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1.
Medicine (Baltimore) ; 99(3): e18600, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32011440

RESUMO

INTRODUCTION: Anti-melanoma differentiation-associated gene 5 antibody (anti-MDA5 Ab) is an autoantigen associated with dermatomyositis (DM). Anti-MDA5 Ab-positive DM patients frequently exhibit clinically amyopathic dermatomyositis (CADM), and develop rapidly progressive interstitial lung disease (RPILD). Even with early detection and potent combination immunosuppressive therapy, anti-MDA5 Ab-positive DM patients have a poor prognosis. In the present case report, we present a rare autopsy case of a patient with anti-MDA5 Ab DM with RPILD who exhibited diffuse alveolar damage (DAD) patterning in lung specimens, and extensive hemorrhages in multiple organs. PATIENT CONCERNS: An 82-year-old Japanese man admitted with bacterial pneumonia was subsequently diagnosed with anti-MDA5 Ab-positive DM based on skin manifestations (mechanic's hand, ulcerated palmar papules, and flagellate erythema), myositis, interstitial pneumonia, and elevation of anti-MDA5 Ab titer. DIAGNOSIS: The patient was diagnosed with anti-MDA5 Ab DM, complicated with RPILD. INTERVENTIONS: The patient received potent immunosuppressive therapy consisting of pulse methylpredonisolone at a dose of 1000 mg for 3 days, followed by prednisolone at 60 mg/d, a 1000 mg pulse of intravenous cyclophosphamide (IVCY), and oral tacrolimus at 6 mg/d. Intravenous immunoglobulin (IVIG) at a dose of 400 mg/kg/d for 5 days was subsequently administered. OUTCOMES: Despite triple immunosuppressive therapy and IVIG, the patients' respiratory status deteriorated, and the patient died of respiratory failure on the twelfth day after admission. An autopsy revealed pulmonary DAD and multiorgan hemorrhages, including the left iliopsoas muscle, gastric and bowl mucosa, spleen, and left adrenal gland. LESSONS: Multiorgan hemorrhages may be a fatal complication in anti-MDA5 Ab DM patients.


Assuntos
Dermatomiosite/complicações , Dermatomiosite/imunologia , Hemorragia/etiologia , Helicase IFIH1 Induzida por Interferon/imunologia , Idoso de 80 Anos ou mais , Autoanticorpos/imunologia , Autopsia , Dermatomiosite/tratamento farmacológico , Humanos , Imunossupressores/uso terapêutico , Pulmão/fisiopatologia , Masculino
2.
Medicine (Baltimore) ; 99(4): e18589, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31977850

RESUMO

To date, there is no clear agreement regarding which is the best method to detect a connective tissue disease (CTD) during the initial diagnosis of interstitial lung diseases (ILD). The aim of our study was to explore the impact of a systematic diagnostic strategy to detect CTD-associated ILD (CTD-ILD) in clinical practice, and to clarify the significance of interstitial pneumonia with autoimmune features (IPAF) diagnosis in ILD patients.Consecutive patients evaluated in an ILD Diagnostic Program were divided in 3 groups: IPAF, CTD-ILD, and other ILD forms. Clinical characteristics, exhaustive serologic testing, high resolution computed tomography (HRCT) images, lung biopsy specimens, and follow-up were prospectively collected and analyzed.Among 139 patients with ILD, CTD was present in 21 (15.1%), 24 (17.3%) fulfilled IPAF criteria, and 94 (67.6%) were classified as other ILD forms. Specific systemic autoimmune symptoms such as Raynaud phenomenon (19%), inflammatory arthropathy (66.7%), and skin manifestations (38.1%) were more frequent in CTD-ILD patients than in the other groups (all P < .001). Among autoantibodies, antinuclear antibody was the most frequently found in IPAF (42%), and CTD-ILD (40%) (P = .04). Nonspecific interstitial pneumonia, detected by HRCT scan, was the most frequently seen pattern in patients with IPAF (63.5%), or CTD-ILD (57.1%) (P < .001). In multivariate analysis, a suggestive radiological pattern by HRCT scan (odds ratio [OR] 15.1, 95% confidence interval [CI] 4.7-48.3, P < .001) was the strongest independent predictor of CTD-ILD or IPAF, followed by the presence of clinical features (OR 14.6, 95% CI 4.3-49.5, P < .001), and serological features (OR 12.4, 95% CI 3.5-44.0, P < .001).This systematic diagnostic strategy was useful in discriminating an underlying CTD in patients with ILD. The defined criteria for IPAF are fulfilled by a considerable proportion of patients referred for ILD.


Assuntos
Doenças do Tecido Conjuntivo/complicações , Doenças do Tecido Conjuntivo/diagnóstico , Doenças Pulmonares Intersticiais/complicações , Doenças Pulmonares Intersticiais/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Autoanticorpos/imunologia , Biópsia , Doenças do Tecido Conjuntivo/patologia , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Doenças Pulmonares Intersticiais/patologia , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X
3.
Gastroenterology ; 158(1): 151-159.e3, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31560892

RESUMO

BACKGROUND & AIMS: Celiac disease can develop at any age, but outcomes of adults with positive results from serologic tests for tissue transglutaminase antibodies (tTGA) without endoscopic determination of celiac disease (called celiac autoimmunity) have not been thoroughly evaluated. We investigated the proportion of adults with celiac autoimmunity at a community medical center and their progression to celiac disease. METHODS: We analyzed waste blood samples from a community clinic from 15,551 adults for tTGA and, if titer results were above 2 U/mL, for endomysial antibody. The blood samples had been collected at 2 time points (median interval, 8.8 years) from 2006 through 2017. We collected data from the clinic on diagnoses of celiac disease based on duodenal biopsy analysis. RESULTS: Of the serum samples collected at the first time point, 15,398 had negative results for tTGA, and 153 had positive results for tTGA (>4 U/mL). Based on medical records, 6 individuals received a diagnosis of celiac disease, for a cumulative incidence of celiac disease diagnosis of 0.06% (95% confidence interval, 0.01-0.11). Forty-nine (0.32%) individuals with a negative result from the first serologic test for tTGA had a positive result from the second test. Among the 153 adults who were tTGA positive at the first time point, 31 (20%) had a subsequent diagnosis of celiac disease, 81 (53%) remained positive for tTGA without a clinical diagnosis of celiac disease, and 41 (27%) had negative test results for tTGA at the second time point. Higher initial tTGA titers, female sex, and a history of hypothyroidism and autoimmune disease were associated with increased risks of subsequent diagnosis of celiac disease. Interestingly, adults whose first blood sample had a positive test result but second blood sample had a negative result for tTGA were older, had lower-than-average initial tTGA titer results, and had a higher mean body mass index than adults whose blood samples were positive for tTGA at both time points and adults later diagnosed with celiac disease. CONCLUSIONS: In an analysis of serum samples collected from a community clinic an average of 8.8 years apart, we found that fewer than 1% of adults with negative results from an initial test for tTGA have a positive result on a second test. Of adults with positive results from the test for tTGA, only 20% are later diagnosed with celiac disease; the remaining individuals maintain persistent increases in tTGA without diagnoses of celiac disease or have negative results from second tests.


Assuntos
Autoanticorpos/sangue , Autoimunidade , Doença Celíaca/epidemiologia , Centros Comunitários de Saúde/estatística & dados numéricos , Proteínas de Ligação ao GTP/imunologia , Transglutaminases/imunologia , Adulto , Autoanticorpos/imunologia , Biópsia , Doença Celíaca/diagnóstico , Doença Celíaca/imunologia , Progressão da Doença , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Minnesota/epidemiologia , Estudos Prospectivos , Estudos Soroepidemiológicos
4.
Zhonghua Er Ke Za Zhi ; 57(12): 928-933, 2019 Dec 02.
Artigo em Chinês | MEDLINE | ID: mdl-31795559

RESUMO

Objective: To report the clinical features of anti-MDA5 antibody positive juvenile dermatomyositis (JDM) complicated with severe interstitial lung disease (ILD). Methods: The clinical data of three patients, who was admitted to the Department of Rheumatology and Immunology, Children's Hospital of the Capital Institute of Pediatrics from September 2016 to July 2017, with anti-melanoma differentiation associated gene 5 (MDA5) antibody positive JDM complicated with ILD were retrospectively extracted and analyzed. Meanwhile, PubMed database, CNKI, Wanfang database and China Biology Medicine disc (from their establishment to February 2019) with the key words "juvenile dermatomyositis" "interstitial lung disease" , and "anti-MAD5 antibody" both in English and Chinese were searched. Results: There were 2 females and 1 male (P1-P3), aged from 10 years 3 months to13 years 4 months, the time from onset to diagnosis were 2 months, 4 months and 10 months. All presented with rash. One of them had decreased muscle strength, and two had decreased activity tolerance. Creatine kinase was 588, 915 and 74 U/L, and serum ferritin were 1 792, >2 000 and 195.4 µg/L. All three patients had positive anti-MDA5 antibodies. At the time of diagnosis, all of them had ILD, pneumothorax and mediastinal emphysema, but had no respiratory symptoms. All three patients received oral methylprednisolone and cyclophosphamide pulse therapy, while human immunoglobulin was given only to P1 and P2. P1 developed rapid progressive pulmonary interstitial disease (RPILD) and died of respiratory failure after 2 months. While P2 and P3 were followed up for 1 to 2 years, who had complete remission, as anti-MDA5 antibody turned to negative and ILD improved significantly. Ten related reports in literature were retrieved, without reported Chinese cases, and most cases initiated with rash and very likely complicated with arthritis. Some of them were more likely to have ILD rather than muscle weakness. It also showed that Japanese JDM children had higher rate of positive anti-MDA5 antibody than patients from the U.S. and U.K., and are more susceptible to ILD and RPILD. The mortality rate of patients with RPILD is extremely high. Conclusions: The cases of JDM with positive anti-MDA5 antibody mainly presented with rash and mild muscle weakness, and could be complicated with ILD, pneumothorax and mediastinal emphysema without respiratory symptoms at early stage. Anti-MDA5 antibody titer is related to disease activity and can turn to negative after treatment.


Assuntos
Autoanticorpos/imunologia , Dermatomiosite/diagnóstico , Helicase IFIH1 Induzida por Interferon/imunologia , Doenças Pulmonares Intersticiais/diagnóstico , Adolescente , Criança , China , Dermatomiosite/imunologia , Feminino , Humanos , Doenças Pulmonares Intersticiais/imunologia , Masculino , Prognóstico , Estudos Retrospectivos
5.
Medicine (Baltimore) ; 98(50): e18012, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31852064

RESUMO

RATIONALE: Hashimoto's encephalopathy (HE) is an autoimmune-mediated encephalopathy rarely seen in Graves' disease, with <20 cases reported previously, associated with elevated concentration of circulating serum anti-thyroid antibodies usually responsive to steroid therapy. PATIENT CONCERNS: We present a HE case (25-year-old male) with Graves' disease, complicated by fever and pancytopenia. The patient presented with fever, gait impairment, delirium, agitation and disorientation. DIAGNOSES: Thyroid-related antibodies were elevated and brain magnetic resonance imaging confirmed symmetrical white-matter lesion. There was no evidence of infection or other reasons to explain all of his clinical manifestations. Hashimoto's encephalopathy (HE) is an autoimmune encephalopathy with various manifestations and the characteristic of elevated anti-thyroid antibodies and has no relationship to thyroid function. INTERVENTIONS: The patient had nonspecific clinical manifestations and excellently respond to glucocorticoid therapy.The symptoms and the radiographic abnormalities disappeared after glucocorticoid therapy. OUTCOMES: We followed up with him for 5 years, in which there was no recurrence and his thyroid function continued to be normal. LESSONS: It is important to evaluate thyroid function and related antibodies in patients present with neuropsychological symptoms to avoid delay in diagnosis.


Assuntos
Autoanticorpos/sangue , Encéfalo/diagnóstico por imagem , Encefalite/etiologia , Doença de Graves/complicações , Doença de Hashimoto/etiologia , Pancitopenia/complicações , Doença Aguda , Adulto , Autoanticorpos/imunologia , Biomarcadores/sangue , Encefalite/diagnóstico , Encefalite/imunologia , Doença de Graves/diagnóstico , Doença de Graves/imunologia , Doença de Hashimoto/diagnóstico , Doença de Hashimoto/imunologia , Humanos , Imagem por Ressonância Magnética , Masculino , Pancitopenia/diagnóstico , Pancitopenia/imunologia , Tomografia Computadorizada por Raios X
6.
Presse Med ; 48(11 Pt 2): 319-327, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31759790

RESUMO

Thrombotic thrombocytopenic purpura (TTP) is a life-threatening disease related to the formation of microvascular thrombosis and subsequent organ failure. The disease is accompanied with microangiopathic haemolytic anaemia, consumptive thrombocytopenia and lies on a severe deficiency in ADAMTS13, the von Willebrand factor-cleaving protease. In the acquired, immune-mediated form, this deficiency is due to the production of autoantibodies directed against the enzyme. Therapeutic plasma exchange has been used empirically for decades and still represents the cornerstone of TTP treatment. However, a better understanding of pathophysiological mechanisms underlying the disease has led these last years to the development of highly effective targeted therapies that might in the future restraint the use of therapeutic plasma exchange.


Assuntos
Proteína ADAMTS13/deficiência , Terapia de Alvo Molecular , Troca Plasmática , Púrpura Trombocitopênica Trombótica/terapia , Proteína ADAMTS13/imunologia , Acetilcisteína/uso terapêutico , Corticosteroides/uso terapêutico , Anemia Hemolítica/complicações , Autoanticorpos/imunologia , Ensaios Clínicos como Assunto , Previsões , Humanos , Fatores Imunológicos/uso terapêutico , Púrpura Trombocitopênica Trombótica/sangue , Púrpura Trombocitopênica Trombótica/complicações , Púrpura Trombocitopênica Trombótica/imunologia , Rituximab/uso terapêutico , Anticorpos de Domínio Único/uso terapêutico
7.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 41(5): 678-684, 2019 Oct 30.
Artigo em Chinês | MEDLINE | ID: mdl-31699200

RESUMO

Systemic lupus erythematosus(SLE)is a chronic autoimmune disease that involves multiple organs and tissues.Its pathogenic mechanism remains unclear.Impaired inflammatory response and reduced clearance of immune cells are key events in the development of SLE,during which the pentraxin family plays an important role.This article summarizes recent advances in the relationship between anti-C-reactive protein autoantibody and SLE.


Assuntos
Autoanticorpos/imunologia , Proteína C-Reativa/imunologia , Lúpus Eritematoso Sistêmico/imunologia , Humanos
8.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 41(5): 714-718, 2019 Oct 30.
Artigo em Chinês | MEDLINE | ID: mdl-31699206

RESUMO

Leucine-rich glioma-inactivated protein 1(LGI1)antibody-associated encephalitis is an autoimmune brain disease mainly seen in mid-aged and elderly people.Its main clinical manifestations include abnormal mental behaviors,facial-arm dystonia,hyponatremia,and hypokalemia.Immunotherapy with gamma globulin and/or hormone is effective.Two patients with LGT1 antibody-associated encephalitis were diagnosed in our center between January 2018 and October 2018,with typical clinical findings.The disease was cursed after immunoglobulin and hormone treatments.


Assuntos
Autoanticorpos/imunologia , Encefalite/diagnóstico , Proteínas/imunologia , Encefalite/terapia , Humanos
9.
An Bras Dermatol ; 94(4): 388-398, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31644609

RESUMO

Paraneoplastic pemphigus is a rare and severe autoimmune blistering disease characterized by mucocutaneous lesions associated with benign and malignant neoplasms. Diagnostic criteria include the presence of chronic mucositis and polymorphic cutaneous lesions with occult or confirmed neoplasia; histopathological analysis exhibiting intraepidermal acantholysis, necrotic keratinocytes, and vacuolar interface dermatitis; direct immunofluorescence with intercellular deposits (IgG and C3) and at the basement membrane zone (IgG); indirect immunofluorescence with intercellular deposition of IgG (substrates: monkey esophagus and simple, columnar, and transitional epithelium); and, autoreactivity to desmogleins 1 and 3, desmocollins 1, 2, and 3, desmoplakins I and II, envoplakin, periplakin, epiplakin, plectin, BP230, and α-2-macroglobulin-like protein 1. Neoplasias frequently related to paraneoplastic pemphigus include chronic lymphocytic leukemia, non-Hodgkin lymphoma, carcinomas, Castleman disease, thymoma, and others. Currently, there is no standardized treatment for paraneoplastic pemphigus. Systemic corticosteroids, azathioprine, mycophenolate mofetil, cyclosporine, rituximab, cyclophosphamide, plasmapheresis, and intravenous immunoglobulin have been used, with variable outcomes. Reported survival rates in 1, 2, and 5 years are 49%, 41%, and 38%, respectively.


Assuntos
Síndromes Paraneoplásicas/patologia , Síndromes Paraneoplásicas/terapia , Pênfigo/patologia , Pênfigo/terapia , Autoanticorpos/imunologia , Eritema/diagnóstico , Eritema/patologia , Humanos , Doenças da Boca/diagnóstico , Doenças da Boca/patologia , Síndromes Paraneoplásicas/diagnóstico , Síndromes Paraneoplásicas/imunologia , Pênfigo/diagnóstico , Pênfigo/imunologia , Pele/patologia
10.
Medicina (B Aires) ; 79 Suppl 3: 60-65, 2019.
Artigo em Espanhol | MEDLINE | ID: mdl-31603846

RESUMO

Neuromyelitis optica (NMO) is an autoimmune, inflammatory and de myelinat ing disorder of the central nervous system with a predilection for the optic nerves and spinal cord. In 2004 the association of NMO with an antibody against the water channel aquaporin 4 (anti-AQP4) was published as a different pathology from multiple sclerosis (MS). Currently the term NMO spectrum disorders (NMOSD) is proposed, because the manifestations of the disease can be more extensive, affecting in addition to the optic nerve and spinal cord, the area postrema of the dorsal medulla, brainstem, diencephalon and typical brain areas (periependymal, corpus callosum, internal capsule and subcortical white matter). NMOSD is also applied to patients who meet the NMO criteria and are negative for AQP4-IgG. Within the latter group, the presence of another antibody, anti-MOG, has been detected in 20%, with a different physiopathological mechanism, but with a similar clinic and a better prognosis. The immunosuppressive treatment in the attack, as well as the long-term treatment in the cases that are indicated, is fundamental to avoid sequelaes and recurrences. The correct diagnosis of this entity is essential since it can be aggravated with the use of drugs useful in the treatment of MS. In this publication we will review the pathophysiology, clinical and diagnostic criteria of NMOSD, and discuss the different therapeutic options.


Assuntos
Autoanticorpos/imunologia , Neuromielite Óptica/diagnóstico , Neuromielite Óptica/tratamento farmacológico , Autoanticorpos/efeitos adversos , Diagnóstico Diferencial , Humanos , Esclerose Múltipla/diagnóstico , Neuromielite Óptica/imunologia , Neuromielite Óptica/fisiopatologia
11.
Life Sci ; 238: 116923, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31610191

RESUMO

Idiopathic membranous nephropathy (IMN) has recently attracted much attention due to the development of auto antibodies, anti-phospholipase A2 receptor and anti-thrombospondin type I domain-containing 7A on podocytes, the establishment of immune networks complexes in circulation as well as the development of autoreactive immune cells against kidney, in both innate and adaptive participants. The auto inflammatory responses in IMN leads to the dysfunction of glomerular cells to represent pathological status. T cells, as a crucial factor in the immune network, support B cell-related responses and develop inflammation and cytotoxicity. They have the most determining roles in the autoimmune diseases. Activation of T cells occurs just before their infiltration in kidney. This process is definitely accompanied by costimulatory factors and cytokines, in order to develop and increase the number of these cells. In addition, altered B cell signaling network by the B cell receptor and co receptors such as B cell-activating factor receptor (BAFFR) stimulates the autoimmune-related pathogenesis. Autoantigens exposure and kidney infiltration of naive T cells lead to their local development. Furthermore, losing peripheral immune tolerance towards kidney antigens, will result in IMN. The growing findings about different immune system factors, cells and molecular mechanism have also revealed new pathways of pathogenesis and diagnosis approaches, such as personalized medicine in MN patients. This review aims to discuss the recent findings in adaptive immune cells, and distinguishes between intact and undone researches about pathogenesis and molecular signaling pathways of immune system in MN disease.


Assuntos
Autoanticorpos/imunologia , Autoantígenos/imunologia , Glomerulonefrite Membranosa/imunologia , Glomerulonefrite Membranosa/patologia , Sistema Imunitário/imunologia , Animais , Humanos
12.
Lakartidningen ; 1162019 Sep 26.
Artigo em Sueco | MEDLINE | ID: mdl-31573670

RESUMO

Systemic sclerosis is an autoimmune systemic disease with an annual incidence in Sweden of only 20 cases per million and a standardised mortality rate of 3-4. Disease onset is usually preceded by a period with Raynaud's phenomenon, combined with structurally abnormal nailbed capillaries and accompanied by presence of scleroderma related autoantibodies. The presenting symptoms are skin thickness, puffy fingers, digital ulcers, dysphagia, joint stiffness and pain, and pruritus. Optimal management involves a number of specialists including allied health professionals. Early recognition, diagnosis and treatment are important. The dominating causes of death are cardiopulmonary.


Assuntos
Escleroderma Sistêmico , Autoanticorpos/imunologia , Humanos , Atenção Primária à Saúde , Doenças Raras/complicações , Doenças Raras/diagnóstico , Doenças Raras/patologia , Doenças Raras/terapia , Doença de Raynaud/etiologia , Encaminhamento e Consulta , Escleroderma Sistêmico/complicações , Escleroderma Sistêmico/diagnóstico , Escleroderma Sistêmico/patologia , Escleroderma Sistêmico/terapia
13.
Medicine (Baltimore) ; 98(38): e17253, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31567996

RESUMO

BACKGROUND: Malignant pleural effusion (MPE) and tuberculosis pleural effusion (TPE) are 2 kinds of common pleural diseases. Finding efficient and accurate biomarkers to distinguish the 2 is of benefit to basic and clinical research. In the present study, we carried out the first high-throughput autoantibody chip to screen the beneficial biomarker with samples of MPE and TPE and the corresponding serum. METHODS: We collected pleural effusion and serum of patients with MPE (n = 10) and TPE (n = 10) who had been in Beijing Chao-Yang hospital from June 2013 to August 2014. Using RayBio Human Protein Array-G2 to measure the concentration of 487 defined autoantibodies. RESULTS: Fold changes of Bcl-2-like protein 11 (BIM) autoantibody in MPE-serum/TPE-serum and MPE/TPE groups were 10 (P = .019) and 6 (P = .001); for decorin autoantibody, MPE-serum/TPE-serum ratio was 0.6 (P = .029), and MPE/TPE ratio was 0.3 (P < .001). CONCLUSION: BIM autoantibody is a promising MPE biomarker by high-throughput autoantibody analysis in MPE and TPE.


Assuntos
Autoanticorpos/sangue , Derrame Pleural Maligno/sangue , Derrame Pleural/sangue , Tuberculose Pleural/sangue , Autoanticorpos/imunologia , Proteína 11 Semelhante a Bcl-2/sangue , Proteína 11 Semelhante a Bcl-2/imunologia , Biomarcadores/sangue , Feminino , Ensaios de Triagem em Larga Escala/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Derrame Pleural/diagnóstico , Derrame Pleural/imunologia , Derrame Pleural Maligno/diagnóstico , Derrame Pleural Maligno/imunologia , Tuberculose Pleural/diagnóstico , Tuberculose Pleural/imunologia
14.
Mol Immunol ; 114: 629-642, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31542608

RESUMO

Neutrophils are essential to the pathogenesis of many inflammatory diseases. In the autoantibody-mediated K/BxN model of inflammatory arthritis, the alternative pathway (AP) of complement and Fc gamma receptors (FcγRs) are required for disease development while the classical pathway is dispensable. The reason for this differential requirement is unknown. We show that within minutes of K/BxN serum injection complement activation (CA) is detected on circulating neutrophils, as evidenced by cell surface C3 fragment deposition. CA requires the AP factor B and FcγRs but not C4, implying that engagement of FcγRs by autoantibody or immune complexes directly triggers AP C3 convertase assembly. The absence of C5 does not prevent CA on neutrophils but diminishes the upregulation of adhesion molecules. In vivo two-photon microscopy reveals that CA on neutrophils is critical for neutrophil extravasation and generation of C5a at the site of inflammation. C5a stimulates the release of neutrophil proteases, which contribute to the degradation of VE-cadherin, an adherens junction protein that regulates endothelial barrier integrity. C5a receptor antagonism blocks the extracellular release of neutrophil proteases, suppressing VE-cadherin degradation and neutrophil transendothelial migration in vivo. These results elucidate the AP-dependent intravascular neutrophil-endothelial interactions that initiate the inflammatory cascade in this disease model but may be generalizable to neutrophil extravasation in other inflammatory processes.


Assuntos
Adesão Celular/imunologia , Ativação do Complemento/imunologia , Complemento C5a/imunologia , Células Endoteliais da Veia Umbilical Humana/imunologia , Neutrófilos/imunologia , Animais , Complexo Antígeno-Anticorpo/imunologia , Autoanticorpos/imunologia , Células Cultivadas , Feminino , Humanos , Masculino , Camundongos Endogâmicos C57BL , Receptores de IgG/imunologia
15.
Isr Med Assoc J ; 21(7): 480-486, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31507125

RESUMO

BACKGROUND: Serum rheumatoid factors are autoantibodies of different isotypes directed against the Fc fraction of immunoglobulin G (IgG) and represent paradigmatic autoantibodies that have been largely used in clinical practice for decades. Traditionally IgG has been associated with rheumatoid arthritis and more recently included also in the classification criteria for SjÓ§gren's syndrome. Researchers have established that rheumatoid factors are positive in a variety of infectious, autoimmune, and neoplastic disorders, thus requiring a comprehensive evaluation of seropositive patients. Of note, hepatitis B and C viruses represent a crossroad that includes the high rheumatoid factor seroprevalence and chronic inflammatory disease, as well as progression to non-Hodgkin's lymphomas. Chronic antigen stimulation is the likely common ground of these processes and rheumatoid factors may represent mere bystanders or drivers of pathology. Mixed cryoglobulinemia and lymphoproliferative disease are prime examples of the deleterious effects of rheumatoid factor-B cell activity, possibly associated with hepatitis B and C. More importantly, they show a clear association in a physiological host response to infection, chronic inflammation, and the slide toward autoimmunity and malignancy. The association between hepatitis B and C infections and the appearance of serum rheumatoid factors is further supported by prevalence data, which support a coexistence of these markers in a significant proportion of cases, with viral infections being frequent causes of rheumatoid factors in patients without a rheumatic condition. We provide a comprehensive overview of the known connections between hepatitis B and C infections and rheumatoid factors.


Assuntos
Hepatite B/imunologia , Hepatite C/imunologia , Fator Reumatoide/imunologia , Autoanticorpos/imunologia , Doenças Autoimunes/imunologia , Autoimunidade/imunologia , Crioglobulinemia/imunologia , Humanos , Transtornos Linfoproliferativos/imunologia , Neoplasias/imunologia , Fator Reumatoide/sangue
16.
Nat Commun ; 10(1): 4415, 2019 09 27.
Artigo em Inglês | MEDLINE | ID: mdl-31562329

RESUMO

Many autoimmune diseases are characterized by the production of autoantibodies. The current view is that CD4+ T follicular helper (Tfh) cells are the main subset regulating autoreactive B cells. Here we report a CXCR5+PD1+ Tfh subset of CD8+ T cells whose development and function are negatively modulated by Stat5. These CD8+ Tfh cells regulate the germinal center B cell response and control autoantibody production, as deficiency of Stat5 in CD8 T cells leads to an increase of CD8+ Tfh cells, resulting in the breakdown of B cell tolerance and concomitant autoantibody production. CD8+ Tfh cells share similar gene signatures with CD4+ Tfh, and require CD40L/CD40 and TCR/MHCI interactions to deliver help to B cells. Our study thus highlights the diversity of follicular T cell subsets that contribute to the breakdown of B-cell tolerance.


Assuntos
Linfócitos B/imunologia , Linfócitos T CD8-Positivos/imunologia , Tolerância Imunológica/imunologia , Receptor de Morte Celular Programada 1/imunologia , Receptores CXCR5/imunologia , Linfócitos T Auxiliares-Indutores/imunologia , Autoanticorpos/imunologia , Autoanticorpos/metabolismo , Doenças Autoimunes/genética , Doenças Autoimunes/imunologia , Doenças Autoimunes/metabolismo , Linfócitos B/metabolismo , Antígenos CD40/genética , Antígenos CD40/imunologia , Antígenos CD40/metabolismo , Ligante de CD40/genética , Ligante de CD40/imunologia , Ligante de CD40/metabolismo , Linfócitos T CD8-Positivos/metabolismo , Perfilação da Expressão Gênica/métodos , Humanos , Tolerância Imunológica/genética , Receptor de Morte Celular Programada 1/genética , Receptor de Morte Celular Programada 1/metabolismo , Receptores CXCR5/genética , Receptores CXCR5/metabolismo , Fator de Transcrição STAT5/genética , Fator de Transcrição STAT5/imunologia , Fator de Transcrição STAT5/metabolismo , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Linfócitos T Auxiliares-Indutores/metabolismo
17.
Magy Onkol ; 63(3): 261-267, 2019 09 18.
Artigo em Húngaro | MEDLINE | ID: mdl-31533147

RESUMO

Paraneoplastic neurologic syndromes (PNS) and autoimmune encephalitis (AE) are rare neurological disorders, which have similar symptoms, but vary in outcome and treatment strategy. In our retrospective statistical study we evaluated the autoantibody test results of serum and CSF from 2362 patients with suspected PNS and 1034 patients with suspected AE. For autoantibody testing, immunoblot assay (PNS) and cell-based indirect immunofluorescence assay (AE) were used. Autoantibodies were present in 8% of patients with suspected PNS: anti-Yo > anti-Hu > anti-Ma2 > anti-CV2 > anti-titin > anti-Zic4 > anti-amphiphysin > anti-Ri > anti-GAD65 > anti-Sox1 > anti-recoverin. Mostly elderly women were affected. Autoantibodies were present in 5.8% of patients with suspected AE: anti-NMDAR (young women) > anti-LGI1 (middle-aged men) > anti-GABABR (elderly men) > anti-Caspr2 (adult men). Our results correspond to the data described in the literature. The number of patients with suspected PNS and AE shows an increasing tendency, where the autoantibody testing with modern laboratory diagnostic methods helps in the early introduction of the appropriate therapy.


Assuntos
Encefalite/diagnóstico , Encefalite/imunologia , Doença de Hashimoto/diagnóstico , Doença de Hashimoto/imunologia , Síndromes Paraneoplásicas do Sistema Nervoso/diagnóstico , Síndromes Paraneoplásicas do Sistema Nervoso/imunologia , Adulto , Idoso , Autoanticorpos/sangue , Autoanticorpos/líquido cefalorraquidiano , Autoanticorpos/imunologia , Encefalite/terapia , Feminino , Doença de Hashimoto/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Síndromes Paraneoplásicas do Sistema Nervoso/terapia , Estudos Retrospectivos
18.
Hypertension ; 74(4): 784-792, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31476909

RESUMO

Primary aldosteronism is a common form of endocrine hypertension mainly caused by a unilateral aldosterone-producing adenoma (APA) or bilateral adrenal hyperplasia (BAH). AT1R-Abs (autoantibodies to the angiotensin II type 1 receptor) have been reported in patients with disorders associated with hypertension. Our objective was to assess AT1R-Ab levels in patients with primary aldosteronism (APA, n=40 and BAH, n=40) relative to patients with primary hypertension (n=40), preeclampsia (n=23), and normotensive individuals (n=25). AT1R-Abs in whole sera were measured using 2 different ELISAs which gave contrasting results. A functional cell-based assay was used to quantify activation of the AT1R (angiotensin II type 1 receptor) using whole sera or affinity-purified antibodies in the absence or presence of losartan (a specific AT1R antagonist). Serum samples from all groups displayed different levels of AT1R activation with different responses to losartan. Patients with BAH displayed higher losartan-independent affinity-isolated agonistic AT1R-Ab levels compared with patients with APA (P<0.01) and with normotensive individuals (P<0.0001). In patients with APA, BAH, and primary hypertension combined, higher aldosterone-to-renin ratios and lower plasma renin concentrations were associated with higher compared with lower agonistic AT1R-Ab levels. In patients with primary aldosteronism, higher AT1R-Ab activity was associated with an increased likelihood of a diagnosis of BAH compared with APA and with the presence of adrenal hyperplasia detected by computed tomography. Taken together, these data suggest that agonistic AT1R-Abs may have a functional role in a subgroup of patients with primary aldosteronism.


Assuntos
Autoanticorpos/imunologia , Hiperaldosteronismo/imunologia , Receptor Tipo 1 de Angiotensina/imunologia , Glândulas Suprarrenais/diagnóstico por imagem , Adulto , Idoso , Feminino , Humanos , Hiperaldosteronismo/diagnóstico por imagem , Hipertensão/imunologia , Masculino , Pessoa de Meia-Idade , Pré-Eclâmpsia/imunologia , Gravidez , Tomografia Computadorizada por Raios X
20.
Int J Mol Sci ; 20(16)2019 08 08.
Artigo em Inglês | MEDLINE | ID: mdl-31398795

RESUMO

Islet autoantibody (iAb)-positive individuals have a high risk of progression to type 1 diabetes (T1D), although the rate of progression is highly variable and factors involved in the rate of progression are largely unknown. The ratio of unmethylated/methylated insulin DNA levels (unmethylated INS ratio) has been shown to be higher in participants at high risk of T1D compared to healthy controls. We aimed to evaluate whether an unmethylated INS ratio may be a useful biomarker of beta cell death and rate of progression to T1D. In TrialNet participants who were followed in the Pathway to Prevention Study and progressed to diabetes (n = 57, median age of onset 15.3 years), we measured unmethylated INS ratio and autoantibodies by electrochemiluminescence (ECL) assays (ECL-IAA, ECL-GADA, and ECL-IA2) and radioimmunoassays (RIA) (mIAA, GADA, IA2A, and ZnT8A) longitudinally for 24 months prior to diagnosis. Linear models were used to test the association between unmethylated INS ratio and the age at T1D diagnosis and unmethylated INS ratio and iAb over time. Close to diabetes onset, the unmethylated INS ratio was associated with mIAA (p = 0.003), ECL-IAA (p = 0.002), and IA2A (p = 0.01) levels, but not with GADA, ECL-GADA, ECL-IA2, or ZnT8A levels. No significant associations were found at baseline (24 months prior to T1D diagnosis). Only mIAA levels were significantly associated with an unmethylated INS ratio over time, with a 0.24 change in the ratio for each 0.1 change in mIAA z-score (p = 0.02). Adjusting for a baseline unmethylated INS ratio, an increased rate of change in unmethylated INS ratio from baseline to diabetes onset was associated with a five-year decrease in age at T1D diagnosis (p = 0.04).


Assuntos
Diabetes Mellitus Tipo 1/etiologia , Diabetes Mellitus Tipo 1/metabolismo , Células Secretoras de Insulina/metabolismo , Insulina/metabolismo , Adolescente , Idade de Início , Autoanticorpos/sangue , Autoanticorpos/imunologia , Biomarcadores , Morte Celular , Criança , Progressão da Doença , Suscetibilidade a Doenças , Feminino , Humanos , Células Secretoras de Insulina/imunologia , Masculino , Metilação , Risco , Adulto Jovem
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