Eculizumab as a New Treatment for Severe Acute Post-infectious Glomerulonephritis: Two Case Reports.

Acute post-infections glomerulonephritis (APIGN) is a frequent cause of glomerulonephritis and represents the most common cause of acute glomerulonephritis in children. It can evolve to severe acute renal failure and chronic kidney disease or even end-stage kidney disease. The precise pathophysiological mechanisms of APIGN are still incompletely understood.

Case Report: A Rare Truncating Variant of the Gene in IgA Nephropathy.

IgA nephropathy (IgAN) is the most common primary glomerulonephritis worldwide. Despite appropriate therapy, 20-40% of affected-patients evolve toward end-stage kidney disease (ESKD). Mesangial IgA deposits are the hallmark of IgAN, and complement deposition (C3) seems to differentiate latent IgA mesangial deposits from active IgAN.

Case Report: Severe Complement-Mediated Thrombotic Microangiopathy in IgG4-Related Disease Secondary to Anti-Factor H IgG4 Autoantibodies.

Objective: To first describe and estimate the potential pathogenic role of Ig4 autoantibodies in complement-mediated thrombotic microangiopathy (TMA) in a patient with IgG4-related disease (IgG4-RD).

Methods: This study is a case report presenting a retrospective review of the patient's medical chart. Plasma complement C3 and C4 levels, immunoglobulin isotypes and subclasses were determined by nephelometry, the complement pathways' activity (CH50, AP50, MBL) using WIESLAB Complement System assays.

[Complement system and kidney].

In the last few years, there has been a growing interest in the study of complement, fueleld mainly by the design of complement modulators, especially the C5-blocker eculizumab. The latter has significantly improved the prognosis of some nephropathies, such as the atypical hemolytic uremic syndrome. This breakthrough is a perfect example of fundamental translational research leading to clinical applications for patients.

Upfront use of eculizumab to treat early acute antibody-mediated rejection after kidney allotransplantation and relevance for xenotransplantation.

Acute antibody-mediated rejection (AMR) early after transplant remains a challenge, both in allotransplantation and in xenotransplantation. We report the case of an early and severe acute AMR episode in a kidney transplant recipient that was successfully treated with upfront eculizumab. A 58-year-old woman had been on dialysis since 2014.

[Complement in diseases].

The complement system is part of the innate immunity. It is a multifunctional system including more than 30 plasma and membrane proteins. These are activated by an enzymatic cascade and proteolytic reactions producing activating fragments.

Blockade of C5 in Severe Acute Postinfectious Glomerulonephritis Associated With Anti-Factor H Autoantibody.

Activation of the complement cascade plays an important role in the pathogenesis of postinfectious glomerulonephritis. We report successful terminal complement pathway blockade using an anti-C5 monoclonal antibody (eculizumab) in an 8-year-old child with severe acute postinfectious glomerulonephritis requiring hemodialysis. The child presented with clinical, serologic, and histopathologic criteria for diffuse crescentic postinfectious glomerulonephritis.

Platelet-Derived Ectosomes Reduce NK Cell Function.

Platelet (PLT) transfusions are potentially life saving for individuals with low PLT numbers; however, previous work revealed that PLT transfusions are associated with increased infection risk. During storage, PLT intended for transfusion continuously shed ectosomes (Ecto) from their surface, which express immunomodulatory molecules like phosphatidylserine or TGF-β1. Recently, PLT-Ecto were shown to reduce proinflammatory cytokine release by macrophages and to favor the differentiation of naive T cells toward regulatory T cells.

Ectosomes of polymorphonuclear neutrophils activate multiple signaling pathways in macrophages.

Ectosomes are vesicles shed directly from the cell surface. Human polymorphonuclear neutrophils release ectosomes (PMN-Ect) upon their activation. PMN-Ect expose phosphatidylserine (PS) on the outer leaflet of the plasma membrane, and down-modulate the inflammatory response of human macrophages and dendritic cells exposed to TLR-2 and -4 ligands.

Microparticles (ectosomes) shed by stored human platelets downregulate macrophages and modify the development of dendritic cells.

Microparticles (MP) shed by platelets (PLT) during storage have procoagulant activities, but little is known about their properties to modify inflammation or immunity. In this study, we studied the capacity of MP present in PLT concentrates to alter the function of macrophages and dendritic cells (DC). The size of the purified MP was between 100 and 1000 nm, and they expressed phosphatidylserine; surface proteins of PLT (CD61, CD36, CD47), including complement inhibitors (CD55, CD59), but not CD63; and proteins acquired from plasma (C1q, C3 fragments, factor H).

Ectosomes as immunomodulators.

Considerable progress has been made in recognizing microvesicles as important mediators of intercellular communication rather than irrelevant cell debris. Microvesicles released by budding directly from the cell membrane surface (i.e.

Ectosomes released by polymorphonuclear neutrophils induce a MerTK-dependent anti-inflammatory pathway in macrophages.

At the earliest stage of activation, human polymorphonuclear neutrophils release vesicles derived directly from the cell surface. These vesicles, called ectosomes (PMN-Ect), expose phosphatidylserine in the outer membrane leaflet. They inhibit the inflammatory response of human monocyte-derived macrophages and dendritic cells to zymosan A (ZymA) and LPS and induce TGF-β1 release, suggesting a reprogramming toward a tolerogenic phenotype.

Erythrocyte-derived ectosomes have immunosuppressive properties.

Several clinical studies have suggested that blood transfusions are immunosuppressive. Whereas there have been reports describing immunosuppression induced by leukocytes or fragments thereof, the possibility that microparticles, released by erythrocytes during storage, are also involved was not investigated. We present evidence here that such microparticles have all the properties of ectosomes including size, the presence of a lipid membrane, and the specific sorting of proteins.

High prevalence of anti-C1q antibodies in biopsy-proven active lupus nephritis.

Background: Anti-C1q antibodies (anti-C1q) have been shown to correlate positively with systemic lupus erythematosus (SLE) nephritis. Several clinical studies indicated a high negative predictive value, suggesting that active lupus nephritis is rarely seen in patients with no anti-C1q. However, the true prevalence of anti-C1q at the time of active lupus nephritis has not been well established.

Clinical value of autoantibodies against C1q in children with glomerulonephritis.

Objective: Autoantibodies against C1q (anti-C1q) have been found in a number of autoimmune and renal diseases. They are best described in adult patients with systemic lupus erythematosus, where a strong correlation between the occurrence of anti-C1q and severe lupus nephritis (LN) has been observed. However, the role of anti-C1q in children with systemic lupus erythematosus has not yet been determined.

Complement mediates the binding of HIV to erythrocytes.

A fraction of HIV is associated with erythrocytes even when the virus becomes undetectable in plasma under antiretroviral therapy. The aim of the present work was to further characterize this association in vitro. We developed an in vitro model to study the factors involved in the adherence of HIV-1 to erythrocytes.

Association of a pool of HIV-1 with erythrocytes in vivo: a cohort study.

Background: Treatment of HIV-1-infected individuals with antiretrovirals can result in sustained suppression of plasma viral RNA at concentrations below the detection limit of available assays. However, continuing virus replication has been detected in patients with viral RNA in plasma suppressed for months to years, and many cell types are known to act as reservoirs or carriers for the virus. In vitro, erythrocytes bind HIV-1 immune complexes, so we tested for a circulating pool of HIV-1 associated with erythrocytes in people with HIV-1 infection.