Antibody-associated Vasculitis Research Articles

Investigating the concomitance of anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitides and inflammatory bowel disease (IBD)

ObjectiveTo assess relationship between Anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis and inflammatory bowel disease (IBD). MethodsThis is a retrospective study design. The patients were identified using a preset criteria of patients who have the diagnosis of ANCA associated vasculitis including a diagnosis of granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) or eosinophilic granulomatosis with polyangiitis (EGPA) with overlapping inflammatory bowel disease (Crohn's disease or ulcerative colitis) in the time period from 01/01/2020 to 08/03/2023. Subsequently data from each patient was collected that will include baseline demographics, disease characteristics, disease activity, treatment information, multiorgan involvement, and pathology findings which were then analyzed. Results39 patients were identified that met criteria. 20 patients carried a diagnosis of GPA, 6 had MPA and 4 patients had EGPA. 20 patients with GPA had inflammatory bowel disease, 13 with ulcerative colitis and 6 with Crohn's disease while 1 GPA patient had unspecified inflammatory bowel disease. 4 patients with EGPA had inflammatory bowel disease, 2 with ulcerative colitis and 2 with Crohn's disease. 6 patients with MPA had inflammatory bowel disease, 4 with ulcerative colitis and 2 with Crohn's disease. IBD diagnosis preceded the diagnosis of ANCA vasculitis in 77.8 % of the cases. ConclusionObjective observation and deductions from this study raise the concern for a possible pathogenic association of ANCA associated vasculitis and inflammatory bowel disease and more research is needed to identify any causal association or influence of the two systemic disease on each other.

378 A Case of Antineutrophilic Cytoplasmic Antibody (ANCA) Associated Vasculitis with Immune Complex Glomerulonephritis (GN) on Kidney Biopsy

378 A Case of Antineutrophilic Cytoplasmic Antibody (ANCA) Associated Vasculitis with Immune Complex Glomerulonephritis (GN) on Kidney Biopsy

Suspected Levamisole-Induced Antineutrophil Cytoplasmic Antibody Vasculitis and Diffuse Alveolar Hemorrhage in a Person Who Uses Cocaine

Suspected Levamisole-Induced Antineutrophil Cytoplasmic Antibody Vasculitis and Diffuse Alveolar Hemorrhage in a Person Who Uses Cocaine

Hydroxychloroquine as a potential therapy for ANCA-associated vasculitis

Antimalarial agents have been used to treat various autoimmune rheumatic diseases for over a century. Hydroxychloroquine is a safe, effective and inexpensive antimalarial drug with additional antithrombotic, cardioprotective, antimicrobial, and anti-neoplastic benefits. It has been used extensively in various diseases, especially systemic lupus erythematosus and rheumatoid arthritis; however, it has not been used in anti-neutrophil cytoplasmic antibody associated vasculitides (AAVs). There exists a significant unmet need for safe and inexpensive treatments for non-severe AAV or those with low-grade “grumbling” disease activity who do not warrant significant escalation of therapy but who remain at risk of disease flares and damage accumulation. Hydroxychloroquine may be an option to help fill this void. Although the mechanisms of action of Hydroxychloroquine are not fully understood, it interacts with various inflammatory mediators involved in the pathogenesis of AAV. Based on these benefits, along with the unmet need in AAV, we present evidence to support the use of Hydroxychloroquine as a potential therapy for AAV.

NETosis Secondary to the Use of Levamisole-Adulterated Cocaine: A Likely Underlying Mechanism of Vasculopathy.

Since 2010, several cases of a new vasculopathy induced by the use of levamisole-adulterated cocaine (LAC) have been reported. This vasculopathy is characterized by retiform purpura, earlobe necrosis, multisystem compromise, and multiple autoantibodies. Given its similarity to antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis, LAC-associated vasculopathy is postulated to be mediated by pathophysiologic processes resulting from neutrophil cell death by NETosis, a phenomenon previously described in ANCA vasculitis. This study tries to establish the presence of NETosis induced by cocaine, levamisole, or both. Methodology. Neutrophils were isolated from the peripheral blood of healthy controls by Ficoll-Hystopaque density gradient centrifugation followed by dextran sedimentation. Cell viability and purity were evaluated by flow cytometry after staining with PI/DiOC6 and labeling with fluorescent anti-CD45/anti-CD3 monoclonal antibodies (mAbs), respectively. Neutrophils were exposed to levamisole, cocaine, a cocaine-levamisole mixture, and sera pools from healthy controls and patients with LAC-associated vasculopathy. NETosis was then assessed by flow cytometry after staining cells with Sytox Green, Hoechst-33342, and fluorescent antineutrophil elastase (NE) and antimyeloperoxidase (MPO) mAbs. In addition, NETosis was morphologically confirmed by fluorescence microscopy. Proinflammatory cytokine levels in culture supernatants and reactive oxygen species (ROS) synthesis were determined by flow cytometry. The involvement of calcium and muscarinic receptors in cell death induction was evaluated in parallel experiments carried out in the presence of 1,2-bis (o-aminophenoxy) ethane-N, N, N', N'-tetraacetic acid (BAPTA) and hyoscine butylbromide (HBB), their respective inhibitors. Cocaine, levamisole, and a cocaine-levamisole mixture induced neutrophil cell death. DNA/MPO extrusion and cell morphology patterns were consistent with NETosis. Neither proinflammatory cytokines nor ROS behaved as proNETotic factors. Preliminary results suggested that muscarinic receptors and calcium-dependent signals were involved in LAC-induced NETosis. Cocaine, levamisole, and a cocaine-levamisole mixture can induce NETosis through mechanisms involving muscarinic receptors and calcium-dependent pathways.

Keratin Expression in Podocytopathies, ANCA-Associated Vasculitis and IgA Nephropathy.

Keratins are the main components of the cell cytoskeleton of epithelial cells. Epithelial cells under stressful stimuli react by modifying their keratin expression pattern. Glomerular diseases are pathological conditions that may lead to loss of kidney function if not timely diagnosed and treated properly. This study aims to examine glomerular and tubular keratin expression in podocytopathies, ANCA-associated vasculitis, and IgA nephropathy and how this expression correlates to clinical outcomes. We included 45 patients with podocytopathies (minimal change disease and focal segmental glomerulosclerosis), ANCA-associated vasculitis, and IgA nephropathy, with or without crescentic lesions, and healthy controls. All tissues were assessed by photon microscopy and immunohistochemistry. Biopsy sections were examined for keratins 7, 8, 18, and 19 expression in the glomerular and tubulointerstitial areas separately. Moreover, we examined how keratin expression was correlated with long-term kidney function outcomes. All four studied keratins had significantly increased glomerular expression in patients with ANCA vasculitis compared to controls and MCD patients. Tubular expression of keratins 7, 8, and 19 was related to kidney outcome in all groups. Patients with crescents had higher expression of all keratins in both glomeruli and tubulointerstitium. The presence of tubular atrophy, interstitial fibrosis, mesangial hyperplasia, and interstitial inflammation did not affect keratin expression. Keratins, an abundant component of renal epithelial cells, have the potential to be featured as a biomarker for kidney function prognosis in patients with glomerular diseases.

CD36 regulates macrophage and endothelial cell activation and multinucleate giant cell formation in anti neutrophil cytoplasm antibody vasculitis

ObjectiveTo investigate CD36 in ANCA-associated vasculitis (AAV), a condition characterized by monocyte/macrophage activation and vascular damage. MethodsCD36 expression was assessed in AAV patients and healthy controls (HC). The impact of palmitic acid (PA) stimulation on multinucleate giant cell (MNGC) formation, macrophage, and endothelial cell activation, with or without CD36 knockdown, was examined. ResultsCD36 was overexpressed on AAV patients' monocytes compared to HC, regardless of disease activity. AAV patients exhibited elevated soluble CD36 levels in serum and plasma and PR3-ANCA patients' monocytes demonstrated increased MNGC formation following PA stimulation compared to HC. PA stimulation of macrophages or endothelial cells resulted in heightened CD36 expression, cell activation, increased macrophage migration inhibitory factor (MIF) production, and c-Myc expression, with attenuation upon CD36 knockdown. ConclusionCD36 participates in macrophage and endothelial cell activation and MNGC formation, features of AAV pathogenesis. AAV treatment may involve targeting CD36 or MIF.

Association of atypical anti-neutrophil cytoplasmic antibody with comorbidities and outcome in a hospital-based population

IntroductionAtypical anti-neutrophil cytoplasmic antibody (a-ANCA) is characterized by a positive fluorescence staining other than typical cytoplasmic or perinuclear ANCA. ANCA is associated with increased risk of dialysis and mortality in patients with ANCA vasculitis. However, comorbidities related to a-ANCA and whether a-ANCA exhibits an increased risk for renal failure and mortality remain unclear. This study aimed to explore the comorbidities and outcome associated with a-ANCA. Materials and methodsThis retrospective study enrolled 164 and 170 patients with typical ANCA and a-ANCA positivity, respectively, who visited Taichung Veterans General Hospital, Taiwan from January 2016 to March 2021. Logistic regression analysis was used to determine risk factors and the rheumatological diagnosis associated with a-ANCA. Cox proportional hazard regression and Kaplan–Meier curves were employed to identify variables associated with 5-year renal survival and mortality. ResultsPatients with a-ANCA had lower chance of ANCA-associated vasculitis (OR: 0.02, 95 % CI: 0.01–0.07 p < 0.001), and systemic lupus erythematosus (OR: 0.23, 95 % CI: 0.11–0.48, p < 0.001), but a higher risk of rheumatoid arthritis (OR: 2.99, 95 % CI: 1.15–7.83, p = 0.025) and ulcerative colitis (OR: 5.50, 95 % CI: 1.20–25.29, p = 0.028). Patients with a-ANCA had a better renal survival (OR: 0.14, 95 % CI: 0.08–0.24, p < 0.001) and lower mortality (OR: 0.31, 95 % CI: 0.16–0.60, p = 0.001) than patents in the typical ANCA group. The 5-year renal survival and mortality was 89.3 % and 8.8 %, respectively, in patients with a-ANCA. ConclusionPatients with a-ANCA had better renal survival and lower mortality rates compared to patients with typical ANCA. These real-world data provide evidence of the long-term outcome and shed light on avenues for the strategic management of patients with a-ANCA.

Race, Ethnicity, Sex, Gender, Socioeconomic Status, and Representativeness of Race and Ethnicity in ANCA Vasculitis Randomized Trials.

Race, Ethnicity, Sex, Gender, Socioeconomic Status, and Representativeness of Race and Ethnicity in ANCA Vasculitis Randomized Trials.

Clinical features, paraclinical characteristics, and etiology of mediastinal bleeding diffusion in children at the Vietnam National Children’s Hospital from 2018 to 2023

Background: In modern life, diffuse alveolar haemorrhage (DAH) is a serious and rare condition in children. Due to the subtle clinical manifestations and diverse causes of the disease, it is easy to be missed or diagnosed late. This study describes clinical and paraclinical characteristics, with the aim to find signs suggesting early diagnosis as well as determine the cause of DAH in children. Objects and methods: Case series. Results: From January 2018 to March 2023, there were 14 children diagnosed with DAH. The age of onset is 4.08 (1.58-5.41) years old, but most patients are diagnosed late with age at diagnosis being 5.25 (1.67-6.16) years old, male/female ratio is 1:1.8. The most common symptoms reported were anaemia (100%), hemoptysis (57.1%), shortness of breath (71.4%), and respiratory failure (85.7%). The common X-ray finding was diffuse infiltrates in both lungs (92.9%). On chest computed tomography scans, 92.9% of patients exhibited images of blurred opacity spreading, 57.1% showed interlobar pleural thickening, and 28.6% presented with images of lung consolidation. 3 patients (22%) had milk allergy, 2 patients (14%) had ANCA (Anti-neutrophil cytoplasmic antibody) vasculitis, and 9 patients (64%) had idiopathic pulmonary haemosiderosis (IPH).

Maintenance of remission of ANCA vasculitis by rituximab based on B cell repopulation versus serological flare: a randomised trial

ObjectiveTo compare two long-term remission maintenance strategies for antineutrophil cytoplasmic antibody (ANCA) vasculitis.MethodsWe conducted a prospective, single-centre, open-label, randomised controlled trial of patients with ANCA vasculitis in remission after completing...

IgA Nephropathy Associated with ANCA Vasculitis: Case Report and Literature Review

IgA nephropathy is the most common primary glomerulonephritis, it’s association with Antineutrophil cytoplasmic antibody (ANCA) vasculitis constitutes a rare way of presentation that is scarcely described in the literature and diagnosed in only 1-2% of the population. The typical clinical presentation is an episode of systemic arterial hypertension with macroscopic hematuria, non-nephrotic proteinuria, acute kidney injury and in the worst-cases if the disturb persists end-stage chronic kidney disease. The definitive diagnosis is made through a biopsy, which shows the main characteristics of this nephropathy, which consists in crescent-shaped glomeruli formation, fibrinoid necrosis, mesangial deposits of IgA, as well as positive ANCA antibodies. Treatment consists in systemic corticosteroids and immunosuppressants to prevent progression to end-stage renal disease. We present a case of a 55-year-old female patient with a history of upper respiratory tract infection 2 weeks prior to the development of macroscopic hematuria, foamy urine, non-nephrotic proteinuria, and persistent acute kidney injury in whom IgA nephropathy was determined, which had a successfully response to treatment with high doses of corticosteroids and systemic immunosuppressants.

Abstract 17436: A Diagnostic Copycat: Culture Negative Endocarditis of A Bioprosthetic Valve Presenting as ANCA Vasculitis

A 59-year-old female with a history of bicuspid aortic valve (AV) complicated by aortic stenosis and ascending aortic aneurysm s/p bioprosthetic AV and ascending aorta replacement presented with a 6-month history of weight loss, fatigue, and lower extremity rash. Initial laboratory workup identified anemia, leukopenia, and acute kidney injury with proteinuria and microscopic hematuria. Further workup included negative blood cultures, elevated inflammatory markers, elevated rheumatoid factor, hypocomplimentemia, and ANCA positivity (PR3 Ab positive). Biopsy of her palpable purpuric rash demonstrated vascular immune deposition pattern consistent with leukocytoclastic vasculitis. Renal biopsy revealed focal and crescentic glomerulonephritis with immune complex deposition. CT abdomen noted mesenteric lymphadenopathy with fluid surrounding the thoracic aortic graft. Surface echocardiogram showed bioprosthetic AV replacement with diffuse cusp thickening without stenosis or regurgitation. At this point, a multidisciplinary team offered a broad differential diagnosis of inflammatory vasculitis versus culture-negative endocarditis with plan for further testing. Follow-up whole-body and cardiac PET scan identified FDG-avid abnormalities involving the aortic graft and AV with hypermetabolic soft tissue thickening surrounding the aortic root. Transesophageal echocardiogram confirmed AV thickening with a 1 cm mobile echodensity. Additional serologic testing identified positive Bartonella henselae IgG (1:8192) and IgM (&gt;1:20) titers. The final diagnosis was B. henselae prosthetic AV endocarditis and ascending aortic graft infection. She underwent repeat AV and ascending aortic graft replacement, with graft material positive for B. henselae PCR and was treated with a course of doxycycline and rifampin. B. henselae is a fastidious gram-negative bacterium that can cause culture negative endocarditis but is very rarely associated with aortic graft infection. This case highlights (1) a rare example of B. henselae aortic graft infection, (2) the difficulty in differentiating B. henselae endocarditis from inflammatory vasculitis, and (3) the importance of engaging multidisciplinary teams to solve difficult diagnostic cases.

A Diagnostic CopyCat: Culture-Negative Infective Endocarditis of a Bioprosthetic Valve Presenting as ANCA Vasculitis.

A Diagnostic CopyCat: Culture-Negative Infective Endocarditis of a Bioprosthetic Valve Presenting as ANCA Vasculitis.

ANCA Vasculitis in a Patient with Significant Silica Exposure

ANCA Vasculitis in a Patient with Significant Silica Exposure

In Vitro Expansion of Regulatory T Cells Restores Functional Capacity in ANCA Vasculitis

In Vitro Expansion of Regulatory T Cells Restores Functional Capacity in ANCA Vasculitis

Enhanced Growth of Gut Bacteria Muribaculaceae Reduces Inflammation and Kidney Injury in an Experimental Model of Anti-Neutrophil Cytoplasmic Antibody Vasculitis

Enhanced Growth of Gut Bacteria Muribaculaceae Reduces Inflammation and Kidney Injury in an Experimental Model of Anti-Neutrophil Cytoplasmic Antibody Vasculitis

An Unusual Case of ANCA Vasculitis Coexisting with Membranous Nephropathy due to Cocaine Use

An Unusual Case of ANCA Vasculitis Coexisting with Membranous Nephropathy due to Cocaine Use

New ACR/EULAR 2022 classification criteria for ANCA-associated vasculitis

The new 2022 classification criteria for antineutrophil cytoplasmic antibodies associated vasculitis (AAV), proposed by the American College of Rheumatology (ACR) and the European Alliance of Associations for Rheumatology (EULAR), was an important stage in the development of the doctrine of systemic vasculitis. Based on the analysis of large international cohorts, the criteria for granulomatosis with polyangiitis and eosinophilic granulomatosis with polyangiitis were revised, and classification criteria for microscopic polyangiitis were proposed for the first time. The creation’s history of the AAV classification criteria is discussed over the past three decades, and their limitations are considered. It should be noted, the ACR/EULAR 2022 criteria were developed for creating homogeneous groups of patients for scientific studies and cannot be widely used in clinical practice for the various AAV nosological forms diagnosis, primarily at early stage of the disease or mono organ damage (for example, kidneys). As before, decisive importance in AVV diagnostic belong to a detailed clinical analysis and a complete examination of patients to identify pathognomonic symptoms, including asymptomatic ones.

The Association Between Age at Diagnosis and Disease Characteristics and Damage in Patients With ANCA-Associated Vasculitis.

This study examined the relationship between age at diagnosis and disease characteristics and damage in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Analysis of a prospective longitudinal cohort of patients with granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic GPA (EGPA) in the Vasculitis Clinical Research Consortium (2013-2021). Disease cohorts were divided by age at diagnosis (years): children (<18), young adults (18-40), middle-aged adults (41-65), and older adults (>65). Data included demographics, ANCA type, clinical characteristics, Vasculitis Damage Index (VDI) scores, ANCA Vasculitis Index of Damage (AVID) scores, and novel disease-specific and non-disease-specific damage scores built from VDI and AVID items. Analysis included data from 1020 patients with GPA/MPA and 357 with EGPA. Female predominance in GPA/MPA decreased with age at diagnosis. AAV in childhood was more often GPA and proteinase 3-ANCA positive. Children with GPA/MPA experienced more subglottic stenosis and alveolar hemorrhage; children and young adults with EGPA experienced more alveolar hemorrhage, need for intubation, and gastrointestinal involvement. Older adults (GPA/MPA) had more neurologic manifestations. After adjusting for disease duration, medications, tobacco, and ANCA, all damage scores increased with age at diagnosis for GPA/MPA (P < 0.001) except the disease-specific damage score, which did not differ (P = 0.44). For EGPA, VDI scores increased with age at diagnosis (P < 0.009), whereas all other scores were not significantly different. Age at diagnosis is associated with clinical characteristics in AAV. Although VDI and AVID scores increase with age at diagnosis, this is driven by non-disease-specific damage items.