Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides are rare systemic diseases that usually occur in adulthood. They comprise granulomatosis with polyangiitis (GPA, Wegener’s), microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (EGPA, Churg-Strauss syndrome). Their clinical presentation is often heterogeneous, with frequent involvement of the respiratory tract, the kidney, the skin and the joints. ANCA-associated vasculitis is rare in childhood but North-American and European cohort studies performed during the last decade have clarified their phenotype, patterns of renal involvement and their prognostic implications, and outcome. Herein, we review the main clinical and therapeutic aspects of childhood-onset ANCA-associated vasculitis, and provide preliminary data on demographic characteristics and organ manifestations of an Italian multicentre cohort.

Introduction: Progression of arterial involvement is often observed in patients with Takayasu arteritis (TA) thought to be in remission. This reflects the failure of currently used biomarkers and activity criteria to detect smouldering inflammation occurring within arterial wall. Pentraxin-3 (PTX3) is a soluble pattern recognition receptor produced at sites of inflammation and could reveal systemic as well as localized inflammatory processes. We verified whether the blood concentrations of PTX3 and of C-reactive protein (CRP) in patients with Takayasu arteritis (TA) might reflect vascular wall involvement, as assessed by signal enhancement after contrast media administration, and the progression of arterial involvement. Methods: A cross-sectional single-centre study was carried out on 42 patients with TA that comprised assessment of PTX3, of CRP and erythrocyte sedimentation velocity (ESR). In total, 20 healthy controls and 20 patients with Systemic Lupus Erythematous (SLE) served as controls. Vascular imaging was carried out by magnetic resonance angiography, doppler ultrasonography and computed tomography angiography. Results: Patients with TA and SLE had higher plasmatic PTX3 and CRP concentrations than healthy controls (P = 0.009 and 0.017, respectively). PTX3 levels did not correlate with those of CRP. Patients with active systemic TA had significantly higher concentrations of CRP but similar levels of PTX3 than patients with quiescent disease. In contrast, patients with vascular inflammation detectable at imaging had higher PTX3 concentrations (P = 0.016) than those in which vessel inflammation was not evident, while CRP levels were similar. The concentration of PTX3 but not that of CRP was significantly higher in TA patients with worsening arterial lesions that were not receiving antagonists of tumor necrosis factor-? or interleukin-6. Conclusions: Arterial inflammation and progression of vascular involvement influence plasma PTX3 levels in TA, while levels of CRP accurately reflect the burden of systemic inflammation. These results support the contention that PTX3 reflects different aspects of inflammation than CRP and might represent a biomarker of actual arteritis in TA.

Allergy and autoimmune diseases are characterised by a multifactorial pathogenic background. Several genes involved in the control of innate and adaptive immunity have been associated with diseases and variably combine with each other as well as with environmental factors and epigenetic processes to shape the characteristics of individual manifestations. Systemic or local perturbations in salt/water balance and in ion exchanges between the intra- and extracellular spaces or among tissues play a role. In this field, usually referred to as elementary immunology, novel evidence has been recently acquired on the role of members of the transient potential receptor (TRP) channel family in several cellular mechanisms of potential significance for the pathophysiology of the immune response. TRP canonical channel 6 (TRPC6) is emerging as a functional element for the control of calcium currents in immune-committed cells and target tissues. In fact, TRPC6 influences leukocytes’ tasks such as transendothelial migration, chemotaxis, phagocytosis and cytokine release. TRPC6 also modulates the sensitivity of immune cells to apoptosis and influences tissue susceptibility to ischemia-reperfusion injury and excitotoxicity. Here, we provide a view of the interactions between ion exchanges and inflammation with a focus on the pathogenesis of immune-mediated diseases and potential future therapeutic implications.

Immunoglobulin G4-related disease (IgG4-RD) promptly responds to glucocorticoids but relapses in a considerable fraction of patients. Reliable biomarkers of flare are currently lacking because the pathophysiology of IgG4-RD remains largely elusive. In the present work, we aimed to identify perturbations of B-cell subpopulations that might predict IgG4-RD relapse. Thirty patients were treated with glucocorticoids according to international guidelines. Circulating CD19+ and CD20+ cells, naive B cells, memory B cells, plasmablasts, and plasma cells were measured by flow cytometry at baseline and every 6 months for 2 years after the initiation of corticosteroid therapy. Patients with active untreated IgG4-RD showed significantly reduced CD19+ B cells, CD20+ B cells, and naive B cells compared with healthy subjects (p < 0.05), but significantly expanded plasmablasts and plasma cells (p < 0.01). After 6 months of corticosteroid treatment, all patients achieved clinical improvement. Naive B cells, plasmablasts, and plasma cells significantly decreased compared with disease onset, whereas memory B cells significantly increased compared with baseline (p < 0.01). Increase of memory B cells was observed only in patients who relapsed within 2 years of follow-up, however (HR, 12.24; 2.99 to 50.2; p = 0.0005). In these patients, the relapse rates at 12 and 24 months were 30% and 100%, respectively. No abnormalities of other B-cell subpopulations at disease onset or after 6 months of glucocorticoid treatment were found to predict IgG4-RD relapse at 2 years. Increase of circulating memory B cells after 6 months of glucocorticoid treatment might predict IgG4-RD relapse.