Augusto Vaglio

University Hospital of Parma | AOUP · Reparto di Nefrologia

Periaortitis includes a spectrum of rare conditions characterized by the presence of a fibro-inflammatory tissue that commonly involves the abdominal aorta and the common iliac arteries that extends to involve the adjacent structures. Periaortitis is in most cases idiopathic, but in a minority of cases it recognizes infectious, neoplastic, or other...

In this work, we present a comprehensive overview of the genetic and non-genetic complexity of eosinophilic granulomatosis with polyangiitis (EGPA). EGPA is a rare complex systemic disease that occurs in people presenting with severe asthma and high eosinophilia. After briefly introducing EGPA and its relationship with the anti-neutrophil cytoplasm...

Early-onset systemic lupus erythematous (SLE) is a distinct clinical entity characterised by the onset of disease manifestations during childhood. Despite some similarities with patients who are diagnosed during adulthood, early-onset SLE typically displays a greater disease severity, with aggressive multiorgan involvement, lower responsiveness to...

Background Erdheim-Chester disease (ECD) is a rare histiocytosis that may overlap with Langerhans Cell Histiocytosis (LCH). This “mixed” entity is poorly characterized. We here investigated the clinical phenotype, outcome, and prognostic factors of a large cohort of patients with mixed ECD-LCH. Methods This retrospective study was performed at two...

Background and Aims The importance of kidney biopsy in ANCA-associated glomerulonephritis (AAV) is widely recognized: both the Berden classification and the ANCA renal risk score (ARRS) are widely used and reliable predictors of prognosis. AAV phenotypes, outcomes and treatment have changed over the last decades: whether and how the existing classi...

Background and Aims Cyclophosphamide (CYC), together with rituximab, is the mainstay for induction therapy in ANCA-associated vasculitis (AAV) [1]. The risk factors influencing the likelihood of relapse in individuals undergoing CYC induction are still unclear. This study aims to score the more robust predictors of relapse in these patients, thereb...

Background and Aims Monogenic systemic lupus erythematosus (SLE) accounts for 7-10% of cases of early-onset SLE. DNASE1L3 is an extracellular nuclease that digests chromatin released from apoptotic cells and its deficiency, enhance autoantibody production and type I interferon responses and cause different autosomal recessive phenotypes including S...

Background and Aims Lupus nephritis (LN) is a common and severe complication of childhood-onset SLE. Little is known about the long-term renal outcome of childhood-onset LN. We investigated predictive factors of end-stage kidney disease (ESKD) and chronic kidney disease (CKD) in a paediatric cohort of patients with LN. Method This is a retrospecti...

Background and Aims Adult-onset IgA Vasculitis (IgAV) is poorly responsive to glucocorticoids (GC) and conventional immunosuppressive therapies, such as cyclophosphamide. Rituximab has been successfully used in a few cases and may represent a safer and potentially more effective option [1]. Crescentic IgA Nephropathy (cIgAN), a rare entity that sha...

Background Giant cell arteritis is an age-related vasculitis that mainly affects the aorta and its branches in individuals aged 50 years and older. Current options for diagnosis and treatment are scarce, highlighting the need to better understand its underlying pathogenesis. Genome-wide association studies (GWAS) have emerged as a powerful tool for...

Rationale Erdheim-Chester disease (ECD) is a rare multisystemic disease characterized by the infiltration of multiple organs by foamy CD68 + CD1a-histiocytes. The genetic background consists of gain-of-function somatic mutations in the mitogen-activated protein kinase pathway. The purpose of the present paper is to make a contribution to the scient...

Objective Lupus nephritis (LN) is a common and severe complication of childhood-onset SLE. Little is known about the long-term renal outcome of childhood-onset LN. We investigated predictive factors of end-stage kidney disease (ESKD) and chronic kidney disease (CKD) in a paediatric cohort of patients with LN. Methods This is a retrospective multic...

Objective Patients with systemic lupus erythematosus (SLE) show accelerated atherosclerosis and are at higher risk of developing myocardial infarction, stroke and peripheral vasculopathy, carrying an overall 2- to 10-fold higher risk of cardiovascular events as compared to the general population. The pathogenetic mechanisms underlying this increase...

Background. Kidney involvement is common in anti-neutrophil cytoplasm antibody-associated vasculitis (AAV) and the prognosis is determined by the severity of kidney damage. This study focused on long-term kidney outcomes, defining possible risk factors and comparing the performance of three different histological classifications to predict outcomes...

b> Introduction: Erdheim-Chester disease (ECD) is a rare histiocytic neoplasm that affects patients, predominantly males aged 40–70 years, with very heterogeneous clinical presentation and prognosis. In 2020, Goyal et al. proposed consensus recommendations for the management of patients with ECD, remarking on the exceptional presentation of the dis...

Introduction This retrospective study on patients with biopsy-proven lupus nephritis (LN) aimed to assess the probability of sustained clinical remission (sCR) and to investigate sCR effects on disease flares and impaired kidney function (IKF). Methods sCR was defined as clinical-Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K)...

Objective Granulomatosis with polyangiitis (GPA) is an antineutrophil cytoplasmic antibody-associated vasculitis. The 2022 American College of Rheumatology/European Alliance of Associations for Rheumatology (ACR/EULAR)-endorsed classification criteria for GPA was derived using data only from adult patients. We aimed to assess the performance of the...

Objective Erdheim‐Chester disease (ECD) is rare histiocytosis with a wide range of clinical manifestations. Somatic mutations are key to the pathogenesis of the disease; however, the relationship between germline genetic variants and ECD has not been examined so far. The present study aims to explore the inherited genetic component of ECD by perfor...

Objectives This study aims to describe the data structure and harmonisation process, explore data quality and define characteristics, treatment, and outcomes of patients across six federated antineutrophil cytoplasmic antibody-associated vasculitis (AAV) registries. Methods Through creation of the vasculitis-specific Findable, Accessible, Interope...

In this geo-epidemiological study performed in Italy-France, Erdheim-Chester disease (ECD) is increasingly diagnosed in the past few years and cases cluster in specific geographic areas, namely Southern Italy and Central France. Disease frequency inversely correlates with the Human Development Index.

Objective Previous studies suggested that distinct phenotypes of eosinophilic granulomatosis with polyangiitis (EGPA) could be determined by presence or absence of antineutrophil cytoplasmic antibodies (ANCA), reflecting predominant vasculitic or eosinophilic processes, respectively. This study explored whether ANCA-based clusters or other clusters...

Objective Previous studies suggested that distinct phenotypes of eosinophilic granulomatosis with polyangiitis (EGPA) could be determined by presence or absence of antineutrophil cytoplasmic antibodies (ANCA), reflecting predominant vasculitic or eosinophilic processes, respectively. This study explored whether ANCA-based clusters or other clusters...

The growing number of disease-specific patient registries for rare diseases has highlighted the need for registry interoperability and data linkage, leading to large-scale rare disease data integration projects using Semantic Web based solutions. These technologies may be difficult to grasp for rare disease experts, leading to limited involvement b...

Erdheim-Chester Disease (ECD) is exceptionally rare in childhood. Among 21 children with ECD, disease phenotype and mutational profile were similar to those observed in adults, although the frequency of some clinical manifestations differed. Targeted therapies were also effective in children.

ABSTRACT Background Despite newer treatments with immunosuppressive agents, there still exists a considerable morbidity and mortality risk among patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Since 1994 the European Vasculitis Society (EUVAS) has aimed for an improved outcome for patients with AAV, conducting...

The management of IgA nephropathy, membranous nephropathy, lupus nephritis, ANCA-associated vasculitis, C3 glomerulonephritis, autoimmune podocytopathies and other immune-mediated glomerular disorders is focused on two major treatment goals, namely preventing overall mortality and the loss of kidney function. As minimizing irreversible kidney damag...

Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis, characterized by asthma, eosinophilia and granulomatous or vasculitic involvement of several organs. The diagnosis and management of EGPA are often challenging and require an integrated, multidisciplinary approach. Curren...

Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis, characterized by asthma, eosinophilia and granulomatous or vasculitic involvement of several organs. The diagnosis and management of EGPA are often challenging and require an integrated, multidisciplinary approach. Curre...

Introduction: IgG4-related disease (IgG4-RD) is a rare fibro-inflammatory disease affecting multiple organs. In recent years basic and translational research has unveiled the role of different cellular subtypes and cytokines in inducing and perpetuating the pathological process, eventually leading to fibrosis of affected tissues. Hopefully, the gr...

Background Since the publication of the EULAR recommendations for the management of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) in 2016, several randomised clinical trials have been published that have the potential to change clinical care and support the need for an update. Methods Using EULAR standardised operating pro...

In recent years, clinical research has increased significantly and therapies for antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis have improved. However, there are still unanswered questions and unmet needs about AAV patients. The purpose of this review is to examine the frontiers of research related to emerging biomarkers eventuall...

Objectives The number of susceptibility loci currently associated with vasculitis is lower than in other immune-mediated diseases due in part to small cohort sizes, a consequence of the low prevalence of vasculitides. This study aimed to identify new genetic risk loci for the main systemic vasculitides through a comprehensive analysis of their gene...

An ambitious project to update the classification of vasculitis syndromes has culminated in the development of new classification criteria for anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis, Takayasu arteritis and giant cell arteritis. Endorsed by the ACR and EULAR, the new criteria reflect progress in the understanding and asses...

Chronic periaortitis (CP) is a rare disease characterised by the presence of a fibro-inflammatory tissue typically enveloping the abdominal aorta, the iliac arteries and, in some cases, the nearby structures, such as the ureters and the inferior vena cava. Imaging plays a key role in the diagnosis and follow-up: computed tomography and magnetic res...

Background: Whole-exome sequencing (WES) increases the diagnostic rate of genetic kidney disorders, but accessibility, interpretation of results, and costs limit use in daily practice. Methods: Univariable analysis of a historical cohort of 392 patients who underwent WES for kidney diseases showed that resistance to treatments, familial history...

Objectives: Rituximab has become the cornerstone of induction treatment in ANCA-associated vasculitis (AAV). B cell depletion may increase the risk of hypogammaglobulinemia, potentially leading to severe infections. This study aims to assess factors associated with hypogammaglobulinemia in AAV patients treated with rituximab. Methods: This retro...

Introduction La maladie d’Erdheim–Chester (MEC) est une histiocytose rare dans laquelle les mutations somatiques impliquant les voies des MAPkinases et PI3K-AKT jouent un rôle pathogénique majeur. Un rôle de l’environnement dans l’apparition de la maladie est envisagé du fait de ces altérations moléculaires somatiques acquises. Pourtant, la géo-épi...

Monoclonal immunoglobulin deposition disease (MIDD) is a systemic disease characterized by the abnormal clonal production and tissue deposition of monoclonal immunoglobulins (mIg). Three subtypes of MIDD have been reported: light chain deposition disease, which is the most common, light- and heavy-chain deposition disease, and heavy-chain depositio...

Only a minority of patients with eosinophilic granulomatosis with polyangiitis (EGPA) can be weaned-off glucocorticoids (GC) using conventional treatment strategies. The development of biological agents specifically inhibiting the IL-5 pathway provided the opportunity to treat EGPA by targeting one of the crucial regulators of eosinophils, reducing...

Purpose of review: The purpose of this review is to discuss the role of the complement system in the pathogenesis of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) as well as the employment of complement inhibitors in AAV treatment. Recent findings: AAV has traditionally been considered a pauci-immune disease until recent...

Purpose of review: To provide an overview of existing literature on pathogenetic and clinical aspects of cardiac and vascular involvement in eosinophilic granulomatosis with polyangiitis (EGPA). Recent findings: In EGPA, cardiac and vascular involvement are more common than previously thought. However, no international recommendations on the top...

Mechanisms for the generation of anti-dsDNA autoantibodies are still not completely elucidated. One theory states that dsDNA interacts for mimicry with antibodies raised versus other antigens but molecular features for mimicry are unknown. Here we show that, at physiological acid-base balance, anti-Annexin A1 binds IgG2 dsDNA in a competitive and d...

Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis that frequently infiltrates the peri-kidney space (“hairy kidney” appearance), kidney pelvis and proximal ureters, leading to obstructive uropathy. Here, we analyzed the clinical characteristics, imaging findings and long-term kidney outcome of a large multicenter cohort comp...

Introduction Proliferative lupus nephritis (LN) progresses to end-stage kidney disease (ESKD) in roughly 10% of the cases despite treatment. Other than achieving < 0.8 g 24-h proteinuria at 12 months after treatment, early biomarkers predicting ESKD or death are lacking. Recent studies encompassing not only LN have highlighted the central role of t...

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) comprises granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (EGPA), that share features of pauci-immune small-vessel vasculitis and the positivity of ANCA targeting proteinase-3 (PR3-ANCA) or myeloperoxidase...

Objectives Patients affected by Eosinophilic Granulomatosis with Polyangiitis (EGPA) display an increased risk of atherothrombotic events compared with the general population. An increased frequency of subclinical markers of atherosclerosis has been observed in other anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), but no sp...

Adenosine deaminase 2 (ADA2) deficiency is a rare autosomal recessive disease, caused by loss-of-function mutations in the ADA2 gene, and is considered a monogenic form of polyarteritis nodosa (PAN) with frequently positive type I interferon (IFN-I) signature. Renal manifestations in ADA2 deficiency are poorly characterised. We herein report two ca...

Background Rituximab (RTX) is an effective remission-induction treatment in ANCA-associated vasculitides (AAVs). Some reports have suggested that it might be effective also in Eosinophilic Granulomatosis with Polyangiitis (EGPA), to induce and maintain remission of vasculitic manifestations [1,2]. However, its effects for preventing respiratory rel...

Eosinophilic granulomatosis with polyangiitis (EGPA) is an anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis. A genome-wide association study showed a correlation between ANCA-negative EGPA and variants of genes encoding proteins with intestinal barrier functions, suggesting that modifications of the mucosal layer and consequent gut...

Background: Jagged ends of plasma DNA are a recently recognized class of fragmentomic markers for cell-free DNA, reflecting the activity of nucleases. A number of recent studies have also highlighted the importance of jagged ends in the context of pregnancy and oncology. However, knowledge regarding the generation of jagged ends is incomplete. Me...

BACKGROUND AND AIMS In the last decade, the use of whole-exome sequencing techniques (WES) has provided many insights into inherited kidney diseases that are thought to represent at least 10%–15% of cases of end-stage CKD [1]. However, among others, cost concerns limit the widespread of genomics use in daily practice [1, 2]. Publicly funded genomic...

BACKGROUND AND AIMS ANCA-associated vasculitis (AAV) is rare among children but leads to kidney failure (KF) in almost 30% of cases with renal involvement [1]. Kidney transplantation (KT) is the treatment of choice in adults with AAV and KF, while data among children are limited to small case series [2, 3]. We report the outcomes of KT in a multice...

BACKGROUND AND AIMS With the spread of whole-exome sequencing techniques (WES), genetic kidney diseases are increasingly recognized across all age groups. However, accessibility, interpretation of results and costs limit the widespread of genomics use in daily practice [1]. In the very last years, first experiences in the implementation of renal ge...

Objective: To investigate second kidney biopsy as predictor of end-stage kidney disease (ESKD) in active lupus nephritis (LN). Methods: Patients with biopsy-proven LN (International Society of Nephrology/Renal Pathology Society 2003) who had undergone a second kidney biopsy between January 1990 and December 2018 were included. Clinical and histo...

The first European Vasculitis Society (EUVAS) meeting report was published in 2017.¹ Herein we report on developments over 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 o...

Introduction Primary Focal Segmental Glomerulosclerosis (FSGS) is a rare, likely immune-mediated disease. Rituximab (RTX) may play a role in management, although data in adults are scanty. Methods We collected cases of RTX-treated primary FSGS within the Italian Society of Nephrology Immunopathology Working Group and explored response rate (24h pr...

Type I interferon (IFN-I) mediates tissue damage in a wide range of kidney disorders, directly affecting the biology and function of several renal cell types including podocytes, mesangial, endothelial and parietal epithelial cells (PECs).Enhanced IFN-I signalling is observed in the context of viral infections, autoimmunity (e.g., systemic lupus er...

Objective Mepolizumab proved to be an efficacious treatment for eosinophilic granulomatosis with polyangiitis (EGPA) at a dose of 300 mg every 4 weeks in the randomized, controlled MIRRA trial. In a few recently reported studies, successful real‐life experiences with the approved dose for treating severe eosinophilic asthma (100 mg every 4 weeks) w...

Introduction La granulomatose éosinophilique avec polyangéite (GEPA) (Churg–Strauss) est une vascularite nécrosante des vaisseaux de petit calibre caractérisée par une éosinophilie sanguine et tissulaire associée à un asthme. Les glucocorticoïdes contrôlent efficacement la maladie, mais les rechutes de la vascularite et la corticodépendance sont fr...

The B-cell-depleting antibody rituximab is frequently used in patients with minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS), but there are no predictors of response [1]. These are particularly needed in adult patients, given the substantial incidence of ‘secondary’ forms in this population and the extremely variable outco...

Background: Erdheim-Chester disease (ECD) is a non-Langerhans cell histiocytic disorder that almost exclusively affects adults. Reports of pediatric-onset ECD are only anecdotal. Additionally, a comprehensive clinical and molecular characterization of pediatric ECD is lacking. Methods: All prevalent and incident cases followed at three ECD referral...

Neutrophil extracellular traps (NETs) are macromolecular structures programmed to trap circulating bacteria and viruses. The accumulation of NETs in the circulation correlates with the formation of anti-double-stranded (ds) DNA antibodies and is considered a causative factor for systemic lupus erythematosus (SLE). The digestion of DNA by DNase1 and...

Clinical Trial registry name and registration number: Zeus study, NCT02403115