Wegener's Granulomatosis Research Articles

Neutrophil Extracellular Trap Formation and Deoxyribonuclease I Activity in Patients with Otitis Media with Antineutrophil Cytoplasmic Antibody-Associated Vasculitis

Introduction: No previous studies have evaluated the levels of neutrophil extracellular trap (NET) remnants or the importance of deoxyribonuclease (DNase) I activity based on the disease activity of otitis media with antineutrophil cytoplasmic antibody-associated vasculitis (OMAAV). The aim of this study was to explore the formation of NETs in the middle ear of patients with OMAAV during the onset and remission phases of the disease, with a particular focus on the relationships between the quantifiable levels of NET remnants and DNase I activity. Methods: OMAAV patients were eligible for inclusion. Patients with otitis media with effusion (OME) were examined as controls. The levels of cell-free deoxyribonucleic acid (DNA), citrullinated-histone H3 (cit-H3)-DNA complex, and myeloperoxidase (MPO)-DNA complex were quantified using an enzyme-linked immunosorbent assay. DNase I activity was measured using a fluorometric method. Results: The quantifiable levels of cell-free DNA, cit-H3-DNA complex, and MPO-DNA complex in the middle ear lavage of patients with OMAAV at onset were significantly higher than those in patients with OMAAV at remission and in patients with OME. DNase I activity in the patients with OMAAV at onset was significantly lower than those in patients with OMAAV at remission and OME and was negatively correlated with the level of MPO-DNA complex. Conclusions: This study suggests that NET remnants and DNase I activity may be potentially useful biomarkers for the diagnosis and disease activity of OMAAV.

Clinical features and prognosis of ANCA-associated vasculitis patients who were double-seropositive for myeloperoxidase-ANCA and proteinase 3-ANCA

Anti-neutrophil cytoplasmic antibody (ANCA)–associated vasculitis (AAV) patients with dual positivity for proteinase 3-ANCA (PR3-ANCA) and myeloperoxidase-ANCA (MPO-ANCA) are uncommon. We aimed to investigate these idiopathic double-positive AAV patients’ clinical features, histological characteristics, and prognosis. We reviewed all the electronic medical records of patients diagnosed with AAV to obtain clinical data and renal histological information from January 2010 to December 2020 in a large center in China. Patients were assigned to the MPO-AAV group or PR3-AAV group or idiopathic double-positive AAV group by ANCA specificity. We explored features of idiopathic double-positive AAV. Of the 340 patients who fulfilled the study inclusion criteria, 159 (46.76%) were female, with a mean age of 58.41 years at the time of AAV diagnosis. Similar to MPO-AAV, idiopathic double-positive AAV patients were older and had more severe anemia, lower Birmingham Vasculitis Activity Score (BVAS) and C-reactive protein (CRP) levels, less ear, nose, and throat (ENT) involvement, higher initial serum creatinine and a lower estimated glomerular filtration rate (eGFR) when compared with PR3-AAV (P < 0.05). The proportion of normal glomeruli of idiopathic double-positive AAV was the lowest among the three groups (P < 0.05). The idiopathic double-positive AAV patients had the worst remission rate (58.8%) among the three groups (P < 0.05). The relapse rate of double-positive AAV (40.0%) was comparable with PR3-AAV (44.8%) (P > 0.05). Although there was a trend toward a higher relapse rate of idiopathic double-positive AAV (40.0%) compared with MPO-AAV (23.5%), this did not reach statistical significance (P > 0.05). The proportion of patients who progressed to ESRD was 47.1% and 44.4% in the idiopathic double-positive AAV group and MPO-AAV group respectively, without statistical significance. Long-term patient survival also varied among the three groups (P < 0.05). Idiopathic double-positive AAV is a rare clinical entity with hybrid features of MPO-AAV and PR3-AAV. MPO-AAV is the “dominant” phenotype in idiopathic double-positive AAV.

The Diagnosis of Granulomatosis With Polyangiitis When Serology and Biopsies are Negative.

Granulomatosis with polyangiitis (GPA) is a potentially fatal condition which often manifests in the head and neck. Currently, diagnosis relies on antineutrophil cytoplasmic autoantibody (c-ANCA) serology and mucosal or renal biopsy. However, a significant proportion of patients with GPA limited to the head and neck are seronegative and biopsy negative. This study evaluates the role of clinical diagnosis of GPA in the absence of positive laboratory findings. Case series with chart review. Academic Tertiary Medical Center. This was a retrospective review of 143 patients treated in an outpatient otolaryngology clinic at a tertiary care hospital for known or suspected GPA from 1998 to 2021. Presenting symptoms, C-ANCA status at initial presentation, biopsy results, long-term serology results, and time to initiation of treatment were analyzed. Twenty-six of 143 (18.2%) patients were seronegative; only 3 of these patients (12%) had positive biopsies. Seventeen (73.9%) of these patients presented with nasal and sinus disease and 12 (52.2%) presented with airway involvement. Only 4 (17.4%) patients had renal involvement. Delay in treatment of patients with negative laboratory workup ranged from 0 months to 11 years. All patients who were seronegative and/or biopsy negative at presentation responded clinically to immunosuppressive therapy. GPA cases are often limited to the upper respiratory tract, making diagnosis difficult, particularly in seronegative patients. These results suggest that, when GPA is suspected, despite negative serology, the diagnosis of GPA should be made on clinical grounds, and empiric therapy encouraged to prevent delay in treatment.

Saddled by the Saddle Nose: A Case of Wegener's Granulomatosis

Wegener's Granulomatosis with polyangiitis (GPA) is a systemic disease of unknown etiology characterized by necrotizing granulomatous inflammation, tissue necrosis, and variable degrees of vasculitis in small- and medium-sized blood vessels. The classical clinical triad consists of involvement of the upper airways, lungs, and kidneys. Saddle-nose deformity is a well-recognized complication of GPA but more commonly occurs due to leprosy, trauma, cocaine abuse, and sarcoidosis. Since this entity is not commonly encountered in our country, we present a unique case of a middle-aged woman presenting with saddle-nose deformity and the diagnostic dilemmas faced by us. This case is being reported due to its rarity in Indian literature.

Modern Perspectives on Peripheral Neuropathology

Recent advances in genetic and antibody testing have limited pathological examination of peripheral nerve specimens. However, when examining peripheral neuropathological findings from a modern perspective, there is often an opportunity to comprehend previously unnoticed observations upon re-examining the same specimen. For example, electron microscopy studies have suggested that the components that distinguish between nodal regions and internodes play a pivotal role in the behavior of macrophages that initiate myelin phagocytosis in the demyelinating form of Guillain-Barré syndrome and chronic inflammatory demyelinating polyneuropathy (CIDP). Conversely, some patients previously diagnosed with CIDP were found to possess distinctive mechanisms initiated by autoantibodies against paranodal junction proteins such as neurofascin 155 leading to the emergence of the concept of autoimmune nodopathy. In vasculitis, the roles of neutrophils in antineutrophil cytoplasmic antibody-associated vasculitis, eosinophils in eosinophilic granulomatosis with polyangiitis, and complements in nonsystemic vasculitic neuropathy in tissue damage have also been demonstrated when viewed from a modern perspective. Furthermore, mechanisms attributable to predominant small-fiber loss in hereditary transthyretin amyloidosis have been clarified at an ultrastructural level.

WCN24-391 Predictive Factors of Renal Recovery and Progression to End-Stage Kidney Disease in Patients with ANCA-Associated Vasculitis with Severe Kidney Disease

WCN24-391 Predictive Factors of Renal Recovery and Progression to End-Stage Kidney Disease in Patients with ANCA-Associated Vasculitis with Severe Kidney Disease

Thyroid disease in ANCA-associated vasculitis: a clinical and epidemiological study

ObjectivesTo describe clinical and laboratory characteristics and outcomes in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and thyroid disease (TD). We also aimed to calculate incidence and identify predictors...

Computable phenotype for real-world, data-driven retrospective identification of relapse in ANCA-associated vasculitis

ObjectiveANCA-associated vasculitis (AAV) is a relapsing-remitting disease, resulting in incremental tissue injury. The gold-standard relapse definition (Birmingham Vasculitis Activity Score, BVAS>0) is often missing or inaccurate in registry settings, leading...

The HLA region in ANCA-associated vasculitis: characterisation of genetic associations in a Scandinavian patient population

ObjectiveThe antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) are inflammatory disorders with ANCA autoantibodies recognising either proteinase 3 (PR3-AAV) or myeloperoxidase (MPO-AAV). PR3-AAV and MPO-AAV have been associated with distinct loci...

WCN24-390 Combined Activity, Recovery, and Chronicity Kidney Biopsy Grading for Prognostic Assessment in ANCA-associated Vasculitis with Glomerulonephritis (AAV-GN)

WCN24-390 Combined Activity, Recovery, and Chronicity Kidney Biopsy Grading for Prognostic Assessment in ANCA-associated Vasculitis with Glomerulonephritis (AAV-GN)

WCN24-389 Impact of Sex in Clinical Presentation and Outcomes of Patients with ANCAAssociated Vasculitis with Severe Kidney Disease

WCN24-389 Impact of Sex in Clinical Presentation and Outcomes of Patients with ANCAAssociated Vasculitis with Severe Kidney Disease

Clinical and electrophysiological characteristics and treatment outcomes of anti-neutrophil cytoplasmic antibody ANCA-associated vasculitic neuropathy

Objective: To investigate the clinical and electrophysiological characteristics of ANCA-associated vasculitic neuropathy (VN) and analyze the predictors of treatment outcomes. Methods: Retrospective case series. In all, 652 consecutive patients with ANCA-associated vasculitis were admitted to the First Medical Center of the Chinese PLA General Hospital between January 2006 and December 2022. Peripheral neuropathy occurred in 91 patients. Patients were excluded if other known causes of neuropathy were present. Sixty-one patients were eventually enrolled, including 17 with eosinophilic granulomatosis with polyangiitis (EGPA), 11 with granulomatosis polyangiitis (GPA), and 33 with microscopic polyangiitis (MPA). Their clinical data were collected and clinical characteristics, VN manifestations, electrophysiological findings (including interside amplitude ratio [IAR]), and treatment outcomes were compared among the three subsets of AAV. Then, factors influencing the treatment outcomes were analyzed using multivariable logistic regression analysis. Results: Peripheral neuropathy occurred in 62.1%(18/29) of EGPA, 8.3%(15/180) of GPA, and 13.1%(58/443) of MPA patients. The age at onset and examination was higher in patients with MPA than those with EGPA or GPA (P<0.01). The occurrence of VN was later in patients with GPA than those with EGPA (P<0.01), and the GPA group had fewer affected nerves than the other two groups (P<0.016). The abnormal IARs of motor nerves in lower limbs were more detected in the EGPA than the MPA group (P<0.01). Logistic regression analysis suggested that higher Birmingham vasculitis activity score-version 3 (BVAS-V3) (OR=6.85, 95%CI 1.33-35.30) was associated with better treatment outcomes of VN. However, central nervous system involvement was a risk factor for poor treatment outcomes (OR=0.13, 95%CI 0.02-0.89). Conclusions: The clinical and electrophysiological characteristics of VN were slightly different among subsets of AAV. Patients with GPA often presented with polyneuropathy and had fewer nerves affected; mononeuritis multiplex was more common in EGPA than GPA and MPA. Higher BVAS-V3 and central nervous system involvement might predict the treatment outcome of VN.

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

Severe Renal Impairment in a Patient with Recent Rheumatoid Arthritis Diagnosis following Methotrexate Initiation: A Case Report

ABSTRACT Rheumatoid arthritis (RA) is a chronic autoimmune disease frequently treated with immunosuppressive agents such as methotrexate (MTX). Although MTX is generally well-tolerated, it can lead to adverse effects, including renal impairment. We present a case of a patient with newly diagnosed RA who developed severe renal impairment shortly after initiating MTX therapy. A 50-year-old male with recently diagnosed RA presented with vomiting, skin itching, mouth ulcers, and a pruritic rash, all occurring shortly after starting MTX treatment. These symptoms led to acute kidney injury (AKI), necessitating hemodialysis. The patient’s symptoms and laboratory findings were indicative of ANCA-associated small-vessel vasculitis with a picture of rapidly progressive glomerulonephritis (RPGN). Treatment included discontinuation of MTX, hemodialysis, immunosuppressive therapy with corticosteroids and cyclophosphamide, and patient education. This case emphasizes the need for close monitoring of RA patients initiated on MTX therapy and prompt evaluation of renal function. Clinicians should be vigilant for signs of renal impairment and be prepared to initiate appropriate interventions, including discontinuation of MTX and consideration of immunosuppressive therapy, to optimize patient outcomes. Further research is warranted to understand better the mechanisms underlying renal complications in RA patients receiving MTX treatment.

Pulmonary pathology in vasculitis.

Pulmonary involvement is frequent in vasculitis, particularly in ANCA-associated small vessel vasculitis. Laboratory and radiological data alone are often sufficient to confirm the clinical hypothesis, but sometimes the pathologist plays a crucial role in the differential diagnosis and the patient's management. In this review, the pathologic features of pulmonary vasculitis and the pathologist's role in this field are illustrated.

82 Subclinical Podocytopathy in the setting of Systemic ANCA-Associated Vasculitis

82 Subclinical Podocytopathy in the setting of Systemic ANCA-Associated Vasculitis

403 Kidney limited ANCA-associated vasculitis in a patient with persistently positive PR3 autoantibodies 1 year prior to biopsy confirmation

403 Kidney limited ANCA-associated vasculitis in a patient with persistently positive PR3 autoantibodies 1 year prior to biopsy confirmation

Diagnostic and prognostic role of serum interleukin-6 and carotid ultrasonography to detect subclinical atherosclerosis in patients with RA and ANCA-associated vasculitis.

ANCA-associated vasculitis (AAV) can affect multiple organs with severe life-threatening manifestations. Disease monitoring is difficult due to a lack of defined biomarkers. We aimed to assess the diagnostic role of serum interleukin-6 and vascular ultrasonography in AAV and subclinical atherosclerosis. The study included 20 AAV patients and two control groups of 34 patients with rheumatoid arthritis (RA) and 35 healthy controls. The levels of Il-6, carotid intima-media thickness test (CIMT), atherosclerotic plaque, and degree of stenosis were investigated. A GRACE-risk score was calculated for AAV and RA patients. The AAV patients had elevated levels of IL-6 (115 ± 23.96) compared to the RA patients (91.25 ± 42.63) and the healthy controls (15.65 ± 3.30), p < 0.001. IL-6 showed a diagnostic accuracy of 73% in distinguishing AAV from RA patients (AUC = 0.730; 95% CI 0.591 to 0834). In the AAV group, CIMT was 1.09, above the upper reference value of 0.90, p < 0.001. The AAV patients had a higher median GRACE risk score, and 60% of them had a high risk of cardiovascular events as compared to 35% of the RA patients. Sonography of extracranial vessels and serum levels of IL-6 can be used in daily clinical practice to diagnose and monitor patients with AAV.

Unveiling cancer risk in ANCA-associated vasculitis: result from the Turkish Vasculitis Study Group (TRVaS)

To investigate cancer incidence in patients with ANCA-associated vasculitis (AAV), compare it with the age/sex-specific cancer risk of the Turkish population, and explore independent risk factors associated with cancer. This multicenter, incidence case–control study was conducted using the TRVaS registry. AAV patients without cancer history before AAV diagnosis were included. Demographic and AAV-related data of patients with and without an incident cancer were compared. Standardized cancer incidence rates were calculated using age-/sex-specific 2017 Turkish National Cancer Registry data for cancers (excluding non-melanoma skin cancers). Cox regression was performed to find factors related to incident cancers in AAV patients. Of 461 AAV patients (236 [51.2%] male), 19 had incident cancers after 2022.8 patient-years follow-up. Median (IQR) disease duration was 3.4 (5.5) years, and 58 (12.6%) patients died [7 with cancer and one without cancer (log-rank, p = 0.04)]. Cancer-diagnosed patients were older, mostly male, and more likely to have anti-PR3-ANCA positivity. The cumulative cyclophosphamide dose was similar in patients with and without cancer. Overall cancer risk in AAV was 2.1 (SIR) ((1.3–3.2), p = 0.004); lung and head-neck [primary target sites for AAV] cancers were the most common. In Cox regression, male sex and ≥ 60 years of age at AAV diagnosis were associated with increased cancer risk, while receiving rituximab was associated with decreased cancer risk. Cancer risk was 2.1 times higher in AAV patients than the age-/sex-specific cancer risk of the Turkish population population, despite a high rate of rituximab use and lower dose of cyclophosphamide doses. Vigilance in cancer screening for AAV patients covering lung, genitourinary, and head–neck regions, particularly in males and the elderly, is vital.

Avacopan's potential to decrease MPO-ANCA titres concurrent with ameliorated activity in ANCA-associated vasculitis.

Avacopan, an orally administered C5a receptor antagonist, is effective in microscopic polyangiitis via the inhibition of neutrophil priming induced by C5a. However, the exact effect of avacopan on the production of myeloperoxidase antineutrophil cytoplasmic antibody (MPO-ANCA) is yet to be clearly established. This report presents a microscopic polyangiitis patient without major organ damage where high levels of MPO-ANCA persisted with high-dose steroid therapy and azathioprine, but the addition of avacopan led to a reduction in MPO-ANCA titres. The present case implies that avacopan-mediated inhibition of C5a may lead to a reduction in MPO-ANCA levels, thereby potentially ameliorating the pathophysiology of ANCA-associated vasculitis. Nevertheless, the impact of avacopan on MPO-ANCA production cannot be asserted solely based on this report; therefore, further examination is necessary through subgroup analysis using data from larger-scale studies.