RESUMEN
Background: Human leukocyte antigen-G (HLA-G) is a pivotal protein involved in immune regulation and tolerance, while systemic lupus erythematosus (SLE) is a multifaceted autoimmune condition influenced by genetic and environmental factors. Research indicates that variations and mutations in HLA-G may impact SLE development. Objective: This study aimed to explore the relationship between polymorphisms in the 3'-untranslated region (UTR) of the HLA-G gene and SLE. Methods: DNA from 100 SLE patients and 100 controls was analyzed using polymerase chain reaction to amplify the target sequence. Allele and genotype frequencies were determined, and haplotypes were assessed using Haploview v.4.2 software, with linkage disequilibrium calculated. Results: Findings revealed that the +2960 Ins allele was significantly linked to SLE as a risk factor, with the Del allele showing a protective effect. In addition, the +3010C allele and +3187A allele were significantly associated with SLE at both allele and genotype levels. The +3142 GG homozygote was notably linked to SLE at the genotype level. Haplotype analysis identified UTR-2 haplotypes as risk factors for SLE, whereas the UTR-1 haplotype was protective, shedding light on genetic factors influencing SLE risk. Conclusion: This study underscores the importance of HLA-G gene 3'-UTR polymorphisms in SLE susceptibility, suggesting their potential as diagnostic or therapeutic targets.
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Regiones no Traducidas 3' , Alelos , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Antígenos HLA-G , Haplotipos , Desequilibrio de Ligamiento , Lupus Eritematoso Sistémico , Polimorfismo de Nucleótido Simple , Humanos , Lupus Eritematoso Sistémico/genética , Antígenos HLA-G/genética , Haplotipos/genética , Regiones no Traducidas 3'/genética , Femenino , Masculino , Adulto , Frecuencia de los Genes/genética , Estudios de Casos y Controles , Polimorfismo de Nucleótido Simple/genética , Persona de Mediana Edad , Genotipo , Estudios de Asociación Genética , Factores de RiesgoRESUMEN
BACKGROUNDS: Progranulin (PGRN) is a growth factor-like molecule with diverse roles in homeostatic and pathogenic processes including the control of immune and inflammatory responses. Pathogenic inflammation is a hallmark of systemic lupus erythematosus (SLE) and elevated serum levels of PGRN has been evaluated as a biomarker of disease activity in SLE. However, the role of PGRN in SLE has not been fully investigated. This study is aimed to determine the potential involvements of PGRN in SLE. METHODS: Wild type (WT) and PGRN knockout (PGRN-/-) C57BL/6 mice received intraperitoneal injection of pristane for induction of a murine model of SLE. Sera were collected every biweekly and levels of anti-dsDNA antibody, IgG, and inflammatory factors were measured. Mice were sacrificed 5 months later and the renal lesions, as well as the proportions of T cell subtypes in the spleen were analyzed. RESULTS: Following exposure to pristane, PGRN-/- mice generated significantly lower levels of anti-dsDNA antibody and IgG relative to WT mice. PGRN-/- mouse kidneys had less IgG and collagen deposition compared with WT mice after pristane injection. CONCLUSION: The results indicate that PGRN participates in inflammatory response and renal damage in pristane induced SLE models, suggesting that PGRN mediates the onset of SLE.
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Anticuerpos Antinucleares , Modelos Animales de Enfermedad , Inmunoglobulina G , Péptidos y Proteínas de Señalización Intercelular , Lupus Eritematoso Sistémico , Ratones Endogámicos C57BL , Ratones Noqueados , Progranulinas , Terpenos , Animales , Lupus Eritematoso Sistémico/inmunología , Ratones , Inmunoglobulina G/sangre , Anticuerpos Antinucleares/sangre , Riñón/metabolismo , Riñón/inmunología , Bazo/inmunología , Bazo/metabolismo , ColágenoRESUMEN
OBJECTIVE: The aim of this study was to assess right atrial (RA) function, including RA phase strain, via speckle-tracking echocardiography (STE) in a cohort of systemic lupus erythematosus (SLE) patients with pulmonary arterial hypertension (PAH) and in particular to explore the relationship between RA phase strain and the occurrence of cardiovascular events. METHODS: STE analyses of RA function were evaluated in patients with SLE-PAH and in 33 healthy control subjects. Clinical associations, serum biomarkers, echocardiographic data, survival times, and adverse cardiovascular events were evaluated. RESULTS: A total of 66 patients with SLE-PAH were enrolled; they were divided into two groups based on the occurrence of adverse clinical events. RA phase strain was significantly reduced in patients with events than in patients without events. The endpoint was defined as the combined outcome of all-cause mortality, right heart failure, and rehospitalization due to disease progression. During a mean follow-up of 17.2 ± 9.9 months, 23 patients (35%) reached the endpoint. Compared with patients with RA reservoir strain (RASr) ≥33.45%, patients with RASr < 33.45% had more adverse long-term outcomes (log rank p < .0001). RASr was independently associated with adverse clinical outcomes according to multivariate analysis (p = .010). CONCLUSION: Our data suggest that RA function has prognostic value for SLE-PAH patients, and strain analysis revealed that the worse the RA function is, the worse the prognosis.
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Ecocardiografía , Atrios Cardíacos , Lupus Eritematoso Sistémico , Humanos , Femenino , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/fisiopatología , Masculino , Atrios Cardíacos/diagnóstico por imagen , Atrios Cardíacos/fisiopatología , Pronóstico , Ecocardiografía/métodos , Persona de Mediana Edad , Adulto , Hipertensión Arterial Pulmonar/fisiopatología , Hipertensión Arterial Pulmonar/complicaciones , Hipertensión Arterial Pulmonar/etiología , Hipertensión Arterial Pulmonar/sangre , Función del Atrio Derecho/fisiología , Hipertensión Pulmonar/fisiopatología , Hipertensión Pulmonar/complicaciones , Hipertensión Pulmonar/etiología , Estudios de SeguimientoAsunto(s)
Lupus Eritematoso Sistémico , Nativos de Hawái y Otras Islas del Pacífico , Resultado del Embarazo , Humanos , Lupus Eritematoso Sistémico/etnología , Femenino , Embarazo , Resultado del Embarazo/epidemiología , Australia/epidemiología , Nativos de Hawái y Otras Islas del Pacífico/etnología , Factores de Confusión Epidemiológicos , Complicaciones del Embarazo/etnología , Complicaciones del Embarazo/epidemiología , Aborigenas Australianos e Isleños del Estrecho de TorresAsunto(s)
Lupus Eritematoso Sistémico , Nativos de Hawái y Otras Islas del Pacífico , Resultado del Embarazo , Humanos , Femenino , Embarazo , Lupus Eritematoso Sistémico/etnología , Lupus Eritematoso Sistémico/diagnóstico , Lupus Eritematoso Sistémico/epidemiología , Resultado del Embarazo/epidemiología , Australia/epidemiología , Nativos de Hawái y Otras Islas del Pacífico/etnología , Adulto , Complicaciones del Embarazo/etnología , Factores de Confusión Epidemiológicos , Aborigenas Australianos e Isleños del Estrecho de TorresRESUMEN
BACKGROUND: Systemic Lupus Erythematosus (SLE) has a strong genetic susceptibility, but little is known about the impact of diet on disease severity. The Western diet is typically deficient in magnesium (Mg), and given the immunomodulatory effects of Mg, we hypothesized that the low Mg intake increases disease risk and that increasing Mg intake would reduce severity of murine lupus. Here, we placed 12-week old MRL/lpr female lupus mice on a normal (Mg500) or a high (Mg2800) Mg diet for 9 weeks. Urine and blood were collected during the study for quantification of urinary albumin, BUN, anti-dsDNA antibodies, and immune phenotyping. RESULTS: MRL/lpr lupus mice on high Mg2800 diet had significantly fewer skin lesions and less severe skin histology score, and reduced levels of pathogenic anti-dsDNA antibodies, compared with the Mg500 group (143.8±75.0 vs. 47.4±36.2 × 106U/ml; P < 0.05). The high Mg2800 group had a nearly two-fold increase in the percentage of CD4+FOXP3+ Treg cells compared to controls (19.9±5.4 vs. 11.4±5.5%; P < 0.05). Treg percentages inversely correlated with the concentration of anti-dsDNA. None of the mice developed arthritis during the observation period and there were no significant differences in weight, proteinuria, BUN or kidney histology. CONCLUSION: In conclusion, oral supplementation of Mg has a protective effect in a murine lupus model and may represent an inexpensive and safe adjuvant in the treatment of SLsE.
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Anticuerpos Antinucleares , Lupus Eritematoso Sistémico , Magnesio , Linfocitos T Reguladores , Animales , Lupus Eritematoso Sistémico/inmunología , Femenino , Ratones , Anticuerpos Antinucleares/inmunología , Anticuerpos Antinucleares/sangre , Magnesio/administración & dosificación , Linfocitos T Reguladores/inmunología , Modelos Animales de Enfermedad , Administración Oral , Ratones Endogámicos MRL lpr , Autoanticuerpos/inmunología , Autoanticuerpos/sangre , Piel/patología , Piel/inmunología , Piel/efectos de los fármacos , Enfermedades de la Piel/inmunología , Enfermedades de la Piel/tratamiento farmacológico , Enfermedades de la Piel/patologíaAsunto(s)
Antígeno de Maduración de Linfocitos B , Inmunosupresores , Lupus Eritematoso Sistémico , Inducción de Remisión , Adulto , Femenino , Humanos , Anticuerpos Biespecíficos/administración & dosificación , Anticuerpos Monoclonales Humanizados/administración & dosificación , Antígeno de Maduración de Linfocitos B/antagonistas & inhibidores , Antígeno de Maduración de Linfocitos B/inmunología , Resistencia a Medicamentos , Inmunosupresores/administración & dosificación , Inyecciones Subcutáneas , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/tratamiento farmacológico , Lupus Eritematoso Sistémico/inmunología , Inducción de Remisión/métodosRESUMEN
Importance: Anti-double-stranded DNA (dsDNA) antibody has been reported to have a close relationship with systemic lupus erythematosus (SLE) flares and participates in the pathogenesis of lupus nephritis (LN) as well as causing damage to other organs. However, whether early use of mycophenolate mofetil (MMF) could prevent SLE flares is not clear. Objective: To assess the efficacy and safety of MMF plus prednisone and hydroxychloroquine sulfate compared with prednisone and hydroxychloroquine sulfate alone in patients with SLE. Design, Setting, and Participants: This investigator-initiated, multicenter, observer-blinded randomized clinical trial enrolled 130 participants aged 18 to 65 years and was conducted in 3 hospitals across China. Treatment-naive patients with newly diagnosed SLE, a high titer of anti-dsDNA antibody, and no major organ involvement were included. The study was started September 1, 2018, and the follow-up was completed September 30, 2021. Data were analyzed from December 1, 2021, to March 31, 2022. Interventions: Patients were randomized 1:1 to receive oral prednisone (0.5 mg/kg/d) and hydroxychloroquine sulfate (5 mg/kg/d) (control group) or prednisone (0.5 mg/kg/d) and hydroxychloroquine sulfate (5 mg/kg/d) plus MMF (500 mg twice daily) (MMF group) for 96 weeks. Main Outcomes and Measures: The primary outcome was the proportion of patients presenting with flares according to the Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) Flare Index. The secondary outcomes included the proportion with lupus low disease activity state at week 96, 36-Item Short Form Health Survey scores before and after treatment, proportion of adverse events (AEs), and changes in SLEDAI-2000 scores and prednisone doses. Results: Among 130 randomized patients (mean [SD] age, 34.5 [12.5] years; 112 [86.2%] women), 119 (91.5%) completed the follow-up. The risk of severe flare was significantly lower in the MMF group (7 of 65 [10.8%]) vs the control group (18 of 65 [27.7%]) (relative risk [RR], 0.39 [95% CI, 0.17-0.87]; P = .01). Additionally, 1 of 65 patients in the MMF group (1.5%) and 9 of 65 in the control group (13.8%) manifested LN (RR, 0.11 [95% CI, 0.01-0.85]; P = .008). Most common serious study drug-related AEs were infections (20 of 65 [30.8%] in the control group and 22 of 65 [33.8%] in the MMF group). Conclusions and Relevance: The findings of this randomized clinical trial suggest that MMF may reduce the rate of severe flare and lower the incidence of LN in patients with new-onset SLE and a high titer of anti-dsDNA antibody without major organ involvement. Trial Registration: Chinese Clinical Trial Registry: ChiCTR1800017540.
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Hidroxicloroquina , Lupus Eritematoso Sistémico , Ácido Micofenólico , Prednisona , Humanos , Ácido Micofenólico/uso terapéutico , Lupus Eritematoso Sistémico/tratamiento farmacológico , Femenino , Adulto , Masculino , Hidroxicloroquina/uso terapéutico , Hidroxicloroquina/efectos adversos , Persona de Mediana Edad , Prednisona/uso terapéutico , Prednisona/efectos adversos , Quimioterapia Combinada , Adolescente , Inmunosupresores/uso terapéutico , Adulto Joven , China , Resultado del TratamientoRESUMEN
The THαß host immunological pathway contributes to the response to infectious particles (viruses and prions). Furthermore, there is increasing evidence for associations between autoimmune diseases, and particularly type 2 hypersensitivity disorders, and the THαß immune response. For example, patients with systemic lupus erythematosus often produce anti-double stranded DNA antibodies and anti-nuclear antibodies and show elevated levels of type 1 interferons, type 3 interferons, interleukin-10, IgG1, and IgA1 throughout the disease course. These cytokines and antibody isotypes are associated with the THαß host immunological pathway. Similarly, the type 2 hypersensitivity disorders myasthenia gravis, Graves' disease, graft-versus-host disease, autoimmune hemolytic anemia, immune thrombocytopenia, dermatomyositis, and Sjögren's syndrome have also been linked to the THαß pathway. Considering the potential associations between these diseases and dysregulated THαß immune responses, therapeutic strategies such as anti-interleukin-10 or anti-interferon α/ß could be explored for effective management.
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Lupus Eritematoso Sistémico , Humanos , Lupus Eritematoso Sistémico/inmunología , Lupus Eritematoso Sistémico/complicaciones , Síndrome de Sjögren/inmunología , Enfermedad Injerto contra Huésped/inmunología , Enfermedades Autoinmunes/inmunología , Citocinas/inmunología , Miastenia Gravis/inmunología , Anemia Hemolítica Autoinmune/inmunología , Enfermedad de Graves/inmunología , Enfermedad de Graves/complicaciones , Dermatomiositis/inmunologíaRESUMEN
CONTEXT: Cognitive deficits are neuropsychiatric syndromes associated with systemic lupus erythematosus. In our context, there are no data on the frequency of cognitive deficit as a manifestation of neuropsychiatric SLE or the associated conditions. OBJECTIVE: To define determinants of cognitive deficit in a cohort of Colombian patients with SLE attending a third-level hospital. METHODS AND PATIENTS: This descriptive cross-sectional study included patients with SLE, explored the presence of cognitive impairment through screening testing using the Montreal Cognitive Assessment (MoCA test), and diagnostic confirmation with a specific neuropsychological test battery recommended by the American College of Rheumatology. Quality of life was assessed using the LupusCol questionnaire and depression using the Beck Depression Inventory. RESULTS: Most patients were women, with a median age of 37 years (IQR, 28.0 - 46.7). Most patients had a level of higher education or technical education. Fifty-nine (62.9%) patients presented with a normal MoCA test result ≥26 points, and 35 (37.1%) patients with a score <26 points that were considered abnormal. The comprehensive neuropsychological test battery was applied to 31 patients (33.0%) with an abnormal MoCA test. Forty-one patients (48.8%) had some degree of depression. The median loss of quality of life was 21.03% (IQR 10.2 - 40.3). 19 patients (20%) presented some degree of cognitive deficit, 15 (15.95% of the total sample) had cognitive impairment, and 4 (4.25%) had cognitive decline. In a logistic regression analysis using data from patients undergoing specific tests, variables related to cognitive deterioration were found to be associated with a lower quality of life, showing an adjusted odds ratio of 1.05 (CI 1.01-0.09). No association was demonstrated with SLEDAI, prednisolone use, cyclophosphamide use, and the presence of depression. CONCLUSION: In this study, it was found in 16% of patients evaluated with the complete neuropsychological test battery and in 37% with the MoCA screening test. Our results suggest that it is crucial to implement strategies to assess cognitive deficit, depression, and quality of life in the consultation of patients with SLE and to raise awareness among health providers who care for patients with lupus about their presence and impact.
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Disfunción Cognitiva , Depresión , Lupus Eritematoso Sistémico , Pruebas Neuropsicológicas , Calidad de Vida , Humanos , Femenino , Estudios Transversales , Colombia/epidemiología , Masculino , Adulto , Persona de Mediana Edad , Disfunción Cognitiva/etiología , Disfunción Cognitiva/epidemiología , Disfunción Cognitiva/diagnóstico , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/psicología , Depresión/epidemiología , Depresión/etiología , Vasculitis por Lupus del Sistema Nervioso Central/psicología , Vasculitis por Lupus del Sistema Nervioso Central/epidemiología , Vasculitis por Lupus del Sistema Nervioso Central/diagnóstico , Vasculitis por Lupus del Sistema Nervioso Central/complicacionesRESUMEN
Myocarditis is a potentially life-threatening inflammatory disease of the myocardium, often resulting from infectious and immune-mediated responses. Clinical presentation in severe cases often results in a devastating illness requiring extracorporeal membrane oxygenation support as a result of cardiogenic shock. Although endomyocardial biopsy is still considered the gold standard for diagnosis, it often reveals nonspecific lymphocytic infiltration. Because the precise cause is usually unknown, the initial treatment typically involves immunosuppression and frequent assessment of myocardial contractility. This report presents 3 rare cases of autoimmune diseases (polymyositis, immunoglobulin G4-related disease, and systemic lupus erythematosus) that require extracorporeal membrane oxygenation support as a result of fulminant myocarditis, including their follow-up periods.
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Oxigenación por Membrana Extracorpórea , Miocarditis , Humanos , Miocarditis/terapia , Miocarditis/diagnóstico , Miocarditis/fisiopatología , Miocarditis/inmunología , Oxigenación por Membrana Extracorpórea/métodos , Masculino , Femenino , Adulto , Biopsia , Persona de Mediana Edad , Enfermedades Autoinmunes/diagnóstico , Enfermedades Autoinmunes/terapia , Enfermedades Autoinmunes/inmunología , Enfermedades Autoinmunes/complicaciones , Miocardio/patología , Miocardio/inmunología , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/diagnóstico , Lupus Eritematoso Sistémico/terapia , Choque Cardiogénico/terapia , Choque Cardiogénico/etiología , Choque Cardiogénico/diagnóstico , Resultado del Tratamiento , Enfermedad Relacionada con Inmunoglobulina G4/diagnóstico , Enfermedad Relacionada con Inmunoglobulina G4/terapia , Enfermedad Relacionada con Inmunoglobulina G4/complicacionesRESUMEN
This review article discusses neonatal lupus syndrome (NLS), an immune-mediated disease caused by maternal antibodies. Maternal antibodies in the fetal circulation are mostly but not always protective. NLS is a disease caused by pathogenic maternal autoantibodies in the fetal circulation. The passive immunization of the fetus by NLS-causing maternal antibodies may occur in the absence of a previously known maternal systemic autoimmune rheumatic disease (SARD). Screening for NLS-related antibodies in patients with related SARD or those in whom there is a risk of NLS including first-degree relatives should occur before pregnancy. This screening is best performed as part of a collaborative relationship between obstetrics and rheumatology. Pregnancy preparations in those with SARD include transitioning to pregnancy-safe medications. The symptoms of NLS range from minor skin rashes to fetal demise from heart block. Fetal screening allows for maternal therapeutic interventions that may be beneficial, as well as the use of fetal pacemakers in the more severe cases that include cardiac NLS.
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Lupus Eritematoso Sistémico , Humanos , Lupus Eritematoso Sistémico/inmunología , Lupus Eritematoso Sistémico/congénito , Lupus Eritematoso Sistémico/diagnóstico , Embarazo , Recién Nacido , Femenino , Autoanticuerpos/inmunología , Autoanticuerpos/sangre , Complicaciones del Embarazo/inmunologíaRESUMEN
Cerebral vasculitis is a rare but severe complication of Systemic Lupus Erythematosus (SLE), presenting significant challenges in management due to its potential for devastating neurological consequences and poor prognosis. We present a case of an 18-year-old female with known SLE who presented with seizures, declining cognitive function, and unresponsiveness. Neurological examination, laboratory investigations, and radiological imaging supported the diagnosis of cerebral vasculitis secondary to SLE. Despite aggressive immunosuppressive therapy, the patient's neurological status continued to deteriorate, leading to respiratory failure and multiorgan dysfunction. Ultimately, the patient succumbed to multiorgan failure attributed to severe CNS vasculitis and its complications. This case underscores the importance of early recognition and aggressive management of cerebral vasculitis in SLE while highlighting the need for further research into more effective therapeutic strategies to improve patient outcomes.
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Lupus Eritematoso Sistémico , Vasculitis del Sistema Nervioso Central , Humanos , Femenino , Adolescente , Lupus Eritematoso Sistémico/complicaciones , Vasculitis del Sistema Nervioso Central/etiología , Vasculitis del Sistema Nervioso Central/complicaciones , Resultado FatalRESUMEN
Background: Osteonecrosis of the femoral head (ONFH) is a severe complication of systemic lupus erythematosus (SLE) and occurs more frequently in SLE patients than in other autoimmune diseases, which can influence patients' life quality. The objective of this research was to analyze risk factors for the occurrence of ONFH in female SLE patients, construct and validate a risk nomogram model. Methods: Clinical records of SLE patients who fulfilled the 1997 American College of Rheumatology SLE classification criteria were retrospectively analyzed. The Least absolute shrinkage and selection operator (LASSO) regression and multivariate logistic regression analysis were used to summarize the independent risk factors of ONFH in female SLE patients, which were used to develop a nomogram. The predictive performance of the nomogram was assessed using the receiver characteristic (ROC) curve, calibration curves and decision curve analysis (DCA). Results: 793 female SLE patients were ultimately included in this study, of which 87 patients (10.9%) developed ONFH. Ten independent risk factors including disease duration, respiratory involvement, menstrual abnormalities, Sjögren's syndrome, osteoporosis, anti-RNP, mycophenolate mofetil, cyclophosphamide, biologics, and the largest daily glucocorticoid (GC) were identified to construct the nomogram. The area under the ROC curve of the nomogram model was 0.826 (95% CI: 0.780-0.872) and its calibration for forecasting the occurrence of ONFH was good (χ2 = 5.589, P = 0.693). DCA showed that the use of nomogram prediction model had certain application in clinical practice when the threshold was 0.05 to 0.95. In subgroup analysis, we found that the risk of ONFH was significantly increased in age at SLE onset of ≤ 50 years old, largest daily GC dose of ≥50 mg and the therapy of GC combined with immunosuppressant patients with menstrual abnormalities. Conclusion: Menstrual abnormalities were the first time reported for the risk factors of ONFH in female SLE patients, which remind that clinicians should pay more attention on female SLE patients with menstrual abnormalities and take early interventions to prevent or slow the progression of ONFH. Besides, the nomogram prediction model could provide an insightful and applicable tool for physicians to predict the risk of ONFH.
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Necrosis de la Cabeza Femoral , Lupus Eritematoso Sistémico , Nomogramas , Humanos , Femenino , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/diagnóstico , Factores de Riesgo , Adulto , Persona de Mediana Edad , Estudios Retrospectivos , Necrosis de la Cabeza Femoral/etiología , Necrosis de la Cabeza Femoral/epidemiología , Medición de RiesgoRESUMEN
Autoimmune diseases such as systemic lupus erythematosus (SLE) display a strong female bias. Although sex hormones have been associated with protecting males from autoimmunity, the molecular mechanisms are incompletely understood. Here we report that androgen receptor (AR) expressed in T cells regulates genes involved in T cell activation directly, or indirectly via controlling other transcription factors. T cell-specific deletion of AR in mice leads to T cell activation and enhanced autoimmunity in male mice. Mechanistically, Ptpn22, a phosphatase and negative regulator of T cell receptor signaling, is downregulated in AR-deficient T cells. Moreover, a conserved androgen-response element is found in the regulatory region of Ptpn22 gene, and the mutation of this transcription element in non-obese diabetic mice increases the incidence of spontaneous and inducible diabetes in male mice. Lastly, Ptpn22 deficiency increases the disease severity of male mice in a mouse model of SLE. Our results thus implicate AR-regulated genes such as PTPN22 as potential therapeutic targets for autoimmune diseases.
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Andrógenos , Autoinmunidad , Lupus Eritematoso Sistémico , Proteína Tirosina Fosfatasa no Receptora Tipo 22 , Receptores Androgénicos , Linfocitos T , Animales , Proteína Tirosina Fosfatasa no Receptora Tipo 22/genética , Proteína Tirosina Fosfatasa no Receptora Tipo 22/metabolismo , Masculino , Femenino , Receptores Androgénicos/metabolismo , Receptores Androgénicos/genética , Ratones , Linfocitos T/inmunología , Linfocitos T/metabolismo , Lupus Eritematoso Sistémico/inmunología , Lupus Eritematoso Sistémico/genética , Andrógenos/metabolismo , Ratones Noqueados , Activación de Linfocitos , Ratones Endogámicos NOD , Ratones Endogámicos C57BL , Modelos Animales de Enfermedad , Transducción de SeñalRESUMEN
BACKGROUND: Systemic Lupus Erythematosus (SLE) patients are more likely than the general population to suffer from thyroid illness. The major goal was to assess the thyroid dysfunctions due to immunological factors in Egyptian SLE children and how they are related to the course and severity of the illness. METHODS: Fifty children and adolescents with SLE are included in this cross-sectional observational study. Every patient underwent a thorough physical examination and a comprehensive history taking. An enzyme-linked immunosorbent assay (ELISA) approach was used to evaluate the thyroid profile, anti-thyroglobulin (Anti-TG), and anti-thyroid peroxidase (anti-TPO) antibodies. RESULTS: Of the 50 patients, the female: male ratio (F: M = 7:1) was 44 females and 6 males (12%). They were between the ages of 5 and 17. Out of the patients, thirty-two (64%) had thyroid dysfunctions, 19 (38%) had euthyroid sick syndrome, ten (20%) had overt hypothyroidism, three (6%) had subclinical hypothyroidism, and none had hyperthyroidism. Of the 50 patients, one (2%) had increased anti-TPO, whereas all other patients had normal anti-TG levels. A statistically significant negative correlation (p-value 0.007) was seen between the disease duration and free thyroxine (FT4). Furthermore, a significant negative correlation (p-values 0.015 and 0.028) was found when comparing the disease duration with thyroid antibodies (anti-TG and anti-TPO). CONCLUSION: In Juvenile Systemic Lupus Erythematosus (JSLE), thyroid dysfunctions can be identified. The disease duration but not its activity was significantly correlated with thyroid antibodies. For children with JSLE, thyroid function testing should be done on a regular basis. It is preferable to carry out additional thyroid antibody tests when necessary.
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Lupus Eritematoso Sistémico , Humanos , Femenino , Masculino , Niño , Estudios Transversales , Adolescente , Lupus Eritematoso Sistémico/complicaciones , Preescolar , Egipto/epidemiología , Pruebas de Función de la Tiroides , Tiroiditis Autoinmune/complicaciones , Tiroiditis Autoinmune/diagnóstico , Tiroiditis Autoinmune/epidemiología , Enfermedades de la Tiroides/complicaciones , Enfermedades de la Tiroides/inmunología , Autoanticuerpos/sangre , Ensayo de Inmunoadsorción Enzimática , Índice de Severidad de la EnfermedadRESUMEN
There is an ongoing search for novel biomarkers of endothelial damage, active disease, and organ dysfunction in systemic lupus erythematosus (SLE). We investigated the role of the vascular endothelial growth factor (VEGF) as a candidate biomarker by conducting a systematic review and meta-analysis of studies examining VEGF concentrations in SLE patients and healthy controls. We searched electronic databases (PubMed, Scopus, and Web of Science) from inception to 31 May 2024 (inclusion criteria: VEGF measurement in SLE patients and healthy controls and SLE patients with and without active disease or specific organ dysfunction in case-control studies, recruitment of adult participants, and availability of the full text in the English language; exclusion criteria: non-case-control studies, participants under 18 years, articles reporting duplicate or irrelevant data, and animal studies). We assessed the risk of bias and the certainty of evidence using the JBI Critical Appraisal Checklist and GRADE, respectively (PROSPERO registration number: CRD42024561636). Circulating VEGF concentrations were significantly higher in SLE patients than in controls (22 studies; standardised mean difference, SMD = 0.71, 95% CI 0.44 to 0.98, p < 0.001; low certainty of evidence). In SLE patients, VEGF concentrations were significantly higher in those with active disease (six studies; SMD = 1.10, 95% CI 0.27 to 1.92, p = 0.009; very low certainty of evidence) and lupus nephritis (four studies; SMD = 0.80, 95% CI 0.03 to 1.57, p = 0.042; very low certainty of evidence). Only one study reported VEGF concentrations in SLE patients with and without pulmonary arterial hypertension. The effect size of the differences in VEGF concentrations between SLE patients and controls was not associated with disease duration, use of glucocorticoids and immunosuppressors, biological matrix assessed, or analytical method used. However, it was significantly associated with the study's geographical location. The evidence was limited by the high but partially explainable heterogeneity and the presence of publication bias which was addressed with the "trim-and-fill" method (SLE presence), the high but partially explainable heterogeneity and lack of assessment of publication bias because of the limited study number (active disease), and the limited study number preventing the identification of sources of heterogeneity, sensitivity analysis, and assessment of publication bias (lupus nephritis). Our results highlight VEGF's potential role as a SLE biomarker and the need for further research, also given the aforementioned limitations, investigating VEGF concentrations in a wide range of SLE patient subgroups.
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Biomarcadores , Lupus Eritematoso Sistémico , Factor A de Crecimiento Endotelial Vascular , Lupus Eritematoso Sistémico/sangre , Humanos , Biomarcadores/sangre , Factor A de Crecimiento Endotelial Vascular/sangre , Adulto , Estudios de Casos y Controles , FemeninoRESUMEN
To investigate the association between single nucleotide polymorphism (SNP) at the rs3918188, rs1799983 and rs1007311 loci of the endothelial nitric oxide synthase (eNOS) gene and genetic susceptibility to systemic lupus erythematosus (SLE) in northeastern China. The base distribution of eNOS gene rs3918188, rs1799983 and rs1007311 in 1712 human peripheral blood samples from Northeast China was detected by SNaPshot sequencing technology. The correlation between genotype, allele and gene model of these loci of the eNOS gene and the genetic susceptibility to SLE was investigated by logistic regression analysis. The results of the differences in the frequency distribution of their gene models were visualised using R 4.3.2 software. Finally, HaploView 4.2 software was used to analyse the relationship between the haplotypes of the three loci mentioned above and the genetic susceptibility to SLE. A multifactor dimensionality reduction (MDR) analysis was used to determine the best SNP-SNP interaction model. The CC genotype and C allele at the rs3918188 locus may be a risk factor for SLE (CC vs AA: OR = 1.827, P < 0.05; C vs A: OR = 1.558, P < 0.001), and this locus increased the risk of SLE in the dominant model and the recessive model (AC + CC vs AA: OR = 1.542, P < 0.05; CC vs AA + AC: OR = 1.707, P < 0.001), while the risk of SLE was reduced in the overdominant model (AC vs AA + CC: OR = 0.628, P < 0.001). The GT genotype and T allele at locus rs1799983 may be a protective factor for SLE (GT vs GG: OR = 0.328, P < 0.001; T vs G: OR = 0.438, P < 0.001) and this locus reduced the risk of SLE in the overdominant model (GT vs GG + TT: OR = 0.385, P < 0.001). There is a strong linkage disequilibrium between the rs1007311 and rs1799983 loci of the eNOS gene. Among them, the formed haplotype AG increased the risk of SLE compared to GG. AT and GT decreased the risk of SLE compared to GG. In this study, the eNOS gene rs3918188 and rs1799983 loci were found to be associated with susceptibility to SLE. This helps to deeply explore the mechanism of eNOS gene and genetic susceptibility to SLE. It provides a certain research basis for the subsequent exploration of the molecular mechanism of these loci and SLE, as well as the early diagnosis, treatment and prognosis of SLE.
Asunto(s)
Predisposición Genética a la Enfermedad , Haplotipos , Lupus Eritematoso Sistémico , Óxido Nítrico Sintasa de Tipo III , Polimorfismo de Nucleótido Simple , Lupus Eritematoso Sistémico/genética , Humanos , China/epidemiología , Óxido Nítrico Sintasa de Tipo III/genética , Femenino , Masculino , Adulto , Persona de Mediana Edad , Genotipo , Alelos , Frecuencia de los Genes , Estudios de Casos y Controles , Desequilibrio de Ligamiento , Estudios de Asociación GenéticaRESUMEN
Systemic lupus erythematosus (SLE) is an autoimmune disorder that varies in clinical presentation and disease course. SLE has a strong female predilection and is more common in certain racial groups than others. There is no single set of universally accepted diagnostic criteria for SLE, which can make the disease challenging to diagnose. The disorder has the potential to affect nearly every organ system in the body, including the oral cavity. A complete understanding of the etiology and pathophysiology of SLE continues to evade the medical profession; however, advances in this area of research have drastically improved the quality of life of SLE patients. There currently is no cure for this condition, so present-day therapies aim to control patient symptoms and reduce SLE flare-ups. This article discusses the pathophysiology, diagnosis, oral and systemic manifestations, therapeutic interventions, and dental management of SLE patients.