Predicting Disease Activity in Systemic Vasculitides: On the Hunt for Potential Candidates

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ANCA associated vasculitis: The journey to complement-targeted therapies.

ANCA associated vasculitis is a serious, very often recurrent disease that despite the current standard treatment with high-dose glucocorticoids and either cyclophosphamide or rituximab, patients have a nine-fold increased mortality risk in the first year compared with healthy controls, attributed to infections, vasculitis activity, and renal disease. During the last few years, novel findings have suggested that activation of the complement system, in particular the alternative complement system, has a significant role in ANCA associated vasculitis pathogenesis. Detection of several components of this system in the circulation and urine reflects disease activity, and thus may be useful for clinical prognosis and to set up personalised treatments. In fact, some components of the complement system, such as C5a, might be potential targets for therapy. In this Review an update on clinical evidence for the role of complement activation in AAV is provided and subsequently we discuss potential therapeutic strategies that target complement components and open the way for clinical use of this target therapy in the near future

Efficacy of eculizumab in a patient with immunoadsorption- dependent catastrophic antiphospholipid syndrome: A case report

Catastrophic antiphospholipid syndrome (CAPS) is a rare but devastating complication in patients with antiphospholipid syndrome (APS) with a high morbidity and mortality. We describe a case of a 30-year old female patient with immunoglobulin A (IgA) deficiency who underwent splenectomy because of idiopathic thrombocytopenic thrombocytopenia. Subsequently, an APS and finally systemic lupus erythematosus was diagnosed. After an uncomplicated pregnancy that was terminated by cesarean section, the patient developed severe CAPS with cerebral, myocardial, renal, and pulmonary involvement. Because of IgA deficiency, standard therapy consisting of plasmapheresis and intravenous immunoglobulins in addition to steroids was not tolerated. After 8 sessions of immunoadsorption (IAS), massive pulmonary hemorrhage was controlled but relapsed twice whenever IAS was terminated. As other immunosuppressive agents were considered dangerous because of the risk of infections in the face of severe hypogammaglobulinemia, we administered eculizumab, an inhibitor of the terminal complement pathway, which led to a persistent control of her disease. Interestingly, eculizumab therapy was associatedwith a further decline of complement C3 and C4 serumlevels. The patient developed a subsequent flare of her systemic lupus erythematosus, potentially indicating that complement inhibition by eculizumab is not effective in preventing lupus flares. Taken together, we describe a unique case of life-threatening and difficult-to-treat CAPS with a good clinical response after terminal complement complex inhibition with eculizumab. Further controlled trials are necessary to investigate the value of eculizumab in patients with CAPS

Glomerular Diseases Across Lifespan:Key Differences in Diagnostic and Therapeutic Approaches

Glomerular diseases are common causes of chronic kidney disease in childhood, adolescence, and adulthood. The epidemiology of glomerular diseases differs between different age groups, with minimal change disease being the leading cause of nephrotic syndrome in childhood, while membranous nephropathy and focal segmental glomerulosclerosis are more common in adulthood. IgA vasculitis is also more common in childhood. Moreover, there is a difference in disease severity with more children presenting with a relapsing form of nephrotic syndrome and a more acute presentation of antineutrophil cytoplasmic antibody–associated vasculitis and concomitant glomerulonephritis, as highlighted by the higher percentage of cellular crescents on kidney biopsy specimens in comparison with older patients. There is also a female preponderance in antineutrophil cytoplasmic antibody–associated vasculitis and more children present with tracheobroncholaryngeal disease. This article aims to summarize differences in the presentation of different glomerular diseases that are encountered commonly by pediatric and adult nephrologists and potential differences in the management.</p

Soluble Urokinase Receptors in Focal Segmental Glomerulosclerosis:A Review on the Scientific Point of View

Focal segmental glomerulosclerosis (FSGS) is one of the primary glomerular disorders in both children and adults which can progress to end-stage renal failure. Although there are genetic and secondary causes, circulating factors have also been regarded as an important factor in the pathogenesis of FSGS, because about 40% of the patients with FSGS have recurrence after renal transplantation. Soluble urokinase-type plasminogen activator receptor (suPAR) is a soluble form of uPAR, which is a membrane-bound protein linked to GPI in various immunologically active cells, including podocytes. It has recently been suggested as a potential circulating factor in FSGS by in vitro podocyte experiments, in vivo mice models, and human studies. However, there have also been controversies on this issue, because subsequent studies showed conflicting results. suPAR levels were also increased in patients with other glomerular diseases and were inversely correlated with estimated glomerular filtration rate. Nevertheless, there has been no balanced review on this issue. In this review, we compare the conflicting data on the involvement of suPAR in the pathogenesis of FSGS and shed light on interpretation by taking into account many points and the potential variables and confounders influencing serum suPAR levels

COVID-19 and ANCA-associated vasculitis: recommendations for vaccine preparedness and the use of rituximab.

COVID-19 and ANCA-associated vasculitis - recommendations for vaccine preparedness and the use of rituximab

The COVID-19 pandemic and ANCA-associated vasculitis - reports from the EUVAS meeting and EUVAS education forum.

The Coronavirus Disease 2019 (COVID-19) pandemic influenced the management of patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis. A paucity of data exists on outcome of patients with vasculitis following COVID-19, but mortality is higher than in the general population and comparable to patients undergoing haemodialysis or kidney transplant recipients (reported mortality rates of 20-25%). Delays in diagnosis have been reported, which are associated with sequelae such as dialysis-dependency. Management of ANCA-associated vasculitis has not changed with the aim to suppress disease activity and reduce burden of disease. The use of rituximab, an important and widely used agent, is associated with a more severe hospital course of COVID-19 and absence of antibodies following severe acute respiratory syndrome (SARS)-CoV-2 infections, which prone patients to re-infection. Reports on vaccine antibody response are scarce at the moment, but preliminary findings point towards an impaired immune response, especially when patients receive rituximab as part of their treatment. Seropositivity was reported in less than 20% of patients when rituximab was administered within the prior six months, and the antibody response correlated with CD19+ B-cell repopulation. A delay in maintenance doses, if disease activity allows, has been suggested using a CD19+ B-cell guided strategy. Other immunosuppressive measures, which are used in ANCA-associated vasculitis, also impair humoral and cellular vaccine responses. Regular measurements of vaccine response or a healthcare-policy time-based strategy are indicated to provide additional doses ("booster") of COVID-19 vaccines. This review summarizes a recent educational forum and a recent virtual meeting of the European Vasculitis Society (EUVAS) focusing on COVID-19