Slowly progressive anti-neutrophil cytoplasmic antibody-associated renal vasculitis: clinico-pathological characterization and outcome.

BACKGROUND: Although rapidly progressive glomerulonephritis is the main renal phenotype of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), slow renal disease progression is sometimes observed. These forms have been rarely discussed; we analysed their prevalence, clinico-pathological characteristics and outcome. METHODS: We screened patients with microscopic  polyangiitis (MPA) and granulomatosis with polyangiitis followed at seven referral centres and selected those with estimated glomerular filtration rate (eGFR) reduction 25% as compared with diagnosis, while 4/34 (12%) had started RRT. CONCLUSIONS: AAV may present with slow renal disease progression; this subset is hallmarked by advanced age at diagnosis, positive MPO-ANCA, subclinical interstitial lung lesions and chronic damage at kidney biopsy. Partial renal recovery may occur following immunosuppression

The Sound of Interconnectivity; The European Vasculitis Society 2022 Report

The first European Vasculitis Society (EUVAS) meeting report was published in 2017. Herein, we report on developments in the past 5 years which were greatly influenced by the pandemic. The adaptability to engage virtually, at this critical time in society, embodies the importance of networks and underscores the role of global collaborations. We outline state-of-the-art webinar topics, updates on developments in the last 5 years, and proposals for agendas going forward. A host of newly reported clinical trials is shaping practice on steroid minimization, maintenance strategies, and the role of newer therapies. To guide longer -term strategies, a longitudinal 10-year study investigating relapse, comorbidity, malignancy, and survival rates is at an advanced stage. Disease assessment studies are refining classification criteria to differentiate forms of vasculitis more fully. A large international validation study on the histologic classification of anti-neutrophil cytoplasmic antibody (ANCA) glomerulonephritis, recruiting new multicenter sites and comparing results with the Kidney Risk Score, has been conducted. Eosinophilic granulomatosis with polyangiitis (EGPA) genomics offers potential pathogenic subset and therapeutic insights. Among bio-markers, ANCA testing is favoring immunoassay as the preferred method for diagnostic evaluation. Consolidated development of European registries is progressing with an integrated framework to analyze large clinical data sets on an unprecedented scale

Rituximab for chronic periaortitis without evidence of IgG4-related disease: A long-term follow-up study of 20 patients

Chronic periaortitis (CP) is a rare condition characterised by a peri-aortoiliac fibro-inflammatory tissue. A total of 20%–50% of the cases are immunoglobulin G4 (IgG4)-related, based on histological evidence of IgG4+ plasma cell infiltration (on a background of dense lymphoplasmacytic infiltrates, storiform fibrosis and tissue eosinophilia) and/or increased serum IgG4.1 Glucocorticoids are the first-line therapy for CP.2 However, some patients are refractory, frequently relapsing or have contraindications to glucocorticoids. The anti-CD20 monoclonal antibody rituximab proved efficacious in systemic forms of IgG4-related disease (IgG4-RD) including IgG4-related CP,3 but data on IgG4-unrelated CP are scarce.4–6 In this study, we tested rituximab in CP patients without evidence of IgG4-RD who had relapsing/refractory disease or contraindications to standard-dose glucocorticoids. We included patients with active, IgG4-unrelated CP who received rituximab (October 2009 to April 2017). Online supplementary methods describe the diagnostic and follow-up procedures, the definitions of remission and refractory, and the statistical analysis

A large-scale genetic analysis reveals an autoimmune origin of idiopathic retroperitoneal fibrosis

Idiopathic retroperitoneal fibrosis (RPF) is a rare condition included in the spectrum of IgG4-related disease characterized by a fibroinflammatory tissue usually surrounding the abdominal aorta and iliac arteries. It was initially thought to result from a reaction to aortic atherosclerosis; however, given its frequent association with autoimmune diseases and its sensitivity to immunosuppressive therapies, it is now considered a systemic autoimmune condition. The genetic basis of the disease is poorly investigated. We performed a large-scale immunogenetic study of idiopathic RPF by using the Immunochip, an array focused on autoimmunity-associated gene variants

Protective role for kidney TREM2high macrophages in obesity- and diabetes-induced kidney injury

Summary: Diabetic kidney disease (DKD), the most common cause of kidney failure, is a frequent complication of diabetes and obesity, and yet to date, treatments to halt its progression are lacking. We analyze kidney single-cell transcriptomic profiles from DKD patients and two DKD mouse models at multiple time points along disease progression—high-fat diet (HFD)-fed mice aged to 90–100 weeks and BTBR ob/ob mice (a genetic model)—and report an expanding population of macrophages with high expression of triggering receptor expressed on myeloid cells 2 (TREM2) in HFD-fed mice. TREM2high macrophages are enriched in obese and diabetic patients, in contrast to hypertensive patients or healthy controls in an independent validation cohort. Trem2 knockout mice on an HFD have worsening kidney filter damage and increased tubular epithelial cell injury, all signs of worsening DKD. Together, our studies suggest that strategies to enhance kidney TREM2high macrophages may provide therapeutic benefits for DKD

Risk of acute arterial and venous thromboembolic events in eosinophilic granulomatosis with polyangiitis (Churg\u2013Strauss syndrome)

Eosinophilic granulomatosis with polyangiitis (EGPA; formerly Churg–Strauss syndrome) is a rare anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) characterised by respiratory manifestations and systemic organ involvement [1]. Particularly, cardiac manifestations occur in 40–60% of patients, representing the leading cause of mortality [2]. Recent reports suggest that venous thromboembolic events might also represent a consistent burden of disease [3, 4], as already known for the other AAVs [5–7], possibly due to eosinophil-mediated vascular inflammation [5]. Nevertheless, the occurrence of arterial and venous thrombotic events (AVTEs) has never been systematically explored in EGPA