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2.
S D Med ; 74(3): 121-126, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34232591

RESUMO

Lupus erythematosus (LE) is a complex autoimmune disease that presents with a wide variety of clinical and immunopathological features, making it challenging to reach a correct and prompt diagnosis. Patients with LE most frequently present with cutaneous and rheumatologic manifestations. As cutaneous findings may be the first sign of disease, their timely recognition is important for proper workup and management of LE. Here we present a case of subacute cutaneous lupus erythematosus (SCLE) and review the cutaneous manifestations of lupus erythematosus and the histopathological correlates to raise awareness and promote faster times to diagnosis and treatment.


Assuntos
Lúpus Eritematoso Cutâneo , Lúpus Eritematoso Sistêmico , Diagnóstico Diferencial , Humanos , Lúpus Eritematoso Cutâneo/diagnóstico , Lúpus Eritematoso Sistêmico/diagnóstico , Pele
3.
Sci Transl Med ; 13(600)2021 06 30.
Artigo em Inglês | MEDLINE | ID: mdl-34193612

RESUMO

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by a loss of tolerance toward self-nucleic acids, autoantibody production, interferon expression and signaling, and a defect in the regulatory T (Treg) cell compartment. In this work, we identified that platelets from patients with active SLE preferentially interacted with Treg cells via the P-selectin/P-selectin glycoprotein ligand-1 (PSGL-1) axis. Selectin interaction with PSGL-1 blocked the regulatory and suppressive properties of Treg cells and particularly follicular Treg cells by triggering Syk phosphorylation and an increase in intracytosolic calcium. Mechanistically, P-selectin engagement on Treg cells induced a down-regulation of the transforming growth factor-ß axis, altering the phenotype of Treg cells and limiting their immunosuppressive responses. In patients with SLE, we found an up-regulation of P- and E-selectin both on microparticles and in their soluble forms that correlated with disease activity. Last, blocking P-selectin in a mouse model of SLE improved cardinal features of the disease, such as anti-dsDNA antibody concentrations and kidney pathology. Overall, our results identify a P-selectin-dependent pathway that is active in patients with SLE and validate it as a potential therapeutic avenue.


Assuntos
Lúpus Eritematoso Sistêmico , Linfócitos T Reguladores , Animais , Humanos , Camundongos , Selectinas , Fator de Crescimento Transformador beta
4.
J Med Case Rep ; 15(1): 339, 2021 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-34233732

RESUMO

BACKGROUND: Rituximab is a novel chimeric monoclonal antibody that has established itself as a potent therapeutic option for autoimmune medical conditions, including systemic lupus erythematosus, owing to its mechanism of action targeting CD20 cells. Rituximab is also known to cause a spectrum of side effects including hematological abnormalities. Acute isolated thrombocytopenia following rituximab is an uncommon occurrence and, when seen, occurs in the presence of underlying hematological malignancies. Its occurrence in autoimmune diseases is rare. Despite this, acute isolated thrombocytopenia in the backdrop of systemic lupus erythematosus is undocumented. CASE PRESENTATION: A young 36-year-old South Asian female with systemic lupus erythematosus with class IV lupus nephritis poorly responding to standard therapy was initiated on rituximab. Ten days later, she presented with mucocutaneous bleeding and ecchymotic skin lesions. Isolated severe thrombocytopenia was noted with a platelet count of 5 × 109/L (150-450). Anticipating life-threatening bleeding, she was given intravenous immunoglobulin, methyl prednisolone, and platelet transfusion considering a spectrum of initial differential diagnosis. Rituximab was also withheld. Though extensively investigated, most investigations were negative. A platelet destructive process was suspected as bone marrow biopsy showed adequate megakaryocytes. Weighing the risk versus benefit, following recovery, she was reinitiated on rituximab. Within 4 days, she presented again with similar symptoms and severe isolated thrombocytopenia was noted. Rituximab-induced acute thrombocytopenia was considered the working clinical diagnosis. CASE DISCUSSION AND CONCLUSION: Rituximab can cause a spectrum of hematological abnormalities, including isolated acute thrombocytopenia. Its occurrence in autoimmune conditions is rare, and its manifestation in systemic lupus erythematosus is undocumented. Its exact etiology is still disputed. Usually considered benign, the platelet numbers tend to show improvement with cessation of therapy. However, in the presence of mucocutaneous bleeding in our patient, we took an aggressive approach to management. Though evidence for corrective therapy is anecdotal, it could be justified on the basis of averting potential catastrophic hemorrhagic manifestations. The spectrum of autoimmune disease that potentially predisposes rituximab to cause thrombocytopenia should be extended to include systemic lupus erythematosus.


Assuntos
Lúpus Eritematoso Sistêmico , Trombocitopenia , Adulto , Anticorpos Monoclonais , Antígenos CD20 , Feminino , Humanos , Rituximab/efeitos adversos
5.
Paediatr Drugs ; 23(4): 331-347, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34244988

RESUMO

Childhood-onset systemic lupus erythematosus (cSLE) is a prototype of a multisystemic, inflammatory, heterogeneous autoimmune condition. This disease is characterized by simultaneous or sequential organ and system involvement, with unpredictable flare and high levels of morbidity and mortality. Racial/ethnic background, socioeconomic status, cost of medications, difficulty accessing health care, and poor adherence seem to impact lupus outcomes and treatment response. In this article, the management of cSLE patients is updated. Regarding pathogenesis, a number of potential targets for drugs have been studied. However, most treatments in pediatric patients are off-label drugs with recommendations based on inadequately powered studies, therapeutic consensus guidelines, or case series. Management practices for cSLE patients include evaluations of disease activity and cumulative damage scores, routine non-live vaccinations, physical activity, and addressing mental health issues. Antimalarials and glucocorticoids are still the most common drugs used to treat cSLE, and hydroxychloroquine is recommended for nearly all cSLE patients. Disease-modifying antirheumatic drugs (DMARDs) should be standardized for each patient, based on disease flare and cSLE severity. Mycophenolate mofetil or intravenous cyclophosphamide is suggested as induction therapy for lupus nephritis classes III and IV. Calcineurin inhibitors (cyclosporine, tacrolimus, voclosporin) appear to be another good option for cSLE patients with lupus nephritis. Regarding B-cell-targeting biologic agents, rituximab may be used for refractory lupus nephritis patients in combination with another DMARD, and belimumab was recently approved by the US Food and Drug Administration for cSLE treatment in children aged > 5 years. New therapies targeting CD20, such as atacicept and telitacicept, seem to be promising drugs for SLE patients. Anti-interferon therapies (sifalimumab and anifrolumab) have shown beneficial results in phase II randomized control trials in adult SLE patients, as have some Janus kinase inhibitors, and these could be alternative treatments for pediatric patients with severe interferon-mediated inflammatory disease in the future. In addition, strict control of proteinuria and blood pressure is required in cSLE, especially with angiotensin-converting enzyme inhibitor and angiotensin receptor blocker use.


Assuntos
Gerenciamento Clínico , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Idade de Início , Anticorpos Monoclonais Humanizados/uso terapêutico , Antirreumáticos/uso terapêutico , Criança , Glucocorticoides/uso terapêutico , Humanos , Imunossupressores/uso terapêutico , Imunoterapia/métodos , Lúpus Eritematoso Sistêmico/imunologia , Ácido Micofenólico/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto
6.
BMJ Case Rep ; 14(5)2021 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-34059537

RESUMO

A 35-year-old woman presented with a constellation of systemic symptoms: rashes, weight loss, arthralgia and mouth ulcers. Six months afterwards, she experienced bilateral and sequential reduction in vision, and was found to have bilateral vaso-occlusive retinopathy, with critical macular ischaemia in the left eye. Her serological markers were consistent with a diagnosis of lupus. A lymph node biopsy confirmed Kikuchi-Fujimoto disease, a benign condition of unknown cause characterised by fever, cervical and axillary lymphadenopathy. Given that this overlap syndrome was associated with a number of systemic features and had affected the eyes, an immunosuppressive regime with rituximab was considered prudent. This rendered her vasculitis stable and non-progressive, and there were signs of partial retinal microvasculature recovery on optical coherence tomography angiography. There is increasing evidence of an overlap between Kikuchi-Fujimoto disease and systemic lupus erythematosus, which is associated with vaso-occlusive retinopathy. In these instances, a multidisciplinary approach is warranted, with consideration of appropriate treatment in order to prevent harmful sequelae of vasculitis. Our treatment with rituximab abated the disease process, although close follow-up is paramount to monitor results and side-effects of treatment.


Assuntos
Linfadenite Histiocítica Necrosante , Lúpus Eritematoso Sistêmico , Doenças Retinianas , Adulto , Biópsia , Feminino , Febre , Linfadenite Histiocítica Necrosante/complicações , Linfadenite Histiocítica Necrosante/diagnóstico , Linfadenite Histiocítica Necrosante/tratamento farmacológico , Humanos , Lúpus Eritematoso Sistêmico/complicações
7.
Medicine (Baltimore) ; 100(25): e26499, 2021 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-34160465

RESUMO

BACKGROUND: Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by multiple organ damage and the production of a variety of autoantibodies. The pathogenesis of SLE has not been fully defined, and it is difficult to treat. Our study aimed to identify candidate genes that may be used as biomarkers for the screening, diagnosis, and treatment of SLE. METHODS: We used the GEO2R tool to identify the differentially expressed genes (DEGs) in SLE-related datasets retrieved from the Gene Expression Omnibus (GEO). In addition, we also identified the biological functions of the DEGs by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis. Additionally, we constructed protein-protein interaction (PPI) networks to identify hub genes, as well as the regulatory network of transcription factors related to DEGs. RESULTS: Two datasets were identified for use from the GEO (GSE50772, GSE4588), and 34 up-regulated genes and 4 down-regulated genes were identified by GEO2R. Pathway analysis of the DEGs revealed enrichment of the interferon alpha/beta signaling pathway; GO analysis was mainly enriched in response to interferon alpha, regulation of ribonuclease activity. PPIs were constructed through the STRING database and 14 hub genes were selected and 1 significant module (score = 12.923) was obtained from the PPI network. Additionally, 11 key transcription factors that interacted closely with the 14 hub DEGs were identified from the gene transcription factor network. CONCLUSIONS: Bioinformatic analysis is an effective tool for screening the original genomic data in the GEO database, and a large number of SLE-related DEGs were identified. The identified hub DEGs may be potential biomarkers of SLE.


Assuntos
Regulação da Expressão Gênica/imunologia , Redes Reguladoras de Genes , Lúpus Eritematoso Sistêmico/genética , Fatores de Transcrição/metabolismo , Biomarcadores/análise , Biologia Computacional , Conjuntos de Dados como Assunto , Perfilação da Expressão Gênica , Humanos , Lúpus Eritematoso Sistêmico/imunologia , Análise de Sequência com Séries de Oligonucleotídeos , Mapeamento de Interação de Proteínas , Mapas de Interação de Proteínas/genética , Transdução de Sinais/genética , Transdução de Sinais/imunologia
8.
Pan Afr Med J ; 38: 302, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34178220

RESUMO

Acute myocardial infarction (AMI) is a major cause of death in a patient with systemic lupus erythematosus (SLE). Due to their chronic inflammatory state, patient with SLE has an increased risk of developing coronary artery disease. We report a case of a middle-aged woman with an acute myocardial infarction (AMI) caused by a right coronary artery (RCA) stenosis complicated with severe coronary artery spasm. Our patient has a history of long-standing SLE. Clinical expression of coronary artery disease (CAD) in SLE is the result of different pathophysiologic mechanism. From this case, we raise the importance of the clinician to be aware of the diverse pathophysiologic pathways involving a coronary artery in a patient with SLE.


Assuntos
Estenose Coronária/complicações , Vasoespasmo Coronário/complicações , Lúpus Eritematoso Sistêmico/complicações , Infarto do Miocárdio/etiologia , Adulto , Estenose Coronária/fisiopatologia , Vasoespasmo Coronário/fisiopatologia , Feminino , Humanos , Lúpus Eritematoso Sistêmico/fisiopatologia , Infarto do Miocárdio/fisiopatologia
9.
Pediatr Rheumatol Online J ; 19(1): 98, 2021 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-34187503

RESUMO

BACKGROUND: Subcutaneous anakinra is an interleukin-1 inhibitor used to treat juvenile idiopathic arthritis. Recent reports suggest anakinra can be a valuable addition to the treatment of COVID-19 associated cytokine storm syndrome and the related multisystem inflammatory syndrome (MIS-C) in children. Herein, we describe our experience with intravenously administered anakinra. FINDINGS: 19 Patients (9 male) received intravenous (IV) anakinra for treatment of macrophage activation syndrome (MAS) secondary to systemic lupus erythematosus (SLE), systemic JIA (SJIA) or secondary hemophagocytic lymphohistiocytosis (sHLH). In most cases the general trend of the fibrinogen, ferritin, AST, and platelet count (Ravelli criteria) improved after initiation of IV anakinra. There were no reports of anaphylaxis or reactions associated with administration of IV anakinra. CONCLUSION: Intravenous administration of anakinra is an important therapeutic option for critically ill patients with MAS/HLH. It is also beneficial for those with thrombocytopenia, subcutaneous edema, neurological dysfunction, or very young, hospitalized patients who need multiple painful subcutaneous injections.


Assuntos
Administração Intravenosa/métodos , COVID-19/tratamento farmacológico , Proteína Antagonista do Receptor de Interleucina 1/administração & dosagem , Lúpus Eritematoso Sistêmico , Linfo-Histiocitose Hemofagocítica , Síndrome de Ativação Macrofágica , Síndrome de Resposta Inflamatória Sistêmica/tratamento farmacológico , Antirreumáticos/administração & dosagem , COVID-19/epidemiologia , COVID-19/imunologia , Criança , Criança Hospitalizada/psicologia , Estado Terminal/psicologia , Estado Terminal/terapia , Síndrome da Liberação de Citocina/tratamento farmacológico , Síndrome da Liberação de Citocina/virologia , Feminino , Humanos , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/imunologia , Lúpus Eritematoso Sistêmico/terapia , Linfo-Histiocitose Hemofagocítica/complicações , Linfo-Histiocitose Hemofagocítica/imunologia , Linfo-Histiocitose Hemofagocítica/terapia , Síndrome de Ativação Macrofágica/sangue , Síndrome de Ativação Macrofágica/tratamento farmacológico , Síndrome de Ativação Macrofágica/etiologia , Masculino , Conforto do Paciente/métodos , Estudos Retrospectivos , SARS-CoV-2
10.
Medicine (Baltimore) ; 100(22): e25688, 2021 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-34087822

RESUMO

RATIONALE: Hydroxychloroquine has excellent anti-inflammatory and immunomodulatory effects as one of the antimalarial drugs. In particular, hydroxychloroquine was once widely used as a treatment for the new coronavirus pneumonia epidemic in 2020. Retinopathy caused by hydroxychloroquine is normally irreversible, but little attention has been paid to it. PATIENT CONCERNS: A 38-year-old young Chinese woman was taking oral hydroxychloroquine 400 mg daily to control lupus disease activity for six years after the diagnosis of systemic lupus erythematosus (SLE). She did not have any history of eye disease and was admitted to the hospital with a sudden blurring of both eyes. DIAGNOSES: The diagnosis of retinal macular degeneration caused by hydroxychloroquine was made after excluding other interfering diseases based on the patient's long-term use of hydroxychloroquine and the results of the eye examination. INTERVENTIONS: The patient was discontinued from hydroxychloroquine. To control the recurrence of SLE, she was given intravenous methylprednisolone, oral tacrolimus and mycophenolate. Meanwhile, she was asked to take extra care of her eyes and to come to the hospital every three months to have her vision checked. OUTCOMES: The patient's blurred vision improved one week later. Three months later, her vision examination showed no further decline (0.4 in the right eye and 0.6 in the left eye). Meanwhile, the SLE disease activity index (SLEDAI) decreased from six points to five points currently. LESSONS: Retinopathy caused by hydroxychloroquine is irreversible and there is no particularly effective treatment. Discontinuation of hydroxychloroquine, better daily eye protection, and regular vision checks are the keys to preventing retinopathy. Although hydroxychloroquine causing retinal toxicity was mentioned several years ago, the rate and severity of retinal toxicity require further research. How to get more patients to take care of their eyes requires continuous and increased education by doctors.


Assuntos
Anti-Inflamatórios/efeitos adversos , Hidroxicloroquina/efeitos adversos , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Doenças Retinianas/induzido quimicamente , Adulto , Anti-Inflamatórios/uso terapêutico , Feminino , Humanos , Hidroxicloroquina/uso terapêutico , Imunossupressores/uso terapêutico , Acuidade Visual
11.
Medicine (Baltimore) ; 100(22): e26238, 2021 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-34087909

RESUMO

RATIONALE: Acute acalculous cholecystitis (AAC) is an extremely rare manifestation of systemic lupus erythematous (SLE). In previous reports, most of the patients were already diagnosed cases of SLE upon confirmation of AAC. PATIENT CONCERNS: A 24-year-old female who initially presented with fever and acute right upper quadrant abdominal pain. She had no medical history. DIAGNOSES: Abdominal ultrasonography and computed tomography (CT) showed gallbladder thickening with pericholecystic edema without gallstones or sludge, demonstrating acalculous cholecystitis. She revealed discoid rash on the both shin. Laboratory tests revealed pancytopenia. The titer of antinuclear antibody (ANA) was 1:1280. Anti-dsDNA antibody, anti-phospholipid antibody, anti-Sm antibody test, and proteinuria in 24 hours were positive. Both C3 and C4 were low. Echocardiography and chest CT showed pericardial effusion and pleural effusion. Using the 2019 European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) classification criteria, the score was 31. We thought AAC of this case that was one of the initial manifestations of SLE. INTERVENTIONS: The patient was treated with high-dose prednisolone (1 mg/kg) and hydroxychloroquine 400 mg. OUTCOMES: After 4 days of administration of high-dose corticosteroid therapy, symptoms rapidly improved. After 35 days of the treatment, her symptoms and disease activity of SLE were markedly improved. LESSONS: Although AAC being the initial manifestation of SLE is very rare, prompt diagnosis and management with corticosteroids precluded surgical intervention. Physicians need to be cognizant of AAC as a disease flare and as a rare initial manifestation of SLE.


Assuntos
Colecistite Acalculosa/etiologia , Vesícula Biliar/patologia , Lúpus Eritematoso Sistêmico/complicações , Colecistite Acalculosa/diagnóstico , Doença Aguda , Adulto , Idoso , Anticorpos Antinucleares/sangue , Antirreumáticos/administração & dosagem , Antirreumáticos/uso terapêutico , Criança , Quimioterapia Combinada , Ecocardiografia/métodos , Feminino , Vesícula Biliar/diagnóstico por imagem , Glucocorticoides/administração & dosagem , Glucocorticoides/uso terapêutico , Humanos , Hidroxicloroquina/administração & dosagem , Hidroxicloroquina/uso terapêutico , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Derrame Pericárdico/diagnóstico , Derrame Pleural/diagnóstico , Prednisolona/administração & dosagem , Prednisolona/uso terapêutico , Proteinúria/diagnóstico , Proteinúria/etiologia , Tomografia Computadorizada por Raios X/métodos , Resultado do Tratamento , Ultrassonografia/métodos , Adulto Jovem
12.
J Int Med Res ; 49(6): 3000605211022510, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34139868

RESUMO

In rare cases, clinical inhibitors of the pro-inflammatory cytokine tumor necrosis factor-α (TNF-α) can induce symptoms of lupus erythematosus (drug-induced lupus, DIL), but this adverse response usually resolves rapidly upon drug withdrawal. We report the case of a 25-year-old Asian woman with rheumatoid arthritis exhibiting severe prolonged DIL even after the termination of TNF-α inhibitor treatment. The patient had been treated intermittently using Traditional Chinese Medicine for 11 years, but this therapy failed to effectively control her clinical symptoms. Subsequently, methotrexate and hydroxychloroquine were prescribed, but a reduced white blood cell count was detected. Finally, the TNF-α inhibitor Anbainuo was prescribed. However, after 2 months of treatment, the patient exhibited elevated serum creatinine, anti-double-stranded DNA (+++), anti-nuclear antibody (1:1000), and urine protein (+++) accompanied by buccal erythema, hair loss, and hand shaking, consistent with Anbainuo-induced lupus, lupus nephritis, and lupus encephalopathy. Moreover, her serum creatinine level remained high after Anbainuo withdrawal and prolonged steroid and immunosuppressive therapy. Careful and sustained monitoring for adverse reactions to Anbainuo (and other TNF-α inhibitors) is recommended.


Assuntos
Antirreumáticos , Artrite Reumatoide , Lúpus Eritematoso Sistêmico , Adulto , Antirreumáticos/efeitos adversos , Artrite Reumatoide/tratamento farmacológico , Feminino , Humanos , Fragmentos Fc das Imunoglobulinas/uso terapêutico , Lúpus Eritematoso Sistêmico/induzido quimicamente , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Metotrexato/uso terapêutico , Receptores Tipo II do Fator de Necrose Tumoral/uso terapêutico , Proteínas Recombinantes de Fusão , Fator de Necrose Tumoral alfa
13.
Medicine (Baltimore) ; 100(22): e25688, 2021 Jun 04.
Artigo em Inglês | MEDLINE | ID: covidwho-1257893

RESUMO

RATIONALE: Hydroxychloroquine has excellent anti-inflammatory and immunomodulatory effects as one of the antimalarial drugs. In particular, hydroxychloroquine was once widely used as a treatment for the new coronavirus pneumonia epidemic in 2020. Retinopathy caused by hydroxychloroquine is normally irreversible, but little attention has been paid to it. PATIENT CONCERNS: A 38-year-old young Chinese woman was taking oral hydroxychloroquine 400 mg daily to control lupus disease activity for six years after the diagnosis of systemic lupus erythematosus (SLE). She did not have any history of eye disease and was admitted to the hospital with a sudden blurring of both eyes. DIAGNOSES: The diagnosis of retinal macular degeneration caused by hydroxychloroquine was made after excluding other interfering diseases based on the patient's long-term use of hydroxychloroquine and the results of the eye examination. INTERVENTIONS: The patient was discontinued from hydroxychloroquine. To control the recurrence of SLE, she was given intravenous methylprednisolone, oral tacrolimus and mycophenolate. Meanwhile, she was asked to take extra care of her eyes and to come to the hospital every three months to have her vision checked. OUTCOMES: The patient's blurred vision improved one week later. Three months later, her vision examination showed no further decline (0.4 in the right eye and 0.6 in the left eye). Meanwhile, the SLE disease activity index (SLEDAI) decreased from six points to five points currently. LESSONS: Retinopathy caused by hydroxychloroquine is irreversible and there is no particularly effective treatment. Discontinuation of hydroxychloroquine, better daily eye protection, and regular vision checks are the keys to preventing retinopathy. Although hydroxychloroquine causing retinal toxicity was mentioned several years ago, the rate and severity of retinal toxicity require further research. How to get more patients to take care of their eyes requires continuous and increased education by doctors.


Assuntos
Anti-Inflamatórios/efeitos adversos , Hidroxicloroquina/efeitos adversos , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Doenças Retinianas/induzido quimicamente , Adulto , Anti-Inflamatórios/uso terapêutico , Feminino , Humanos , Hidroxicloroquina/uso terapêutico , Imunossupressores/uso terapêutico , Acuidade Visual
14.
Autoimmun Rev ; 20(8): 102869, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34118461

RESUMO

Reactive oxygen species (ROS) are produced by immune cells in response to antigens. They are produced mostly in the mitochondria and their levels are tightly controlled by a series of metabolic processes. ROS are necessary for the development of the immune response but the role of ROS in the development of autoimmune disease needs further clarification. Early clinical information points to the beneficial role of supplementation of antioxidant agents or the reduction of ROS production. We review recent information in the field in an effort to identify areas more studies are needed.


Assuntos
Doenças Autoimunes , Lúpus Eritematoso Sistêmico , Autoimunidade , Humanos , Espécies Reativas de Oxigênio
15.
Egypt J Immunol ; 28(2): 65-74, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-34147051

RESUMO

One of the most remarkable presentations of systemic lupus erythematosus (SLE) is depression. Our aim was to elucidate the potential relationship between disease activity, depressive symptoms, and tumor necrosis factor alpha (TNF-α) in patients with SLE. Sixty female patients with SLE and thirty comparable healthy controls were recruited. According to systemic lupus erythematosus disease activity index, patients were subdivided into two similar groups; active and inactive. Complete clinical and laboratory assessments were done to authenticate the diagnosis of SLE and outline its activity. All participants were assessed using the Beck depression Inventory (BDI) to diagnose and determine the severity of depressive symptoms. TNF-α level was assessed using Enzyme linked immunosorbent assay technique. Using BDI, patients with SLE activity showed higher prevalence of depression 19 (63.3%) compared to those with inactive SLE and control groups (P < 0.001). TNF-α level was markedly elevated amongst patients with active SLE in comparison to inactive and control groups (P <0.001). TNF-α differentiated SLE patients into with and without depression at cut-off value (>360 ng/l) (AUC = 0.726; P=0.0008; 95% CI 1.3-2.7). Multivariable regression analysis for prediction of depression revealed that TNF-α was the only independent predictor of depression (P= 0.011). In conclusion, patients with increased SLE activity are more prone to depression especially, moderate to severe degree. TNF-α level could be of significance in predilection of depression and SLE activity in patients with SLE. Hence, future studies are essential to test the treatment modalities targeting TNF-α in those patients.


Assuntos
Lúpus Eritematoso Sistêmico , Fator de Necrose Tumoral alfa , Depressão/epidemiologia , Egito/epidemiologia , Feminino , Humanos , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/epidemiologia , Prevalência
16.
Braz J Biol ; 83: e244123, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34161457

RESUMO

Toll-like receptor 9 (TLR9) is an important component of the innate immune system and have been associated with several autoimmune diseases, such as Systemic Lupus Erythematosus (SLE). The aim of this study was to investigate polymorphisms in TLR9 gene in a Brazilian SLE patients group and their association with clinical manifestation, particularly Jaccoud's arthropathy (JA). We analyzed DNA samples from 204 SLE patients, having a subgroup of them presenting JA (n=24). A control group (n=133) from the same city was also included. TLR9 single nucleotide polymorphisms (SNPs) (-1237 C>T and +2848 G>A) were identified by sequencing analysis. The TLR9 gene genotype frequency was similar both in SLE patients and the control group. In the whole SLE population, an association between the homozygosis of allele C at position -1237 with psychosis and anemia (p < 0.01) was found. Likewise, the homozygosis of allele G at position +2848 was associated with a discoid rash (p < 0.05). There was no association between JA and TLR9 polymorphisms. These data show that TLR9 polymorphisms do not seem to be a predisposing factor for SLE in the Brazilian population, and that SNPs are not associated with JA.


Assuntos
Lúpus Eritematoso Sistêmico , Receptor Toll-Like 9 , Brasil , Frequência do Gene/genética , Predisposição Genética para Doença/genética , Humanos , Lúpus Eritematoso Sistêmico/genética , Projetos Piloto , Receptor Toll-Like 9/genética
17.
BMJ Case Rep ; 14(6)2021 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-34155029

RESUMO

Scurvy is a disease caused by chronic vitamin C deficiency. The greater prevalence was found in the paediatric population with neurodevelopmental disorders such as autism spectrum disorders due to their restricted dietary intake. Our case reported a child with autism who presented with arthralgia and anaemia. Systemic lupus erythematosus was the first diagnostic impression, resulting in over investigation and delayed diagnosis of vitamin C deficiency. After the child was treated with ascorbic acid, the child's symptoms resolved. This case highlighted the importance of developmental and nutritional history taking in the paediatric population. Furthermore, parents and physicians should be concerned about nutritional status, especially in children with restrictive dietary intake.


Assuntos
Deficiência de Ácido Ascórbico , Transtorno do Espectro Autista , Lúpus Eritematoso Sistêmico , Escorbuto , Ácido Ascórbico/uso terapêutico , Criança , Humanos , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/diagnóstico , Escorbuto/diagnóstico , Escorbuto/tratamento farmacológico
18.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 37(7): 633-640, 2021 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-34140075

RESUMO

Objective To detect and analyze the plasma levels and immunoactivities of different forms of circulating-free DNA (cfDNA) in systemic lupus erythematosus (SLE) patients. Methods The study enrolled 58 patients with SLE, 66 patients with other autoimmune diseases (non-SLE) and 60 healthy individuals. Total cfDNA, exosome cfDNA and immune complex cfDNA were extracted from the plasma and detected using a fluorescence method. Overall methylation levels of cfDNA were measured. Macrophages and dendritic cells induced in vitro were co-cultured with exosomes or immune complexes derived from SLE patients pre-treated with deoxyribonuclease 1-like 3(DNASE1L3) or immunoglobulin G (IgG) specific degradation enzyme or none. Then, cytokines and cell surface activation markers were detected by the multiple fluorescent microsphere assay. Results Among the three groups, SLE patients had the highest levels of exosomes and immune complex cfDNA, followed by non-SLE patients, and no significant differences were found in the simple cfDNA. The methylation levels of different types of cfDNA (except simple cfDNA) in the plasma of SLE patients were significantly lower than that of the non-SLE group and healthy individuals. Non-SLE patients and healthy individuals presented no significant differences for the methylation levels of all cfDNA types. After DNASE1L3 and IgG enzyme treatment, the macrophages and dendritic cells stimulated by exosomes and immune complex cfDNA secreted significantly lower levels of cytokines including MIP-1a, MIP-1b, IL-4, IL-1ß, IL-2, IL-1ra, MCP-1, IL-6, IL-9, IL-8, TNF-α and IFN-α. Compared with IgG enzyme treatment, DNASE1L3-treated exosomes and immune complex induced the lower level of cytokines secretion. The expression of CD80, CD86 and CD40 on the surfaces of macrophages and dendritic cells stimulated with exosomes and immune complexes pre-treated with DNASE1L3 enzyme were significantly reduced, but the expression of CD86 on the macrophages was slightly changed. The expression of CD80, CD86 and CD40 showed no difference in the two types of cells stimulated with exosomes and immune complexes pre-treated with IgG enzymes or none, but an overall downward trend existed indeed. Conclusion Exosomes and immune complex cfDNA increase significantly in the plasma of SLE patients, and they can stimulate strong responses of macrophages and dendritic cells.


Assuntos
Ácidos Nucleicos Livres , Lúpus Eritematoso Sistêmico , Complexo Antígeno-Anticorpo , Citocinas , DNA , Humanos
19.
Med Clin North Am ; 105(4): 757-782, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34059249

RESUMO

Connective tissue diseases (CTDs) encompass a broad spectrum of clinical presentations that involve multidisciplinary management. Cutaneous findings are common in CTD and careful examination of these features aids in appropriate diagnosis and subsequent evaluation. Thorough work-up of CTD is crucial to properly identify disease subtypes and systemic involvement. Management plans can be developed based on diagnosis and systemic manifestations of disease. Disease management often requires treatment with pharmacotherapies with potential for toxicities, further underscoring the importance of diagnostic accuracy in this patient population. Evolving research strives to better elucidate the pathogenic mechanisms of CTDs allowing for more targeted treatment modalities.


Assuntos
Doenças do Tecido Conjuntivo/complicações , Doenças do Tecido Conjuntivo/tratamento farmacológico , Doenças do Tecido Conjuntivo/patologia , Tratamento Farmacológico/métodos , Adulto , Comorbidade , Doenças do Tecido Conjuntivo/diagnóstico , Dermatomiosite/diagnóstico , Dermatomiosite/etiologia , Dermatomiosite/patologia , Diagnóstico Diferencial , Tratamento Farmacológico/estatística & dados numéricos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Diagnóstico Precoce , Feminino , Humanos , Comunicação Interdisciplinar , Lúpus Eritematoso Cutâneo/diagnóstico , Lúpus Eritematoso Cutâneo/etiologia , Lúpus Eritematoso Cutâneo/patologia , Lúpus Eritematoso Discoide/diagnóstico , Lúpus Eritematoso Discoide/etiologia , Lúpus Eritematoso Discoide/patologia , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/etiologia , Lúpus Eritematoso Sistêmico/patologia , Masculino , Administração dos Cuidados ao Paciente/métodos , Escleroderma Sistêmico/diagnóstico , Escleroderma Sistêmico/etiologia , Escleroderma Sistêmico/patologia , Vasculite/diagnóstico , Vasculite/etiologia , Vasculite/patologia
20.
Nat Commun ; 12(1): 3391, 2021 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-34099646

RESUMO

Increased risk of premature cardiovascular disease (CVD) is well recognized in systemic lupus erythematosus (SLE). Aberrant type I-Interferon (IFN)-neutrophil interactions contribute to this enhanced CVD risk. In lupus animal models, the Janus kinase (JAK) inhibitor tofacitinib improves clinical features, immune dysregulation and vascular dysfunction. We conducted a randomized, double-blind, placebo-controlled clinical trial of tofacitinib in SLE subjects (ClinicalTrials.gov NCT02535689). In this study, 30 subjects are randomized to tofacitinib (5 mg twice daily) or placebo in 2:1 block. The primary outcome of this study is safety and tolerability of tofacitinib. The secondary outcomes include clinical response and mechanistic studies. The tofacitinib is found to be safe in SLE meeting study's primary endpoint. We also show that tofacitinib improves cardiometabolic and immunologic parameters associated with the premature atherosclerosis in SLE. Tofacitinib improves high-density lipoprotein cholesterol levels (p = 0.0006, CI 95%: 4.12, 13.32) and particle number (p = 0.0008, CI 95%: 1.58, 5.33); lecithin: cholesterol acyltransferase concentration (p = 0.024, CI 95%: 1.1, -26.5), cholesterol efflux capacity (p = 0.08, CI 95%: -0.01, 0.24), improvements in arterial stiffness and endothelium-dependent vasorelaxation and decrease in type I IFN gene signature, low-density granulocytes and circulating NETs. Some of these improvements are more robust in subjects with STAT4 risk allele.


Assuntos
Aterosclerose/prevenção & controle , Inibidores de Janus Quinases/administração & dosagem , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Piperidinas/administração & dosagem , Pirimidinas/administração & dosagem , Adulto , Idoso , Animais , Aterosclerose/sangue , Aterosclerose/genética , Aterosclerose/imunologia , HDL-Colesterol/sangue , Método Duplo-Cego , Feminino , Predisposição Genética para Doença , Fatores de Risco de Doenças Cardíacas , Humanos , Inibidores de Janus Quinases/efeitos adversos , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/imunologia , Masculino , Pessoa de Meia-Idade , Piperidinas/efeitos adversos , Pirimidinas/efeitos adversos , Fator de Transcrição STAT4/genética , Resultado do Tratamento , Rigidez Vascular/efeitos dos fármacos , Vasodilatação/efeitos dos fármacos , Adulto Jovem
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