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1.
BMC Infect Dis ; 20(1): 828, 2020 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-33176707

RESUMO

BACKGROUND: Severe and disseminated non-tuberculous mycobacterial (NTM) infections are frequently linked to a genetic predisposition but acquired defects of the interferon gamma (IFNγ) / interleukin 12 (IL-12) pathway need to be considered in adult patients with persistent or recurrent infections. Neutralizing anti-IFNγ autoantibodies disrupting IFNγ signalling have been identified as the cause of a severe and unique acquired immunodeficiency syndrome with increased susceptibility to NTM and other intracellular pathogens. CASE PRESENTATION: An adult Asian female with a previous history of recurrent NTM infections presented with persistent diarrhea, abdominal pain, night sweats and weight loss. Severe colitis due to a simultaneous infection with cytomegalovirus (CMV) and Salmonella typhimurium was diagnosed, with both pathogens also detectable in blood samples. Imaging studies further revealed thoracic as well as abdominal lymphadenopathy and a disseminated Mycobacterium intracellulare infection was diagnosed after a lymph node biopsy. Further diagnostics revealed the presence of high-titer neutralizing anti-IFNγ autoantibodies, allowing for the diagnosis of adult-onset immunodeficiency with anti-IFNγ autoantibodies (AIIA). CONCLUSIONS: We here present a severe case of acquired immunodeficiency with anti-IFNγ autoantibodies with simultaneous, disseminated infections with both viral and microbial pathogens. The case illustrates how the diagnosis can cause considerable difficulties and is often delayed due to unusual presentations. Histological studies in our patient give further insight into the pathophysiological significance of impaired IFNγ signalling. B-cell-depleting therapy with rituximab offers a targeted treatment approach in AIIA.


Assuntos
Autoanticorpos/imunologia , Infecções por Citomegalovirus/diagnóstico , Citomegalovirus/isolamento & purificação , Síndromes de Imunodeficiência/diagnóstico , Interferon gama/imunologia , Linfadenopatia/diagnóstico , Complexo Mycobacterium avium/isolamento & purificação , Infecção por Mycobacterium avium-intracellulare/diagnóstico , Infecções por Salmonella/diagnóstico , Salmonella typhimurium/isolamento & purificação , Adulto , Antibacterianos/uso terapêutico , Antivirais/uso terapêutico , Autoanticorpos/sangue , Biópsia , Infecções por Citomegalovirus/complicações , Infecções por Citomegalovirus/tratamento farmacológico , Infecções por Citomegalovirus/virologia , Diagnóstico Tardio , Feminino , Seguimentos , Humanos , Síndromes de Imunodeficiência/complicações , Síndromes de Imunodeficiência/tratamento farmacológico , Fatores Imunológicos/uso terapêutico , Interferon gama/metabolismo , Interleucina-12/metabolismo , Linfadenopatia/complicações , Linfadenopatia/tratamento farmacológico , Linfadenopatia/patologia , Infecção por Mycobacterium avium-intracellulare/complicações , Infecção por Mycobacterium avium-intracellulare/tratamento farmacológico , Infecção por Mycobacterium avium-intracellulare/microbiologia , Infecções por Salmonella/complicações , Infecções por Salmonella/tratamento farmacológico , Infecções por Salmonella/microbiologia , Resultado do Tratamento
4.
Arq. ciências saúde UNIPAR ; 24(3): 133-138, set-dez. 2020.
Artigo em Português | LILACS | ID: biblio-1129455

RESUMO

Quando um indivíduo é exposto a antígenos eritrocitários não próprios, ocorre uma resposta imunológica, que leva à produção de anticorpos irregulares voltados contra esses antígenos. Esse processo é conhecido como aloimunização eritrocitária e acontece em decorrência de transfusões de sangue ou gestações incompatíveis. Na medicina transfusional a pesquisa de anticorpos irregulares é fundamental, pois a falha na detecção de um aloanticorpo pode provocar reações transfusionais, aloimunizações, anemias hemolíticas autoimunes e doença hemolítica perinatal. Este estudo tem por objetivo analisar a frequência de anticorpos irregulares de pacientes atendidos no Hemocentro Regional de Francisco Beltrão, Paraná, no ano de 2017. Os dados foram coletados a partir da revisão de registros em arquivos do Laboratório de Imunohematologia do Hemonúcleo. Foram avaliados dados de 49 protocolos de pacientes que apresentaram dificuldades transfusionais no ano de 2017. Dentre os pesquisados, 37 pacientes (75,5%) apresentaram anticorpos irregulares. Dentre os anticorpos anti-eritrocitários observados neste estudo, evidenciou-se a presença de doze pacientes com anti-D (27,2%), seis pacientes com anti-K (13,6%), quatro pacientes com anti-C (9,0%) e em seis pacientes (13,6%) foi observada a presença de autoanticorpos. Este estudo indica que, nos pacientes transfundidos, os anticorpos mais frequentes foram os aloanticorpos Anti-D do Sistema Rh, provavelmente devido ao seu alto grau de imunogenicidade. A prevalência desses anticorpos é semelhante a vários estudos encontrados na literatura.


When an individual is exposed to not-self red blood cell antigens, an immune response occurs, which leads to the production of irregular antibodies directed against these antigens. This process is known as erythrocyte alloimmunization and occurs as a result of blood transfusions or incompatible pregnancies. In transfusion medicine, the search for irregular antibodies is essential, since failure to detect an alloantibody can cause transfusion reactions, alloimmunizations, autoimmune hemolytic anemias, and perinatal hemolytic disease. This study aims at analyzing the frequency of irregular antibodies of patients seen at the Regional Blood Center of Francisco Beltrão, Paraná, in 2017. The data were collected from the review of records in files of the Immunohematology Laboratory of Hemonúcleo. Data from 49 protocols of patients who had transfusion difficulties in 2017 were evaluated. Among those surveyed, 37 patients (75.5%) had irregular antibodies. Among the anti-erythrocyte antibodies observed in this study, the presence of twelve patients with anti-D (27.2%), six patients with anti-K (13.6%), four patients with anti-C (9.0 %), and in six patients (13.6%) with the presence of autoantibodies were observed. This study indicates that, in transfused patients, the most frequent antibodies were the Rh System Anti-D alloantibodies, probably due to their high degree of immunogenicity. The prevalence of these antibodies is similar to several studies found in the literature.


Assuntos
Humanos , Masculino , Feminino , Adolescente , Adulto , Pessoa de Meia-Idade , Anticorpos/imunologia , Autoanticorpos/imunologia , Sangue/imunologia , Transfusão de Sangue , Eritrócitos/imunologia , Medicina Transfusional , Reação Transfusional/imunologia , Variação Biológica da População/imunologia , Isoanticorpos/imunologia , Formação de Anticorpos , Antígenos/sangue
5.
Neurol Sci ; 41(12): 3391-3394, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33006723

RESUMO

We report the clinical and immunological features in a case of SARS-CoV-2-induced Guillain-Barré syndrome (Si-GBS), suggesting that (1) Si-GBS can develop even after paucisymptomatic COVID-19 infection; (2) a distinctive cytokine repertoire is associated with this autoimmune complication, with increased CSF concentration of IL-8, and moderately increased serum levels of IL-6, IL-8, and TNF-α; (3) a particular genetic predisposition can be relevant, since the patient carried several HLA alleles known to be associated with GBS, including distinctive class I (HLA-A33) and class II alleles (DRB1*03:01 and DQB1*05:01). To the best of our knowledge, this is the first case of GBS in which SARS-CoV-2 antibodies were detected in the CSF, further strengthening the role of the virus as a trigger. In conclusion, our study suggests that SARS-CoV-2 antibodies need to be searched in the serum and CSF in patients with GBS living in endemic areas, even in the absence of a clinically severe COVID-19 infection, and that IL-8 pathway can be relevant in Si-GBS pathogenesis. Further studies are needed to conclude on the relevance of the genetic findings, but it is likely that HLA plays a role in this setting as in other autoimmune neurological syndromes, including those triggered by infections.


Assuntos
Infecções por Coronavirus/complicações , Síndrome de Guillain-Barré/genética , Síndrome de Guillain-Barré/imunologia , Síndrome de Guillain-Barré/virologia , Pneumonia Viral/complicações , Anticorpos Antivirais/imunologia , Autoanticorpos/imunologia , Autoantígenos/imunologia , Betacoronavirus , Citocinas/imunologia , Genótipo , Antígenos HLA/genética , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias
6.
PLoS One ; 15(10): e0240025, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33002091

RESUMO

BACKGROUND: Primary membranous nephritis (PMN) is an autoimmune disease induced by the deposit of antibodies (Ab) to the phospholipase receptor A2 receptor (PLA2R) on podocytes. In this context, we aimed to assess the relationships between anti-PLA2R Ab, PLA2R rs4664308 SNP, PLA2R mRNA levels and PMN susceptibility and outcome. METHODS: Sixty-eight PMN patients, 30 systemic lupus erythematosus (SLE) patients with secondary MN and 30 healthy control subjects served for anti-PLA2R Ab measurement by ELISA and PLA2R rs4664308 SNP genotyping by a commercial real-time PCR. Twenty patients with tubulo-interstitial nephritis (TIN) were used as controls for renal PLA2R mRNA quantification in PMN patients from kidney biopsies. PLA2R mRNA quantification was carried-out by real-time PCR after RNA extraction. RESULTS: Forty-three (63.2%) PMN patients received initial therapy consisting of alternating monthly cycles of corticosteroids and cyclophosphamide. Twelve (17.6%) patients had resistant PMN to initial therapy and were consecutively treated by cyclosporine or tacrolimus. Anti-PLA2R Ab were positive in 54 (79.4%) PMN patients, while all SLE patients and controls were negative, p<0.0001. Moreover, anti-PLA2R Ab levels were significantly higher in PMN patients (134.85 [41.25-256.97] RU/ml) than in SLE patients (3.35 [2.3-4.35] RU/ml) and controls (2 [2-2.3]), p<0.0001. Consequently, a ROC curve showed for 100% specificity a sensitivity of 94.1% at a threshold of 2.6 RU/ml. Besides, Anti-PLA2R antibodies levels were significantly associated to non-remission; p = 0.002. The rs4664308*A wild-type allele was significantly more frequent in PMN patients (0.809) than in controls (0.633) and SLE patients (0.65); p = 0.008, OR [95% CI] = 2.44 [1.24-4.82] and p = 0.016, OR [95% CI] = 2.27 [1.15-4.5], respectively. Renal PLA2R mRNA levels were significantly higher in PMN patients (218.29 [66.05-486.07]) than in TIN patients (22.09 [13.62-43.34]), p<0.0001. Moreover, PLA2R mRNA levels were significantly higher in non-remission patients (fold-factor vs. partial remission = 2.46 and fold-factor vs. complete remission = 12.25); p = 1.56 10E-8. In addition, PLA2R mRNA and anti-PLA2R Ab levels were significantly correlated, Spearman Rho = 0.958, p<0.0001. CONCLUSION: Anti-PLA2R Ab and renal PLA2R mRNA could be useful markers for PMN outcome predicting. The PLA2R rs6446308 SNP is associated with PMN susceptibility in Tunisians.


Assuntos
Autoanticorpos/sangue , Glomerulonefrite Membranosa/genética , Glomerulonefrite Membranosa/imunologia , Polimorfismo de Nucleotídeo Único , Receptores da Fosfolipase A2/genética , Receptores da Fosfolipase A2/imunologia , Autoanticorpos/imunologia , Biópsia , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença/genética , Glomerulonefrite Membranosa/sangue , Glomerulonefrite Membranosa/patologia , Humanos , Rim/patologia , Masculino , Pessoa de Meia-Idade , RNA Mensageiro/genética , Tunísia
7.
BMC Neurol ; 20(1): 355, 2020 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-32967629

RESUMO

BACKGROUND: Paraneoplastic cerebellar degeneration (PCD) is a devastating paraneoplastic syndrome that occasionally occurs in patients with Hodgkin lymphoma (HL). Anti-Ma2 is a well-characterized onconeuronal antibody and one of the causes of PCD. There has been only one previous report of anti-Ma2-associated paraneoplastic syndrome as a complication of HL. Here we present a rare case of anti-Ma2-associated PCD in a patient with nodular lymphocyte-predominant HL (NLPHL). CASE PRESENTATION: A 77-year-old man with a 3-month history of gait instability and a 2-month history of oscillopsia was referred to our hospital for further investigation. On examination, his cognition was normal. He had nystagmus in all directions of gaze; specifically, he had horizontal and rotatory nystagmus in the primary position, downbeat nystagmus after right, left, and up gaze, and upbeat nystagmus after down gaze. Although his limb ataxia was mild, his trunk ataxia was so pronounced that he was unable to walk without support. We strongly suspected paraneoplastic syndrome and tested for neuronal autoantibodies. The anti-Ma2 antibody was strongly positive in the blood and cerebrospinal fluid but other antineuronal autoantibodies were negative. Computed tomography showed an enlarged lymph node in the right axilla but no masses. Biopsy confirmed a diagnosis of NLPHL. The NLPHL cells stained with anti-Ma-2 antibody in the cytoplasm, suggesting these abnormal cells contained protein that was cross-reactive with Ma-2. CONCLUSIONS: To the best of our knowledge, this is the first case of anti-Ma2-associated PCD in a patient with NLPHL that was confirmed using immunostaining of the lymph node tissue with anti-Ma2 antibody. Our case confirms an association between anti-Ma2-associated PCD and NLPHL.


Assuntos
Antígenos de Neoplasias/imunologia , Doença de Hodgkin/complicações , Proteínas do Tecido Nervoso/imunologia , Degeneração Paraneoplásica Cerebelar/etiologia , Degeneração Paraneoplásica Cerebelar/imunologia , Idoso , Autoanticorpos/sangue , Autoanticorpos/imunologia , Autoantígenos/imunologia , Doença de Hodgkin/imunologia , Humanos , Masculino , Degeneração Paraneoplásica Cerebelar/diagnóstico , Tomografia Computadorizada por Raios X
8.
Proc Natl Acad Sci U S A ; 117(40): 24957-24963, 2020 10 06.
Artigo em Inglês | MEDLINE | ID: mdl-32963096

RESUMO

B lymphocytes acquire self-reactivity as an unavoidable byproduct of antibody gene diversification in the bone marrow and in germinal centers (GCs). Autoreactive B cells emerging from the bone marrow are silenced in a series of well-defined checkpoints, but less is known about how self-reactivity that develops by somatic mutation in GCs is controlled. Here, we report the existence of an apoptosis-dependent tolerance checkpoint in post-GC B cells. Whereas defective GC B cell apoptosis has no measurable effect on autoantibody development, disruption of post-GC apoptosis results in accumulation of autoreactive memory B cells and plasma cells, antinuclear antibody production, and autoimmunity. The data presented shed light on mechanisms that regulate immune tolerance and the development of autoantibodies.


Assuntos
Apoptose/genética , Autoimunidade/genética , Genes de Imunoglobulinas/genética , Tolerância Imunológica/genética , Animais , Anticorpos Antinucleares/imunologia , Apoptose/imunologia , Autoanticorpos/imunologia , Autoimunidade/imunologia , Linfócitos B/imunologia , Genes de Imunoglobulinas/imunologia , Centro Germinativo/imunologia , Humanos , Memória Imunológica/genética , Memória Imunológica/imunologia , Camundongos , Plasmócitos/imunologia
9.
Nat Metab ; 2(10): 1021-1024, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32879473

RESUMO

Here we report a case where the manifestations of insulin-dependent diabetes occurred following SARS-CoV-2 infection in a young individual in the absence of autoantibodies typical for type 1 diabetes mellitus. Specifically, a 19-year-old white male presented at our emergency department with diabetic ketoacidosis, C-peptide level of 0.62 µg l-1, blood glucose concentration of 30.6 mmol l-1 (552 mg dl-1) and haemoglobin A1c of 16.8%. The patient´s case history revealed probable COVID-19 infection 5-7 weeks before admission, based on a positive test for antibodies against SARS-CoV-2 proteins as determined by enzyme-linked immunosorbent assay. Interestingly, the patient carried a human leukocyte antigen genotype (HLA DR1-DR3-DQ2) considered to provide only a slightly elevated risk of developing autoimmune type 1 diabetes mellitus. However, as noted, no serum autoantibodies were observed against islet cells, glutamic acid decarboxylase, tyrosine phosphatase, insulin and zinc-transporter 8. Although our report cannot fully establish causality between COVID-19 and the development of diabetes in this patient, considering that SARS-CoV-2 entry receptors, including angiotensin-converting enzyme 2, are expressed on pancreatic ß-cells and, given the circumstances of this case, we suggest that SARS-CoV-2 infection, or COVID-19, might negatively affect pancreatic function, perhaps through direct cytolytic effects of the virus on ß-cells.


Assuntos
Betacoronavirus , Infecções por Coronavirus/complicações , Infecções por Coronavirus/diagnóstico , Diabetes Mellitus Tipo 1/complicações , Pneumonia Viral/complicações , Pneumonia Viral/diagnóstico , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Autoanticorpos/sangue , Autoanticorpos/imunologia , Betacoronavirus/imunologia , Biomarcadores , Infecções por Coronavirus/imunologia , Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 1/imunologia , Antígenos HLA-D/genética , Antígenos HLA-D/imunologia , Humanos , Imunoglobulina M/imunologia , Insulina/metabolismo , Células Secretoras de Insulina/imunologia , Células Secretoras de Insulina/metabolismo , Ilhotas Pancreáticas/imunologia , Masculino , Pandemias , Pneumonia Viral/imunologia , Adulto Jovem
10.
PLoS One ; 15(9): e0237492, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32877432

RESUMO

Oncimmune's EarlyCDT®-Lung is a simple ELISA blood test that measures seven lung cancer specific autoantibodies and is used in the assessment of malignancy risk in patients with indeterminate pulmonary nodules (IPNs). The objective of this study was to examine the cost-effectiveness of EarlyCDT-Lung in the diagnosis of lung cancer amongst patients with IPNs in addition to CT surveillance, compared to CT surveillance alone which is the current recommendation by the British Thoracic Society guidelines. A model consisting of a combination of a decision tree and Markov model was developed using the outcome measure of the quality adjusted life year (QALY). A life-time time horizon was adopted. The model was parameterized using a range of secondary sources. At £70 per test, EarlyCDT-Lung and CT surveillance was found to be cost-effective compared to CT surveillance alone with an incremental cost-effectiveness ratio (ICER) of less than £2,500 depending on the test accuracy parameters used. It was also found that EarlyCDT-Lung can be priced up to £1,177 and still be cost-effective based on cost-effectiveness acceptance threshold of £20,000 / QALY. Further research to resolve parameter uncertainty, was not found to be of value. The results here demonstrate that at £70 per test the EarlyCDT-Lung will have a positive impact on patient outcomes and coupled with CT surveillance is a cost-effective approach to the management of patients with IPNs. The conclusions drawn from this analysis are robust to realistic variation in the parameters used in the model.


Assuntos
Autoanticorpos/imunologia , Análise Custo-Benefício , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/economia , Nódulos Pulmonares Múltiplos/complicações , Tomografia Computadorizada por Raios X , Progressão da Doença , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/imunologia , Cadeias de Markov , Nódulos Pulmonares Múltiplos/diagnóstico por imagem , Probabilidade , Análise de Sobrevida
11.
Medicine (Baltimore) ; 99(38): e22214, 2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-32957357

RESUMO

Anti-thyroid peroxidase antibody (TPO-Ab), which is the known cause of autoimmune thyroid disease, enhances proinflammatory cytokine responses. Since low-grade inflammation is a known risk factor for atherosclerosis, a normal range of TPO-Ab (TPO-Ab negative) could be positively associated with atherosclerosis among participants with normal thyroid function. However, no study reported the association between normal range of TPO-Ab and atherosclerosis among eu-thyroid participants. A cross-sectional study was conducted with 1165 Japanese individuals with normal thyroid function (ie, normal range of free triiodothyronine [free T3] and free thyroxine [free T4]), aged 40 to 74 years, who participated in an annual health checkup in 2014. Among the study population, 115 were diagnosed as having atherosclerosis. A normal range value of TPO-Ab titer is revealed to be positively associated with atherosclerosis; sex, age, thyroid function (free T3 and thyroid-stimulating hormone), and known cardiovascular risk factor adjusted odds ratio and 95% confidence interval of atherosclerosis for logarithmic values of TPO-Ab was 2.23 (1.11, 4.47). When we limited the analysis to participants with normal levels of thyroid-stimulating hormone, this association became slightly stronger (2.65 [1.27,5.51]). Among the eu-thyroid general population, a normal range of TPO-Ab titer is revealed to be positively associated with atherosclerosis. Even though a TPO-Ab titer is not clinically relevant and is not associated with autoimmune thyroid disease, it could influence endothelial remodeling including atherosclerosis.


Assuntos
Aterosclerose/sangue , Autoanticorpos/sangue , Iodeto Peroxidase/imunologia , Idoso , Grupo com Ancestrais do Continente Asiático , Aterosclerose/imunologia , Autoanticorpos/imunologia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valores de Referência , Tireotropina/sangue
12.
PLoS Med ; 17(9): e1003296, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32960885

RESUMO

BACKGROUND: Based on different genetic and environmental risk factors and histology, it has been proposed that rheumatoid arthritis (RA) consists of 2 types: autoantibody-positive and autoantibody-negative RA. However, until now, this remained hypothetical. To assess this hypothesis, we studied whether the long-term outcomes differed for these 2 groups of RA patients. METHODS AND FINDINGS: In the Leiden Early Arthritis Clinic cohort, 1,285 consecutive RA patients were included between 1993 and 2016 and followed yearly. Treatment protocols in routine care improved over time, irrespective of autoantibody status, and 5 inclusion periods were used as instrumental variables: 1993-1996, delayed mild disease-modifying antirheumatic drug (DMARD) initiation (reference period); 1997-2000, early mild DMARDs; 2001-2005, early methotrexate; 2006-2010, early methotrexate followed by treat-to-target adjustments; 2011-2016, similar to 2006-2010 plus additional efforts for very early referral. Three long-term outcomes were studied: sustained DMARD-free remission (SDFR) (persistent absence of clinical synovitis after DMARD cessation), mortality, and functional disability measured by yearly Health Assessment Questionnaire (HAQ). Treatment response in the short term (disease activity) was measured by Disease Activity Score-28 with erythrocyte sedimentation rate (DAS28-ESR). Linear mixed models and Cox regression were used, stratified for autoantibody positivity, defined as IgG anti-CCP2 and/or IgM rheumatoid factor positivity. In total, 823 patients had autoantibody-positive RA (mean age 55 years, 67% female); 462 patients had autoantibody-negative RA (age 60 years, 64% female). Age, gender, and percentage of autoantibody-positive patients were stable throughout the inclusion periods. Disease activity significantly decreased over time within both groups. SDFR rates increased after introduction of treat-to-target (hazard ratio [HR] 2006-2010 relative to 1993-1996: 3.35 [95% CI 1.46 to 7.72; p = 0.004]; HR 2011-2016: 4.57 [95% CI 1.80 to 11.6; p = 0.001]) in autoantibody-positive RA, but not in autoantibody-negative RA. In autoantibody-positive RA, mortality decreased significantly after the introduction of treat-to-target treatment adjustments (HR 2006-2010: 0.56 [95% CI 0.34 to 0.92; p = 0.023]; HR 2011-2016: 0.33 [95% CI 0.14 to 0.77; p = 0.010]), but not in autoantibody-negative RA (HR 2006-2010: 0.79 [95% CI 0.40 to 1.56; p = 0.50]; HR 2011-2016: 0.36 [95% CI 0.10 to 1.34; p = 0.13]). Similarly, functional disability improved in autoantibody-positive RA for the periods after 2000 relative to 1993-1996 (range -0.16 [95% CI -0.29 to -0.03; p = 0.043] to -0.32 [95% CI -0.44 to -0.20; p < 0.001] units of improvement), but not in autoantibody-negative RA (range 0.10 [95% CI -0.12 to 0.31; p = 0.38] to -0.13 [95% CI -0.34 to 0.07; p = 0.20] units of improvement). Limitations to note were that treatment was not randomized-but it was protocolized and instrumental variable analysis was used to obtain comparable groups-and that a limited spread of ethnicities was included. CONCLUSIONS: Although disease activity has improved in both autoantibody-positive and autoantibody-negative RA in recent decades, the response in long-term outcomes differed. We propose that it is time to subdivide RA into autoantibody-positive RA (type 1) and autoantibody-negative RA (type 2), in the hope that this leads to stratified treatment in RA.


Assuntos
Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/epidemiologia , Artrite Reumatoide/genética , Adulto , Idoso , Antirreumáticos/efeitos adversos , Antirreumáticos/uso terapêutico , Autoanticorpos/genética , Autoanticorpos/imunologia , Biomarcadores Farmacológicos/sangue , Estudos de Coortes , Progressão da Doença , Feminino , Humanos , Estudos Longitudinais , Masculino , Metotrexato/efeitos adversos , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Índice de Gravidade de Doença
13.
Medicine (Baltimore) ; 99(36): e21738, 2020 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-32899003

RESUMO

INTRODUCTION: Anti-interferon-gamma (anti-IFN-γ) autoantibody increases susceptibility to lower-virulence pathogens and causes immunodeficiency syndrome in HIV-negative patients. PATIENT CONCERNS: A 69-year-old Chinese man presented with a 2-month history of pruritic skin lesions on his forearms, trunk, and legs. He was diagnosed with 5 opportunistic infections without conventional immunosuppression-associated factors in past. The most conspicuous characteristics were recurrent pulmonary infection, persistent immunoglobulin E elevation and eosinophilia during the whole disease course. DIAGNOSIS: Enzyme-linked immunosorbent assay showed anti-IFN-γ autoantibody positive. The final diagnosis for the patient was adult-onset immunodeficiency due to anti-IFN-γ autoantibody, non-tuberculous mycobacterial (NTM) infection and reactive dermatosis. INTERVENTIONS: The patient underwent long-term anti-NTM and corticosteroid maintenance treatment. OUTCOMES: The patient was followed for 2 years during which opportunistic infection no longer happened, the immunoglobulin E level and eosinophil count reduced, the autoantibody levels remained largely steady and lung lesions absorbed. CONCLUSION: Clinicians should be vigilant for NTM infection in patients with anti-IFN-γ autoantibodies, even when culture results are negative. Long-term anti-non-tuberculous mycobacteria and glucocorticoid regimens were effective.


Assuntos
Autoanticorpos/imunologia , Síndromes de Imunodeficiência/complicações , Interferon gama/imunologia , Infecções por Mycobacterium não Tuberculosas/complicações , Idoso , Humanos , Síndromes de Imunodeficiência/diagnóstico , Síndromes de Imunodeficiência/imunologia , Masculino , Infecções por Mycobacterium não Tuberculosas/diagnóstico , Infecções por Mycobacterium não Tuberculosas/imunologia , Infecções Oportunistas/complicações , Dermatopatias/complicações , Dermatopatias/imunologia
14.
Eur J Gastroenterol Hepatol ; 32(12): 1523-1526, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32956181

RESUMO

OBJECTIVES: Recent guidelines for celiac disease have allowed a biopsy-free approach in endomysial antibodies (EMAs) positive children with high antitransglutaminase (TGA-IgA) titer [>10 time upper limit of normal (ULN)]. Esophagogastroduodenoscopy is still necessary for diagnosis in children with lower title. Because elective pediatric endoscopy has been substantially shouted down during coronavirus disease (COVID-19) pandemic, many children remained undiagnosed - and therefore untreated - for a long time. We aimed to analyze the feasibility and accuracy of a biopsy-free approach in suspected celiac disease children with TGA-IgA values <10 ULN to facilitate the diagnostic process by avoiding endoscopy. METHODS: In this study cohort, we retrospectively analyzed all biopsy-confirmed diagnosis of celiac disease in our center (between 2014 and 2019). The positive predictive value (PPV) of TGA-IgA titers between 5 and 10 ULN and positive EMA in diagnosing celiac disease were determined. Mucosal atrophy and resolution of symptoms after gluten-free diet (GFD) were considered to confirm initial diagnosis. RESULTS: Of 430 celiac disease patients (F: 274; mean age 7.54 years) diagnosed by endoscopy, 84 (F: 46; mean age 8 years) with TGA-IgA between 5 and 10 ULN and positive EMA were identified. The PPV of TGA-IgA between 5 and 10 ULN and positive EMA was 0.93 (95% confidence interval 0.90-0.96). All these children had a symptom resolution and antibodies normalization after GFD. CONCLUSION: During the COVID-19 outbreak, a temporarily reduction of the TGA-IgA threshold for biopsy-sparing approach seems feasible in EMA positive children with TGA-IgA between 5 and 10 ULN.


Assuntos
Autoanticorpos/sangue , Betacoronavirus , Doença Celíaca/diagnóstico , Infecções por Coronavirus/epidemiologia , Pneumonia Viral/epidemiologia , Guias de Prática Clínica como Assunto , Transglutaminases/imunologia , Autoanticorpos/imunologia , Biópsia , Doença Celíaca/epidemiologia , Doença Celíaca/imunologia , Criança , Comorbidade , Infecções por Coronavirus/enzimologia , Infecções por Coronavirus/imunologia , Endoscopia do Sistema Digestório , Feminino , Humanos , Masculino , Pandemias , Pneumonia Viral/enzimologia , Pneumonia Viral/imunologia , Estudos Retrospectivos , Transglutaminases/sangue
15.
Nat Med ; 26(8): 1247-1255, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32770166

RESUMO

Type 1 diabetes (T1D)-an autoimmune disease that destroys the pancreatic islets, resulting in insulin deficiency-often begins early in life when islet autoantibody appearance signals high risk1. However, clinical diabetes can follow in weeks or only after decades, and is very difficult to predict. Ketoacidosis at onset remains common2,3 and is most severe in the very young4,5, in whom it can be life threatening and difficult to treat6-9. Autoantibody surveillance programs effectively prevent most ketoacidosis10-12 but require frequent evaluations whose expense limits public health adoption13. Prevention therapies applied before onset, when greater islet mass remains, have rarely been feasible14 because individuals at greatest risk of impending T1D are difficult to identify. To remedy this, we sought accurate, cost-effective estimation of future T1D risk by developing a combined risk score incorporating both fixed and variable factors (genetic, clinical and immunological) in 7,798 high-risk children followed closely from birth for 9.3 years. Compared with autoantibodies alone, the combined model dramatically improves T1D prediction at ≥2 years of age over horizons up to 8 years of age (area under the receiver operating characteristic curve ≥ 0.9), doubles the estimated efficiency of population-based newborn screening to prevent ketoacidosis, and enables individualized risk estimates for better prevention trial selection.


Assuntos
Autoanticorpos/sangue , Diabetes Mellitus Tipo 1/epidemiologia , Cetose/sangue , Medição de Risco , Autoanticorpos/imunologia , Autoimunidade/genética , Criança , Pré-Escolar , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/imunologia , Feminino , Predisposição Genética para Doença , Humanos , Lactente , Recém-Nascido , Insulina/deficiência , Insulina/imunologia , Ilhotas Pancreáticas/imunologia , Ilhotas Pancreáticas/patologia , Cetose/imunologia , Masculino , Triagem Neonatal , Fatores de Risco
16.
PLoS One ; 15(8): e0237109, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32804939

RESUMO

INTRODUCTION: There is no evidence on the role of Human Anti Nucleolus Antibody (ANCAb) in type 2 diabetes mellitus (T2DM). We compared prevalence and concentration of ANCAb between age and a gender-matched sample of T2DM with and without diabetes-related complications. METHODS: In this study, the reaction to ANCAb was compared quantitatively between 38 T2DM patients complicated with microvascular conditions and 43 T2DM without complications as controls. RESULTS: The patients in complicated and non-complicated groups were comparable in diabetes duration (9.0 vs. 5.0 years; P = 0.065), respectively. The study found that 27 cases (71.1%) of the complicated group reacted to ANCAb test compared to 25 (58.1%) in non-complicated patients (P = 0.226; 3.53 vs. 2.72 ng/mL; P = 0.413). The reaction response to ANCAb in patients with neuropathy and cardiovascular complications was 80.0%, 76.2% in patients with neuropathy compared to 58.1% in the control group (P = 0.398). The reaction response to ANCAb in patients with mono-complication was 72.7% compared 68.8% in patients with multi-complication (P = 0.466). Similarly, 76.2% of patients with T2DM and complicated with neuropathy (n = 21 patients) reacted to ANCAb compared to 58.1% in control patients with (P = 0.158). CONCLUSIONS: Reaction to ANCAb was not statistically different between the T2DM patients with and without complications.


Assuntos
Autoanticorpos/sangue , Nucléolo Celular/imunologia , Diabetes Mellitus Tipo 2/sangue , Angiopatias Diabéticas/sangue , Neuropatias Diabéticas/sangue , Adulto , Autoanticorpos/imunologia , Biomarcadores/sangue , Diabetes Mellitus Tipo 2/complicações , Feminino , Humanos , Pessoa de Meia-Idade
17.
PLoS One ; 15(8): e0237072, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32745151

RESUMO

BACKGROUND: Rheumatoid arthritis (RA) is associated with an increased cardiovascular disease (CVD) risk which may start even before diagnosis. To explore this CVD risk prior to RA, we determined multiple risk factors and two 10-year clinical risk scores in a cohort of individuals at-risk of RA. We also analyzed associations with arthritis development and autoantibody status and compared a subset of at-risk individuals to an age and sex matched seronegative control group. METHODS: In a cohort of 555 consecutive arthralgia patients positive for rheumatoid factor (RF) and / or anti-citrullinated protein antibody (ACPA) we retrospectively identified patients with preclinical arthritis (i.e. those who developed arthritis), and non-arthritis patients (those without arthritis development during maximum 5 years follow up). Demographics, CVD risk factors and the 10-year cardiovascular risk according to the SCORE and QRISK3 system were determined at baseline. RESULTS: Preclinical arthritis patients (n = 188) had a higher heart rate (68 vs 63 bpm, p = 0.048) and lower cholesterol (5.2 mmol/l vs 5.5, p = 0.006), HDL (1.0 mmol/l vs 1.1, p0.003) and ApoB (0.85 g/l vs 0.91, p = 0.011) compared to non-arthritis patients (n = 367). Lipid levels were associated with ACPA status in both the preclinical arthritis and non-arthritis group. Ten-year CVD risk scores did not differ between preclinical arthritis and non-arthritis patients, in total, 7% (SCORE) and 8% (QRISK3) of seropositive arthralgia patients were classified as high risk. Seropositive at-risk patients (n = 71) had higher total cholesterol (5.4 vs 4.9, p<0.001), TC/HDL ratio (4.0 vs 3.0, p<0.001), triglycerides (1.4 vs 1.0, p = 0.001), ApoB (1.0 vs 0.9, p = 0.019) and 10-year risk scores (median SCORE 1.0 vs 0.0, p = 0.030 and median QRISK3 4.4 vs 3.1, p<0.001) compared to seronegative controls. CONCLUSION: Our results suggest that lipid changes commence prior to RA diagnosis and that ACPAs might play a role.


Assuntos
Artrite Reumatoide/complicações , Artrite Reumatoide/fisiopatologia , Doenças Cardiovasculares/etiologia , Adulto , Anticorpos Anti-Proteína Citrulinada , Artralgia , Artrite Reumatoide/imunologia , Autoanticorpos/imunologia , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/fisiopatologia , Estudos de Coortes , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fator Reumatoide/imunologia , Fatores de Risco
19.
Proc Natl Acad Sci U S A ; 117(35): 21512-21518, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32817492

RESUMO

Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system (CNS), with characteristic inflammatory lesions and demyelination. The clinical benefit of cell-depleting therapies targeting CD20 has emphasized the role of B cells and autoantibodies in MS pathogenesis. We previously introduced an enzyme-linked immunospot spot (ELISpot)-based assay to measure CNS antigen-specific B cells in the blood of MS patients and demonstrated its usefulness as a predictive biomarker for disease activity in measuring the successful outcome of disease-modifying therapies (DMTs). Here we used a planar protein array to investigate CNS-reactive antibodies in the serum of MS patients as well as in B cell culture supernatants after polyclonal stimulation. Anti-CNS antibody reactivity was evident in the sera of the MS cohort, and the antibodies bound a heterogeneous set of molecules, including myelin, axonal cytoskeleton, and ion channel antigens, in individual patients. Immunoglobulin reactivity in supernatants of stimulated B cells was directed against a broad range of CNS antigens. A group of MS patients with a highly active B cell component was identified by the ELISpot assay. Those antibody reactivities remained stable over time. These assays with protein arrays identify MS patients with a highly active B cell population with antibodies directed against a swathe of CNS proteins.


Assuntos
Autoanticorpos/imunologia , Linfócitos B/imunologia , Esclerose Múltipla/imunologia , Adulto , Antígenos , Doenças Autoimunes/patologia , Sistema Nervoso Central/imunologia , Sistema Nervoso Central/metabolismo , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Bainha de Mielina/metabolismo
20.
Neurol Clin ; 38(3): 661-678, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32703475

RESUMO

Inflammatory myopathies are a group of immune-mediated muscle disorders comprising dermatomyositis; polymyositis; overlap myositis, including antisynthetase syndromes and nonspecific myositis, immune-mediated necrotizing myopathies, and sporadic inclusion body myositis. They are now much more eloquently classified both pathologically and clinically because of the discovery of several myositis-specific and myositis-associated antibodies. These antibodies also aid in choosing the best treatment options in each case. Based on the initial classifications of inflammatory myopathies, inclusion body myositis, overlap myositis, and necrotizing myositis were all included in the polymyositis group. This article discusses cases, diagnostic tools, associated antibodies, and pathology.


Assuntos
Autoanticorpos/sangue , Miosite/sangue , Miosite/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Autoanticorpos/imunologia , Feminino , Humanos , Masculino , Metilprednisolona/uso terapêutico , Pessoa de Meia-Idade , Miosite/imunologia , Miosite de Corpos de Inclusão/sangue , Miosite de Corpos de Inclusão/diagnóstico , Miosite de Corpos de Inclusão/imunologia
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