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Background and Aims: Anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitides (AAV) is associated with an increased cardiovascular risk, particularly the myeloperoxidase AAV serotype (MPO-AAV). Distinct alterations in monocyte phenotypes may cause accelerated atherosclerotic disease in AAV., Methods: A cohort including 43 AAV patients and 19 healthy controls was included for downstream analyses. Extensive phenotyping of monocytes and monocyte-derived macrophages was performed using bulk RNA-sequencing and flow cytometry. An in vitro transendothelial migration assay reflecting intrinsic adhesive and migratory capacities of monocytes was employed. Subsequent sub-analyses were performed to investigate differences between serological subtypes., Results: Monocyte subset analysis showed increased classical monocytes during active disease, whereas non-classical monocytes were decreased compared to healthy controls (HC). RNA-sequencing revealed upregulation of distinct inflammatory pathways and lipid metabolism-related markers in monocytes of active AAV patients. No differences were detected in the intrinsic monocyte adhesion and migration capacity. Compared to proteinase-3(PR3)-AAV, monocytes of MPO-AAV patients in remission expressed genes related to inflammation, coagulation, platelet-binding and interferon signalling, whereas the expression of chemokine receptors indicative of acute inflammation and monocyte extravasation (i.e., CCR2 and CCR5) was increased in monocytes of PR3-AAV patients. During active disease, PR3-AAV was linked with elevated serum CRP and increased platelet counts compared to MPO-AAV., Conclusions: These findings highlight changes in monocyte subset composition and activation, but not in the intrinsic migration capacity of AAV monocytes. MPO-AAV monocytes are associated with sustained upregulation of inflammatory genes, whereas PR3-AAV monocytes exhibit chemokine receptor upregulation. These molecular changes may play a role in elevating cardiovascular risk as well as in the underlying pathophysiology of AAV., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Because anti-neutrophil cytoplasmatic antibody (ANCA)-associated vasculitis (AAV) is a rare, life-threatening, auto-immune disease, conducting research is difficult but essential. A long-lasting challenge is to identify rare AAV patients within the electronic-health-record (EHR)-system to facilitate real-world research. Artificial intelligence (AI)-search tools using natural language processing (NLP) for text-mining are increasingly postulated as a solution., Methods: We employed an AI-tool that combined text-mining with NLP-based exclusion, to accurately identify rare AAV patients within large EHR-systems (>2.000.000 records). We developed an identification method in an academic center with an established AAV-training set (n = 203) and validated the method in a non-academic center with an AAV-validation set (n = 84). To assess accuracy anonymized patient records were manually reviewed., Results: Based on an iterative process, a text-mining search was developed on disease description, laboratory measurements, medication and specialisms. In the training center, 608 patients were identified with a sensitivity of 97.0 % (95%CI [93.7, 98.9]) and positive predictive value (PPV) of 56.9 % (95%CI [52.9, 60.1]). NLP-based exclusion resulted in 444 patients increasing PPV to 77.9 % (95%CI [73.7, 81.7]) while sensitivity remained 96.3 % (95%CI [93.8, 98.0]). In the validation center, text-mining identified 333 patients (sensitivity 97.6 % (95%CI [91.6, 99.7]), PPV 58.2 % (95%CI [52.8, 63.6])) and NLP-based exclusion resulted in 223 patients, increasing PPV to 86.1 % (95%CI [80.9, 90.4]) with 98.0 % (95%CI [94.9, 99.4]) sensitivity. Our identification method outperformed ICD-10-coding predominantly in identifying MPO+ and organ-limited AAV patients., Conclusions: Our study highlights the advantages of implementing AI, notably NLP, to accurately identify rare AAV patients within large EHR-systems and demonstrates the applicability and transportability. Therefore, this method can reduce efforts to identify AAV patients and accelerate real-world research, while avoiding bias by ICD-10-coding., Competing Interests: Declaration of competing interest The work of YKOT is supported by the Dutch Kidney Foundation (17OKG04) and by the Arthritis Research and Collaboration Hub (ARCH) foundation. ARCH is funded by Dutch Arthritis Foundation (ReumaNederland). YKOT received an unrestricted research grant from GlaxoSmithKline, Aurinia Pharmaceuticals and Vifor Pharma. The LUMC received consulting fees from Aurinia Pharmaceuticals, Novartis, GSK, KezarBio, Vifor Pharma, Otsuka Pharmaceuticals on consultancies delivered by YKOT., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: ANCA-associated vasculitis (AAV) has been associated with increased risk of cardiovascular (CV) events. The aim was to assess traditional and disease-related CV risk determinants in a two-centre prospective cohort of AAV patients., Methods: Patients were recruited from centres in the Netherlands and Canada. A comprehensive CV risk assessment was performed at inclusion. Subjects were followed up yearly for 3-5 years until the first CV event, death or end of follow-up. Cox proportional hazards analyses were performed to relate baseline characteristics to the first CV event., Results: A total of 144 patients were included (mean age 62 years, female sex 44%, median Framingham risk score 14.3%). Insulin resistance was present in 73% of patients tested at inclusion, independent of concurrent prednisone therapy. After a median follow-up of 2.90 years, 16 patients (11%) experienced a CV event (14 non-fatal and 2 fatal). The incidence of CV events was 5.45 per 100 patient-years. Age, Framingham risk score, HbA1c level, Diabetes Mellitus (DM), and previous CV event were significantly associated with CV events. Other factors, such as sex, impaired renal function, dyslipidemia, hypertension, smoking history and microalbuminuria, or disease-specific variables, like ANCA serotype or disease activity, were not significantly related to CV events in univariable or age-adjusted cox regression analysis., Conclusions: Determinants of an increased CV risk were identified. Disease-related factors and treatments can further modify individual risk factors, such as for steroids causing chronic insulin resistance and DM. Treatment of risk factors is essential to optimize long-term outcomes in AAV patients., (Copyright © 2023 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

Objectives: Patients with ANCA-associated vasculitis are at increased risk of cardiovascular events. The aim of the present study was to assess predictors of cardiovascular events in patients with granulomatosis with polyangiitis or eosinophilic granulomatosis with polyangiitis., Methods: This retrospective cohort study included patients from the Canadian Vasculitis Research Network cohort in Toronto. Characteristics at diagnosis were collected. During follow-up, non-fatal cardiovascular events were determined from the Vasculitis Damage Index; mortality and causes of death were recorded. Cox regression models were developed to determine predictors of cardiovascular events, defined as stroke or myocardial infarction., Results: A total of 336 patients were included (231 [69%] granulomatosis with polyangiitis; 105 [31%] eosinophilic granulomatosis with polyangiitis). The mean age at diagnosis was 44 (±18) years and 44% were male. The incidence rate for the combined outcome of all fatal and non-fatal events was 7.2 events per 1000 patient-years. In a multivariate model, family history of cardiovascular events and a higher Birmingham Vasculitis Activity Score at diagnosis were predictive of cardiovascular events (hazard ratio and 95% confidence interval 3.46 [1.06-11.28] and 1.09 [1.02-1.16] respectively). In a subgroup analysis there was no association between cardiovascular or disease-specific characteristics and cardiovascular events in eosinophilic granulomatosis with polyangiitis., Conclusions: In this cohort of patients with granulomatosis with polyangiitis and eosinophilic granulomatosis with polyangiitis, both traditional and disease-related risk factors were predictive of cardiovascular events. Further prospective studies should elucidate the impact of these and other modifiable risk factors on cardiovascular risk in ANCA-associated vasculitis., (Copyright © 2020 Société française de rhumatologie. Published by Elsevier Masson SAS. All rights reserved.)

Objectives: Several chronic inflammatory diseases are associated with cardiovascular disease, but the risk in ANCA-associated vasculitis is poorly quantified. The aim of the present study was to review the evidence for an increased cardiovascular risk, including ischaemic heart disease, cerebrovascular accidents and peripheral arterial disease, in patients with ANCA-associated vasculitis., Methods: A comprehensive systematic review was conducted in accordance with guidelines of preferred reporting items for systematic reviews and meta-analyses. The databases PubMed, Embase.com and the Cochrane Library (Wiley) were searched for original observational studies comparing vasculitis patients with at least one control group. Summary estimates were derived with a random-effects model and reported as relative risks., Results: One thousand three hundred and seventy-five studies were identified. Seven studies were included, comprising almost 14 000 ANCA-associated vasculitis patients vs general population controls in six studies and chronic kidney disease patients in one study. ANCA-associated vasculitis carried a relative risk of 1.65 (95% CI: 1.23, 2.22) for all cardiovascular events, 1.60 (95% CI: 1.39, 1.84) for ischaemic heart disease and 1.20 (95% CI: 0.98, 1.48) for cerebrovascular accidents. We did not find studies that addressed the risk for peripheral arterial disease separately. No heterogeneity was seen in the estimates., Conclusion: This meta-analysis of observational studies supports an increase in cardiovascular risk in patients with ANCA-associated vasculitis of ∼65%, similar to that found in other chronic inflammatory diseases. Hence, there is a clear need for active cardiovascular risk management in patients with ANCA-associated vasculitis., (© The Author 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com)

Background: In ANCA-associated vasculitis the acute phase of the disease is often preceded by prodromal symptoms. The aim of the present study was to analyze the relation between the duration of the prodromal phase and renal damage., Methods: Patients with ANCA-associated vasculitis and renal involvement from a retrospective single-center cohort were divided into two equal groups based on the duration of the prodromal phase. The prodromal phase was defined as the time between first vasculitis related symptoms and the date of diagnosis. Clinical characteristics at diagnosis and renal items on the vasculitis damage index at 6 months were compared between the two groups. In addition, the relation between a long prodromal phase and 3-year end-stage renal disease and mortality as a composite outcome was studied., Results: A total of 72 patients were included (age 64 ± 12 years; 74% male; 96% Caucasian). At diagnosis, in patients with a prodromal phase ≤22 weeks versus >22 weeks estimated glomerular filtration rate and proteinuria did not differ significantly (35 (interquartile range 50) versus 30 (50) ml/min p = 0.84; 75% versus 87%, p = 0.21 respectively). Furthermore, Birmingham Vasculitis Activity Scores were comparable (7 (3), p = 0.71). At 6 months, a long prodromal phase was associated with proteinuria (odds ratio 5.38, 95% confidence interval (CI) 1.47-19.62), but not with an estimated glomerular filtration rate ≤ 50 ml/min (odds ratio 0.89, 95% CI 0.33-2.37) in multivariable analyses. In addition, a long prodromal phase was associated with end-stage renal disease/mortality (hazard ratio 5.22, 95% CI 1.13-24.20)., Conclusions: A long prodromal phase was associated with proteinuria and 3-year end-stage renal disease/mortality, but not with a reduced renal function at 6 months. These results underline the importance of an early diagnosis in ANCA-associated vasculitis patients in order to improve renal outcomes.

Background: Renal involvement in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) requires prompt and aggressive immunosuppressive therapy. The aim of this study was to evaluate screening practice for renal involvement in AAV and its potential effect on renal outcomes., Methods: Between 2005 and 2015, ANCA-positive AAV patients in a teaching hospital in the Netherlands were retrospectively included. Complete screening for renal involvement was defined as: assessment of erythrocyturia, proteinuria and serum creatinine within two weeks of the diagnosis of AAV. Characteristics at presentation and at 12 months were compared between patients with and without complete screening., Results: A total of 109 AAV patients (63% male) were identified with a mean age of 62 ±; 14 years. Complete screening for renal involvement was performed in 90 of the 109 patients (83%). Patients with incomplete screening had a lower serum creatinine (86 ±; 53 vs. 190 ±; 185 μmol/l, p < 0.001) and were more often diagnosed outside the renal department (100% vs. 78%, p = 0.02). Three patients with incomplete screening had a rise in serum creatinine of ≥ 30% at 12 months. Incomplete screening was not associated with the development of end-stage renal disease. Urine analysis of patients with renal biopsy-proven AAV (n = 31) showed erythrocyturia in 58% after one sample and in 94% after three samples., Conclusion: Screening for renal involvement in AAV was suboptimal, primarily in patients who presented outside the renal department. A higher sensitivity for erythrocyturia is achieved if urine analysis is repeated. Incomplete screening may lead to renal impairment if renal involvement is not treated appropriately.

Currently no validated diagnostic system for antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is available. Therefore, diagnosing AAV is often challenging. We aimed to identify factors that lead to a clinical diagnosis AAV in ANCA positive patients in a teaching hospital in The Netherlands.In this study, all patients that tested positive for ANCA proteinase 3 (PR3) and/or myeloperoxidase (MPO) between 2005 and 2015 were analysed. Patients with a clinical diagnosis of AAV were compared with patients without a clinical diagnosis of AAV. Clinical symptoms and laboratory variables at presentation, including the ANCA titre, were collected for both patients with and without AAV. Clinical and laboratory variables related with AAV were investigated, using multivariable logistic regression.Two hundred thirty seven consecutive patients with a positive ANCA were included, of whom 119 were clinically diagnosed with AAV. Of the 118 ANCA positive patients without AAV, 87 patients had an alternative diagnosis, including inflammatory bowel disease (n = 24), other rheumatic diseases (n = 23), infection (n = 11), malignancy (n = 4), and other diagnoses (n = 25). In a multivariable regression model, a high ANCA titre (odds ratio [OR] 14.16, 95% confidence interval [CI] 6.93-28.94) and a high number of affected organ systems (OR 7.67, 95% CI 3.69-15.94) were associated with AAV.MPO and PR3 ANCA can be positive in a variety of diseases that mimic AAV. A higher ANCA titre and multiple affected organ systems may help to discriminate between AAV and other systemic illnesses in anti-PR3 and anti-MPO positive patients. A diagnostic scoring system incorporating these factors should be considered., Competing Interests: The authors have no conflicts of interest to disclose.