RESUMO
OBJECTIVE: Previous gene expression analyses seeking genes specific to antineutrophil cytoplasmic antibody-associated vasculitis (AAV) have been limited due to crude cell separation and the use of microarrays. This study aims to identify AAV-specific gene expression profiles in a way that overcomes those limitations. METHODS: Blood samples were collected from 26 AAV patients and 28 healthy controls (HCs). Neutrophils were isolated by negative selection, whereas 19 subsets of peripheral blood mononuclear cells were sorted by fluorescence assisted cell sorting. RNA-sequencing was then conducted for each sample, and iterative weighted gene correlation network analysis (iterativeWGCNA) and random forest were consecutively applied to identify the most influential gene module in distinguishing AAV from HCs. Correlations of the identified module with clinical parameters were evaluated, and the biological role was assessed with hub gene identification and pathway analysis. Particularly, the module's association with neutrophil extracellular trap formation, NETosis, was analyzed. Finally, the module's overlap with GWAS-identified autoimmune disease genes (GADGs) was assessed for validation. RESULTS: A neutrophil module (Neu_M20) was ranked top in the random forest analysis among 255 modules created by iterativeWGCNA. Neu_M20 correlated with disease activity and neutrophil counts but not with the presence of antineutrophil cytoplasmic antibody. The module comprised pro-inflammatory genes, including those related to NETosis, supported by experimental evidence. The genes in the module significantly overlapped GADGs. CONCLUSION: We identified the distinct group of pro-inflammatory genes in neutrophils, which characterize AAV. Further investigations are warranted to confirm our findings as they could serve as novel therapeutic targets.
Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/diagnóstico , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/etiologia , Biomarcadores , Suscetibilidade a Doenças , Regulação da Expressão Gênica , Transcriptoma , Anticorpos Anticitoplasma de Neutrófilos/efeitos adversos , Anticorpos Anticitoplasma de Neutrófilos/imunologia , Estudos de Casos e Controles , Biologia Computacional , Armadilhas Extracelulares/imunologia , Armadilhas Extracelulares/metabolismo , Perfilação da Expressão Gênica , Redes Reguladoras de Genes , Estudo de Associação Genômica Ampla , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Imunofenotipagem , Neutrófilos/imunologia , Neutrófilos/metabolismoRESUMO
INTRODUCTION: Cocaine use is associated with multiple complications, some of which can mimic systemic diseases, especially Antineutrophil Cytoplasmic Antibody (ANCA) associated vasculitis. We report a case of Cocaine Induced Midline Destructive Lesions (CIMDL) for which a diagnosis of granulomatosis with polyangiitis (GPA) was discussed. CASE REPORT: A 42-year-old male, cocaine consumer, was admitted in our department for a centrofacial destructive process. He had no extra ear, nose and throat (ENT) involvement. ANCA were positive with a perinuclear fluorescence pattern and an anti-Proteinase 3 specificity. Regarding this unusual immunologic pattern and in the absence of histological argument for a GPA, a diagnosis of CIMDL was made. CONCLUSION: CIMDL is a centrofacial destructive process due to intranasal cocaine use. It is frequently associated with the presence of p-ANCA with both anti-HNE and anti-PR3 specificity.
Assuntos
Transtornos Relacionados ao Uso de Cocaína/complicações , Granulomatose com Poliangiite/etiologia , Perfuração do Septo Nasal/etiologia , Adulto , Anticorpos Anticitoplasma de Neutrófilos/efeitos adversos , Anticorpos Anticitoplasma de Neutrófilos/sangue , Transtornos Relacionados ao Uso de Cocaína/diagnóstico , Diagnóstico Diferencial , Granuloma Letal da Linha Média/diagnóstico , Granuloma Letal da Linha Média/etiologia , Granulomatose com Poliangiite/diagnóstico , Humanos , Masculino , Perfuração do Septo Nasal/diagnósticoRESUMO
Eosinophilic granulomatosis with polyangiitis (EGPA, formerly Churg-Strauss syndrome) is the least frequent antineutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV). Major advances of our knowledge on its pathophysiology have revealed features of both AAV and eosinophilic disorders. The development of targeted biotherapies for both diseases opened new possibilities for EGPA management. In this review, we highlight the rationale underlying the routine treatment strategy, which relies mainly on corticosteroids, with immunosuppressant adjunction for severe disease. However, novel therapies are still needed for refractory/relapsing disease and to alleviate the corticosteroid-dependence of asthma and chronic rhinosinusitis. At present, the most promising biotherapies target either eosinophil biology, like mepolizumab, an anti-interleukin-5, or the B-cell compartment, with rituximab. Recent clinical data on new treatment options are discussed and therapeutic strategies are proposed.
Assuntos
Síndrome de Churg-Strauss/terapia , Corticosteroides/uso terapêutico , Anticorpos Anticitoplasma de Neutrófilos/efeitos adversos , Anticorpos Monoclonais Humanizados/uso terapêutico , Terapia Biológica/métodos , Terapia Biológica/tendências , Síndrome de Churg-Strauss/patologia , Glucocorticoides/uso terapêutico , Granulomatose com Poliangiite/patologia , Granulomatose com Poliangiite/terapia , Humanos , Imunossupressores/uso terapêutico , Rituximab/uso terapêuticoRESUMO
BACKGROUND: Prior work has shown that urinary soluble CD163 (usCD163) displays excellent biomarker characteristics for detection of active renal vasculitis using samples that included new diagnoses with highly active renal disease. This study focused on the use of usCD163 in the detection of the more clinically relevant state of mild renal flare and compared results of usCD163 testing directly to testing of urinary monocyte chemoattractant protein-1 (uMCP-1). METHODS: Patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV, n = 88) were identified within a serially sampled, longitudinal and multicentre cohort. Creatinine-normalized usCD163 and uMCP-1 levels were measured by enzyme-linked immunosorbent assay and, both alone and in combination, were compared between times of active renal AAV and during remission and/or active non-renal AAV. RESULTS: Samples from 320 study visits included times of active renal vasculitis (n = 39), remission (n = 233) and active extrarenal vasculitis (n = 48). Median creatinine levels were 0.9 mg/dL [interquartile range (IQR) 0.8-1.2] in remission and 1.4 mg/dL (IQR 1.0-1.8) during renal flare. usCD163 levels were higher in patients with active renal vasculitis compared with patients in remission and those with active extrarenal vasculitis, with median values of 162 ng/mmol (IQR 79-337), 44 (17-104) and 38 (7-76), respectively (P < 0.001). uMCP-1 levels were also higher in patients with active renal vasculitis compared with patients in remission and those with active extrarenal vasculitis, with median values of 10.6 pg/mmol (IQR 4.6-23.5), 4.1 (2.5-8.4) and 4.1 (1.9-6.8), respectively (P < 0.001). The proposed diagnostic cut-points for usCD163 and uMCP-1 were 72.9 ng/mmol and 10.0 pg/mmol, respectively. usCD163 and uMCP-1 levels were marginally correlated (r2 = 0.11, P < 0.001). Combining novel and existing biomarkers using recursive tree partitioning indicated that elevated usCD163 plus either elevated uMCP-1 or new/worse proteinuria improved the positive likelihood ratio (PLR) of active renal vasculitis to 19.2. CONCLUSION: A combination of usCD163 and uMCP-1 measurements appears to be useful in identifying the diagnosis of subtle renal vasculitis flare.
Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/complicações , Anticorpos Anticitoplasma de Neutrófilos/efeitos adversos , Antígenos CD/urina , Antígenos de Diferenciação Mielomonocítica/urina , Biomarcadores/urina , Quimiocina CCL2/urina , Nefropatias/diagnóstico , Adulto , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/imunologia , Anticorpos Anticitoplasma de Neutrófilos/imunologia , Feminino , Humanos , Nefropatias/etiologia , Nefropatias/urina , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Receptores de Superfície Celular , UrináliseRESUMO
Antineutrophil cytoplasmic antibody-associated vasculitis (AAV) is a group of systemic necrotising vasculitides, which often involve small vessels, and which lead to few or no immune deposits in affected organs. According to clinical manifestations and pathological features, AAV is classified into three variants: microscopic polyangiitis, granulomatosis with polyangiitis (GPA), and eosinophilic GPA. The American College of Rheumatology 1990 criteria contributed to the classification of AAV, although currently the algorithm suggested by the European Medicines Agency in 2007 and the Chapel Hill Consensus Conference Nomenclature of Vasculitides proposed in 2012 have encouraged physicians to classify AAV patients properly. So far, there have been noticeable advancements in studies on the pathophysiology of AAV and the classification criteria for AAV in Western countries. However, studies analysing clinical features of Korean patients with AAV have only been conducted and reported since 2000. One year-, 5 year-, and 10 year-cumulative patient survival rates are reported as 96.1, 94.8, and 92.8%. Furthermore, initial vasculitis activity, prognostic factor score, age and specific organ-involvement have been found to be associated with either all-cause mortality or poor disease course. The rate of serious infection is 28.6%, and 1 year-, 5 year- and 10 year-cumulative hospitalised infection free survival rates range from 85.1% to 72.7%. The overall standardised incidence ratio of cancer in AAV patients was deemed 1.43 compared to the general Korean population.
Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/epidemiologia , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/classificação , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/etiologia , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/mortalidade , Anticorpos Anticitoplasma de Neutrófilos/efeitos adversos , Humanos , Incidência , Prognóstico , República da Coreia/epidemiologiaRESUMO
We report a rare case of Hydralazine-induced ANCA associated glomerulonephritis with alveolar hemorrhage in the setting of acute Clostridium Difficile Infection. A 71-year-old Caucasian woman with hypertension, who was being treated with hydralazine 25 mg twice a day for six years, presented to the hospital with diarrhea, nausea, vomiting and anemia. She had acute kidney injury and urinalysis showed proteinuria, dysmorphic RBCs, and rare RBC cast. She was found to have Clostridium difficile colitis which was successfully treated. She became hypoxemic; CT scan findings showed bilateral pulmonary infiltrates. Broncho-alveolar lavage was consistent with pulmonary hemorrhage. Kidney biopsy revealed focal segmental necrotizing and diffuse crescentic glomerulonephritis, pauci-immune type (ANCA-associated). Hydralazine was discontinued and the patient was treated with corticosteroids, intravenous cyclophosphamide and plasmapheresis. To our knowledge, hydralazine-associated low complement in the setting of C-diff infection has not been previously reported. This is considered a potentially life-threatening condition requiring immediate discontinuation of the offending medication and expedited lifesaving measures. [Full article available at http://rimed.org/rimedicaljournal-2016-11.asp].
Assuntos
Anti-Hipertensivos/efeitos adversos , Infecções por Clostridium/complicações , Glomerulonefrite/induzido quimicamente , Hemorragia/induzido quimicamente , Hidralazina/efeitos adversos , Vasculite/induzido quimicamente , Corticosteroides/uso terapêutico , Idoso , Anticorpos Anticitoplasma de Neutrófilos/efeitos adversos , Clostridioides difficile , Ciclofosfamida/uso terapêutico , Enterocolite Pseudomembranosa , Feminino , Glomerulonefrite/tratamento farmacológico , Hemorragia/tratamento farmacológico , Humanos , Hipertensão/tratamento farmacológico , Rim/patologia , Tomografia Computadorizada por Raios X , Vasculite/tratamento farmacológicoRESUMO
ANCA-associated vasculitis is characterized by the presence of anti-neutrophil cytoplasmic antibody (ANCA) in the serum. ANCA is a pathogenic autoantibody as well as the disease marker. It has been realized that ANCA-cytokine sequence is involved in the pathogenesis of ANCA-associated vasculitis. Recent studies have revealed that neutrophil extracellular traps induced by ANCA are also involved in the pathogenesis. In this study, we review the roles of neutrophils, eosinophils, macrophages/dendritic cells, complements, B cells/plasma cells, T cells, and cytokines/chemokines/cell growth factors in the pathogenesis of ANCA-associated vasculitis.
Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/etiologia , Anticorpos Anticitoplasma de Neutrófilos/efeitos adversos , Animais , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/patologia , Linfócitos B/imunologia , Quimiocinas , Proteínas do Sistema Complemento/imunologia , Citocinas , Células Dendríticas/imunologia , Eosinófilos , Humanos , Peptídeos e Proteínas de Sinalização Intercelular , Macrófagos/imunologia , Macrófagos/fisiologia , Camundongos , Neutrófilos/imunologia , Neutrófilos/patologia , Plasmócitos/imunologia , Linfócitos T/imunologiaAssuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/terapia , Quimioterapia de Manutenção , Padrão de Cuidado , Anticorpos Anticitoplasma de Neutrófilos/efeitos adversos , Humanos , Quimioterapia de Manutenção/métodos , Padrões de Prática Médica/tendências , Medicina de Precisão , Rituximab/uso terapêuticoRESUMO
ANCA-activated phagocytes cause vasculitis and necrotizing crescentic GN (NCGN). ANCA-induced phagocyte NADPH oxidase (Phox) may contribute by generating tissue-damaging reactive oxygen species. We tested an alternative hypothesis, in which Phox restrains inflammation by downregulating caspase-1, thereby reducing IL-1ß generation and limiting NCGN. In an antimyeloperoxidase (anti-MPO) antibody-mediated disease model, mice transplanted with either gp91(phox)-deficient or p47(phox)-deficient bone marrow showed accelerated disease with increased crescents, necrosis, glomerular monocytes, and renal IL-1ß levels compared with mice transplanted with wild-type bone marrow. IL-1ß receptor blockade abrogated aggravated NCGN in gp91(phox)-deficient mice. In vitro, challenge with anti-MPO antibody strongly enhanced caspase-1 activity and IL-1ß generation in gp91(phox)-deficient and p47(phox)-deficient monocytes compared with wild-type monocytes. This enhanced IL-1ß generation was abrogated when caspase-1 was blocked. ANCA-induced superoxide and IL-1ß generation were inversely related in human monocytes. Furthermore, transplantation of gp91(phox)/caspase-1 double-deficient bone marrow rescued the accelerated NCGN phenotype in gp91(phox) bone marrow-deficient mice. These results suggest that Phox-generated reactive oxygen species downregulate caspase-1, thereby keeping the inflammasome in check and limiting ANCA-induced inflammation. IL-1 receptor blockade may provide a promising strategy in NCGN, whereas our data question the benefit of antioxidants.
Assuntos
Anticorpos Anticitoplasma de Neutrófilos/efeitos adversos , Glomerulonefrite/induzido quimicamente , Glomerulonefrite/fisiopatologia , Inflamassomos/fisiologia , NADPH Oxidases/fisiologia , Fagócitos/enzimologia , Animais , Caspase 1/metabolismo , Células Cultivadas , Modelos Animais de Doenças , Glomerulonefrite/metabolismo , Humanos , Técnicas In Vitro , Proteína Antagonista do Receptor de Interleucina 1/farmacologia , Interleucina-1beta/metabolismo , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/patologia , Camundongos , Camundongos Knockout , NADPH Oxidases/deficiência , NADPH Oxidases/genética , NADPH Oxidases/metabolismo , Peroxidase/metabolismo , Fagócitos/patologia , Espécies Reativas de Oxigênio/metabolismo , Receptores Imunológicos/deficiência , Receptores Imunológicos/genética , Receptores Imunológicos/metabolismo , Superóxidos/metabolismoRESUMO
Drug-induced vessel vasculitis is a rare complication of chemotherapy. In particular, few reports have investigated drug-induced large vessel vasculitis. We herein report the case of a 57-year-old woman with advanced lung adenocarcinoma who developed perinuclear anti-neutrophil cytoplastic antibodies (p-ANCA)-positive periaortitis induced by bevacizumab combination chemotherapy. With the increasing use of combination therapy with bevacizumab, the incidence of vascular complications will potentially increase. A noninfectious fever occurring during chemotherapy might be a sign of vasculitis; therefore, we must ensure that possible periaortitis is not overlooked.
Assuntos
Anticorpos Anticitoplasma de Neutrófilos/efeitos adversos , Anticorpos Anticitoplasma de Neutrófilos/biossíntese , Anticorpos Monoclonais Humanizados/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Aortite/diagnóstico , Adenocarcinoma/diagnóstico , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/imunologia , Adenocarcinoma de Pulmão , Anticorpos Monoclonais Humanizados/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Aortite/tratamento farmacológico , Aortite/imunologia , Bevacizumab , Feminino , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/imunologia , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: To report the first case of concomitant drug- and infection-induced antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) in a patient treated with propylthiouracil (PTU) and suffering from tuberculosis. PRESENTATION AND INTERVENTION: A 28-year-old woman with PTU-treated hyperthyroidism presented with fever, purpura, pulmonary cavitations and ANCA to myeloperoxidase, bactericidal/permeability-increasing protein (BPI), proteinase-3 and elastase. Skin histopathology confirmed vasculitis. However, sputum examination revealed Mycobacterium tuberculosis. Remission was achieved after PTU withdrawal and treatment with antituberculosis drugs. CONCLUSION: Our case confirmed that BPI-ANCA are elevated in active tuberculosis. Multispecific ANCA were helpful for the diagnosis of concomitant PTU- and M. tuberculosis-induced AAV.
Assuntos
Anticorpos Anticitoplasma de Neutrófilos/efeitos adversos , Anticorpos Anticitoplasma de Neutrófilos/imunologia , Antitireóideos/efeitos adversos , Propiltiouracila/efeitos adversos , Vasculite/etiologia , Adulto , Antitireóideos/uso terapêutico , Antituberculosos/uso terapêutico , Feminino , Humanos , Hipertireoidismo/tratamento farmacológico , Propiltiouracila/uso terapêutico , Tuberculose Pulmonar/diagnóstico , Tuberculose Pulmonar/tratamento farmacológico , Vasculite/induzido quimicamente , Vasculite/diagnóstico , Vasculite/microbiologiaRESUMO
The pathogenesis of anti-neutrophil cytoplasmic antibody (ANCA)-associated necrotizing crescentic GN (NCGN) is incompletely understood. Dipeptidyl peptidase I (DPPI) is a cysteine protease required for the activation of neutrophil serine proteases (NSPs) cathepsin G, neutrophil elastase, and proteinase 3, which are enzymes that modulate inflammation. We used a mouse model of anti-myeloperoxidase (MPO) antibody-induced NCGN to determine whether active NSPs contribute to its pathogenesis. MPO-deficient animals immunized with murine MPO, irradiated, and transplanted with wild-type bone marrow developed NCGN. In contrast, transplantation with bone marrow that lacked DPPI or lacked both neutrophil elastase and proteinase 3 protected mice from NCGN induced by anti-MPO antibody. The kidneys of mice reconstituted with DPPI-deficient bone marrow generated significantly less IL-1ß than did those of mice reconstituted with wild-type bone marrow; similarly, in vitro, DPPI-deficient monocytes produced significantly less IL-1ß in response to anti-MPO antibody than did wild-type monocytes. This reduction in IL-1ß was NSP dependent; exogenous addition of PR3 restored IL-ß production in DPPI-deficient monocytes. Last, the IL-1 receptor antagonist anakinra protected animals against anti-MPO antibody-induced NCGN (16.7%±6.0% versus 2.4%±1.7% crescents), suggesting that IL-1ß is a critical inflammatory mediator in this model. These data suggest that the development of anti-MPO antibody-induced NCGN requires NSP-dependent IL-1ß generation and that these processes may provide therapeutic targets for ANCA-mediated diseases in humans.
Assuntos
Glomerulonefrite/metabolismo , Interleucina-1beta/metabolismo , Necrose do Córtex Renal/metabolismo , Rim/metabolismo , Rim/patologia , Neutrófilos/metabolismo , Serina Proteases/metabolismo , Animais , Anticorpos Anti-Idiotípicos/efeitos adversos , Anticorpos Anticitoplasma de Neutrófilos/efeitos adversos , Transplante de Medula Óssea , Catepsina C/genética , Catepsina C/metabolismo , Movimento Celular , Modelos Animais de Doenças , Feminino , Glomerulonefrite/induzido quimicamente , Glomerulonefrite/patologia , Humanos , Proteína Antagonista do Receptor de Interleucina 1/farmacologia , Necrose do Córtex Renal/induzido quimicamente , Necrose do Córtex Renal/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Monócitos/metabolismo , Monócitos/patologia , Neutrófilos/patologia , Peroxidase/deficiência , Peroxidase/genética , Peroxidase/imunologia , Receptores de Interleucina-1/antagonistas & inibidores , Receptores de Interleucina-1/efeitos dos fármacos , Serina Proteases/deficiênciaAssuntos
Acetilcisteína/uso terapêutico , Anticorpos Anticitoplasma de Neutrófilos/efeitos adversos , Quimioterapia Adjuvante , Vasculite/tratamento farmacológico , Vasculite/etiologia , Ensaios Clínicos como Assunto , Progressão da Doença , Sequestradores de Radicais Livres/uso terapêutico , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Antimyeloperoxidase antibodies can cause crescentic glomerulonephritis and pulmonary hemorrhage. Toll-like receptors (TLRs) respond to infectious agents activating host defenses, whereas infections potentially initiate disease and provoke relapses. Neutrophils were found to be key effector cells of injury in experimental models, as disease does not occur in their absence and injury is enhanced by lipopolysaccharide (LPS). In this study, highly purified LPS (a pure TLR4 ligand) acted with antimyeloperoxidase antibodies to synergistically increase kidney and lung neutrophil recruitment and functional injury; effects abrogated in TLR4-deficient mice. Increased kidney TLR4 expression after stimulation predominantly occurred in glomerular endothelial cells. Enhanced glomerular neutrophil recruitment correlated with increased kidney mRNA expression of CXCL1 and CXCL2 (homologs of human CXCL8), whereas their preemptive neutralization decreased neutrophil recruitment. Disease induction in bone marrow chimeric mice showed that TLR4 in both bone marrow and renal parenchymal cells is required for maximal neutrophil recruitment and glomerular injury. Further studies in human glomerular cell lines stimulated with LPS found that glomerular endothelial cells were the prominent sources of CXCL8. Thus, our results define a role for TLR4 expression in bone marrow-derived and glomerular endothelial cells in neutrophil recruitment and subsequent functional and histological renal injury in experimental antimyeloperoxidase glomerulonephritis.
Assuntos
Anticorpos Anti-Idiotípicos/efeitos adversos , Glomerulonefrite/induzido quimicamente , Glomerulonefrite/metabolismo , Rim/metabolismo , Leucócitos/metabolismo , Peroxidase/imunologia , Receptor 4 Toll-Like/metabolismo , Animais , Anticorpos Anti-Idiotípicos/imunologia , Anticorpos Anti-Idiotípicos/farmacologia , Anticorpos Anticitoplasma de Neutrófilos/efeitos adversos , Anticorpos Anticitoplasma de Neutrófilos/farmacologia , Linhagem Celular , Quimiocina CXCL1/metabolismo , Quimiocina CXCL2/metabolismo , Modelos Animais de Doenças , Glomerulonefrite/patologia , Humanos , Interleucina-8/metabolismo , Rim/efeitos dos fármacos , Rim/patologia , Glomérulos Renais/metabolismo , Glomérulos Renais/patologia , Leucócitos/efeitos dos fármacos , Leucócitos/patologia , Lipopolissacarídeos/efeitos adversos , Lipopolissacarídeos/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos KnockoutRESUMO
Os anticorpos anticitoplasma de neutrófilos são autoanticorps contra componentes neutrofílicos, úteis nos dianósticos diferenciais das vasculites. A imunofluorescência indireta determina três padrões de fluorescência: citoplasmático (cANCA), específico para granulomatose de Wegener; perinuclear (pANCA), observado na síndrome de Churg-Strauss, poliangiite microscópica e em outras vasculites; o terceiro padrão, atípico (aANCA), ocorre na doença de Crohn, colite ulcerativa e em outras doenças. O objetivo deste artigo é abordar os pontos importantes para a correta valorização dos achados da pesquisa de ANCAs, que possa auxiliar o clínico nos diagnósticos das síndromes vasculíticas. Os autores descutem a importância dos padrões de fluorescência, sua correlação antigênica e a possível significação clínica do ANCA positivo.
Antineutrophil cytoplasmatic antibodies (ANCA) are autoantibodies against components of neutrophils, and they help with the identification of different forms of vasculitis. The ANCA pattern, determined by indirect immunofluorescence, can be either cytoplasmatic (cANCA), which are predominantly associated sith Wegener's granulomatosis; or perinuclear (PANCA) are more likely seen in mocroscopic polyangiitis, Churg-Strauss syndrome and other vasculitides. The third pattern is atypical (aANCA) and it's reported in patients with ulcerative colitis, in patients with Crohn's disease and other illnesses. The present article seeks to make an approach on the most important points to be considered in the analyses and evaluation of ANCA test that might help the physician on diagnostic of vasculitis diseases. Authors discuss the importance of these immunofluorescence patterns, the antigen's correlation and the probably clinical significance of ANCA positive.
Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos , Anticorpos Anticitoplasma de Neutrófilos/efeitos adversos , Anticorpos Anticitoplasma de Neutrófilos/história , Anticorpos Anticitoplasma de Neutrófilos/imunologia , Autoanticorpos , Autoantígenos , Doenças Autoimunes , Síndrome de Churg-Strauss , Granulomatose com Poliangiite , Poliangiite Microscópica , Técnica Indireta de Fluorescência para AnticorpoRESUMO
Anti-thyroid drugs, like carbimazole and propylthiouracil (PTU) are commonly prescribed for the treatment of hyperthyroidism. One should be aware of the side effects of antithyroid medications. Antineutrophil cytoplasmic antibody (ANCA)--associated vasculitis is a potentially life-threatening adverse effect of antithyroidmedications. We report a patient with Graves' disease who developed ANCA positive carbimazole induced vasculitis. The episode was characterized by a vasculitic skin rash associated with large joint arthritis, pyrexia and parotiditis but no renal or pulmonary involvement. He was referred to us for neurological evaluation because he had difficulty in getting up from squatting position and was suspected to have myositis. Carbimazole and methimazole have a lower incidence of reported ANCA positive side effects than PUT. To the best of our knowledge this is the first ANCA positive carbimazole induced vasculitis case reported from India.
Assuntos
Anticorpos Anticitoplasma de Neutrófilos/efeitos adversos , Antitireóideos/efeitos adversos , Carbimazol/efeitos adversos , Doença de Graves/complicações , Fatores Imunológicos/efeitos adversos , Vasculite/induzido quimicamente , Adulto , Anticorpos Anticitoplasma de Neutrófilos/uso terapêutico , Antitireóideos/uso terapêutico , Carbimazol/uso terapêutico , Doença de Graves/tratamento farmacológico , Humanos , Fatores Imunológicos/uso terapêutico , Masculino , Resultado do Tratamento , Vasculite/tratamento farmacológicoRESUMO
Biological therapies enable us to apply highly selective targeting components to modulate the immune response. Until now, a few controlled studies investigated the efficacy of TNF-alpha blocking agents in systemic vasculitis have been carried out, but, in general, they were falling short of expectations. However, there is conducive evidence that TNF-alpha blockers are advantageous in antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis, at least in selected disease stages. Likewise, although the efficacy of the monoclonal CD20 antibody rituximab in ANCA-associated vasculitis is obvious, the effect on predominantly granulomatous disease activity in Wegener's granulomatosis is less clear. In addition, interferon-alpha is used for induction treatment particularly in Churg-Strauss syndrome. Even though the effectiveness and safety of short-term administration was confirmed by case series, severe side effects after long-term treatment relativized the initial results. This review presents the recent data on the use of biologicals in vasculitis and appraises the knowledge in the clinical context.