Infective endocarditis (IE) may be misdiagnosed as ANCA-associated vasculitis (AAV), especially when antineutrophil cytoplasmic antibodies (ANCA) are detected. Distinguishing IE from AAV is crucial... Show moreInfective endocarditis (IE) may be misdiagnosed as ANCA-associated vasculitis (AAV), especially when antineutrophil cytoplasmic antibodies (ANCA) are detected. Distinguishing IE from AAV is crucial to guide therapy. However, little is known about ANCA positivity in IE patients. We present a case report and systematic review of the literature on patients with ANCA-positive IE, aiming to provide a comprehensive overview of this entity and to aid clinicians in their decisions when encountering a similar case. A systematic review of papers on original cases of ANCA-positive IE without a previous diagnosis of AAV was conducted on PubMed in accordance with PRISMA-IPD guidelines. A predefined set of clinical, laboratory, and kidney biopsy findings was extracted for each patient and presented as a narrative and quantitative synthesis. A total of 74 reports describing 181 patients with ANCA-positive IE were included (a total of 182 cases including our own case). ANCA positivity was found in 18-43% of patients with IE. Patients usually presented with subacute IE (73%) and had positive cytoplasmic ANCA-staining or anti-proteinase-3 antibodies (79%). Kidney function was impaired in 72%; kidney biopsy findings were suggestive of immune complexes in 59%, while showing pauci-immune glomerulonephritis in 37%. All were treated with antibiotics; 39% of patients also received immunosuppressants. During follow-up, 69% of patients became ANCA-negative and no diagnosis of systemic vasculitis was reported. This study reviewed the largest series of patients with ANCA-positive IE thus far and shows the overlap in clinical manifestations between IE and AAV. We therefore emphasize that clinicians should be alert to the possibility of an underlying infection when treating a patient with suspected AAV, even when reassured by ANCA positivity. Show less
Background. The primary challenge of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) patient care is the early detection of relapses to prevent organ damage and increase... Show moreBackground. The primary challenge of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) patient care is the early detection of relapses to prevent organ damage and increase survival. Potential biomarkers for relapses are ANCA and B cells, but their predictive value is a matter of debate. Therefore this study investigated how ANCA and B-cell status related to relapses in AAV patients treated with rituximab (RTX) as remission induction (RI).Methods. This single-centre cohort study identified 110 ANCA-positive AAV patients treated with RTX between 2006 and 2018. Serial ANCA, CD19(+) B-cell status and relapses were assessed >2years.Results. Patients (31/110) relapsed within 2years after RTX RI treatment. Patients who achieved and maintained PR3-ANCA negativity (n=29) had few relapses (3%), while persistent proteinase 3 (PR3)-ANCA positivity (n=49) and reappearance of PR3-ANCAs (n=10) associated significantly with more relapses (37%, P=0.002 and 50%, P=0.002). Patients with incomplete B-cell depletion (n=11) had significantly more relapses (54%) as compared with patients with B-cell depletion [n=76 (26%), P=0.02]. Also, patients with repopulation of B cells (n=58) had significantly more relapses (41%) as compared with patients without B-cell repopulation [n=27 (15%), P=0.03]. Overall, the absence of PR3- or myeloperoxidase (MPO)-ANCA positivity was highly predictive for remaining relapse-free. In PR3-ANCA-positive patients, 96% of the relapses occurred with persistent or reappearance of PR3-ANCAs and 81% with B-cell repopulation. In MPO-ANCA-positive patients, all relapses were restricted to patients with persistent MPO-ANCAs and B-cell repopulation.Conclusions. Upon RI treatment with RTX in AAV patients, ANCA and B-cell status were predictive of the majority of relapses and specifically their absence strongly predicted a relapse-free status. Therefore the implementation of ANCA and B-cell monitoring could guide therapeutic decision-making to prevent relapses in AAV patients treated with RTX. Show less
Background and objectives The histopathologic classification for ANCA-associated GN distinguishes four classes on the basis of patterns of injury. In the original validation study, these classes... Show moreBackground and objectives The histopathologic classification for ANCA-associated GN distinguishes four classes on the basis of patterns of injury. In the original validation study, these classes were ordered by severity of kidney function loss as follows: focal, crescentic, mixed, and sclerotic. Subsequent validation studies disagreed on outcomes in the crescentic and mixed classes. This study, driven by the original investigators, provides several analyses in order to determine the current position of the histopathologic classification of ANCA-associated GN.Design, setting, participants, & measurements Avalidation study was performed with newly collected data from 145 patients from ten centers worldwide, including an analysis of interobserver agreement on the histopathologic evaluation of the kidney biopsies. This study also included a meta-analysis on previous validation studies and a validation of the recently proposed ANCA kidney risk score.Results The validation study showed that kidney failure at 10-year follow-up was significantly different between the histopathologic classes (P < 0.001). Kidney failure at 10-year follow-up was 14% in the crescentic class versus 20% in the mixed class (P=0.98). In themeta-analysis, no significant difference in kidney failure was also observed when crescentic class was compared with mixed class (relative risk, 1.15; 95% confidence interval, 0.94 to 1.41). When we applied the ANCA kidney risk score to our cohort, kidney survival at 3 years was 100%, 96%, and 77% in the low-, medium-, andhigh-risk groups, respectively (P<0.001). These survival percentages are higher compared with the percentages in the original study.Conclusions The crescentic and mixed classes seem to have a similar prognosis, also after adjusting for differences in patient populations, treatment, and interobserver agreement. However, at this stage, we are not inclined to merge the crescentic and mixed classes because the reported confidence intervals do not exclude important differences in prognosis and because an important histopathologic distinction would be lost. Show less
Bajema, I.M.; Bruijn, J.A.; Casian, A.; Cid, M.C.; Csernok, E.; Daalen, E. van; ... ; Jayne, D. 2017
The complement system has been shown to have a role in various systemic autoimmune (AI) diseases which have a renal component. This includes systemic lupus erythematosus (SLE), goodpastures... Show moreThe complement system has been shown to have a role in various systemic autoimmune (AI) diseases which have a renal component. This includes systemic lupus erythematosus (SLE), goodpastures syndrome and anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitides. In particular the classical pathway (CP) of complement is involved in SLE, with the exact mechanism of how these SLE autoantigens along with their autoantibodies interact with complement in the glomerulus remaining ambiguous. Furthermore, recent studies have demonstrated the expanding role of the alternative pathway (AP) of complement activation in steady state or in aspects of ANCA associated vasculitides or anti-GBM disease. The precise means of activation of the AP in these immune complex mediated disease settings remains unclear. Regulation is imperative in the AP due to its inherent ability to autoactivate. Factor H and properdin are both key opposing regulators in the AP with novel emerging roles in initiation and control of the AP. Deciphering the specific modes of AP activation and involvement is an ever expanding field requiring further elucidation, with previously unexpected roles for AP components revealing the diversity and complexity of this ancient pathway. Show less
The work presented in this thesis concerns various, mainly clinicopathological, studies of ANCA-associated vasculitis. The first chapter provides a general introduction to the topic and the studies... Show moreThe work presented in this thesis concerns various, mainly clinicopathological, studies of ANCA-associated vasculitis. The first chapter provides a general introduction to the topic and the studies. Chapters 2 and 3 describe long-term patient and renal survival data concerning 535 patients. The emphasis in these chapters is on the results of multivariable models, developed to detect baseline patient characteristics that can provide reliable prognostic information to treating physicians. Chapter 4 comprises a clinicopathological study performed on renal biopsies of patients experimentally treated with a rituximab-based regimen. Specific attention is paid to the presence of B cell, T cell and plasma cell infiltrates in the diagnostic renal biopsy and the relation of these infiltrates to renal outcome under rituximab treatment. Chapter 5 reviews known disturbances in cellular immunity in vasculitis. In chapter 6 the presence of anti-plasminogen antibodies is described in two independent patient cohorts, one from the United Kingdom and one from the Netherlands. Chapter 7 illustrates that a simple classification schema comprising only four histological classes correlates well with renal outcome in a first validation exercise. Finally, the results described in this thesis are summarized and discussed in chapter 8. Show less
The body against itself When the immune system derails, antibodies directed against patients__ own molecules can be formed. This happens in ANCA-associated vasculitis, a vascular inflammation where... Show moreThe body against itself When the immune system derails, antibodies directed against patients__ own molecules can be formed. This happens in ANCA-associated vasculitis, a vascular inflammation where antineutrophil cytoplasm autoantibodies (ANCA) cause damage, predominantly in the kidney. Untreated, vasculitis is fatal. However, treatment causes a high risk of complications and death. A major challenge in clinical practice is to distinguish which patients will respond well to treatment, and which will not. New insights PhD candidate Rob de Lind van Wijngaarden discusses several factors in his dissertation that may play a role in the formation of antibodies in patients with ANCA-associated vasculitis. He describes which lesions in the diagnostic renal biopsy predict outcome at one year and long term outcome at five years. Additionally, he discovered that ear, nose and throat involvement in vasculitis is a relatively beneficial factor, since it allows earlier discovery of renal damage. In summary, in his dissertation de Lind van Wijngaarden tries to render insight into the different prognoses of different patient groups and the influence of the clinical picture and the renal biopsy on the prognosis. Show less
