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1.
Arterioscler Thromb Vasc Biol ; 39(8): 1520-1541, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31189432

RESUMO

Vasculitis is a systemic disease characterized by immune-mediated injury of blood vessels. Current treatments for vasculitis, such as glucocorticoids and alkylating agents, are associated with significant side effects. Furthermore, the management of both small and large vessel vasculitis is challenging because of a lack of robust markers of disease activity. Recent research has advanced our understanding of the pathogenesis of both small and large vessel vasculitis, and this has led to the development of novel biologic therapies capable of targeting key cytokine and cellular effectors of the inflammatory cascade. In parallel, a diverse range of imaging modalities with the potential to monitor vessel inflammation are emerging. Continued expansion of combined structural and molecular imaging using positron emission tomography with computed tomography or magnetic resonance imaging may soon provide reliable longitudinal tracking of vascular inflammation. In addition, the emergence of radiotracers able to assess macrophage activation and immune checkpoint activity represents an exciting new frontier in imaging vascular inflammation. In the near future, these advances will allow more precise imaging of disease activity enabling clinicians to offer more targeted and individualized patient management.


Assuntos
Vasculite Sistêmica/diagnóstico por imagem , Vasculite Sistêmica/tratamento farmacológico , Eosinófilos/imunologia , Humanos , Depleção Linfocítica , Imagem por Ressonância Magnética , Imagem Molecular , Poliarterite Nodosa/diagnóstico por imagem , Poliarterite Nodosa/imunologia , Tomografia por Emissão de Pósitrons , Vasculite Sistêmica/imunologia , Tomografia Computadorizada por Raios X
2.
Int J Rheum Dis ; 22 Suppl 1: 21-27, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29707909

RESUMO

The classification of the systemic vasculitides has been controversial for several decades. The Chapel Hill consensus Conference definitions originally developed in 1994, but revised and extended in 2012 are now widely accepted. The American College of Rheumatology (ACR) criteria were first published in 1990, are now generally accepted to be out of date and new criteria are needed. More recently the classical division of the ANCA vasculitides using clinical phenotype has come under scrutiny with evidence from epidemiological, genetic and outcome studies that perhaps these conditions should be classified on the basis of ANCA specificity into PR3-ANCA positive and MPO-ANCA positive groups. The traditional distinction between giant cell arteritis and Takayasu arteritis has been questioned and some recent studies of GCA have included patients with only extra-cranial disease. The Diagnostic and Classification Criteria of Vasculitis study (DCVAS) will provide new validated classification criteria for the systemic vasculitides.


Assuntos
Pesquisa Biomédica/tendências , Reumatologia/tendências , Vasculite Sistêmica/classificação , Vasculite Sistêmica/diagnóstico , Terminologia como Assunto , Consenso , Conferências de Consenso como Assunto , Previsões , Humanos , Fenótipo , Vasculite Sistêmica/genética , Vasculite Sistêmica/imunologia
3.
Clin Exp Rheumatol ; 36 Suppl 111(2): 12-32, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29799395
5.
Ann Rheum Dis ; 77(4): 589-595, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29374629

RESUMO

OBJETIVE: Systemic vasculitides represent a heterogeneous group of rare complex diseases of the blood vessels with a poorly understood aetiology. To investigate the shared genetic component underlying their predisposition, we performed the first cross-phenotype meta-analysis of genetic data from different clinically distinct patterns of vasculitis. METHODS: Immunochip genotyping data from 2465 patients diagnosed with giant cell arteritis, Takayasu's arteritis, antineutrophil cytoplasmic antibody-associated vasculitis or IgA vasculitis as well as 4632 unaffected controls were analysed to identify common susceptibility loci for vasculitis development. The possible functional consequences of the associated variants were interrogated using publicly available annotation data. RESULTS: The strongest association signal corresponded with an intergenic polymorphism located between HLA-DQB1 and HLA-DQA2 (rs6932517, P=4.16E-14, OR=0.74). This single nucleotide polymorphism is in moderate linkage disequilibrium with the disease-specific human leucocyte antigen (HLA) class II associations of each type of vasculitis and could mark them. Outside the HLA region, we identified the KDM4C gene as a common risk locus for vasculitides (highest peak rs16925200, P=6.23E-07, OR=1.75). This gene encodes a histone demethylase involved in the epigenetic control of gene expression. CONCLUSIONS: Through a combined analysis of Immunochip data, we have identified KDM4C as a new risk gene shared between systemic vasculitides, consistent with the increasing evidences of the crucial role that the epigenetic mechanisms have in the development of complex immune-mediated conditions.


Assuntos
Loci Gênicos/genética , Histona Desmetilases com o Domínio Jumonji/genética , Fenótipo , Vasculite Sistêmica/genética , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/genética , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/imunologia , Estudos de Casos e Controles , Epigênese Genética , Feminino , Loci Gênicos/imunologia , Predisposição Genética para Doença , Arterite de Células Gigantes/genética , Arterite de Células Gigantes/imunologia , Antígenos HLA-DQ/genética , Antígenos HLA-DQ/imunologia , Cadeias beta de HLA-DQ/genética , Cadeias beta de HLA-DQ/imunologia , Humanos , Histona Desmetilases com o Domínio Jumonji/imunologia , Desequilíbrio de Ligação , Masculino , Polimorfismo de Nucleotídeo Único , Análise Serial de Proteínas , Vasculite Sistêmica/imunologia , Arterite de Takayasu/genética , Arterite de Takayasu/imunologia
6.
Joint Bone Spine ; 85(2): 177-183, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-28602810

RESUMO

Apheresis has been used in the treatment of severe systemic vasculitides, in conjunction with immunosuppressive therapies, for over 40 years. The aim is to rapidly remove autoantibodies or circulating immune complexes from the plasma. The two main indications at present are vasculitis associated with Antineutrophil Cytoplasmic Antibodies (ANCAs) manifesting as severe renal involvement and/or intraalveolar hemorrhage and antiglomerular basement membrane disease (Goodpasture syndrome). The ongoing PEXIVAS randomized controlled trial is assessing plasmapheresis to treat ANCA-associated vasculitis with or without severe renal involvement or intraalveolar hemorrhage. The two main apheresis techniques used to treat systemic vasculitis are plasmapheresis (by filtration, centrifugation, or double filtration) and immunoadsorption. The advantages and drawbacks of each technique are discussed here. Whether one technique is superior over the other in the current indications has not been proven.


Assuntos
Doença Antimembrana Basal Glomerular/imunologia , Doença Antimembrana Basal Glomerular/terapia , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/imunologia , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/terapia , Remoção de Componentes Sanguíneos/métodos , Doença Antimembrana Basal Glomerular/fisiopatologia , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/fisiopatologia , Autoanticorpos/sangue , Feminino , Humanos , Masculino , Plasmaferese/métodos , Prognóstico , Ensaios Clínicos Controlados Aleatórios como Assunto , Medição de Risco , Índice de Gravidade de Doença , Vasculite Sistêmica/imunologia , Vasculite Sistêmica/fisiopatologia , Vasculite Sistêmica/terapia , Resultado do Tratamento
7.
J Physiol Biochem ; 74(1): 9-16, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29098611

RESUMO

Obesity is a risk factor for vascular endothelial cell dysfunction characterized by low-grade, chronic inflammation. Increased levels of arginase I and concomitant decreases in L-arginine bioavailability are known to play a role in the pathogenesis of vascular endothelial cell dysfunction. In the present study, we focused on changes in the systemic expression of arginase I as well as L-arginine metabolism in the pre-disease state of early obesity prior to the onset of atherosclerosis. C57BL/6 mice were fed a control diet (CD; 10% fat) or high-fat diet (HFD; 60% fat) for 8 weeks. The mRNA expression of arginase I in the liver, adipose tissue, aorta, and muscle; protein expression of arginase I in the liver and plasma; and systemic levels of L-arginine bioavailability and NO2- were assessed. HFD-fed mice showed early obesity without severe disease symptoms. Arginase I mRNA and protein expression levels in the liver were significantly higher in HFD-fed obese mice than in CD-fed mice. Arginase I levels were slightly increased, whereas L-arginine levels were significantly reduced, and these changes were followed by reductions in NO2- levels. Furthermore, hepatic arginase I levels positively correlated with plasma arginase I levels and negatively correlated with L-arginine bioavailability in plasma. These results suggested that increases in the expression of hepatic arginase I and reductions in plasma L-arginine and NO2- levels might lead to vascular endothelial dysfunction in the pre-disease state of early obesity.


Assuntos
Arginase/metabolismo , Arginina/sangue , Endotélio Vascular/metabolismo , Fígado/metabolismo , Óxido Nítrico/sangue , Obesidade/metabolismo , Vasculite Sistêmica/metabolismo , Animais , Aorta/enzimologia , Aorta/metabolismo , Arginase/sangue , Arginase/genética , Aterosclerose/etiologia , Biomarcadores/sangue , Biomarcadores/metabolismo , Dieta Hiperlipídica/efeitos adversos , Endotélio Vascular/imunologia , Endotélio Vascular/patologia , Indução Enzimática , Fígado/imunologia , Fígado/patologia , Masculino , Camundongos Endogâmicos C57BL , Músculo Esquelético/enzimologia , Músculo Esquelético/metabolismo , Obesidade/etiologia , Obesidade/imunologia , Obesidade/patologia , Especificidade de Órgãos , Índice de Gravidade de Doença , Vasculite Sistêmica/etiologia , Vasculite Sistêmica/imunologia , Vasculite Sistêmica/fisiopatologia , Ganho de Peso
8.
Front Immunol ; 9: 2974, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30619331

RESUMO

The exact classification of Kawasaki disease (KD) has been debated. Infectious disease specialists have claimed it as an infection with a classic immune responses to an as yet unidentified pathogen that localizes to the coronary arteries. Others have favored an autoreactive hypothesis that KD is triggered by an antigen that shares homology with structures in the vascular wall, and molecular mimicry resulting in an immune response directed to that tissue. Rheumatologists have classified it as a systemic vasculitis, while some immunologists have stressed the robust nature of the innate immune response that causes both systemic inflammation as well as damage to the coronary arterial wall and questioned whether KD falls within the spectrum of autoinflammatory diseases. This review will describe the evidences available up to now regarding these hypotheses.


Assuntos
Doenças Autoimunes/diagnóstico , Doenças Hereditárias Autoinflamatórias/diagnóstico , Síndrome de Linfonodos Mucocutâneos/diagnóstico , Vasculite Sistêmica/diagnóstico , Doenças Autoimunes/imunologia , Vasos Coronários/imunologia , Vasos Coronários/patologia , Diagnóstico Diferencial , Doenças Hereditárias Autoinflamatórias/imunologia , Humanos , Inflamação/imunologia , Síndrome de Linfonodos Mucocutâneos/classificação , Síndrome de Linfonodos Mucocutâneos/imunologia , Vasculite Sistêmica/imunologia
10.
Clin Exp Rheumatol ; 35 Suppl 103(1): 67-76, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28466806

RESUMO

OBJECTIVES: To investigate the clinical and laboratory patterns of HCV-unrelated cryoglobulinaemic vasculitis (CV), and the factors influencing its outcome. METHODS: Prospective study of all anti-HCV and HCV-RNA negative patients with CV who have been observed since January 2004 in 17 centres participating in the Italian Group for the Study of Cryoglobulinaemias (GISC). RESULTS: 175 enrolled were followed up for 677 person-years. The associated conditions were primary Sjögren's syndrome (21.1%), SLE (10.9%), other autoimmune disorders (10.9%), lymphoproliferative diseases (6.8%), solid tumours (2.3%) and HBsAg positivity (8.6%), whereas 69 patients (39.4%) had essential CV. There were significant differences in age (p<0.001), gender (p=0.002), the presence of purpura (p=0.005), arthralgia (p=0.009), liver abnormalities (p<0.001), sicca syndrome (p<0.001), lymphadenopathy (p=0.003), splenomegaly (p=0.002), and rheumatoid factor titres (p<0.001) among these groups. Type II mixed cryoglobulins were present in 96 cases (54.9%) and were independently associated with purpura and fatigue (odds ratio [OR]4.3; 95% confidence interval [CI] 1.8-10.2; p=0.001; and OR2.8; 95%CI 1.3-6.3; p=0.012). Thirty-one patients died during follow-up, a mortality rate of 46/1000 person-years. Older age (for each additional year, adjusted hazard ratio [aHR] 1.13; 95%CI 1.06-1.20; p<0.001), male gender (aHR 3.45; 95%CI 1.27-9.40; p=0.015), type II MCG (aHR 3.31; 95%CI 0.09-1.38; p=0.047) and HBsAg positivity (aHR 7.84; 95%CI 1.20-36.04; p=0.008) were independently associated with greater mortality. CONCLUSIONS: HCV-unrelated CV is a multifaceted and often disabling disorder. The associated conditions influence its clinical severity, giving rise to significantly different clinical and laboratory profiles and outcomes.


Assuntos
Crioglobulinemia/epidemiologia , Vasculite Sistêmica/epidemiologia , Biomarcadores/sangue , Proteínas do Sistema Complemento/metabolismo , Crioglobulinemia/sangue , Crioglobulinemia/imunologia , Crioglobulinemia/mortalidade , Crioglobulinas/metabolismo , Progressão da Doença , Feminino , Humanos , Incidência , Mediadores da Inflamação/sangue , Itália/epidemiologia , Estimativa de Kaplan-Meier , Modelos Logísticos , Masculino , Análise Multivariada , Razão de Chances , Prevalência , Prognóstico , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores de Risco , Índice de Gravidade de Doença , Vasculite Sistêmica/sangue , Vasculite Sistêmica/imunologia , Vasculite Sistêmica/mortalidade , Fatores de Tempo
11.
Clin Exp Rheumatol ; 35 Suppl 103(1): 5-26, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28375840

RESUMO

Systemic vasculitis is a group of heterogeneous, disabling disorders. Great interest has recently arisen in pathophysiology, clinical phenotypes and therapy of large- and small-vessel vasculitis. The general work hypothesis has been to promote research focused on disease-related pathogenetic pathways, with the ultimate goal of identifying novel diagnostic and prognostic biomarkers, thus leading towards more effective targeted treatments. Following the previous annual reviews of this series, we will hereby provide a critical digest of the recent literature on small- and large-vessel systemic vasculitis, with a specific focus on novel possible disease-related biomarkers and their impact on current and future therapies.


Assuntos
Vasculite Sistêmica , Animais , Anti-Inflamatórios/uso terapêutico , Anticorpos Anticitoplasma de Neutrófilos/sangue , Biomarcadores/sangue , Crioglobulinemia/sangue , Crioglobulinemia/diagnóstico , Crioglobulinemia/tratamento farmacológico , Crioglobulinemia/imunologia , Granulomatose com Poliangiite/sangue , Granulomatose com Poliangiite/diagnóstico , Granulomatose com Poliangiite/tratamento farmacológico , Granulomatose com Poliangiite/imunologia , Humanos , Imunossupressores/uso terapêutico , Mediadores da Inflamação/sangue , Valor Preditivo dos Testes , Prognóstico , Vasculite Sistêmica/sangue , Vasculite Sistêmica/diagnóstico , Vasculite Sistêmica/tratamento farmacológico , Vasculite Sistêmica/imunologia
12.
Clin Exp Rheumatol ; 35 Suppl 103(1): 185-188, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-27974095

RESUMO

Human immunodeficiency virus (HIV)-associated vasculitis is a rare secondary systemic vasculitis involving small and medium arteries. We report a 42-year-old man with uncontrolled HIV infection presenting with long-lasting abdominal pain. An abdominal CT angiography revealed multiple microaneurysms and stenoses in intrarenal arteries, with involvement of mesenteric and hepatic arteries. HIV-associated vasculitis was diagnosed and glucocorticoids and raltegravir-based antiretroviral therapy were administered with good initial clinical and virological response. Several episodes of acute intestinal ischaemia were later developed requiring bowel resections of which histological examination showed vascular occlusive fibrotic changes without active vasculitic lesions. Vasculitis persisted in remission and intrarenal microaneurysms disappeared.


Assuntos
Aneurisma/etiologia , Infecções por HIV/complicações , Artéria Hepática , Artérias Mesentéricas , Isquemia Mesentérica/etiologia , Oclusão Vascular Mesentérica/etiologia , Artéria Renal , Vasculite Sistêmica/etiologia , Dor Abdominal/etiologia , Adulto , Aneurisma/diagnóstico por imagem , Aneurisma/imunologia , Aneurisma/terapia , Biópsia , Angiografia por Tomografia Computadorizada , Glucocorticoides/uso terapêutico , Infecções por HIV/diagnóstico , Infecções por HIV/tratamento farmacológico , Infecções por HIV/imunologia , Inibidores de Integrase de HIV/uso terapêutico , Artéria Hepática/diagnóstico por imagem , Humanos , Hospedeiro Imunocomprometido , Masculino , Artérias Mesentéricas/diagnóstico por imagem , Isquemia Mesentérica/diagnóstico por imagem , Isquemia Mesentérica/imunologia , Isquemia Mesentérica/terapia , Oclusão Vascular Mesentérica/diagnóstico por imagem , Oclusão Vascular Mesentérica/imunologia , Oclusão Vascular Mesentérica/terapia , Raltegravir Potássico/uso terapêutico , Indução de Remissão , Artéria Renal/diagnóstico por imagem , Vasculite Sistêmica/diagnóstico por imagem , Vasculite Sistêmica/imunologia , Vasculite Sistêmica/terapia , Fatores de Tempo , Resultado do Tratamento
13.
J Nutr Biochem ; 36: 1-20, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27692243

RESUMO

The mantra that dietary (saturated) fat must be minimized to reduce cardiovascular disease (CVD) risk has dominated nutritional guidelines for decades. Parallel to decreasing intakes of fat and saturated fatty acids (SFA), there have been increases in carbohydrate and sugar intakes, overweight, obesity and type 2 diabetes mellitus. The "lipid hypothesis" coined the concept that fat, especially SFA, raises blood low-density lipoprotein-cholesterol and thereby CVD risk. In view of current controversies regarding their adequate intakes and effects, this review aims to summarize research regarding this heterogenic group of fatty acids and the mechanisms relating them to (chronic) systemic low-grade inflammation, insulin resistance, metabolic syndrome and notably CVD. The intimate relationship between inflammation and metabolism, including glucose, fat and cholesterol metabolism, revealed that the dyslipidemia in Western societies, notably increased triglycerides, "small dense" low-density lipoprotein and "dysfunctional" high-density lipoprotein, is influenced by many unfavorable lifestyle factors. Dietary SFA is only one of these, not necessarily the most important, in healthy, insulin-sensitive people. The environment provides us not only with many other proinflammatory stimuli than SFA but also with many antiinflammatory counterparts. Resolution of the conflict between our self-designed environment and ancient genome may rather rely on returning to the proinflammatory/antiinflammatory balance of the Paleolithic era in consonance with the 21st century culture. Accordingly, dietary guidelines might reconsider recommendations for SFA replacement and investigate diet in a broader context, together with nondietary lifestyle factors. This should be a clear priority, opposed to the reductionist approach of studying the effects of single nutrients, such as SFA.


Assuntos
Doenças Cardiovasculares/etiologia , Gorduras na Dieta/efeitos adversos , Medicina Baseada em Evidências , Ácidos Graxos/efeitos adversos , Vasculite Sistêmica/etiologia , Animais , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/imunologia , Doenças Cardiovasculares/prevenção & controle , Dieta com Restrição de Gorduras/efeitos adversos , Estilo de Vida Saudável , Humanos , Imunidade Inata , Risco , Vasculite Sistêmica/epidemiologia , Vasculite Sistêmica/imunologia , Vasculite Sistêmica/prevenção & controle
14.
BMC Immunol ; 17(1): 40, 2016 10 21.
Artigo em Inglês | MEDLINE | ID: mdl-27769184

RESUMO

BACKGROUND: Circulating follicular helper T (Tfh) cells are a heterogeneous population of CD4+ helper T cells that promotes pathogenic immune responses in autoimmune diseases. In this study, we examined the status of different subpopulations of Tfh cells in peripheral circulation and their associations with various clinical characteristics of IgA vasculitis (IgAV). METHODS: According to the phenotypic expressions of different molecules, focus was given on six subpopulations of Tfh cells: CD4+CXCR5+, CD4+CXCR5+ICOS+, CD4+CXCR5+ICOS+PD-1+, CD4+CXCR5+ICOShighPD-1high, CD4+CXCR5+ICOS-PD-1+, and CXCR5+CD45RA-IL-21+. The frequencies of these six subpopulations and the circulating level of Tfh-related cytokine interleukin 21 (IL-21) were measured from 27 patients with IgAV and 15 healthy controls (HC) by flow cytometry and flow cytometric bead array, respectively. RESULTS: Significantly higher frequencies of CD4+CXCR5+, CD4+CXCR5+ICOS+, CD4+CXCR5+ICOS+PD-1+, CD4+CXCR5+ICOShighPD-1high and CXCR5+CD45RA-IL-21+ Tfh cells, as well as higher levels of plasma IL-21, were detected in IgAV patients compared to HC. The level of each Tfh subpopulation varied by the presenting symptoms of IgAV, but did not differ between patients treated or not treated with glucocorticoids. When the disease entered the remission stage following treatment, circulating levels of CD4+CXCR5+, CD4+CXCR5+ICOS+, CD4+CXCR5+ICOS+PD-1+, CD4+CXCR5+ICOShighPD-1high and CXCR5+CD45RA-IL-21+ Tfh cells, as well as plasma IL-21 levels were reduced. Among the six subpopulations of Tfh cells, both CD4+CXCR5+ICOS+ and CXCR5+CD45RA-IL-21+ significantly and positively correlated with serum IgA and plasma IL-21 levels, but only CXCR5+CD45RA-IL-21+ significantly and negatively correlated with the serum C4 level. CONCLUSIONS: Tfh cells may differentially contribute to the development of IgAV or predict disease progression. These findings provide novel insights in the pathogenesis of IgAV and may benefit treatment development targeting organ-specific presenting symptoms of IgAV.


Assuntos
Centro Germinativo/imunologia , Imunoglobulina A/metabolismo , Vasculite Sistêmica/imunologia , Subpopulações de Linfócitos T/fisiologia , Linfócitos T Auxiliares-Indutores/fisiologia , Adolescente , Antígenos CD4/metabolismo , Criança , Pré-Escolar , Progressão da Doença , Feminino , Humanos , Imunofenotipagem , Interleucinas/metabolismo , Masculino , Terapia de Alvo Molecular , Fenótipo , Receptores CXCR5/metabolismo
15.
Arthritis Care Res (Hoboken) ; 68(6): 853-60, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-26474373

RESUMO

OBJECTIVE: Patients with systemic vasculitis (SV) have an increased risk of all-cause mortality, often due to infection, compared to the healthy population. We investigated whether humoral response to vaccination and biomarkers of immune dysfunction were associated with infection and death. METHODS: Patients with SV in remission were vaccinated with pneumococcal 7-valent conjugate, Haemophilus influenzae type b, and meningococcal group C conjugate vaccine and meningococcal polysaccharide groups A, C, Y, and W135 vaccines. Total IgG and antibody titers against specific antigens and lymphocyte subset analysis were performed before vaccination. Postvaccination antibody titers were measured at 4 weeks and 2 years, from which an antibody response score was calculated. Infections and death following vaccination were collected prospectively following vaccination. RESULTS: A total of 92 patients were safely vaccinated with no increase in disease relapse, median followup 4.6 years (interquartile range [IQR] 3.6-4.8 years). Eighteen patients died at a median of 2 years and the overall infection rate was 0.4 (IQR 0.2-1.3) infections/patient/year. Reduced serum IgG, B cell count, and CD4+ cell counts predicted poor vaccine response and infection but not death. The response rates to individual vaccine antigens was highly variable, with a median response rate of 46% (IQR 39-58%) of patients responding to each individual antigen. Vaccine response, age, and reduced renal function were independent predictors of all-cause mortality in multivariate analysis. CONCLUSION: Total IgG and B cell counts predict infection and response to vaccination. Vaccination in patients with SV in remission is safe and the response predicts all-cause mortality. Vaccine response is a surrogate marker of immune system health.


Assuntos
Linfócitos B/imunologia , Hospedeiro Imunocomprometido/imunologia , Vasculite Sistêmica/imunologia , Vacinas/imunologia , Idoso , Estudos de Coortes , Feminino , Humanos , Imunoglobulina G , Vacinas contra Influenza/imunologia , Contagem de Linfócitos , Masculino , Vacinas Meningocócicas/imunologia , Pessoa de Meia-Idade , Vacinas Pneumocócicas/imunologia , Vacinação
16.
Nephrology (Carlton) ; 21(4): 301-7, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26369898

RESUMO

AIM: Pauci-immune extracapillary glomerulonephritis (PEGN) is one of the most common causes of rapidly progressive glomerulonephritis and is usually associated with circulating anti-neutrophil cytoplasmic antibodies (ANCAs). However, a significant number of individuals with PEGN test negative for ANCA and this study aimed to analyze the characteristics of this subgroup of patients. METHODS: Patients from two centres who were diagnosed with PEGN between 1997 and 2014 were studied retrospectively. Clinicopathological characteristics and renal outcome were compared between patients presenting with pauci-immune necrotizing extracapillary glomerulonephritis associated or not with the presence of circulating ANCA. RESULTS: Among the 114 patients with PEGN, 29 (25.4%) were ANCA negative. Compared with the 85 ANCA-positive patients, ANCA-negative patients were younger at the onset (54.8 ± 17.2 vs. 62 ± 14.0 years; P < 0.05). The median level of urinary protein excretion was significantly higher among ANCA-negative patients (3.1 vs. 1 g/24 h; P < 0.001), whereas no differences were found in renal function and need for dialysis between ANCA-negative and positive groups. Extrarenal involvement was present independently of ANCA status. Histological analysis showed that ANCA-negative patients were more likely to have mesangial proliferation (P < 0.05). Renal and global survival were similar between ANCA-negative and positive patients, and treatment response and relapse rates were comparable in both groups. CONCLUSIONS: ANCA-negative pauci-immune extracapillary glomerulonephritis is not a rare condition and is part of a systemic vasculitis disease. Although ANCA-negative patients have renal and histological characteristics that differ from ANCA-positive patients, renal survival and treatment response in PEGN are independent of ANCA status.


Assuntos
Anticorpos Anticitoplasma de Neutrófilos/imunologia , Glomerulonefrite/imunologia , Rim/imunologia , Vasculite Sistêmica/imunologia , Adulto , Idoso , Anticorpos Anticitoplasma de Neutrófilos/sangue , Biomarcadores/sangue , Proliferação de Células , Progressão da Doença , Feminino , Glomerulonefrite/diagnóstico , Glomerulonefrite/mortalidade , Glomerulonefrite/terapia , Humanos , Imunossupressores/uso terapêutico , Estimativa de Kaplan-Meier , Rim/patologia , Masculino , Pessoa de Meia-Idade , Necrose , Plasmaferese , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Recidiva , Estudos Retrospectivos , Fatores de Risco , Testes Sorológicos , Espanha , Vasculite Sistêmica/diagnóstico , Vasculite Sistêmica/mortalidade , Vasculite Sistêmica/terapia , Fatores de Tempo , Resultado do Tratamento
17.
Rheumatol Int ; 36(2): 169-82, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26403285

RESUMO

Innate immune system forms the first line of defense against foreign substances. Neutrophils, eosinophils, erythrocytes, platelets, monocytes, macrophages, dendritic cells, γδ T cells, natural killer and natural killer T cells comprise the innate immune system. Genetic polymorphisms influencing the activation of innate immune cells predispose to development of vasculitis and influence its severity. Abnormally activated innate immune cells cross-talk with other cells of the innate immune system, present antigens more efficiently and activate T and B lymphocytes and cause tissue destruction via cell-mediated cytotoxicity and release of pro-inflammatory cytokines. These secreted cytokines further recruit other cells to the sites of vascular injury. They are involved in both the initiation as well as the perpetuation of vasculitis. Evidences suggest reversal of aberrant activation of immune cells in response to therapy. Understanding the role of innate immune cells in vasculitis helps understand the potential of therapeutic modulation of their activation to treat vasculitis.


Assuntos
Plaquetas/imunologia , Sistema Imunitário/imunologia , Imunidade Inata , Monócitos/imunologia , Células Mieloides/imunologia , Vasculite Sistêmica/imunologia , Animais , Plaquetas/patologia , Comunicação Celular , Humanos , Sistema Imunitário/patologia , Sistema Imunitário/fisiopatologia , Mediadores da Inflamação/imunologia , Monócitos/patologia , Células Mieloides/patologia , Fenótipo , Transdução de Sinais , Vasculite Sistêmica/patologia , Vasculite Sistêmica/fisiopatologia
18.
Curr Opin Rheumatol ; 28(1): 8-14, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26599378

RESUMO

PURPOSE OF REVIEW: Antineutrophil cytoplasmic autoantibodies (ANCAs) are considered important diagnostic tests in the work-up of patients suspected of vasculitis. Here we discuss new developments in the methodology of testing, the pitfalls in using these tests as diagnostic tools, and the value of serial ANCA testing for the follow-up of patients with ANCA-associated vasculitis including treatment decisions. RECENT FINDINGS: Both the indirect immunofluorescence (IIF) test and antigen-specific assays should be performed. New methodologies include automated reading in the IIF test and third-generation assays (anchor ELISA and bead-based multiplex assay) for the antigenic-specific assays. ANCA testing should be done in the right clinical context as positive results for PR3-ANCA and MPO-ANCA do occur in other conditions than vasculitis as well. These ANCAs develop in about 10% of patients with infective endocarditis. The occurrence of drug-induced ANCA and ANCA, also directed against elastase, following use of levamisole-adulterated cocaine should be recognized. In the right clinical context, ANCA are highly sensitive and specific for their associated disease. The value of serial ANCA testing for the follow-up of patients with ANCA-associated vasculitis is still under discussion but may be relevant in patients with renal involvement and in patients treated with rituximab. SUMMARY: The techniques for ANCA testing improve further but new tests should be standardized and validated. Their diagnostic value in the right clinical context is undisputed. Their value for the follow-up of patients is still under discussion.


Assuntos
Vasculite Sistêmica/diagnóstico , Vasculite Sistêmica/imunologia , Anticorpos Anticitoplasma de Neutrófilos/sangue , Autoanticorpos , Humanos , Imuno-Histoquímica , Prognóstico , Vasculite Sistêmica/sangue
19.
Curr Opin Rheumatol ; 28(1): 15-20, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26599379

RESUMO

PURPOSE OF REVIEW: The present review discusses the evidence supporting the use of B-cell-targeted therapy in the treatment of various forms of systemic vasculitis with a focus on the use of rituximab (RTX), in the antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitides (AAV). RECENT FINDINGS: Long-term follow-up of the two studies establishing the efficacy of a RTX-based induction regimen for severe AAV have demonstrated noninferiority of a single course of RTX compared with conventional therapy for remission maintenance. In addition, these observations highlight an association between relapse and B-cell reconstitution in patients treated with RTX. The maintenance of remission using rituximab in systemic ANCA-associated vasculitis trial compared a regimen of RTX infusions every 6 months to azathioprine for remission maintenance and concluded that serial RTX lead to higher rates of sustained remission.RTX is also an established therapy for cryoglobulinemic vasculitis associated with hepatitis C viral (HCV) infection. Recently published data support the long-term efficacy and safety of RTX for cryoglobulinemic vasculitis. SUMMARY: B-cell depletion with RTX is an established therapy for both remission induction and maintenance in severe AAV and in HCV-related cryoglobulinemic vasculitis. There are limited data to support use of B-cell-targeted therapy in refractory cases of other forms of systemic vasculitis such as eosinophilic granulomatosis with polyangiitis and Takayasu's arteritis.


Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/tratamento farmacológico , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/imunologia , Linfócitos B/imunologia , Vasculite Sistêmica/tratamento farmacológico , Vasculite Sistêmica/imunologia , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/terapia , Síndrome de Churg-Strauss/tratamento farmacológico , Síndrome de Churg-Strauss/imunologia , Crioglobulinemia/tratamento farmacológico , Crioglobulinemia/imunologia , Granulomatose com Poliangiite/tratamento farmacológico , Granulomatose com Poliangiite/imunologia , Humanos , Fatores Imunológicos/uso terapêutico , Poliangiite Microscópica/tratamento farmacológico , Poliangiite Microscópica/imunologia , Terapia de Alvo Molecular , Rituximab/uso terapêutico , Vasculite Sistêmica/terapia , Arterite de Takayasu/tratamento farmacológico , Arterite de Takayasu/imunologia
20.
Angiol Sosud Khir ; 21(4): 21-6, 2015.
Artigo em Russo | MEDLINE | ID: mdl-26673291

RESUMO

The authors studied peculiarities of the immune status in angiosurgical patients with systemic vasculitis, as well as possibilities of immunodiagnosis and immunocorrection in prevention of early coagulopathic and reparative complications after angiosurgical interventions in this cohort of patients. A total of 172 angiosurgical patients presenting with systemic vasculitis were subdivided into two groups depending on the preoperative preparation methods used. In Group One (Study Group) comprising 81 patients preoperative preparation was carried out using immunosuppressive therapy with hormones and cytostatics according to the rheumatologist's indications. In Group Two (n=91) hormones and/or cytostatics were replaced by the proposed four-component immunocorrection including various combinations of correcting the lifestyle, use of antioxidative-activity immunomodulators, plasmapheresis and intravenous administration of immunoglobulins. It was determined that using this method of correction made it possible to achieve a good anti-inflammatory effect in angiosurgical patients with systemic vasculitis, thus avoiding negative aftermaths of immunosuppression. The developed method of immunocorrection makes it possible to decrease the rate of early postoperative coagulopathic and reparative complications in angiosurgical patients as compared to therapy with hormones and/or cytostatics.


Assuntos
Imunidade Inata , Imunossupressão/métodos , Plasmaferese/métodos , Complicações Pós-Operatórias/prevenção & controle , Cuidados Pré-Operatórios/métodos , Vasculite Sistêmica/terapia , Adulto , Idoso , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Vasculite Sistêmica/imunologia , Fatores de Tempo , Adulto Jovem
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