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1.
Front Immunol ; 12: 724047, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34512651

RESUMO

Objectives: Impact of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic on individuals with arthritis has been highlighted whereas data on other rheumatic diseases, e.g., systemic lupus erythematosus (SLE), are scarce. Similarly to SLE, severe SARS-CoV-2 infection includes risks for thromboembolism, an unbalanced type I interferon response, and complement activation. Herein, SARS-CoV-2 antibodies in longitudinal samples collected prior to vaccination were analyzed and compared with SLE progression and antinuclear antibody (ANA) levels. Methods: One hundred patients (83 women) with established SLE and a regular visit to the rheumatologist (March 2020 to January 2021) were included. All subjects donated blood and had done likewise prior to the pandemic. SARS-CoV-2 antibody isotypes (IgG, IgA, IgM) to the cell receptor-binding S1-spike outer envelope protein were detected by ELISA, and their neutralizing capacity was investigated. IgG-ANA were measured by multiplex technology. Results: During the pandemic, 4% had PCR-confirmed infection but 36% showed SARS-CoV-2 antibodies of ≥1 isotype; IgA was the most common (30%), followed by IgM (9%) and IgG (8%). The antibodies had low neutralizing capacity and were detected also in prepandemic samples. Plasma albumin (p = 0.04) and anti-dsDNA (p = 0.003) levels were lower in patients with SARS-CoV-2 antibodies. Blood group, BMI, smoking habits, complement proteins, daily glucocorticoid dose, use of hydroxychloroquine, or self-reported coronavirus disease 2019 (COVID-19) symptoms (except fever, >38.5°C) did not associate with SARS-CoV-2 antibodies. Conclusion: Our data from early 2021 indicate that a large proportion of Swedish SLE patients had serological signs of exposure to SARS-CoV-2 but apparently with a minor impact on the SLE course. Use of steroids and hydroxychloroquine showed no distinct effects, and self-reported COVID-19-related symptoms correlated poorly with all antibody isotypes.


Assuntos
Anticorpos Antivirais/imunologia , COVID-19/epidemiologia , COVID-19/imunologia , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Antinucleares/sangue , Anticorpos Antinucleares/imunologia , Anticorpos Antivirais/sangue , Feminino , Humanos , Isotipos de Imunoglobulinas/sangue , Isotipos de Imunoglobulinas/imunologia , Imunossupressores/uso terapêutico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , SARS-CoV-2
2.
Nat Commun ; 12(1): 5417, 2021 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-34521836

RESUMO

COVID-19 is associated with a wide range of clinical manifestations, including autoimmune features and autoantibody production. Here we develop three protein arrays to measure IgG autoantibodies associated with connective tissue diseases, anti-cytokine antibodies, and anti-viral antibody responses in serum from 147 hospitalized COVID-19 patients. Autoantibodies are identified in approximately 50% of patients but in less than 15% of healthy controls. When present, autoantibodies largely target autoantigens associated with rare disorders such as myositis, systemic sclerosis and overlap syndromes. A subset of autoantibodies targeting traditional autoantigens or cytokines develop de novo following SARS-CoV-2 infection. Autoantibodies track with longitudinal development of IgG antibodies recognizing SARS-CoV-2 structural proteins and a subset of non-structural proteins, but not proteins from influenza, seasonal coronaviruses or other pathogenic viruses. We conclude that SARS-CoV-2 causes development of new-onset IgG autoantibodies in a significant proportion of hospitalized COVID-19 patients and are positively correlated with immune responses to SARS-CoV-2 proteins.


Assuntos
Autoanticorpos/imunologia , COVID-19/imunologia , Imunoglobulina G/imunologia , SARS-CoV-2/imunologia , Idoso , Anticorpos Antinucleares/sangue , Anticorpos Antinucleares/imunologia , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Autoanticorpos/sangue , Autoantígenos/imunologia , Doenças do Tecido Conjuntivo/imunologia , Citocinas/imunologia , Feminino , Hospitalização , Humanos , Imunoglobulina G/sangue , Masculino , Pessoa de Meia-Idade , SARS-CoV-2/patogenicidade , Proteínas Virais/imunologia
3.
Life Sci Alliance ; 4(11)2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34504035

RESUMO

High levels of autoimmune antibodies are observed in COVID-19 patients but their specific contribution to disease severity and clinical manifestations remains poorly understood. We performed a retrospective study of 115 COVID-19 hospitalized patients with different degrees of severity to analyze the generation of autoimmune antibodies to common antigens: a lysate of erythrocytes, the lipid phosphatidylserine (PS) and DNA. High levels of IgG autoantibodies against erythrocyte lysates were observed in a large percentage (up to 36%) of patients. Anti-DNA and anti-PS antibodies determined upon hospital admission correlated strongly with later development of severe disease, showing a positive predictive value of 85.7% and 92.8%, respectively. Patients with positive values for at least one of the two autoantibodies accounted for 24% of total severe cases. Statistical analysis identified strong correlations between anti-DNA antibodies and markers of cell injury, coagulation, neutrophil levels and erythrocyte size. Anti-DNA and anti-PS autoantibodies may play an important role in the pathogenesis of COVID-19 and could be developed as predictive biomarkers for disease severity and specific clinical manifestations.


Assuntos
Anticorpos Antinucleares/imunologia , Autoanticorpos/imunologia , COVID-19/imunologia , COVID-19/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Antinucleares/sangue , Autoanticorpos/sangue , Biomarcadores , DNA/química , DNA/imunologia , Eritrócitos/imunologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fosfatidilserinas/imunologia , Prognóstico , Estudos Retrospectivos , SARS-CoV-2/isolamento & purificação , Índice de Gravidade de Doença
4.
Front Immunol ; 12: 690908, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34484186

RESUMO

The IL-23/IL-17 axis plays causative roles in the development and progression of systemic lupus erythematosus (SLE). However, it remains unclear if the IL-17RA+ and IL-23R+ T helper (Th) cells populations are associated with the serum IL-17 and IL-23 levels, or with the immunological parameters and disease activities in SLE patients. Herein, we examined the proportion of IL-17RA+ and IL-23R+ Th cells and serum levels of IL-17 and IL-23 in established SLE patients (n = 50) compared with healthy controls (n = 50). The associations of these interleukins and their receptors with immunological parameters [anti-nuclear antibody (ANA), anti-dsDNA antibody, and C-reactive protein (CRP)] and SLE disease activity (SLEDAI-2K scores) in SLE patients were assessed. CD3+CD4+ Th cells of SLE patients demonstrated significantly elevated IL-17RA+ (p = 1.12 x 10-4) or IL-23R+ (p = 1.98 x 10-29) populations compared with the healthy controls. Serum IL-17 levels were significantly lower in SLE patients compared with the healthy controls (p = 8.32 x 10-5), while no significant difference was observed for the IL-23 serum levels between both groups. IL-23R+ Th cells population was significantly associated with higher SLEDAI-2K scores (p = 0.017). In multivariate analysis, the proportion of IL-23R+ Th cells remained significantly associated with higher SLEDAI-2K scores independent of prednisolone intake (p = 0.027). No associations were observed between the interleukin parameters (i.e., IL-17, IL-23, IL-17RA+ Th cells, and IL-23R+ Th cells) with ANA, anti-dsDNA, and CRP status, suggesting that the IL-17/IL-23 axis acts independently of these immunological parameters. In conclusion, our results support that therapeutic inhibition of the IL-23/IL-17 axis receptors on Th cells, particularly IL-23R, is potentially relevant in SLE patients.


Assuntos
Interleucina-17/imunologia , Interleucina-23/imunologia , Lúpus Eritematoso Sistêmico/imunologia , Receptores de Interleucina-17/imunologia , Receptores de Interleucina/imunologia , Linfócitos T Auxiliares-Indutores/imunologia , Adulto , Anticorpos Antinucleares/sangue , Proteína C-Reativa/análise , Feminino , Humanos , Interleucina-17/sangue , Interleucina-23/sangue , Lúpus Eritematoso Sistêmico/sangue , Masculino , Índice de Gravidade de Doença , Adulto Jovem
5.
PLoS One ; 16(9): e0257946, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34587214

RESUMO

BACKGROUND: Though many previous studies have indicated immunological alterations in psychotic disorders, the role and prevalence of neuroinflammation is still unknown. Studies previously investigating immune related biomarkers in the cerebrospinal fluid (CSF) of these patients are mainly small studies on few markers, and many have not compared patients to healthy controls. METHODS: We will conduct a large case-control study including at least 100 patients with recent onset psychotic disorders and 100 sex- and age matched healthy controls. The cases will include patients diagnosed with a psychotic disorder according to ICD-10 (F20/F22-29) within a year prior to inclusion. We will collect both CSF, blood and fecal samples, to gain insight into possible immunological alterations. The psychopathology of all participants will thoroughly be evaluated using the SCAN interview, and multiple rating scales covering different symptom groups. All participants will partake in a detailed neurological examination, including the Neurological Evaluation Scale assessing neurological soft signs. Additionally, we will assess cognitive functioning, evaluate quality of life and level of functioning, and collect data on a broad array of possible confounders. Our primary outcomes will include CSF leucocytes, CSF/serum albumin ratio, CSF total protein, IgG index, CSF levels of IL-6 and IL-8, and presence of antineuronal autoantibodies in CSF and blood. For our secondary outcomes, exploratory analyses will be performed on a broader panel of neuroimmunological markers. All participants will be invited for a follow-up visit to assess longitudinal changes. The current study is part of a larger CSF biobank build-up for severe mental disorders (PSYCH-FLAME). DISCUSSION: This study will represent the largest investigation of CSF in patients with psychotic disorders compared to healthy controls to date. We expect the study to contribute with new, important knowledge on pathophysiological mechanisms, and to help pave the way for future investigations of individualized treatment options. TRIAL REGISTRATION: The study is approved by The Regional Committee on Health Research Ethics (Capital Region, j.no: H-16030985) and The Danish Data Protection Agency (j.no: RHP-2016-020, I-Suite no.: 04945).


Assuntos
Anticorpos Antinucleares/líquido cefalorraquidiano , Biomarcadores/líquido cefalorraquidiano , Interleucina-6/líquido cefalorraquidiano , Interleucina-8/líquido cefalorraquidiano , Transtornos Psicóticos/imunologia , Adulto , Idade de Início , Anticorpos Antinucleares/sangue , Estudos de Casos e Controles , Feminino , Humanos , Leucócitos/metabolismo , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Transtornos Psicóticos/líquido cefalorraquidiano , Qualidade de Vida , Albumina Sérica Humana/líquido cefalorraquidiano , Adulto Jovem
6.
Sci Rep ; 11(1): 16162, 2021 08 09.
Artigo em Inglês | MEDLINE | ID: mdl-34373559

RESUMO

CD226 is an activating receptor expressed on the cell surface of natural killer cells and T cells. Although CD226 polymorphism is known to be involved in systemic lupus erythematosus (SLE), the involvement of soluble CD226 (sCD226) in SLE is still unknown. In the present study, we measured serum sCD226 levels using an enzyme-linked immunosorbent assay in 58 SLE patients and 33 healthy controls (HCs) and evaluated their associations with SLE Disease Activity Index 2000 (SLEDAI-2K), clinical manifestations, laboratory data, and the cumulative probability of flare. Serum sCD226 levels showed no significant differences between SLE patients and HCs. However, sCD226 levels were significantly elevated in active SLE patients with a SLEDAI-2K score of ≥ 20 compared with HCs. In SLE patients, sCD226 levels were significantly correlated with SLEDAI-2K scores and anti-dsDNA antibody titers. Moreover, the cumulative probability of flare was markedly higher in patients with high sCD226 than in those with low sCD226. In patients with neuropsychiatric involvement, sCD226 levels were elevated and reflected neuropsychiatric disease activity. These findings indicate that serum sCD226 levels are associated with disease activity and flares of SLE. Thus, it may be a useful biomarker for SLE, and its monitoring allows for more precise SLE management.


Assuntos
Antígenos de Diferenciação de Linfócitos T/sangue , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/imunologia , Adulto , Anticorpos Antinucleares/sangue , Biomarcadores/sangue , Estudos de Casos e Controles , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Lúpus Eritematoso Sistêmico/classificação , Vasculite Associada ao Lúpus do Sistema Nervoso Central/sangue , Vasculite Associada ao Lúpus do Sistema Nervoso Central/classificação , Vasculite Associada ao Lúpus do Sistema Nervoso Central/imunologia , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Solubilidade
7.
Chest ; 160(1): e45-e50, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34246388

RESUMO

CASE PRESENTATION: A 12-year-old girl presented with shortness of breath with exercise for 2 weeks. Her oxygen saturation was 85% during exercise. Birth and family histories were unremarkable. The girl was healthy until 7.1 years of age, when she suffered a "pneumonia" with fever, dyspnea, and hypoxemia, which diminished after a 19-day treatment with antibiotics and methylprednisolone. These symptoms relapsed 8 months later, and she was diagnosed with rapidly progressive interstitial lung disease (ILD) and a Mycoplasma pneumoniae infection. At that time, her symptoms failed to respond to a course of antibiotic therapy but resolved with IV methylprednisolone at 2.7 mg/kg/day. She remained on a tapering dose of methylprednisolone plus methotrexate for the next 18 months until withdrawal of these medications because of return of almost normal lung imaging. She had never had myalgia, muscle weakness, arthritis, rashes, mechanic's hands, Raynaud's phenomenon, dry mouth, or dry eyes.


Assuntos
Anticorpos Antinucleares/sangue , Dispneia/etiologia , Ligases/metabolismo , Doenças Pulmonares Intersticiais/diagnóstico , Pulmão/diagnóstico por imagem , Criança , Dispneia/diagnóstico , Feminino , Humanos , Pulmão/metabolismo , Doenças Pulmonares Intersticiais/enzimologia , Imageamento por Ressonância Magnética , Síndrome , Tomografia Computadorizada por Raios X
8.
Front Immunol ; 12: 677970, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34248959

RESUMO

Objective: The contribution of sustained autologous autoantibody production by B cells to the pathogenesis of systemic sclerosis (SSc) and granulomatosis with polyangiitis (GPA) is not fully understood. To investigate this, a humanized mouse model was generated by transferring patient-derived peripheral blood mononuclear cells (PBMC) into immunocompromised mice. Methods: PBMC derived from patients with SSc and GPA as well as healthy controls (HD) were isolated, characterized by flow cytometry, and infused into Rag2-/-/IL2rg-/- mice. In addition, PBMC from SSc patients treated with rituximab were transferred into mice. Twelve weeks later, human autoantibodies were determined in blood of the recipient mice and affected tissues were analyzed for pathological changes by histology and immunohistochemistry. Results: Mice engrafted with PBMC derived from SSc patients developed autoantibodies such as antinuclear antibodies (ANA) mimicking the pattern of the respective donors. Moreover, cellular infiltrates dominated by B cells were observed in lung, kidney and muscles of the recipient mice. By contrast, PBMC derived from HD or GPA patients survived in recipient mice after transfer, but neither human autoantibodies nor inflammatory infiltrates in tissues were detected. Furthermore, these pathological changes were absent in mice transferred with PBMC from rituximab-treated SSc patients. Conclusion: This humanized mouse model is indicative for cross-reactivity of human lymphocytes to murine autoantigens and argues for a pivotal role of B cells as well as of sustained autoimmunity in the pathogenesis of SSc. It provides a powerful tool to study interstitial lung disease and so far, under-recognized disease manifestations such as myositis and interstitial nephritis.


Assuntos
Anticorpos Antinucleares/imunologia , Proteínas de Ligação a DNA/metabolismo , Granulomatose com Poliangiite/sangue , Subunidade gama Comum de Receptores de Interleucina/metabolismo , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/transplante , Escleroderma Sistêmico/sangue , Adulto , Idoso , Animais , Anticorpos Antinucleares/sangue , Linfócitos B/imunologia , Reações Cruzadas , Proteínas de Ligação a DNA/genética , Feminino , Granulomatose com Poliangiite/imunologia , Humanos , Hospedeiro Imunocomprometido , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Fatores Imunológicos/uso terapêutico , Inflamação/imunologia , Subunidade gama Comum de Receptores de Interleucina/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Pessoa de Meia-Idade , Modelos Animais , Rituximab/uso terapêutico , Escleroderma Sistêmico/tratamento farmacológico , Escleroderma Sistêmico/imunologia , Resultado do Tratamento , Adulto Jovem
9.
Virchows Arch ; 479(5): 997-1005, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34302213

RESUMO

Exostosin 1 and exostosin 2 (EXT1/EXT2) on glomerular basement membrane (GBM) were recently reported as novel putative antigens in secondary membranous nephropathy with autoimmune disease. However, the clinical significance of glomerular EXT1/EXT2 remains elusive in patients with lupus nephritis (LN). The immunofluorescence staining pattern of glomerular EXT1/EXT2 is also undetermined in membranous LN (MLN) or proliferative LN (PLN). We cross-sectionally analyzed patients with MLN (pure class V, n = 11) and PLN (class III, IV, and mixed class III/IV + V, n = 22) who underwent renal biopsies between 2010 and 2020 at Showa University Hospital. Glomerular EXT1/EXT2 expressions were evaluated by immunofluorescence. T-helper (Th) cell-related serum inflammatory cytokines were measured using enzyme-linked immunosorbent assay. The positivity for both EXT1/EXT2 was higher in patients with MLN than PLN (90.9% vs 63.6%, P = 0.212). MLN showed global and bright granular EXT1/EXT2 expressions along GBM, while PLN showed segmental and moderate expressions on GBM. Additionally, glomerular EXT1/EXT2 positivity was not associated with the degree of proteinuria or renal function in MLN and PLN patients, but the levels of serum anti-dsDNA antibody and circulating immune complexes were lower in patients with EXT1/EXT2-positive MLN than EXT1/EXT2-negative PLN. Moreover, serum complement levels and IL-4/IFN-γ ratios were elevated in EXT1/EXT2-positive MLN than EXT1/EXT2-negative PLN. Collectively, immunofluorescence staining for glomerular EXT1/EXT2 had characteristic patterns between MLN and PLN. Glomerular EXT1/EXT2 expressions tended to be high in Th2-dominant MLN patients without severe hypocomplementemia and elevated autoantibodies. Thus, EXT1/EXT2 might be involved in the unique developmental mechanism of MLN.


Assuntos
Imuno-Histoquímica , Glomérulos Renais/química , Nefrite Lúpica/metabolismo , N-Acetilglucosaminiltransferases/análise , Adulto , Anticorpos Antinucleares/sangue , Complexo Antígeno-Anticorpo/sangue , Biomarcadores/sangue , Biópsia , Estudos Transversais , Citocinas/sangue , Feminino , Humanos , Mediadores da Inflamação/sangue , Japão , Glomérulos Renais/patologia , Nefrite Lúpica/imunologia , Nefrite Lúpica/patologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Linfócitos T Auxiliares-Indutores/imunologia , Linfócitos T Auxiliares-Indutores/metabolismo
11.
Arterioscler Thromb Vasc Biol ; 41(9): 2417-2430, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34320837

RESUMO

Objective: Systemic lupus erythematosus (SLE) is associated to boosted atherosclerosis development and a higher cardiovascular disease risk. This study aimed to delineate the role of anti-double stranded DNA (anti-dsDNA) antibodies on the molecular profile and the activity of immune and vascular cells, as well as on their enhanced cardiovascular risk. Approach and Results: Eighty SLE patients were included. Extensive clinical/analytical evaluation was performed, including cardiovascular disease parameters (endothelial function, proatherogenic dyslipidemia, and carotid intima-media thickness). Gene and protein expression profiles were evaluated in monocytes from patients diagnosed positive or negative for anti-dsDNA antibodies by using NanoString and cytokine arrays, respectively. NETosis and circulating inflammatory profile was assessed in both neutrophils and plasma. Positivity and persistence of anti-dsDNA antibodies in SLE patients were associated to endothelial dysfunction, proatherogenic dyslipidemia, and accelerated atherosclerosis. In parallel, anti-dsDNA antibodies were linked to the aberrant activation of innate immune cells, so that anti-dsDNA(+) SLE monocytes showed distinctive gene and protein expression/activity profiles, and neutrophils were more prone to suffer NETosis in comparison with anti-dsDNA(−) patients. Anti-dsDNA(+) patients further displayed altered levels of numerous circulating mediators related to inflammation, NETosis, and cardiovascular risk. In vitro, Ig-dsDNA promoted NETosis on neutrophils, apoptosis on monocytes, modulated the expression of inflammation and thrombosis-related molecules, and induced endothelial activation, at least partially, by FcR (Fc receptor)-binding mechanisms. Conclusions: Anti-dsDNA antibodies increase the cardiovascular risk of SLE patients by altering key molecular processes that drive a distinctive and coordinated immune and vascular activation, representing a potential tool in the management of this comorbidity.


Assuntos
Anticorpos Antinucleares/sangue , Doenças Cardiovasculares/imunologia , DNA/imunologia , Células Endoteliais/imunologia , Imunoglobulina G/sangue , Leucócitos/imunologia , Lúpus Eritematoso Sistêmico/imunologia , Adulto , Apoptose , Biomarcadores/sangue , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/diagnóstico por imagem , Doenças Cardiovasculares/genética , Células Cultivadas , Técnicas de Cocultura , Estudos Transversais , Citocinas/genética , Citocinas/metabolismo , Células Endoteliais/metabolismo , Armadilhas Extracelulares/metabolismo , Feminino , Fatores de Risco de Doenças Cardíacas , Humanos , Leucócitos/metabolismo , Lipídeos/sangue , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/genética , Masculino , Pessoa de Meia-Idade , Monócitos/imunologia , Monócitos/metabolismo , Neutrófilos/imunologia , Neutrófilos/metabolismo , Estresse Oxidativo , Estudos Retrospectivos , Medição de Risco , Transdução de Sinais
12.
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
13.
Front Immunol ; 12: 635072, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34122404

RESUMO

Interactions between gut microbes and the immune system influence autoimmune disorders like systemic lupus erythematosus (SLE). Recently, Enterococcus gallinarum, a gram-positive commensal gut bacterium, was implicated as a candidate pathobiont in SLE. The present study was undertaken to evaluate the influence of E. gallinarum exposure on clinical parameters of SLE. Since circulating IgG antibodies to whole bacteria have been established as a surrogate marker for bacterial exposure, anti-E. gallinarum IgG antibodies were measured in banked serum samples from SLE patients and healthy controls in the Oklahoma Cohort for Rheumatic Diseases. The associations between anti-E. gallinarum antibody titers and clinical indicators of lupus were studied. Antibodies to human RNA were studied in a subset of patients. Our results show that sera from both patients and healthy controls had IgG and IgA antibodies reactive with E. gallinarum. The antibody titers between the two groups were not different. However, SLE patients with Ribosomal P autoantibodies had higher anti-E. gallinarum IgG titers compared to healthy controls. In addition to anti-Ribosomal P, higher anti-E. gallinarum titers were also significantly associated with the presence of anti-dsDNA and anti-Sm autoantibodies. In the subset of patients with anti-Ribosomal P and anti-dsDNA, the anti-E. gallinarum titers correlated significantly with antibodies to human RNA. Our data show that both healthy individuals and SLE patients were sero-reactive to E. gallinarum. In SLE patients, the immune response to E. gallinarum was associated with antibody response to a specific subset of lupus autoantigens. These findings provide additional evidence that E. gallinarum may be a pathobiont for SLE in susceptible individuals.


Assuntos
Anticorpos Antinucleares/sangue , Anticorpos Antibacterianos/sangue , Enterococcus/imunologia , Microbioma Gastrointestinal/imunologia , Imunoglobulina A/sangue , Imunoglobulina G/sangue , Intestinos/microbiologia , Lúpus Eritematoso Sistêmico/imunologia , Biomarcadores/sangue , Humanos , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/diagnóstico , Estudos Retrospectivos
14.
Isr Med Assoc J ; 23(6): 373-375, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34155851

RESUMO

BACKGROUND: Surgical interventions in patients with systemic sclerosis (SSc), in particular plastic procedures, might cause undesired consequences. Notably, liposuction seems to possess greater risk as adipose tissue has been shown to play an important role in treating wounds and ulcers in patients with SSc. While anticentromere antibodies were found to be correlated with vasculopathy in SSc, patients with SSc and anticentromere antibodies might be more vulnerable to surgical wound complications following liposuction. A 46-year-old female patient, who had been diagnosed with SSc at the age of 31 years, had antinuclear as well as anticentromere antibodies. She underwent abdominoplasty with liposuction and developed severe skin necrosis of the abdomen following the procedure and at the site of liposuction. The correlation with anticentromere and the role of liposuction in skin necrosis in SSc are presented.


Assuntos
Abdominoplastia , Tecido Adiposo/imunologia , Obesidade Abdominal/cirurgia , Escleroderma Sistêmico , Pele/patologia , Deiscência da Ferida Operatória , Abdominoplastia/efeitos adversos , Abdominoplastia/métodos , Anticorpos Antinucleares/sangue , Cicatriz/diagnóstico , Cicatriz/etiologia , Contraindicações de Procedimentos , Feminino , Humanos , Lipectomia/efeitos adversos , Lipectomia/métodos , Pessoa de Meia-Idade , Necrose/etiologia , Necrose/imunologia , Necrose/cirurgia , Obesidade Abdominal/complicações , Obesidade Abdominal/diagnóstico , Reoperação/efeitos adversos , Reoperação/métodos , Escleroderma Sistêmico/complicações , Escleroderma Sistêmico/imunologia , Escleroderma Sistêmico/cirurgia , Cirurgia Plástica/efeitos adversos , Cirurgia Plástica/métodos , Deiscência da Ferida Operatória/diagnóstico , Deiscência da Ferida Operatória/etiologia , Deiscência da Ferida Operatória/cirurgia , Resultado do Tratamento
15.
Clin Immunol ; 229: 108781, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34144197

RESUMO

The safety, tolerance, and selected renal and non-renal outcome measures were evaluated in 73 SLE patients who received sirolimus therapy for more than 3 months in our institution over the past 21 years. In 12 patients who had lupus nephritis, proteinuria (p = 0.0287), hematuria (p = 0.0232), anti-DNA antibody levels (p = 0.0028) and steroid use were reduced (p = 0.0200). In the non-renal cohort of 61 patients, anti-DNA antibody levels (p = 0.0332) and steroid use were reduced (p = 0.0163). Both in the renal and non-renal cohorts, C3 (renal p = 0.0070; non-renal p = 0.0021) and C4 complement levels were increased (renal p = 0.0063; non-renal p = 0.0042) Adverse effects of mouth sores (2/73), headaches (1/73), and gastrointestinal discomfort were noted in a minority of patients (6/73). Sirolimus was only discontinued in two of 73 patients due to headache and recurrent infections, respectively. This study suggests that sirolimus is well tolerated and exerts long-term therapeutic efficacy in controlling renal and non-renal manifestations of SLE.


Assuntos
Imunossupressores/uso terapêutico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Nefrite Lúpica/tratamento farmacológico , Sirolimo/uso terapêutico , Adulto , Idoso , Anticorpos Antinucleares/sangue , Estudos de Coortes , Feminino , Seguimentos , Humanos , Imunossupressores/efeitos adversos , Lúpus Eritematoso Sistêmico/imunologia , Lúpus Eritematoso Sistêmico/fisiopatologia , Nefrite Lúpica/imunologia , Nefrite Lúpica/fisiopatologia , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Sirolimo/efeitos adversos , Resultado do Tratamento
16.
J Stroke Cerebrovasc Dis ; 30(8): 105896, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34144337

RESUMO

OBJECTIVES: French national guidelines recommend searching for anti-SS-A antibodies during the second-line assessment of stroke in adults < 55 years of age in the absence of an identified etiology. We aimed to assess the impact of finding anti-SS-A antibodies during the etiological investigations of stroke in young adults. METHODS: Medical files from all patients ≤ 55 years of age admitted to a single stroke unit during a five-year period and for whom anti-SS-A antibodies were positive were retrospectively analyzed. RESULTS: Twelve patients were included (9 women; median age 48.5 years), with a rate of anti-SS-A antibody positivity of 1.6% (95% confidence interval [0.71-2.55] %; 12/735 admissions). The etiologies of the 12 ischemic events based on the TOAST classification were large-artery atherosclerosis (n = 1), cardioembolism (n = 1), small-vessel disease (n = 1), other determined etiology (n = 3), multiple etiology (n = 1), and no determined etiology (n = 5). A connective tissue disease (CTD) was discovered in 8/12 patients (1 primary Sjögren's Syndrome, 1 mixed CTD, 1 systemic sclerosis, 2 antiphospholipid syndromes, 1 undetermined CTD, 2 lupus). Anti-SSA antibodies were not directly responsible for the stroke in any of the 12 cases. A link between the autoimmune disease and the neurological vascular episode could be hypothesized for four patients, but it never influenced the therapeutic decision. CONCLUSIONS: Finding anti-SS-A antibodies during the etiological assessment of a stroke of young adults is rare. However, it may be worthwhile to refer the patient to a rheumatologist/an internist because CTD may be discovered and may require specific follow-up.


Assuntos
Anticorpos Antinucleares/sangue , Autoimunidade , Acidente Vascular Cerebral/sangue , Adulto , Fatores Etários , Biomarcadores/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/imunologia
18.
J Immunol Res ; 2021: 5547635, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34036107

RESUMO

Objective: To investigate microRNA (miRNA) expression profiles in individuals with systemic lupus erythematosus (SLE) and identify the valuable miRNA biomarkers in diagnosing and monitoring SLE. Methods: Next-generation sequencing (NGS) was performed to assess miRNA amounts in peripheral blood mononuclear cells (PBMCs) from four SLE cases and four healthy controls. Quantitative polymerase chain reaction (qPCR) was carried out for validating candidate miRNAs in 32 SLE cases and 32 healthy controls. In addition, receiver operating characteristic (ROC) curve analysis was completed to evaluate diagnostic performance. Finally, the associations of candidate miRNAs with various characteristics of SLE were analyzed. Results: A total of 157 miRNAs were upregulated, and 110 miRNAs were downregulated in PBMCs from SLE cases in comparison to healthy controls, of which the increase of miR-183-5p and decrease of miR-374b-3p were validated by qPCR and both showed good diagnostic performance for SLE diagnosis. Besides, miR-183-5p expression levels displayed a positive association with SLE disease activity index (SLEDAI) and anti-dsDNA antibody amounts. Conclusion: Our data indicated that miR-183-5p is a promising biomarker of SLE.


Assuntos
Leucócitos Mononucleares/imunologia , Lúpus Eritematoso Sistêmico/diagnóstico , MicroRNAs/sangue , Adulto , Anticorpos Antinucleares/sangue , Biomarcadores/sangue , Biomarcadores/metabolismo , Estudos de Casos e Controles , Feminino , Perfilação da Expressão Gênica , Voluntários Saudáveis , Humanos , Leucócitos Mononucleares/metabolismo , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/genética , Lúpus Eritematoso Sistêmico/imunologia , Masculino , MicroRNAs/metabolismo , Curva ROC , Regulação para Cima/imunologia , Adulto Jovem
19.
Front Immunol ; 12: 667991, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33968071

RESUMO

B- and T-lymphocyte attenuator (BTLA/CD272) is an inhibitory checkpoint molecule expressed on T and B cells. Prior studies reported defective function of BTLA by T cells in patients with systemic lupus erythematosus (SLE), whereas nothing is known about its role on B cells in SLE, a disease with various B cell abnormalities. Peripheral blood mononuclear cells (PBMCs) from 23 healthy donors (HD) and 34 SLE patients were stained for BTLA and its expression on B cells was assessed. PBMCs or CD27-IgD+ naive B cells were stimulated together with an activating anti-BTLA antibody or an inhibitor of spleen tyrosine kinase (SYK) and differentiation as well as the expression of activation markers CD71, PD-1 and CD86 were analyzed. Our phenotypic and functional studies revealed reduced BTLA expression on CD27-IgD+ naïve B cells from SLE patients (p=0.0017) related to anti-dsDNA antibody titers (p=0.0394) and SIGLEC-1/CD169 expression on monocytes (p=0.0196), a type I interferon marker related to disease activity. BTLA engagement was found to control CpG/TLR9 activation limiting plasmablast (p=0.0156) and B cell memory induction (p=0.0078) in normal B cells in contrast to other B cell activation pathways (CD40, BCR). These BTLA functions were impaired in SLE B cells. Inhibition of SYK was found to mimic the effects of BTLA activity in vitro. Thus, is it possible that reduced BTLA expression and function of CD27-IgD+ antigen- and T cell-inexperienced SLE B cells could be overcome by SYK inhibition which should be tested in future studies as potential therapeutic principle.


Assuntos
Linfócitos B/metabolismo , Lúpus Eritematoso Sistêmico/metabolismo , Receptores Imunológicos/metabolismo , Adulto , Anticorpos Antinucleares/sangue , Linfócitos B/efeitos dos fármacos , Linfócitos B/imunologia , Estudos de Casos e Controles , Diferenciação Celular , Células Cultivadas , DNA/imunologia , Feminino , Humanos , Memória Imunológica , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/imunologia , Masculino , Pessoa de Meia-Idade , Monócitos/imunologia , Monócitos/metabolismo , Fenótipo , Fosforilação , Inibidores de Proteínas Quinases/farmacologia , Lectina 1 Semelhante a Ig de Ligação ao Ácido Siálico/metabolismo , Quinase Syk/antagonistas & inibidores , Quinase Syk/metabolismo , Adulto Jovem
20.
Front Immunol ; 12: 633658, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34012432

RESUMO

Systemic lupus erythematosus (SLE) is a severe autoimmune disease of unknown etiology. The major histocompatibility complex (MHC) class I-related chain A (MICA) and B (MICB) are stress-inducible cell surface molecules. MICA and MICB label malfunctioning cells for their recognition by cytotoxic lymphocytes such as natural killer (NK) cells. Alterations in this recognition have been found in SLE. MICA/MICB can be shed from the cell surface, subsequently acting either as a soluble decoy receptor (sMICA/sMICB) or in CD4+ T-cell expansion. Conversely, NK cells are frequently defective in SLE and lower NK cell numbers have been reported in patients with active SLE. However, these cells are also thought to exert regulatory functions and to prevent autoimmunity. We therefore investigated whether, and how, plasma membrane and soluble MICA/B are modulated in SLE and whether they influence NK cell activity, in order to better understand how MICA/B may participate in disease development. We report significantly elevated concentrations of circulating sMICA/B in SLE patients compared with healthy individuals or a control patient group. In SLE patients, sMICA concentrations were significantly higher in patients positive for anti-SSB and anti-RNP autoantibodies. In order to study the mechanism and the potential source of sMICA, we analyzed circulating sMICA concentration in Behcet patients before and after interferon (IFN)-α therapy: no modulation was observed, suggesting that IFN-α is not intrinsically crucial for sMICA release in vivo. We also show that monocytes and neutrophils stimulated in vitro with cytokines or extracellular chromatin up-regulate plasma membrane MICA expression, without releasing sMICA. Importantly, in peripheral blood mononuclear cells from healthy individuals stimulated in vitro by cell-free chromatin, NK cells up-regulate CD69 and CD107 in a monocyte-dependent manner and at least partly via MICA-NKG2D interaction, whereas NK cells were exhausted in SLE patients. In conclusion, sMICA concentrations are elevated in SLE patients, whereas plasma membrane MICA is up-regulated in response to some lupus stimuli and triggers NK cell activation. Those results suggest the requirement for a tight control in vivo and highlight the complex role of the MICA/sMICA system in SLE.


Assuntos
Membrana Celular/imunologia , Antígenos de Histocompatibilidade Classe I/sangue , Células Matadoras Naturais/imunologia , Lúpus Eritematoso Sistêmico/imunologia , Ativação Linfocitária , Anticorpos Antinucleares/sangue , Biomarcadores/sangue , Estudos de Casos e Controles , Membrana Celular/metabolismo , Células Cultivadas , Humanos , Células Matadoras Naturais/metabolismo , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/diagnóstico , Subfamília K de Receptores Semelhantes a Lectina de Células NK/metabolismo , Nucleossomos/imunologia , Nucleossomos/metabolismo , Fenótipo , Ribonucleoproteínas/imunologia , Síndrome de Sjogren/sangue , Síndrome de Sjogren/diagnóstico , Síndrome de Sjogren/imunologia , Regulação para Cima
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