Systemic lupus erythematosus (SLE) is an autoimmune disease in which the immune system attacks its own tissues and organs. However, the causes of SLE remain unknown. Dyslipidemia is a common symptom observed in SLE patients and animal models and is closely correlated to disease activity. Lipid metabolic reprogramming has been considered as a hallmark of the dysfunction of T cells in patients with SLE, therefore, manipulating lipid metabolism provides a potential therapeutic target for treating SLE. A better understanding of the underlying mechanisms for the metabolic events of immune cells under pathological conditions is crucial for tuning immunometabolism to manage autoimmune diseases such as SLE. In this review, we aim to summarize the cross-link between lipid metabolism and the function of T cells as well as the underlying mechanisms, and provide light on the novel therapeutic strategies of active compounds from herbals for the treatment of SLE by targeting lipid metabolism in immune cells.
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Lupus Eritematoso Sistémico , Linfocitos T , Animales , Linfocitos T/metabolismo , Metabolismo de los Lípidos , Lupus Eritematoso Sistémico/metabolismoRESUMEN
OBJECTIVES: Mesenchymal stromal cells (MSCs) and low-dose interleukin-2 (IL-2) both have demonstrated efficacy in treating systemic lupus erythematosus (SLE). The aim of this study is to conduct a head-to-head comparison between the 2 treatments and provide insights for clinical applications. METHODS: Lupus-prone mice were treated with umbilical cord-derived MSCs (UC-MSCs), IL-2, or a combination of UC-MSCs and IL-2, respectively. The lupus-like symptoms, renal pathology, and T-cell response were assessed 1 or 4 weeks later. Modulation of IL-2 production by MSCs on immune cells was investigated by the coculture assay. Disease activity and serum IL-2 of SLE patients were determined before and after receiving UC-MSCs. RESULTS: Both UC-MSCs and IL-2 improved lupus symptoms in lupus-prone mice 1 week after treatment, while the effects of UC-MSCs lasted up to 4 weeks. Moreover, the UC-MSC-treated group showed better renal pathology improvement. Importantly, UC-MSCs combined with IL-2 did not provide better efficacy than UC-MSCs alone. Consistent with this, UC-MSCs alone and UC-MSCsâ +â IL-2 resulted in similar levels of serum IL-2 and frequencies of Tregs. Neutralization of IL-2 partly reduced the promotion of Tregs by UC-MSCs, suggesting that IL-2 was involved in the upregulation of Tregs by UC-MSCs. Lastly, an increase in serum IL-2 positively correlated with the reduction of disease activity of SLE patients by UC-MSCs. CONCLUSION: Both the single injection of UC-MSCs and repeated IL-2 administration exerted comparable efficacy in alleviating SLE manifestations, but UC-MSCs provided sustained alleviation and showed better improvement in renal pathology.
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Lupus Eritematoso Sistémico , Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas , Animales , Ratones , Interleucina-2/farmacología , Lupus Eritematoso Sistémico/terapia , Técnicas de Cocultivo , Cordón Umbilical , Trasplante de Células Madre Mesenquimatosas/métodosRESUMEN
To explore the etiology of risk factors and quantify the mortality differences in systemic lupus erythematosus (SLE) patients with different initial disease activity. The Jiangsu Lupus database was established by collecting medical records from first-hospitalized SLE patients during 1999-2009 from 26 centers in Jiangsu province, China, and their survival status every five years. The initial SLEDAI scores [high (>12) vs. low-moderate (≤12)] differences in mortality attributable to risk factors were quantified using population attributable fraction (PAF), relative attributable risk (RAR) and adjusted relative risk (ARR). Among 2446 SLE patients, 83 and 176 deaths were observed in the low-moderate and high activity groups, with mortality rates of 7.7 and 14.0 per 1000 person years, respectively. Anemia was the leading contributor to mortality, with PAFs of 40.4 and 37.5 in the low-moderate and high activity groups, respectively, and explained 23.2% of the mortality differences with an ARR of 1.66 between the two groups. Cardiopulmonary involvement caused the highest PAFs in the low-moderate (20.5%) and high activity (13.6%) groups, explaining 18.3% of the mortality differences. The combination of anemia and cardiopulmonary involvement had the highest RAR, causing 39.8% of the mortality differences (ARR = 1.52) between the two groups. In addition, hypoalbuminemia and a decrease in the creatinine clearance rate accounted for 20-30% of deaths and explained 10-20% of the mortality differences between the two groups, while antimalarial drug nonuse accounted for about 35% of deaths and explained 3.6% of the mortality differences. Anemia, cardiopulmonary involvement and hypoalbuminemia may cause substantial mortality differences across disease activity states, suggesting additional strategies beyond disease activity assessment to monitor SLE outcomes.
RESUMEN
To assess the remission rate of eltrombopag in the treatment of severe immune thrombocytopenia (ITP) secondary to connective tissue disease (CTD) and to explore factors related to drug efficacy in the context of literature reports, seventeen CTD patients accompanied with severe ITP treated with eltrombopag between June 2019 and February 2021 were included, with their follow-up information recorded. Combined with literature review, patients were divided into two groups depending on whether the treatment was effective or not to determine efficacy-related factors. Totally, 7 patients with systemic lupus erythematosus, 6 with Sjögren's syndrome, and 4 with undifferentiated connective tissue disease were enrolled. The median duration of eltrombopag treatment was 8 weeks, and the median time to response was 4 weeks. Twelve (70.6%) patients responded to eltrombopag. Patients with higher serum white blood cell counts, lower serum triglyceride levels, or previously received multiple immunosuppressants achieved a better efficacy (p < 0.05), while those with megakaryocytopenia in bone marrow tended to have lower remission rate (p = 0.08). By using pooled data including literature reported cases, we demonstrated that evidence of leukopenia, megakaryocytopenia, and being treated with fewer prior immunosuppressants were still associated with poor remission (p < 0.05). Meanwhile, there was a trend indicating the primary disease might affect the treatment efficacy (p = 0.06). Eltrombopag is a viable option for treating severe ITP secondary to CTDs, yet it may be less effective for patients with leukopenia, megakaryocytopenia, and being treated with fewer prior immunosuppressants. Key Points ⢠Eltrombopag provides an alternative to the current treatment of CTD-ITP. ⢠White blood cell levels, bone marrow megakaryocyte counts, and prior use of immunosuppressants may affect the efficacy of eltrombopag.
Asunto(s)
Enfermedades del Tejido Conjuntivo , Leucopenia , Púrpura Trombocitopénica Idiopática , Trombocitopenia , Humanos , Púrpura Trombocitopénica Idiopática/complicaciones , Púrpura Trombocitopénica Idiopática/tratamiento farmacológico , Trombocitopenia/complicaciones , Trombocitopenia/tratamiento farmacológico , Benzoatos/uso terapéutico , Hidrazinas/uso terapéutico , Enfermedades del Tejido Conjuntivo/complicaciones , Enfermedades del Tejido Conjuntivo/tratamiento farmacológico , Resultado del Tratamiento , Leucopenia/complicaciones , Inmunosupresores/uso terapéuticoRESUMEN
OBJECTIVE: To explore the clinical features of patients with systemic lupus erythematosus and Sjögren's syndrome overlap (SLE-SS) compared to concurrent SLE or primary SS (pSS) patients, we utilized a predictive machine learning-based tool to study SLE-SS. METHODS: This study included SLE, pSS, and SLE-SS patients hospitalized at Nanjing Drum Hospital from December 2018 to December 2020. To compare SLE versus SLE-SS patients, the patients were randomly assigned to discovery cohorts or validation cohorts by a computer program at a ratio of 7:3. To compare SS versus SLE-SS patients, computer programs were used to randomly assign patients to the discovery cohort or the validation cohort at a ratio of 7:3. In the discovery cohort, the best predictive features were determined using a least absolute shrinkage and selection operator (LASSO) logistic regression model among the candidate clinical and laboratory parameters. Based on these factors, the SLE-SS prediction tools were constructed and visualized as a nomogram. The results were validated in a validation cohort, and AUC, calibration plots, and decision curve analysis were used to assess the discrimination, calibration, and clinical utility of the predictive models. RESULTS: This study of SLE versus SLE-SS included 290 patients, divided into a discovery cohort (n = 203) and a validation cohort (n = 87). The five best characteristics were selected by LASSO logistic regression in the discovery cohort of SLE versus SLE-SS and were used to construct the predictive tool, including dry mouth, dry eye, anti-Ro52 positive, anti-SSB positive, and RF positive. This study of SS versus SLE-SS included 266 patients, divided into a discovery cohort (n = 187) and a validation cohort (n = 79). In the discovery cohort of SS versus SLE-SS, by using LASSO logistic regression, the eleven best features were selected to build the predictive tool, which included age at diagnosis (years), fever, dry mouth, photosensitivity, skin lesions, arthritis, proteinuria, hematuria, hypoalbuminemia, anti-dsDNA positive, and anti-Sm positive. The prediction model showed good discrimination, good calibration, and fair clinical usefulness in the discovery cohort. The results were validated in a validation cohort of patients. CONCLUSION: The models are simple and accessible predictors, with good discrimination and calibration, and can be used as a routine tool to screen for SLE-SS.