Adult-Onset ANCA-Associated Vasculitis in SAVI: Extension of the Phenotypic Spectrum, Case Report and Review of the Literature.
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ABSTRACT:
SUBMITTER: Staels F
PROVIDER: S-EPMC7550674 | biostudies-literature | 2020
REPOSITORIES: biostudies-literature
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Project description:In patients with GN or vasculitis, ANCAs are directed against proteinase 3 (PR3) or myeloperoxidase (MPO). The differences between PR3-ANCA-associated vasculitis (AAV) and MPO-AAV described in the past have been supplemented during the last decade. In this review, we discuss the differences between these two small-vessel vasculitides, focusing especially on possible etiologic and pathophysiologic differences. PR3-AAV is more common in northern parts of the world, whereas MPO-AAV is more common in southern regions of Europe, Asia, and the Pacific, with the exception of New Zealand and Australia. A genetic contribution has been extensively studied, and there is a high prevalence of the HLA-DPB1*04:01 allele in patients with PR3-AAV as opposed to patients with MPO-AAV and/or healthy controls. Histologically, MPO-AAV and PR3-AAV are similar but show qualitative differences when analyzed carefully. Clinically, both serotypes are difficult to distinguish, but quantitative differences are present. More organs are affected in PR3-AAV, whereas renal limited vasculitis occurs more often in patients with MPO-AAV. For future clinical trials, we advocate classifying patients by ANCA serotype as opposed to the traditional disease type classification.
| S-EPMC4587702 | biostudies-literature
Project description:T cell-mediated immune responses are thought to play an important role in the pathogenesis of anti-neutrophil cytoplasmic antibody- (ANCA-) associated vasculitides (AAV). CD4+ T cells can be divided into subsets depending on their expression of chemokine receptors. In this study, different CD4+ T cell populations in patients with AAV were analysed and compared to healthy blood donors as well as therapy controls. 18 patients with active AAV, 46 in remission, 21 healthy controls (HBD), and 15 therapy controls (TC) were enrolled. CD4+ T cells were divided into Th1, Th2, and Th17 cells and further subdivided into naïve, central memory, effector memory, and effector cells. Regulatory T cells were also analysed. Concentrations of cytokines and chemokines produced by the respective CD4+ T cell subset in plasma from 33 of the patients were measured by ELISA and compared to HBD. Clinical data were collected on all patients. CCL20 concentrations and percentages of Th17 cells (p = 0.019) were elevated in AAV patients compared to HBD. AAV patients had lower percentages of naïve CD4+ T cells (p = 0.0016) and a corresponding increase in proportion of effector memory CD4+ T cells when comparing to HBD (p = 0.027). Therapy controls showed similar results as AAV patients. In this study, we found that CD4+ T cell phenotype distribution is altered in AAV patients, in line with previously published work. However, no differences were found between AAV patients and TC, stressing the importance of treatment impact on this kind of studies.
| S-EPMC6232803 | biostudies-literature
Project description:ObjectiveThe aim of this study was to clarify the clinical characteristics and long-term outcomes of ANCA-associated vasculitis (AAV) patients with pulmonary involvement from a single Chinese cohort.MethodsNewly diagnosed AAV patients with pulmonary involvement, as defined by CT, were recruited from January 2010 to June 2020. Clinical data and CT images were collected retrospectively. Baseline CTs were evaluated and re-classified into four categories: interstitial lung disease (ILD), airway involvement (AI), alveolar hemorrhage (AH), and pulmonary granuloma (PG).ResultsA total of 719 patients were newly diagnosed with AAV, 366 (50.9%) of whom combined with pulmonary involvement at baseline. Among the AAV cases with pulmonary involvement, 55.7% (204/366) had ILD, 16.7% (61/366) had AI alone, 14.8% (54/366) had PG, and 12.8% (47/366) had AH alone. During follow-up of a median duration of 42.0 months, 66/366 (18.0%) patients died, mainly died from infections. Survival, relapse, and infection were all significantly different based on the radiological features. Specifically, the ILD group tends to have a poor long-term prognosis, the PG group is prone to relapse, and the AI group is apt to infection. The AH group has a high risk of both early infection and relapse, thus a poor short-term prognosis.ConclusionAAV patients with diverse radiological features have different clinical characteristics and outcomes. Therefore, the intensity of immunosuppressive therapy must be carefully valued by considering the baseline CT findings among AAV patients with pulmonary involvement.
| S-EPMC8756656 | biostudies-literature
Project description:Background:Recurrent endometrial cancer after definitive therapy is a lethal disease. Recently, immune checkpoint inhibitors (ICI) have improved the management of mismatch repair-deficient (MSI-H) endometrial cancer. Autoimmune side effects are known to occur with ICI. As a result, patients with preexisting autoimmune diseases are excluded from studies involving these drugs. This has led to challenges in clinical practice regarding the use of ICI in otherwise eligible patients with underlying autoimmune disease. Case Presentation. We present the case of an 81-year-old woman with an underlying autoimmune vasculitis and recurrent, metastatic endometrial adenocarcinoma with microsatellite instability, who was treated with an immune checkpoint inhibitor. This patient received pembrolizumab, an immune checkpoint inhibitor that targets the programmed cell death-1 immune checkpoint. Ultimately, she was treated for 4 months with pembrolizumab and benefited from stable disease during this period. She remained asymptomatic from her underlying autoimmune P-ANCA vasculitis. A review of the scientific literature reveals several cases of the successful use of immune checkpoint inhibitors in patients with autoimmune diseases, including systemic lupus erythematosus, rheumatoid arthritis, and inflammatory bowel disease. Conclusion:This is one of the first reports of a patient with an underlying autoimmune vasculitis successfully treated with an immune checkpoint inhibitor without exacerbating her underlying autoimmune condition. Carefully selected patients with underlying autoimmune vasculitis can be safely treated with ICI.
| S-EPMC7479461 | biostudies-literature
Project description:The prognosis of patients with ANCA-associated vasculitis has improved over the past decades, but overall survival rates are still unsatisfactory. Recent research has focused on complications of immunosuppressive measures and comorbidities of ANCA-associated vasculitis. This review focuses on thromboembolic and cardiovascular events. A considerably increased risk of thromboembolic events has been reported, which is associated with active disease and impaired coagulation factors. There is mounting evidence that a hypercoagulable state is present even in patients in remission, and studies investigating the impact of tailored anticoagulation are needed to reduce the burden of thromboembolism. Cardiovascular mortality is one of the leading causes of death and accelerated atherosclerosis is frequently observed in patients with ANCA-associated vasculitis. A high frequency of patients develops hypertension, diabetes mellitus and hypercholesterolaemia, either as a consequence of immunosuppression or associated with the underlying disease. The current control of modifiable cardiovascular risk factors is insufficient and thorough reviews should be performed periodically. Treatment of these risk factors should be adopted according to current recommendations related to individual cardiovascular risk prediction.
| S-EPMC7190116 | biostudies-literature
Project description:Antineutrophil cytoplasm antibody (ANCA)-associated vasculitides are small-vessel vasculitides that include granulomatosis with polyangiitis (formerly Wegener's granulomatosis), microscopic polyangiitis, and eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome). Renal-limited ANCA-associated vasculitides can be considered the fourth entity. Despite their rarity and still unknown cause(s), research pertaining to ANCA-associated vasculitides has been very active over the past decades. The pathogenic role of antimyeloperoxidase ANCA (MPO-ANCA) has been supported using several animal models, but that of antiproteinase 3 ANCA (PR3-ANCA) has not been as strongly demonstrated. Moreover, some MPO-ANCA subsets, which are directed against a few specific MPO epitopes, have recently been found to be better associated with disease activity, but a different method than the one presently used in routine detection is required to detect them. B cells possibly play a major role in the pathogenesis because they produce ANCAs, as well as neutrophil abnormalities and imbalances in different T-cell subtypes [T helper (Th)1, Th2, Th17, regulatory cluster of differentiation (CD)4+ CD25+ forkhead box P3 (FoxP3)+ T cells] and/or cytokine-chemokine networks. The alternative complement pathway is also involved, and its blockade has been shown to prevent renal disease in an MPO-ANCA murine model. Other recent studies suggested strongest genetic associations by ANCA type rather than by clinical diagnosis. The induction treatment for severe granulomatosis with polyangiitis and microscopic polyangiitis is relatively well codified but does not (yet) really differ by precise diagnosis or ANCA type. It comprises glucocorticoids combined with another immunosuppressant, cyclophosphamide or rituximab. The choice between the two immunosuppressants must consider the comorbidities, past exposure to cyclophosphamide for relapsers, plans for pregnancy, and also the cost of rituximab. Once remission is achieved, maintenance strategy following cyclophosphamide-based induction relies on less toxic agents such as azathioprine or methotrexate. The optimal maintenance strategy following rituximab-based induction therapy remains to be determined. Preliminary results on rituximab for maintenance therapy appear promising. Efforts are still under way to determine the optimal duration of maintenance therapy, ideally tailored according to the characteristics of each patient and the previous treatment received.
| S-EPMC5058451 | biostudies-literature
Project description:Efficacy of immunosuppressive treatment of Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is complicated by its toxicity. With the replacement of cyclophosphamide with rituximab, serious adverse events seem to be associated especially with high-dose corticosteroids. Activation of alternative complement pathway plays an important role in the pathogenesis of AAV. Avacopan (C5a receptor inhibitor) was demonstrated to have at least similar efficacy and better safety (in terms of corticosteroid-related adverse events) compared with high-dose corticosteroids in the induction treatment of AAV. Other modes of the inhibition of alternative complement pathway are currently tested in AAV or could be considered on the basis of the experience in other glomerular diseases.
| S-EPMC9307875 | biostudies-literature
Project description:IntroductionThe value of antineutrophil cytoplasmic antibody (ANCA) measurements among patients with an established diagnosis of ANCA-associated vasculitis (AAV) to assess disease activity or predict relapse remains controversial, but recent evidence suggests a possible role for rituximab-treated patients.Patients and methodsAll patients with active vasculitis and positive proteinase 3 (PR3)-ANCA who were starting a 2-year treatment course of rituximab for induction of remission at Addenbrooke's Hospital between January 2011 and January 2016 were included in this study. Common department practice consists of 6 g of rituximab given over 2 years, concomitant corticosteroids (0.5-1.0 mg/kg) with rapid taper over 3 months, and cessation of oral maintenance immunosuppressive agents at time of first rituximab dose. Clinical and laboratory data were collected retrospectively using electronic patient records.ResultsFifty-seven patients with current PR3-ANCA positivity were included in the analysis. Median follow-up was 59 months. PR3-ANCA negativity was achieved in 25 patients (44%) with a median time of 14 months. Clinical remission was achieved in 53 patients (93%) with a median time of 3 months. Among the 53 patients who achieved remission during follow-up, 24 (45%) relapsed with a median time to relapse of 36 months from remission. Both PR3-ANCA-negative status and 50% reduction in PR3-ANCA from baseline (as time-varying covariates) were significantly associated with a longer time to relapse (PR3-ANCA-negative status: hazards ratio, 0.08 [95% confidence interval, 0.01-0.63, p = 0.016]; 50% reduction in PR3-ANCA: hazards ratio, 0.25 [95% confidence interval, 0.18-0.99, p = 0.046]).ConclusionsAchieving and maintaining PR3-ANCA negativity after rituximab was associated with longer-lasting remission.
| S-EPMC7612177 | biostudies-literature
Project description:BACKGROUND:Mutations occurring in the orthodenticle homeobox 2 gene (OTX2) are responsible for a rare genetic syndrome, characterized mainly by microphthalmia/anophthalmia associated with extra-ocular defects such as brain malformations, pituitary abnormalities, short stature and intellectual disability. To date, the spectrum of radiological features observed in patients with OTX2 mutations has never been summarized. CASE PRESENTATION:In this report, we describe a case of large microdeletion encompassing OTX2 but not BMP4 presenting with a syndromic anophthalmia with corpus callosum hypoplasia, pituitary gland hypoplasia and vermian hypoplasia. CONCLUSION:Our case report provides an illustration of the neuroradiological spectrum in a case of OTX2-related syndrome and the first radiological evidence of 14q22.2q23.1 deletion associated posterior cranial fossa anomalies.
| S-EPMC6162925 | biostudies-literature
Project description:Autoantibodies to neutrophil cytoplasmic antigen-associated vasculitis (AAV) is characterised by inflammation of blood vessels. The introduction of immunosuppressive therapy with glucocorticoids and cyclophosphamide transformed AAV from a fatal condition to a largely treatable condition. Over the past 30 years, considerable progress has been made refining immunosuppressive regimens with a focus on minimising toxicity. There is, however, a high unmet need in the treatment of AAV. A proportion of patients are refractory to current therapies; 50% experience a relapse within 5 years and treatment toxicity contributes to mortality and chronic disability. As knowledge of the pathogenesis of vasculitis grows, it is mirrored by the availability of biological agents, which herald a revolution in the treatment of vasculitis. Lymphocyte-targeted and cytokine-targeted agents have been evaluated for the treatment of AAV and are entering the routine therapeutic arena with the potential to improve patient outcomes. As rare diseases, treatment advances in vasculitis depend on international collaborative research networks both to establish an evidence base for newer agents and to develop recommendations for patient management.
| S-EPMC3446448 | biostudies-literature