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1.
Autoimmun Rev ; 19(9): 102618, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32663621

RESUMO

This document follows up on a 2017 revised international consensus on anti-neutrophil cytoplasm antibodies (ANCA) testing in granulomatosis with polyangiitis and microscopic polyangiitis and focuses on the clinical and diagnostic value of ANCA detection in patients with connective tissue diseases, idiopathic interstitial pneumonia, autoimmune liver diseases, inflammatory bowel diseases, anti-glomerular basement membrane (GBM) disease, infections, malignancy, and during drug treatment. Current evidence suggests that in certain settings beyond systemic vasculitis, ANCA may have clinical, pathogenic and/or diagnostic relevance. Antigen-specific ANCA targeting proteinase-3 and myeloperoxidase should be tested by solid phase immunoassays in any patient with clinical features suggesting ANCA-associated vasculitis and in all patients with anti-GBM disease, idiopathic interstitial pneumonia, and infective endocarditis associated with nephritis, whereas in patients with other aforementioned disorders routine ANCA testing is not recommended. Among patients with autoimmune liver diseases or inflammatory bowel diseases, ANCA testing may be justified in patients with suspected autoimmune hepatitis type 1 who do not have conventional autoantibodies or in case of diagnostic uncertainty to discriminate ulcerative colitis from Crohn's disease. In these cases, ANCA should be tested by indirect immunofluorescence as the target antigens are not yet well characterized. Many questions concerning the optimal use of ANCA testing in patients without ANCA-associated vasculitis remain to be answered.


Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos , Anticorpos Anticitoplasma de Neutrófilos/análise , Consenso , Granulomatose com Poliangiite/imunologia , Hepatite Autoimune/imunologia , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/imunologia , Humanos , Mieloblastina/imunologia , Peroxidase/imunologia
3.
Clin Sci (Lond) ; 134(12): 1475-1489, 2020 06 26.
Artigo em Inglês | MEDLINE | ID: mdl-32538435

RESUMO

Sphingosine-1-phosphate (S1P) is a pleiotropic lysosphingolipid derived from the metabolism of plasma membrane lipids. The interaction between S1P and its ubiquitously expressed G-protein-coupled receptors (S1PR1-5) is crucial in many pathophysiological processes. Emerging evidence suggested a potential role for S1P receptors in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). In the present study, we investigated the effects of three different S1P receptors modulators (FTY720, SEW2871 and TY52156) in a recognized rat model of experimental autoimmune vasculitis (EAV). The effects of treatments were evaluated with clinico-pathological parameters including hematuria, proteinuria, crescent formation, pulmonary hemorrhage, etc. In vitro functional studies were performed in a Jurkat T-cell line following stimulations of serum from myeloperoxidase-AAV patients. We found that only the FTY720 treatment significantly alleviated hematuria and proteinuria, and diminished glomerular crescent formation, renal tubulointerstitial lesions and pulmonary hemorrhage in EAV. The attenuation was accompanied by less renal T-cell infiltration, up-regulated mRNA of S1PR1 and down-regulated IL-1ß in kidneys, but not altered circulating ANCA levels, suggesting that the therapeutic effects of FTY720 were B-cell independent. Further in vitro studies demonstrated that FTY720 incubation could significantly inhibit the proliferation, adhesion, and migration, and increase apoptosis of T cells. In conclusion, the S1P modulator FTY720 could attenuate EAV through the reduction and inhibition of T cells, which might become a novel treatment of ANCA-associated vasculitis.


Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/tratamento farmacológico , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/imunologia , Cloridrato de Fingolimode/uso terapêutico , Peroxidase/metabolismo , Receptores de Esfingosina-1-Fosfato/metabolismo , Linfócitos T/imunologia , Adolescente , Adulto , Idoso , Animais , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/sangue , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/urina , Anticorpos/imunologia , Apoptose , Feminino , Cloridrato de Fingolimode/farmacologia , Hematúria/complicações , Humanos , Células Jurkat , Rim/patologia , Pulmão/patologia , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Proteinúria/complicações , Ratos Endogâmicos WKY , Transdução de Sinais
5.
Medicine (Baltimore) ; 99(5): e18857, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32000387

RESUMO

RATIONALE: IgG4-related disease (IgG4-RD) is a slowly progressing inflammatory disease that can involve multiple organ systems. There is considerable overlap between IgG4-RDs and anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Herein, we present an unusual case of IgG4-associated tubulointerstitial nephritis (IgG4-TIN) and ANCA-associated glomerulonephritis (ANCA-GN) co-occurring with C3 glomerulonephritis (C3GN). PATIENT CONCERNS: A 72-year-old male was admitted to hospital because of fever and fatigue. He was diagnosed with elevated serum creatinine and IgG4 levels, and was positive for ANCA. DIAGNOSIS: Initially, the pathology supported a diagnosis of IgG4-TIN and ANCA-GN; however, further examination revealed he also had C3GN. INTERVENTIONS: The patient was treated with methylprednisolone and cyclophosphamide and received regular follow-up care. OUTCOMES: After treatment, the patient no longer exhibited fever or fatigue and had no complications. The seven-month follow-up showed downward trends in IgG4 and MPO-ANCA levels and stable 24-hour urine protein, serum creatinine levels. LESSONS: Anti-neutrophil cytoplasmic antibody-associated glomerulonephritis and IgG4-associated tubulointerstitial nephritis with C3glomerulonephritis rarely occur simultaneously. Laboratory analysis and pathology are both needed to ensure diagnostic accuracy. However, in this case, the three diseases overlapped to such a large extent that achieving a definitive diagnosis was particularly challenging. Timely and accurate diagnosis is crucial for selecting the best treatment course and optimizing patient outcome.


Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/diagnóstico , Glomerulonefrite/diagnóstico , Nefrite Intersticial/diagnóstico , Idoso , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/tratamento farmacológico , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/imunologia , Anticorpos Anticitoplasma de Neutrófilos/imunologia , Complemento C3/imunologia , Ciclofosfamida/uso terapêutico , Glomerulonefrite/tratamento farmacológico , Glomerulonefrite/imunologia , Glucocorticoides/uso terapêutico , Humanos , Imunoglobulina G/imunologia , Imunossupressores/uso terapêutico , Masculino , Metilprednisolona/uso terapêutico , Nefrite Intersticial/tratamento farmacológico , Nefrite Intersticial/imunologia
6.
Biomarkers ; 25(2): 194-200, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32024392

RESUMO

Purpose: We examined the relationship between autoantibodies to erythropoietin receptor (EPOR) and renal outcome in patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV).Materials and methods: Sixty-three Japanese patients with AAV were enrolled and followed for a median of 31.4 months. Patients were screened for serum anti-EPOR antibodies using an enzyme-linked immunosorbent assay. Associations of anti-EPOR antibodies with clinical parameters were analyzed using logistic-regression models.Results: Anti-EPOR antibodies were detected in 7 (11%) of the 63 patients, and levels of the antibodies decreased with immunosuppressive therapy. The presence of anti-EPOR antibodies was associated with a higher Birmingham vasculitis activity score. In addition, anti-EPOR antibodies were more frequently observed in patients with renal outcomes, which was defined as a sustained 50% reduction in the estimated glomerular filtration rate from baseline, than in those without. Multiple logistic regression analysis revealed that presence of anti-EPOR antibodies, as well as age at disease onset, were as risk factors for the renal outcome.Conclusion: Anti-EPOR antibodies were associated with the progression of renal dysfunction in patients with AAV.


Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/imunologia , Autoanticorpos/sangue , Nefropatias , Receptores da Eritropoetina/imunologia , Adulto , Idade de Início , Idoso , Progressão da Doença , Feminino , Taxa de Filtração Glomerular , Humanos , Japão , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Fatores de Risco
7.
Am J Kidney Dis ; 75(1): 124-137, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31358311

RESUMO

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a group of disorders characterized by inflammation and destruction of small- and medium-sized blood vessels and the presence of circulating ANCA. Clinical disease phenotypes include granulomatosis with polyangiitis, microscopic polyangiitis, eosinophilic granulomatosis with polyangiitis, and renal-limited vasculitis. Serologic classification of AAV into proteinase 3-ANCA disease and myeloperoxidase-ANCA disease correlates with a number of disease characteristics. AAV has a predilection for the kidney, with >75% of patients having renal involvement characterized by rapidly progressive glomerulonephritis. The cause and pathogenesis of AAV are multifactorial and influenced by genetics, environmental factors, and responses of the innate and adaptive immune system. Randomized controlled trials in the past 2 decades have refined the therapy of AAV and transformed AAV from a fatal disease to a chronic illness with relapsing course and associated morbidity. This article in AJKD's Core Curriculum in Nephrology series provides a detailed review of the epidemiology, pathogenesis, diagnosis, and advances in the management of AAV.


Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/terapia , Glomerulonefrite/terapia , Glucocorticoides/uso terapêutico , Imunossupressores/uso terapêutico , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/genética , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/imunologia , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/patologia , Anticorpos Anticitoplasma de Neutrófilos/imunologia , Síndrome de Churg-Strauss/genética , Síndrome de Churg-Strauss/imunologia , Síndrome de Churg-Strauss/patologia , Síndrome de Churg-Strauss/terapia , Ciclofosfamida/uso terapêutico , Progressão da Doença , Glomerulonefrite/genética , Glomerulonefrite/imunologia , Glomerulonefrite/patologia , Granulomatose com Poliangiite/genética , Granulomatose com Poliangiite/imunologia , Granulomatose com Poliangiite/patologia , Granulomatose com Poliangiite/terapia , Humanos , Transplante de Rim , Poliangiite Microscópica/genética , Poliangiite Microscópica/imunologia , Poliangiite Microscópica/patologia , Poliangiite Microscópica/terapia , Ácido Micofenólico/uso terapêutico , Mieloblastina/imunologia , Peroxidase/imunologia , Indução de Remissão , Diálise Renal , Rituximab/uso terapêutico
9.
Autoimmun Rev ; 19(1): 102424, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31734405

RESUMO

Anti-neutrophil cytoplasmic autoantibodies (ANCA)-associated vasculitides (AAVs) are small vessel vasculitides involving predominantly ear-nose-throat, kidneys, lungs and nerves. AAVs are life-threatening diseases, especially in their most severe forms such as necrotizing crescentic glomerulonephritis (GN) and/or intra-alveolar hemorrhage. Unlike immune complex GN or anti-glomerular basement membrane GN, AAVs are classified as pauci-immune GN. However, based on recent insights from animal models, the view of AAVs as a complement-unrelated disease has been challenged. Indeed, complement activation, and especially complement alternative pathway (cAP) activation, has been shown to be determinant in AAV pathogenesis through C5a generation, a potent chemoattractant for neutrophils with priming capacities. Here, we review in vitro and in vivo data supporting the role of cAP in murine models and in human AAVs. These findings, together with the need to eradicate glucocorticoid toxicity, led to the development of an anti-C5aR molecule, CCX168, also known as avacopan. Its development and future opportunities are also discussed.


Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/imunologia , Via Alternativa do Complemento , Animais , Ativação do Complemento , Proteínas do Sistema Complemento/imunologia , Glomerulonefrite/imunologia , Humanos , Camundongos
10.
J Immunol Res ; 2019: 5071687, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31815154

RESUMO

Autophagy is an important biology process, central to the maintenance of biology process in both physiological and pathological situations. It is regarded as a "double-edged sword"-exerting both protective and/or detrimental effects. These two-way effects are observed in immune cells as well as renal resident cells, including podocytes, mesangial cells, tubular epithelial cells, and endothelial cells of the glomerular capillaries. Mounting evidence suggests that autophagy is implicated in the pathological process of various immune-related renal diseases (IRRDs) as well as the kidney that underwent transplantation. Here, we provide an overview of the pathological role of autophagy in IRRDs, including lupus nephritis, IgA nephropathy, membrane nephropathy, ANCA-associated nephritis, and diabetic nephropathy. The understanding of the pathogenesis and regulatory mechanisms of autophagy in these renal diseases may lead to the identification of new diagnostic targets and refined therapeutic modulation.


Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/imunologia , Proteínas Relacionadas à Autofagia/imunologia , Autofagia/imunologia , Nefropatias Diabéticas/imunologia , Glomerulonefrite por IGA/imunologia , Hematúria/imunologia , Nefrite Lúpica/imunologia , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/genética , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/patologia , Anticorpos Anticitoplasma de Neutrófilos/biossíntese , Anticorpos Anticitoplasma de Neutrófilos/imunologia , Autofagia/genética , Proteínas Relacionadas à Autofagia/genética , Linfócitos B/imunologia , Linfócitos B/patologia , Células Dendríticas , Nefropatias Diabéticas/genética , Nefropatias Diabéticas/patologia , Regulação da Expressão Gênica , Glomerulonefrite por IGA/genética , Glomerulonefrite por IGA/patologia , Hematúria/genética , Hematúria/patologia , Humanos , Transplante de Rim , Nefrite Lúpica/genética , Nefrite Lúpica/patologia , Macrófagos/imunologia , Macrófagos/patologia , Células Mesangiais/imunologia , Células Mesangiais/patologia , Podócitos/imunologia , Podócitos/patologia , Linfócitos T/imunologia , Linfócitos T/patologia
11.
Mediators Inflamm ; 2019: 8421479, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31885499

RESUMO

Antineutrophil cytoplasmic antibody- (ANCA-) associated vasculitis (AAV) is characterized by small-vessel inflammation in association with autoantibodies. Balance between T follicular helper (Tfh) cells and T follicular regulatory (Tfr) cells is critical for humoral immune responses. Accumulating evidence supports that Tfh and Tfr are involved in autoimmune diseases; however, their roles in AAV are unclear. In this study, we tested the changes of circulatory Tfh and Tfr in patients with AAV. Twenty patients with AAV and twenty healthy controls were enrolled. Sixteen AAV patients had kidney involvement. We found that the AAV patients had increased circulating Tfh cells (CD4+CXCR5+CD25-CD127interm-hi), decreased Tfr cells (CD4+CXCR5+CD25+CD127lo-interm), and elevated Tfh/Tfr ratios compared with healthy controls (P < 0.01). The Tfh percentage and Tfh/Tfr ratio, but not Tfr percentage, were positively correlated to proteinuria levels and BVAS scores in patients with AAV (P < 0.01). In addition, AAV patients had decreased circulating Tfh1 (CCR6-CXCR3+), but increased Tfh2 cells (CCR6-CXCR3-), compared with healthy controls (P < 0.01), indicating a Tfh1-to-Tfh2 shift. Furthermore, remission achieved by immunosuppressive treatment markedly attenuated the increase of total Tfh (P < 0.01) and Tfh2 cells (P < 0.05), promoted the Tfh1 response (P < 0.05), and recovered the balance between Tfh/Tfr cells (P < 0.05) and between Tfh1/Tfh2 cells (P < 0.05) in patients with AAV. Plasma levels of IL-21, a cytokine secreted by Tfh cells, were elevated in AAV patients compared with healthy controls (P < 0.01), which was attenuated by immunosuppressive treatment (P < 0.05). Taken together, our findings indicate that circulatory Tfh/Tfr ratios, Tfh2/Tfh1 shift, and plasma IL-21 levels are associated with AAV and disease activity.


Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/imunologia , Linfócitos T Auxiliares-Indutores/citologia , Linfócitos T Reguladores/citologia , Lesão Renal Aguda/imunologia , Idoso , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/sangue , Ensaio de Imunoadsorção Enzimática , Feminino , Citometria de Fluxo , Humanos , Interleucinas/sangue , Masculino , Pessoa de Meia-Idade , Linfócitos T Auxiliares-Indutores/imunologia , Linfócitos T Reguladores/imunologia
12.
Int J Mol Sci ; 20(23)2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31756913

RESUMO

: Background: The role of the T helper 17 (Th17) cell subset in anti-neutrophil cytoplasm antibodies (ANCA) associated vasculitis (AAV) is controversial. We hypothesized that a specific Th17 response to myeloperoxidase (MPO) or proteinase 3 (PR3) is detectable in AAV patients and is different among the disease phases. METHODS: We analyzed 43 AAV patients with renal involvement (21 acute and 22 remission patients), and 12 healthy controls. Peripheral blood mononuclear cells (PBMCs) were cultured with PR3/MPO over 48 h. Thereafter, frequencies of MPO/PR3-specific Th17 cells were assessed using an enzyme-linked immunosorbent spot (ELISpot) assay. Supernatant IL-17 concentration was quantified using ELISA. Finally, specific Th17 response after depletion of T regulatory lymphocytes (T-regs) in some remission patients was compared to the non T-reg-depleted response. RESULTS: Specific Th17 cell number was higher in acute patients compared to remission (p = 0.004). Specific Th17 cell number performed well in the disease activity detection (ROC curve area under the curve (AUC) = 0.87; p = 0.0001) with an optimal cut-off of 6 spots/million. Patients above this cut-off showed higher serum creatinine (p = 0.004), C-reactive protein (CRP) (p = 0.001) and ANCA titer (p = 0.032). Supernatant IL-17 concentration was higher in acute patients compared to remission (p = 0.035) and did not normalize to healthy control levels (p = 0.01). CONCLUSIONS: A specific Th17 cell response is present in AAV patients. This response is more pronounced in the acute phase, but persists in remission.


Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/diagnóstico , Células Th17/imunologia , Adulto , Idoso , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/sangue , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/imunologia , Biomarcadores/sangue , ELISPOT/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mieloblastina/imunologia , Peroxidase/imunologia , Testes Sorológicos/métodos
13.
Medicine (Baltimore) ; 98(48): e18178, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31770269

RESUMO

RATIONALE: Occasionally, tubulointerstitial lesions can be found in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). However, significantly isolated tubulointerstitial nephritis (TIN) with germinal centers is rare. PATIENT CONCERNS: A 17-year-old Chinese Han patient showed rapidly progressive glomerulonephritis, anuria, and serum creatinine of 19.4 mg/dL. DIAGNOSIS: He had positive ANCA targeting myeloperoxidase (55.0 RU/mL). The renal biopsy showed crescent formation in 100% of glomeruli. Of special note, the glomerular crescents were surrounded by granulomatous inflammation, extensive tubular destruction or disappearance, and massive interstitial infiltration. A diagnosis of AAV was thus made with the involved organ restricted to the kidney. INTERVENTIONS: The patient underwent 7 rounds of plasmapheresis, 3 pulses of methylprednisolone therapy (500 mg per pulse), and oral prednisolone (50 mg/d). Rituximab (500 mg) was used after the plasma exchange treatment. OUTCOMES: ANCA was negative, while anti-modified C-reactive protein (anti-mCRP) antibodies remained positive. The patient was dependent on hemodialysis. We found anti-mCRP antibody in the serum of the patient, with the major epitope on amino acids 35 to 47 of mCRP. LESSONS: We proposed that the anti-mCRP antibody might play an important role in this case of acute TIN in AAV.


Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos , Proteína C-Reativa/imunologia , Glucocorticoides/administração & dosagem , Nefrite Intersticial , Troca Plasmática/métodos , Plasmaferese/métodos , Rituximab/administração & dosagem , Adolescente , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/diagnóstico , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/imunologia , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/fisiopatologia , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/terapia , Anticorpos Anticitoplasma de Neutrófilos/sangue , Progressão da Doença , Centro Germinativo/patologia , Humanos , Fatores Imunológicos/administração & dosagem , Testes de Função Renal/métodos , Glomérulos Renais/patologia , Glomérulos Renais/fisiopatologia , Masculino , Nefrite Intersticial/diagnóstico , Nefrite Intersticial/imunologia , Nefrite Intersticial/fisiopatologia , Nefrite Intersticial/terapia , Resultado do Tratamento
14.
BMC Pulm Med ; 19(1): 194, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31675941

RESUMO

BACKGROUND: Myeloperoxidase anti-neutrophil cytoplasmic antibody-related nephritis (MPO-ANCA nephritis) is occasionally accompanied by lung abnormalities such as pulmonary fibrosis. However, the clinical features of pulmonary fibrosis in patients with MPO-ANCA nephritis have not been well documented. This study was performed to compare the prognosis of a usual interstitial pneumonia (UIP) pattern of lung fibrosis in patients with MPO-ANCA nephritis with the prognosis of idiopathic pulmonary fibrosis (IPF). METHODS: We retrospectively reviewed the medical records of 126 patients with MPO-ANCA nephritis and identified 31 with a UIP pattern of lung fibrosis on high-resolution or thin-slice computed tomography (CT). We compared the characteristics and prognosis of these patients with those of 32 patients with IPF. In 18 patients from both groups, we assessed and compared the decline in lung volume over time using three-dimensional (3D) CT images reconstructed from thin-section CT data. RESULTS: The numbers of male and female patients were nearly equal among patients with MPO-ANCA nephritis exhibiting a UIP pattern; in contrast, significant male dominancy was observed among patients with IPF (p = 0.0021). Significantly fewer smokers were present among the patients with MPO-ANCA nephritis with a UIP pattern than among those with IPF (p = 0.0062). There was no significant difference in the median survival time between patients with MPO-ANCA nephritis with a UIP pattern (50.8 months) and IPF (55.8 months; p = 0.65). All patients with IPF in this cohort received antifibrotic therapy (pirfenidone or nintedanib). Almost half of the deaths that occurred in patients with MPO-ANCA nephritis with a UIP pattern were caused by non-respiratory-related events, whereas most deaths in patients with IPF were caused by respiratory failure such as acute exacerbation. In the 3D CT lung volume analyses, the rate of decline in lung volume was equivalent in both groups. CONCLUSIONS: MPO-ANCA nephritis with a UIP pattern on CT may have an unfavorable prognosis equivalent to that of IPF with a UIP pattern treated with antifibrotic agents.


Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/imunologia , Fibrose Pulmonar Idiopática/diagnóstico por imagem , Pulmão/patologia , Nefrite/imunologia , Fibrose Pulmonar/diagnóstico por imagem , Idoso , Idoso de 80 Anos ou mais , Anticorpos Anticitoplasma de Neutrófilos/sangue , Causas de Morte , Feminino , Humanos , Fibrose Pulmonar Idiopática/mortalidade , Imageamento Tridimensional , Pulmão/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Peroxidase/imunologia , Prognóstico , Fibrose Pulmonar/mortalidade , Insuficiência Respiratória/etiologia , Estudos Retrospectivos , Taxa de Sobrevida , Tomografia Computadorizada por Raios X
15.
Nephrol Ther ; 15(6): 409-412, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31631015

RESUMO

A role for the alternative complement pathway has emerged in the understanding of ANCA vasculitis pathogenesis. Current therapies of ANCA vasculitis are limited by partial efficacy and toxicity and many patients pursue a relapsing course. Improved therapies are needed. Inhibition of the alternative complement pathway component C5a is attractive due to its role in neutrophil activation and migration, and engagement of other inflammatory and thrombotic mechanisms. Two inhibitors of C5a are in clinical development for ANCA vasculitis: avacopan, an oral C5a receptor inhibitor has demonstrated efficacy, safety and steroid sparing in two Phase II trials; and IFX-1, a monoclonal antibody to C5a which is entering Phase II development. Complement inhibition has the potential to contribute to remission induction protocols achieving a higher quality of remission as well as replacing steroids. Confirmation of safety, especially infective risk, and the potential to replace steroids depends on further studies and a role in relapse prevention needs to be explored.


Assuntos
Compostos de Anilina/uso terapêutico , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/imunologia , Complemento C5a/antagonistas & inibidores , Inativadores do Complemento/uso terapêutico , Via Alternativa do Complemento/efeitos dos fármacos , Ácidos Nipecóticos/uso terapêutico , Compostos de Anilina/farmacologia , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/tratamento farmacológico , Ensaios Clínicos Fase II como Assunto , Complemento C5a/imunologia , Inativadores do Complemento/farmacologia , Humanos , Ativação de Neutrófilo/efeitos dos fármacos , Ácidos Nipecóticos/farmacologia
16.
Int J Rheum Dis ; 22(12): 2143-2150, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31631507

RESUMO

AIM: The characteristics and the pathogenesis of the concomitant antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) and immunoglobulin G4-related disease (IgG4-RD) have not been elucidated. METHOD: We included 92 AAV patients with renal biopsy results. Among them, 10 patients met both AAV and IgG4-RD criteria (concomitant group). The IgG subclasses of myeloperoxidase (MPO)-ANCA in both serum and renal tissue were measured and complement activation components were detected in serum. RESULTS: Patients in the concomitant group had both elevated serum IgG4 levels and positive MPO-ANCA. They had higher levels of eosinophil counts, serum globulin, IgG, IgE and C-reactive protein than patients in the AAV alone group. All 10 patients had glomerulonephritis with crescents and seven patients also had segmental necrosis of the glomerular capillary wall. Most of them also presented with storiform fibrosis and lymphoplasmacytic infiltration in renal interstitium with IgG4 positive plasma cells more than 10/high-power field. Eight patients achieved remission with improved renal function, the other two patients were on maintenance dialysis. The IgG4 subclass of MPO-ANCA was higher in the concomitant group than that in AAV alone group. A merge of IgG4 and MPO immunofluorescence was observed in parts of the mesangium of concomitant AAV and IgG4-RD patients. For complement components, Bb and mannose-binding lectin were elevated in serum of concomitant AAV and IgG4-RD patients. CONCLUSION: We showed a new overlap syndrome of AAV and IgG4-RD, in which the IgG4 subclass of ANCA may be a pathogenic factor.


Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/diagnóstico , Anticorpos Anticitoplasma de Neutrófilos/sangue , Doença Relacionada a Imunoglobulina G4/diagnóstico , Imunoglobulina G/sangue , Nefropatias/diagnóstico , Rim/imunologia , Peroxidase/imunologia , Idoso , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/sangue , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/imunologia , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/patologia , Biomarcadores/sangue , Proteína C-Reativa/metabolismo , Estudos de Casos e Controles , Ativação do Complemento , Proteínas do Sistema Complemento/metabolismo , Feminino , Humanos , Imunoglobulina E/sangue , Doença Relacionada a Imunoglobulina G4/sangue , Doença Relacionada a Imunoglobulina G4/imunologia , Doença Relacionada a Imunoglobulina G4/patologia , Rim/patologia , Nefropatias/sangue , Nefropatias/imunologia , Nefropatias/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico
17.
Ren Fail ; 41(1): 907-913, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31658846

RESUMO

Background: The characteristic lesion of pauci-immune glomerulonephritis is focal necrotizing and crescentic glomerulonephritis. The underlying mechanisms in the formation or progression of crescent formation need further investigations. Therefore, we aimed to evaluate the role of mammalian target of rapamycin (mTOR), which might be a potential therapeutic target, in kidney biopsies of patients with pauci-immune glomerulonephritis. Methods: The patients diagnosed as pauci-immune glomerulonephritis at an outpatient nephrology clinic were retrospectively reviewed and those patients who had a kidney biopsy before receiving an immunosuppressive treatment were included in the study. Kidney biopsy specimens were immunohistochemically stained with mTOR, antibodies of phosphatase and tensin homolog (PTEN) and transforming growth factor-ß (TGF-ß) and scored by an experienced renal pathologist. Results: In total, 54 patients with pauci-immune glomerulonephritis (28 [52%] female) were included. According to the histopathologic examination, 22% of our cases were classified as focal, 33% crescentic, 22% mixed, and 22% as sclerotic. The mTOR was expressed in substantial percentages of glomeruli of patients with pauci-immune glomerulonephritis. However, we observed PTEN expression in all samples and mTOR in all tubulointerstitial areas. mTOR expression was found to be related with the presence of crescentic and sclerotic changes observed in glomeruli and the degree of fibrosis in interstitial areas. Serum creatinine level or response to treatment was not found to be associated with mTOR pathway expression. Conclusion: Our results suggest that mTOR pathway may play role in the pathogenesis of pauci-immune glomerulonephritis, besides targeting this signaling may be an alternative option for those patients.


Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/complicações , Glomerulonefrite/imunologia , Glomérulos Renais/patologia , Transdução de Sinais/imunologia , Serina-Treonina Quinases TOR/metabolismo , Adulto , Idoso , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/tratamento farmacológico , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/imunologia , Autoanticorpos/imunologia , Autoanticorpos/isolamento & purificação , Biópsia , Progressão da Doença , Feminino , Glomerulonefrite/tratamento farmacológico , Glomerulonefrite/patologia , Humanos , Imuno-Histoquímica , Imunossupressores/farmacologia , Imunossupressores/uso terapêutico , Glomérulos Renais/irrigação sanguínea , Glomérulos Renais/imunologia , Masculino , Pessoa de Meia-Idade , PTEN Fosfo-Hidrolase/imunologia , PTEN Fosfo-Hidrolase/metabolismo , Estudos Retrospectivos , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/antagonistas & inibidores , Serina-Treonina Quinases TOR/imunologia , Fator de Crescimento Transformador beta/imunologia , Fator de Crescimento Transformador beta/metabolismo
18.
Int J Rheum Dis ; 22(10): 1926-1932, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31571413

RESUMO

BACKGROUND: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and immunoglobulin G4-related disease (IgG4-RD) have some common features. The co-occurrence/concurrence of AAV and IgG4-RD was recently published by the collaborative European Vasculitis Study Group. First, we aimed to investigate ANCA positivity of our IgG4-RD cohort. Second, a literature review of co-occurrence/concurrence of AAV and IgG4-RD was done. METHODS: Data of 62 patients with IgG4-RD in Hacettepe Vasculitis Center Database were used. Patient dataset was designed to include demographic data, clinical characteristics, imaging and IgG4-RD, AAV and ANCA test results. At the next step, we performed a systematic literature review in PUBMED database covering the time period from 1976 until April 2018. Relevant publications were searched using these MeSH terms ''IgG4-related disease and Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis'', "IgG4-related disease and Eosinophilic Granulomatosis with Polyangiitis", "IgG4-related disease and Microscopic Polyangiitis" and "IgG4-related disease and Granulomatosis with Polyangiitis". RESULTS: Three (10.3%) of 29 patients had low titer ANCA positivity. These three patients didn't have any findings of vasculitis and no granuloma was seen in biopsy. In the literature review, we found 17 cases had features of both IgG4-RD and AAV. These cases were re-evaluated according to the Comprehensive Diagnostic Criteria for IgG4-RD. ANCA were positive in 15 of 17 patients (88%). CONCLUSION: None of our IgG4-RD patients overlapped with AAV. Only two patients in the literature review seemed to be fully compatible with both diseases. Even though AAV and IgG4-RD share similar clinical features, we think this might be a co-occurrence instead of a histopathological link.


Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/diagnóstico , Anticorpos Anticitoplasma de Neutrófilos/imunologia , Doença Relacionada a Imunoglobulina G4/diagnóstico , Imunoglobulina G/imunologia , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/sangue , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/imunologia , Anticorpos Anticitoplasma de Neutrófilos/sangue , Biomarcadores/sangue , Biópsia , Ensaio de Imunoadsorção Enzimática , Feminino , Seguimentos , Humanos , Imunoglobulina G/sangue , Doença Relacionada a Imunoglobulina G4/sangue , Doença Relacionada a Imunoglobulina G4/imunologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
19.
Clin Exp Nephrol ; 23(12): 1373-1381, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31485791

RESUMO

BACKGROUND: When we encounter glomerulonephritis of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides demonstrating many plasma cell infiltrations, histological overlapping of immunoglobulin G4-related disease (IgG4-RD) often comes into the differential diagnosis. No previous study has focused on the degree of plasma cells in the kidney infiltrate in ANCA-associated glomerulonephritis (ANCA-GN), and the significance of massive plasma cell infiltrate has not been investigated. METHODS: To clarify the plasma cell ratio in renal biopsy specimens of ANCA-GN and the histological characteristic of "plasma cell-rich" ANCA-GN, 20 cases of ANCA-GN were reviewed and clinicopathologically analyzed. RESULTS: Plasma cell ratio was widely distributed between 1.4 and 81%, and the median ratio was 10%. Three patients were categorized in "plasma cell-rich" ANCA-GN, defined as over 45% plasma cell ratio. They tended to include many active glomerular lesions compared to chronic lesions and to display severe tubulointerstitial inflammation. It is suggested that plasma cell-rich ANCA-GN may be acute onset of the disease, and the target of early inflammation may also be in the tubulointerstitial region. Two of the three plasma cell-rich ANCA-GN cases demonstrated numerous IgG4+ cells, but no bird's-eye pattern fibrosis or obliterative phlebitis. CONCLUSIONS: Plasma cell-rich ANCA-GN is not rare and demonstrates distinct clinicopathological characteristics. This study also reminds us that the presence of the significant number of plasma cells in ANCA-GN, as such, is not a histological diagnostic basis for overlap ANCA-GN and IgG4-related disease.


Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/imunologia , Anticorpos Anticitoplasma de Neutrófilos/sangue , Glomerulonefrite/imunologia , Glomérulos Renais/imunologia , Plasmócitos/imunologia , Idoso , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/sangue , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/patologia , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/urina , Biomarcadores/sangue , Biomarcadores/urina , Proteína C-Reativa/análise , Diagnóstico Diferencial , Feminino , Glomerulonefrite/sangue , Glomerulonefrite/patologia , Glomerulonefrite/urina , Humanos , Imunoglobulina G/sangue , Doença Relacionada a Imunoglobulina G4/imunologia , Doença Relacionada a Imunoglobulina G4/patologia , Glomérulos Renais/patologia , Masculino , Plasmócitos/patologia , Valor Preditivo dos Testes , Microglobulina beta-2/urina
20.
Int Immunopharmacol ; 76: 105883, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31536905

RESUMO

BACKGROUND: Pulse methylprednisolone (MP) was routinely used before commencing standard immunosuppressive therapy for induction of remission in patients with dialysis-dependent anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) in spite of the paucity of evidence of benefit. The aim of this study was thus to determine whether the addition of pulse MP to standard induction immunosuppressive therapy in severe myeloperoxidase (MPO) -AAV patients who were on dialysis at onset is associated with an improvement in kidney recovery and patient survival. Furthermore, we analyzed the factors associated with restoration of kidney function and mortality in a single Chinese cohort. METHODS: 69 MPO-AAV patients who were on dialysis at the time of diagnosis were included in this study. The MP group (n = 30) received pulse MP (5-10 mg/kg/day) for 3 days before the standard immunosuppressive therapy. The Non-MP group (n = 39) had no MP pulses. The outcomes and adverse events between the two groups were compared. In addition, the predictive value of the clinical and histological parameters for kidney and patient survival was assessed using univariate and multivariate logistic regression analysis. RESULT: There was no difference in patient survival, kidney recovery and the rates of adverse events between the two groups. A higher Birmingham Vasculitis Activity Score (BVAS) was shown to be a negative prognostic factor for kidney function restoration (p = 0.046, OR 0.811, 95% CI 0.660-0.997). BVAS was also demonstrated to be an independent predictor for both all-cause death (p = 0.007, OR 1.324, 95% CI 1.079-1.624) and therapy-related death (p = 0.003, OR 1.574, 95% CI 1.171-2.115). Patients' eGFR at the presentation of the disease was shown to be an independent predictor for therapy-related death (p = 0.027, OR 2.535, 95% CI 1.112-5.779). CONCLUSIONS: This retrospective study of MPO-AAV patients who required dialysis at presentation in a single Chinese center suggests that the addition of pulse MP to standard immunosuppressive induction therapy for remission appears to confer no benefit in terms of improving patient outcomes. Further research is required to determine the role of pulse MP in severe MPO-AAV.


Assuntos
Anti-Inflamatórios/administração & dosagem , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/tratamento farmacológico , Imunossupressores/administração & dosagem , Metilprednisolona/administração & dosagem , Diálise Renal , Adulto , Idoso , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/imunologia , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/fisiopatologia , Anticorpos Anticitoplasma de Neutrófilos/imunologia , Grupo com Ancestrais do Continente Asiático , Feminino , Humanos , Quimioterapia de Indução , Rim/efeitos dos fármacos , Rim/fisiopatologia , Masculino , Pessoa de Meia-Idade , Peroxidase/imunologia , Resultado do Tratamento
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