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1.
BMC Infect Dis ; 19(1): 664, 2019 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-31349802

RESUMO

BACKGROUND: Several studies have identified predictors of severe infections in antineutrophil cytoplasmic antibody-associated vasculitis (AAV). However, the development of oral candidiasis (OC) as a predictor of subsequent severe infections has not been evaluated. The aim of this study was to assess the association between OC and subsequent severe infection requiring hospitalization during immunosuppressive therapy in AAV. METHODS: This single-center retrospective cohort study included 71 consecutive patients with newly diagnosed AAV from Aichi Medical University Hospital, Japan, starting immunosuppressive therapy between March 2013 and December 2018. The relationships between OC and subsequent severe infections were assessed using multivariate Cox proportional hazards models, adjusted for clinically relevant factors. RESULTS: During the follow-up period (median, 23 months; interquartile range, 11-51 months), 25 severe infectious episodes occurred in 19 patients (26.8%) and OC occurred in 17 patients (23.9%). A log-rank test showed that the OC group was significantly associated with severe infection (P <  0.001). Multivariate Cox proportional hazards models identified lower serum albumin (per 1 g/dl adjusted hazard ratio (HR)  = 0.38, 95% confidence interval (CI): 0.15-0.85; P  =  0.018), use of methylprednisolone pulse (adjusted HR  =  5.44, 95% CI: 1.54-20.0; P  =  0.010), and OC (adjusted HR  = 5.31, 95% CI: 1.86-15.8; P  =  0.002) as significant predictors of severe infection. Furthermore, a significant effect modification of the use of methylprednisolone pulse on OC was observed (P <  0.001). CONCLUSIONS: OC is one of the predictors of subsequent severe infections. The results suggest the importance of prolonging infection surveillance, especially for patients who developed OC under strong immunosuppressive therapy.


Assuntos
Candidíase Bucal/etiologia , Imunossupressores/efeitos adversos , Idoso , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/tratamento farmacológico , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/imunologia , Feminino , Seguimentos , Humanos , Imunossupressão , Imunossupressores/administração & dosagem , Japão , Masculino , Modelos de Riscos Proporcionais , Estudos Retrospectivos
2.
Mol Immunol ; 112: 394-398, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31291610

RESUMO

ANCA associated vasculitis is a serious, very often recurrent disease that despite the current standard treatment with high-dose glucocorticoids and either cyclophosphamide or rituximab, patients have a nine-fold increased mortality risk in the first year compared with healthy controls, attributed to infections, vasculitis activity, and renal disease. During the last few years, novel findings have suggested that activation of the complement system, in particular the alternative complement system, has a significant role in ANCA associated vasculitis pathogenesis. Detection of several components of this system in the circulation and urine reflects disease activity, and thus may be useful for clinical prognosis and to set up personalised treatments. In fact, some components of the complement system, such as C5a, might be potential targets for therapy. In this Review an update on clinical evidence for the role of complement activation in AAV is provided and subsequently we discuss potential therapeutic strategies that target complement components and open the way for clinical use of this target therapy in the near future.


Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/imunologia , Proteínas do Sistema Complemento/imunologia , Animais , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/tratamento farmacológico , Ativação do Complemento/efeitos dos fármacos , Ativação do Complemento/imunologia , Ciclofosfamida/farmacologia , Glucocorticoides/farmacologia , Humanos , Rituximab/farmacologia
3.
Autoimmun Rev ; 18(8): 751-760, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31181324

RESUMO

Neutrophils derive from hematopoietic stem cells (HSCs) with systemic inflammation driving their activation and differentiation to myeloid progenitors to ensure enhanced myelopoiesis. Epigenetic reprograming and re-education of these HSCs produces neutrophils primed towards elimination of pathogens and increased inflammatory response. Neutrophils -an important component of acute inflammation- are not present in chronic inflammatory tissues leading to the false assumption that they may not be as important for the latter. Activated neutrophils may release Neutrophil Extracellular Traps (NETs) during a distinct form of cell death, named NETosis; NETs are rich in bioactive molecules that promote thrombosis (including atherothrombosis), inflammation and fibrosis. Thus, although neutrophils may not be present in chronic inflammatory lesions, their remnants may amplify the inflammatory response beyond their short life-span in the tissues. Herein, we review current evidence supporting a role of neutrophils and NETosis in tissue injury and dysfunction in systemic autoimmunity using as disease paradigms Systemic Lupus Erythematosus (SLE) and the ANCA-associated vasculitides (AAV). We also discuss the mechanisms involved and their potential as targets for novel therapy and drug repositioning.


Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/imunologia , Lúpus Eritematoso Sistêmico/imunologia , Neutrófilos/imunologia , Animais , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/patologia , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/terapia , Morte Celular , Diferenciação Celular , Armadilhas Extracelulares/imunologia , Fibrose , Células-Tronco Hematopoéticas/citologia , Células-Tronco Hematopoéticas/imunologia , Humanos , Inflamação/imunologia , Inflamação/patologia , Inflamação/terapia , Lúpus Eritematoso Sistêmico/patologia , Lúpus Eritematoso Sistêmico/terapia , Mielopoese , Neutrófilos/patologia
4.
Z Rheumatol ; 78(6): 518-528, 2019 Aug.
Artigo em Alemão | MEDLINE | ID: mdl-31028473

RESUMO

Granulomatosis with polyangiitis (GPA, formerly Wegener's granulomatosis) and microscopic polyangiitis (MPA) are associated with the detection of antibodies against neutrophilic cytoplasmic antigens (ANCA) and are referred to as ANCA-associated vasculitides (AAV). In the event of the clinical suspicion of AAV the ANCA should first be determined by means of an antigen-specific immunoassay for proteinase 3­ANCA and myeloperoxidase-ANCA, according to current consensus recommendations. The diagnosis of AAV should also be confirmed by biopsy if possible. The classification criteria for AAV are currently being revised. Diagnostic criteria do not exist. The standard induction therapy consists of rituximab or cyclophosphamide, each in combination with glucocorticoids (GC). In the absence of severe organ involvement, methotrexate can alternatively be used. Recent study data suggest that additive plasmapheresis does not improve the long-term outcome. After remission, remission-preserving treatment with azathioprine, methotrexate or rituximab should be given for at least 48 months. The risk of severe infections is markedly increased, especially during the remission induction phase but can also be reduced during treatment with rituximab by the prophylactic administration of trimethoprim-sulfamethoxazole. In view of the increased risk of infection, GC-reduced or GC-free treatment regimens are currently the focus of clinical development.


Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos , Anticorpos Anticitoplasma de Neutrófilos/imunologia , Granulomatose com Poliangiite , Poliangiite Microscópica , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/diagnóstico , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/imunologia , Azatioprina , Produtos Biológicos/uso terapêutico , Ciclofosfamida/uso terapêutico , Quimioterapia Combinada , Granulomatose com Poliangiite/diagnóstico , Granulomatose com Poliangiite/imunologia , Humanos , Poliangiite Microscópica/diagnóstico , Poliangiite Microscópica/imunologia , Mieloblastina , Indução de Remissão , Resultado do Tratamento
5.
BMJ Case Rep ; 12(3)2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30826782

RESUMO

Denosumab is a fully human antibody to receptor activator of nuclear factor kappa-B ligand (RANKL), and it is administered every 6 months in women with postmenopausal osteoporosis (PMO) at high risk for fracture. Adverse effects of denosumab include musculoskeletal pain, hypercholesterolaemia, symptomatic hypocalcaemia, osteonecrosis of the jaw and cutaneous events such as angioedema, cellulitis and pustular dermatitis. While the possibility of vasculitis was mentioned in the product Monograph as well as in the WHO Newsletter, this is the first case, to our knowledge, of cytoplasmic-ANCA (c-ANCA) associated vasculitis officially published in the literature. 1 2 The pathogenic mechanisms behind drug-induced vasculitis remain to be defined and appear to be multifactorial. Once suspicion for drug-induced vasculitis arises, the offending agent should be discontinued and immunosuppressive therapy should be initiated according to the severity of organ involvement to inhibit progression to severe, irreversible disease. As new medications continue to be developed, the number of agents causing drug-induced vasculitis is expected to increase.


Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/induzido quimicamente , Conservadores da Densidade Óssea/efeitos adversos , Denosumab/efeitos adversos , Osteoporose Pós-Menopausa/tratamento farmacológico , Idoso de 80 Anos ou mais , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/imunologia , Anticorpos Anticitoplasma de Neutrófilos/efeitos dos fármacos , Feminino , Humanos
6.
Clin Exp Rheumatol ; 37 Suppl 117(2): 86-89, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30767872

RESUMO

OBJECTIVES: We aimed to elucidate the frequency and associations of MPO-ANCA positivity in patients without ANCA-associated vasculitis (AAV), in a large urban, multi-ethnic teaching hospital. METHODS: Retrospective review of 200 patients identified as MPO-ANCA positive over a five-year period at Royal Free Hospital, London, UK. RESULTS: The incidence of anti-MPO positivity in patients without AAV was 39.5%. Gastrointestinal tract disorders, infections and other connective tissue disorders made up the majority of diagnoses, and there was a higher incidence of other concomitant autoantibodies compared to the group with known AAV. Renal disease was common in non-vasculitic patients with anti-MPO antibody positivity (occurring in 48%), the majority of whom went on to renal biopsy to exclude vasculitic involvement. CONCLUSIONS: The high incidence of MPO-ANCA positivity in patients with non-vasculitic conditions highlights the need for careful clinical correlation and confirmatory tissue diagnosis.


Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos , Anticorpos Anticitoplasma de Neutrófilos/análise , Peroxidase , Adulto , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/sangue , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/diagnóstico , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/imunologia , Feminino , Humanos , Londres , Masculino , Peroxidase/sangue , Peroxidase/imunologia , Estudos Retrospectivos
8.
Zhonghua Nei Ke Za Zhi ; 57(10): 738-742, 2018 Oct 01.
Artigo em Chinês | MEDLINE | ID: mdl-30293334

RESUMO

Objective: To investigate the change of circulating follicular helper T cells (cTfh) in patients with anti-neutrophil cytoplasmic myeloperoxidase antibody-associated vasculitis (MPO-AAV), and to analyze the relationship between cTfh and disease activity. Methods: Thirty-eight untreated MPO-AAV patients (patient group) and thirty-eight healthy volunteers (control group) were enrolled in this study. cTfh and membrane expression of inducible co-stimulator (ICOS) and programmed cell death protein 1 (PD-1) were detected by flow cytometry (FCM). Serum anti-neutrophil cytoplasmic myeloperoxidase antibody (MPO-ANCA) was measured by ELISA. Disease activity was evaluated by Birmingham vasculitis activity score (BVAS). Results: Compared with those in control group, the proportions of cTfh, ICOS(+)Tfh and PD-1(+) Tfh cells in patient group were significantly higher [(25.9±3.8)% vs. (21.0±5.3)%, P<0.001; (1.8±0.8)% vs. (0.8±0.5)%, P<0.001 and (10.2±2.8)% vs. (8.2±2.2)%, P=0.001, respectively]. Meanwhile, the expression of ICOS and PD-1 on cTfh in patient group was markedly more intensive (59.6±10.0 vs.49.2±6.9, P<0.001 and 532.6±104.2 vs. 485.1±73.4, P=0.025, respectively). In patient group, the proportion of cTfh was positively correlated with the ratio of ICOS(+)Tfh, the expression of ICOS, the level of MPO-ANCA and BVAS (r=0.407, P=0.011; r=0.705, P<0.001; r=0.737, P<0.001 and r=0.663, P<0.001, respectively). The expression intensity of ICOS on cTfh was positively associated with ICOS(+)Tfh ratio, serum MPO-ANCA and BVAS (r=0.388, P=0.016; r=0.645, P<0.001 and r=0.653, P<0.001, respectively). Nevertheless, the expression of PD-1 on cTfh was only positively correlated with the ratio of PD-1(+) Tfh (r=0.473, P=0.003). Conclusions: Enhanced cTfh in patients with MPO-AAV might produce MPO-ANCA, which is related to the aggravation of MPO-AAV. Thus, cTfh and its ICOS could be potentially targeted for the treatment of MPO-AAV.


Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/imunologia , Anticorpos Anticitoplasma de Neutrófilos/análise , Anticorpos Anticitoplasma de Neutrófilos/imunologia , Neutrófilos/imunologia , Peroxidase/sangue , Linfócitos T Auxiliares-Indutores/metabolismo , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/sangue , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/patologia , Anticorpos Anticitoplasma de Neutrófilos/sangue , Estudos de Casos e Controles , Ensaio de Imunoadsorção Enzimática , Citometria de Fluxo , Humanos , Interleucina-2 , Peroxidase/imunologia , Peroxidase/metabolismo
9.
Yonsei Med J ; 59(7): 865-871, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30091320

RESUMO

PURPOSE: We investigated whether C-reactive protein (CRP) to serum albumin ratio (CAR) could be an independent predictor of all-cause mortality in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). MATERIALS AND METHODS: We retrospectively reviewed the medical records of 170 patients with AAV. We collected clinical and laboratory data. We also examined AAV-related and traditional risk factors of all-cause mortality. To assess the hazard ratios of variables, we performed univariable and multivariable Cox hazard model analyses. RESULTS: The mean age was 55.0 years and 53 patients (31.2%) were male among 170 patients with AAV (88 microscopic polyangiitis, 43 granulomatosis with polyangiitis, and 39 eosinophilic granulomatosis with polyangiitis). ANCA was detected in 129 patients (75.9%). The initial mean CRP and serum albumin were 41.1 (mg/L) and 3.6 (g/dL), and the mean CAR at diagnosis was 14.8. The most common risk factor of mortality was hypertension (42.4%), followed by chronic kidney disease ≥stage 3 (25.9%). Fourteen patients (8.2%) died during the mean follow-up of 56.7 months. In both multivariable Cox hazard model analyses, CAR at diagnosis was identified as an independent predictor of all-cause of mortality comparable to diabetes mellitus (DM). Moreover, patients with CAR ≥10.35 and having DM exhibited a higher frequency of all-cause mortality than those without. CONCLUSION: CAR at diagnosis can be an independent predictor of all-cause mortality, comparable to DM, the conventional risk factor of mortality.


Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/mortalidade , Proteína C-Reativa/metabolismo , Poliangiite Microscópica/mortalidade , Mortalidade , Albumina Sérica/metabolismo , Adulto , Idoso , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/sangue , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/imunologia , Anticorpos Anticitoplasma de Neutrófilos/imunologia , Feminino , Humanos , Hipertensão/complicações , Masculino , Poliangiite Microscópica/imunologia , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , República da Coreia/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida
11.
Clin Exp Rheumatol ; 36 Suppl 111(2): 12-32, 2018 Mar-Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29799395
12.
Clin Exp Rheumatol ; 36 Suppl 111(2): 143-151, 2018 Mar-Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29745882

RESUMO

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a potentially lethal autoimmune disease whose pathology comprises disturbed T cell differentiation and functionality accompanied by dysfunctional autoreactive immunoglobulin development, culminating in destructive innate immune response as well. Purines, adenine nucleotides and adenosine in particular, have been elucidated as potent extracellular mediators for fine adjustment of these pivotal processes establishing human immunity. Therefore, the extracellular purinergic microenvironment is under control of ectonucleotidases CD39 and CD73 degrading pro-inflammatory adenosine triphosphate (ATP) to anti-inflammatory adenosine as well as adenosine deaminase bound to CD26 deactivating adenosine. Accordingly, the ATP P2X7 receptor was elicited to be responsible for promotion of inflammation, while predominantly the adenosine A2A receptor demonstrated the opposite. Recent reports pointed at the adenosinergic system to be crucially involved in AAV pathogenesis. Here, experimental evidence on ecto-enzymes controlling extracellular adenine nucleotide concentrations and purinergic signaling in the immune system with respect to its contribution to the AAV pathomechanism is reviewed besides unsolved problems being identified that require further investigation in order to develop new treatment strategies for AAV.


Assuntos
Adenosina/imunologia , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/imunologia , Receptor A2A de Adenosina/imunologia , Receptores Purinérgicos P2X7/imunologia , 5'-Nucleotidase/metabolismo , Adenosina/metabolismo , Adenosina Desaminase/metabolismo , Trifosfato de Adenosina/metabolismo , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/metabolismo , Antígenos CD/metabolismo , Apirase/metabolismo , Diferenciação Celular , Humanos , Inflamação , Transdução de Sinais , Linfócitos T/imunologia
13.
Intern Med ; 57(18): 2739-2745, 2018 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-29709950

RESUMO

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and cryoglobulinemic vasculitis (CV) rarely coexist. An 83-year-old woman was admitted with rapidly progressive renal failure, gastrointestinal hemorrhage and purpura with myeloperoxidase (MPO)-ANCA positivity and cryoglobulinemia. Despite intensive immunosuppressive treatment, she died of aspergillus pneumonia. Autopsy revealed necrotizing crescentic glomerulitis in the majority of the glomeruli, accompanied by partially membranoproliferative-like glomerular changes. Immunofluorescence staining revealed the presence of neutrophil extracellular trap (NET) formation in the glomeruli and cutaneous arteries. These pathological findings suggested that MPO-AAV and/or CV caused NET formation, leading to lethal systemic vasculitis.


Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/complicações , Crioglobulinemia/complicações , Crioglobulinemia/patologia , Vasculite Sistêmica/complicações , Vasculite Sistêmica/patologia , Idoso de 80 Anos ou mais , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/imunologia , Autopsia , Armadilhas Extracelulares/imunologia , Evolução Fatal , Feminino , Trato Gastrointestinal/patologia , Glomerulonefrite/imunologia , Humanos , Rim/patologia , Glomérulos Renais/imunologia , Glomérulos Renais/patologia , Peroxidase/imunologia , Pele/imunologia , Pele/patologia
14.
Yonsei Med J ; 59(3): 397-405, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29611402

RESUMO

PURPOSE: Delta neutrophil index (DNI) represents the immature granulocytes count associated with neutrophil-consumption. We investigated whether DNI might be associated with Birmingham vasculitis activity score (BVAS) at diagnosis and could predict relapse during the follow-up in patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV). MATERIALS AND METHODS: We reviewed the medical records of 97 patients having DNI results. Twenty patients had granulomatosis with polyangiitis (GPA), 58 had microscopic polyangiitis (MPA), and 19 had eosinophilic GPA (EGPA). We collected clinical and laboratory data including BVAS, five factor score (FFS), and DNI. The correlation coefficient and cumulative relapse free survival rate were obtained. The optimal cut-off of DNI was extrapolated by calculating the area under the receiver operator characteristic curve. RESULTS: DNI was significantly related to cross-sectional BVAS. Furthermore, among continuous variables, only DNI could reflect BVAS of GPA and MPA, but not EGPA. Severe AAV was defined as BVAS ≥20 (the highest quartile). At diagnosis, patients having DNI ≥0.65% had a significantly higher risk of severe GPA and MPA than those having not (relative risk 4.255) at diagnosis. During the follow-up, DNI ≥0.65% could predict the higher relapse rate. CONCLUSION: DNI could reflect BVAS at diagnosis and furthermore, DNI ≥0.65% could not only identify severe AAV at diagnosis, but also predict relapse during the follow-up in patients with GPA and MPA.


Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/diagnóstico , Granulomatose com Poliangiite/imunologia , Poliangiite Microscópica/imunologia , Neutrófilos , Recidiva , Adulto , Idoso , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/epidemiologia , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/imunologia , Anticorpos Anticitoplasma de Neutrófilos , Estudos Transversais , Feminino , Granulomatose com Poliangiite/diagnóstico , Granulomatose com Poliangiite/epidemiologia , Humanos , Poliangiite Microscópica/diagnóstico , Poliangiite Microscópica/epidemiologia , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Qualidade de Vida , Estudos Retrospectivos , Risco , Índice de Gravidade de Doença
15.
Clin Exp Rheumatol ; 36(3): 490-493, 2018 May-Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29533748

RESUMO

OBJECTIVES: Guidelines for preventing Pneumocystis pneumonia (PCP) in HIV patients are based on CD4 below 200/mm3. Such cut-off value is suggested to guide prophylaxis in non-HIV conditions (NHIV) especially in autoimmune and inflammatory diseases (AD). We aimed to determine if CD4 could be used to guide PCP prophylaxis in AD. METHODS: CD4 and lymphocyte-count were retrospectively studied in patients diagnosed with PCP between January 2013 and February 2016. RESULTS: 129 patients were included. The median CD4-count was 302/mm3 in AD, which was significantly higher than in HIV patients (19/mm3; p<0.0001). Fifty percent (n=10) of AD patients had CD4 counts greater than 300/mm3. CONCLUSIONS: Prophylaxis for PCP cannot rely solely on CD4-count in NHIV patients especially in AD.


Assuntos
Doenças Autoimunes/tratamento farmacológico , Linfócitos T CD4-Positivos/imunologia , Infecções por HIV/terapia , Imunossupressores/efeitos adversos , Linfopenia/tratamento farmacológico , Pneumonia por Pneumocystis/prevenção & controle , Adulto , Idoso , Idoso de 80 Anos ou mais , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/complicações , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/tratamento farmacológico , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/imunologia , Artrite Reumatoide/complicações , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/imunologia , Doenças Autoimunes/complicações , Doenças Autoimunes/imunologia , Contagem de Linfócito CD4 , Crioglobulinemia/complicações , Crioglobulinemia/tratamento farmacológico , Crioglobulinemia/imunologia , Dermatomiosite/complicações , Dermatomiosite/tratamento farmacológico , Dermatomiosite/imunologia , Gerenciamento Clínico , Feminino , Arterite de Células Gigantes/complicações , Arterite de Células Gigantes/tratamento farmacológico , Arterite de Células Gigantes/imunologia , Infecções por HIV/complicações , Hepatite Autoimune/complicações , Hepatite Autoimune/tratamento farmacológico , Hepatite Autoimune/imunologia , Humanos , Hospedeiro Imunocomprometido , Linfopenia/etiologia , Linfopenia/imunologia , Masculino , Pessoa de Meia-Idade , Neoplasias/complicações , Neoplasias/imunologia , Neoplasias/terapia , Transplante de Órgãos , Pneumonia por Pneumocystis/etiologia , Pneumonia por Pneumocystis/imunologia , Guias de Prática Clínica como Assunto , Estudos Retrospectivos
16.
Clin Rheumatol ; 37(4): 1065-1074, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29520673

RESUMO

The classification of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) remains controversial. The main objective of this study was to define the respective values of ANCA serotype-based classification, clinicopathological classification, and histopathological classification in predicting patient and renal outcomes in a Spanish cohort of patients with ANCA with specificity for myeloperoxidase, MPO-ANCA, versus ANCA with specificity for proteinase 3, PR3-ANCA. Two hundred and forty-five patients with ANCA-AAV and biopsy-proven renal involvement diagnosed between 2000 and 2104 were recruited in 12 nephrology services. Clinical and histologic data, renal outcomes, and mortality were analyzed. We applied the Chapel Hill Consensus Conference definition with categories for granulomatosis with the polyangiitis (GPA) and microscopic polyangiitis (MPA), the classification based on ANCA specificity, and the histopathological classification proposed in 2010. Eighty-two percent were MPO-ANCA positive and 18.0% PR3-ANCA positive. Altogether, 82.9% had MPA and 17.1% GPA. The median follow-up was 43.2 months (0.1-169.3). Neither ANCA-based serological nor clinical classification was predictive of renal outcomes or patient survival on bivariate or multivariate Cox regression analysis. Histopathological classification was found to predict development of end-stage renal disease (p = 0.005) in Kaplan-Meier analysis. ANCA specificity was more predictive of relapse than clinicopathological classification in multivariate analysis (HR 2.086; 95% CI 1.046-4.158; p = 0.037). In our Spanish cohort, a majority of patients had an MPO-ANCA-AAV. A classification based on ANCA specificity has a higher predictive value for relapse occurrence and could be used for decision-making with respect to induction treatment and maintenance therapies.


Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/fisiopatologia , Anticorpos Anticitoplasma de Neutrófilos/imunologia , Rim/fisiopatologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/imunologia , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/patologia , Feminino , Humanos , Rim/imunologia , Rim/patologia , Masculino , Pessoa de Meia-Idade , Mieloblastina/imunologia , Estudos Retrospectivos , Espanha , Adulto Jovem
17.
Clin Rheumatol ; 37(4): 875-884, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29525845

RESUMO

Anti-neutrophil cytoplasmic antibodies (ANCA) are a group of autoantibodies that cause systemic vascular inflammation by binding to target antigens of neutrophils. These autoantibodies can be found in serum from patients with systemic small-vessel vasculitis and they are considered as a biomarker for ANCA-associated vasculitis (AAV). A conventional screening test to detect ANCA in the serum is indirect immunofluorescence study, and subsequently confirmed by enzyme-linked immunosorbent assay. A positive staining of ANCA can be classified into three main categories based on the staining patterns: cytoplasmic, perinuclear, and atypical. Patients with granulomatosis with polyangiitis (GPA) mostly have a positive cytoplasmic staining pattern (c-ANCA) whilst a perinuclear pattern (p-ANCA) is more common in microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (EGPA) patients. Atypical pattern (a-ANCA) is rarely seen in patients with systemic small-vessel vasculitis but it can be found in other conditions. Here, techniques for ANCA detection, ANCA staining patterns and their clinical significances are reviewed.


Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/imunologia , Anticorpos Anticitoplasma de Neutrófilos/sangue , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/sangue , Humanos
18.
Clin Exp Rheumatol ; 36 Suppl 111(2): 65-72, 2018 Mar-Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29465370

RESUMO

OBJECTIVES: We estimated the cumulative patient survival rates, the causes of death and the initial predictors of death in Korean patients with microscopic polyangiitis (MPA), granulomatosis with polyangiitis (GPA) and eosinophilic GPA (EGPA). METHODS: We reviewed the medical records of 153 patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). We collected clinical and laboratory data including ANCA, Birmingham vasculitis activity score (BVAS), five factor score (FFS) (2009), comorbidities, medications and prognosis (death and relapse). The hazard ratio (HR) of variables at diagnosis for death in the disease course was assessed by the Cox hazard model analysis. RESULTS: The mean age of 153 AAV patients (47 men and 106 women) was 55.2 years and the mean follow-up duration was 51.5 months. Fourteen of 153 patients (9.2%) died (7 MPA and 7 GPA patients) during the mean follow-up of 56.9 months. In all patients with AAV, 1 year-, 5 year- and 10 year-cumulative patient survival rates were 96.1%, 94.8% and 92.8%, respectively. The most common cause of death was infection of various causes. FFS (2009) ≥2 (HR 16.520, p=0.012) and diffuse alveolar haemorrhage (DAH) (HR 3.705, p=0.042) at diagnosis could predict death during the follow-up in AAV patients in multivariate COX regression analysis. CONCLUSIONS: The overall mortality rate was 9.2% and 10-year cumulative patient survival rate was 92.8%. At diagnosis, FFS (2009) ≥ 2 and DAH were independent predictors of death during the follow-up in Korean patients with MPA, GPA and EGPA.


Assuntos
Síndrome de Churg-Strauss/mortalidade , Granulomatose com Poliangiite/mortalidade , Poliangiite Microscópica/mortalidade , Adulto , Idoso , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/tratamento farmacológico , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/imunologia , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/mortalidade , Anticorpos Anticitoplasma de Neutrófilos/imunologia , Antirreumáticos/uso terapêutico , Causas de Morte , Síndrome de Churg-Strauss/imunologia , Comorbidade , Feminino , Granulomatose com Poliangiite/imunologia , Humanos , Hipertensão/epidemiologia , Hipertireoidismo/epidemiologia , Modelos Logísticos , Masculino , Poliangiite Microscópica/imunologia , Pessoa de Meia-Idade , Mortalidade , Análise Multivariada , Prognóstico , Modelos de Riscos Proporcionais , Recidiva , República da Coreia/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida
19.
Autoimmun Rev ; 17(4): 413-421, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29428808

RESUMO

Anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitides (AAV) are systemic autoimmune diseases characterized by necrotizing inflammation of small- to medium-sized blood vessels, affecting primarily the lungs and kidneys. Both animal and human studies show that the balance between inflammatory- and regulatory T- and B cells determines the AAV disease pathogenesis. Recent evidence shows malfunctioning of the regulatory lymphocyte compartment in AAV. In this review we summarize the immune regulatory properties of both T- and B cells in patients with AAV and discuss how aberrations herein might contribute to the disease pathogenesis.


Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/imunologia , Imunidade Celular/imunologia , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/patologia , Humanos
20.
Rheumatology (Oxford) ; 57(4): 639-650, 2018 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-29340623

RESUMO

Objectives: To study the determinants of the pharmacokinetics (PK) of rituximab (RTX) in patients with ANCA-associated vasculitis (AAV) and its association with clinical outcomes. Methods: This study included data from 89 patients from the RTX in AAV trial who received the full dose of RTX (four weekly infusions of 375 mg/m2). RTX was quantified at weeks 2, 4, 8, 16 and 24, and summarized by computing the trapezoidal area under the curve. We explored potential determinants of the PK-RTX, and analysed its association with clinical outcomes: achievement of remission at 6 months, duration of B-cell depletion and time to relapse in patients who achieved complete remission. Results: RTX serum levels were significantly lower in males and in newly diagnosed patients, and negatively correlated with body surface area, baseline B-cell count and degree of disease activity. In multivariate analyses, the main determinants of PK-RTX were sex and new diagnosis. Patients reaching complete remission at month 6 had similar RTX levels compared with patients who did not reach complete remission. Patients with higher RTX levels generally experienced longer B-cell depletion than patients with lower levels, but RTX levels at the different time points and area under the curve were not associated with time to relapse. Conclusion: Despite the body-surface-area-based dosing protocol, PK-RTX is highly variable among patients with AAV, its main determinants being sex and newly diagnosed disease. We did not observe any relevant association between PK-RTX and clinical outcomes. The monitoring of serum RTX levels does not seem clinically useful in AAV.


Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/tratamento farmacológico , Rituximab/farmacocinética , Adulto , Idoso , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/sangue , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/imunologia , Linfócitos B/imunologia , Linfócitos B/patologia , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Humanos , Fatores Imunológicos/administração & dosagem , Fatores Imunológicos/farmacocinética , Infusões Intravenosas , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Indução de Remissão , Rituximab/administração & dosagem , Resultado do Tratamento
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