AHUS Caused by Complement Dysregulation: New Therapies on the Horizon

Overview

Journal Pediatr Nephrol

Specialties Nephrology
Pediatrics

Date 2010 Jun 18

PMID 20556434

Citations 60

Authors

Aoife M Waters

Christoph Licht

Affiliations

Soon will be listed here.

Abstract

Atypical hemolytic uremic syndrome (aHUS) is a heterogeneous disease that is caused by defective complement regulation in over 50% of cases. Mutations have been identified in genes encoding both complement regulators [complement factor H (CFH), complement factor I (CFI), complement factor H-related proteins (CFHR), and membrane cofactor protein (MCP)], as well as complement activators [complement factor B (CFB) and C3]. More recently, mutations have also been identified in thrombomodulin (THBD), an anticoagulant glycoprotein that plays a role in the inactivation of C3a and C5a. Inhibitory autoantibodies to CFH account for an additional 5-10% of cases and can occur in isolation or in association with mutations in CFH, CFI, CFHR 1, 3, 4, and MCP. Plasma therapies are considered the mainstay of therapy in aHUS secondary to defective complement regulation and may be administered as plasma infusions or plasma exchange. However, in certain cases, despite initiation of plasma therapy, renal function continues to deteriorate with progression to end-stage renal disease and renal transplantation. Recently, eculizumab, a humanized monoclonal antibody against C5, has been described as an effective therapeutic strategy in the management of refractory aHUS that has failed to respond to plasma therapy. Clinical trials are now underway to further evaluate the efficacy of eculizumab in the management of both plasma-sensitive and plasma-resistant aHUS.

Citing Articles

A Case of Atypical Hemolytic Uremic Syndrome With a Complement Factor I Mutation Triggered by a Femoral Neck Fracture.

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The Inhibitory Effects of a Factor B-Binding DNA Aptamer Family Supersede the Gain of Function of Factor B Variants Associated with Atypical Hemolytic Uremic Syndrome.

Duan H, Zhang Y, Otis M, Drolet D, Geisbrecht B J Immunol. 2024; 213(11):1691-1702.

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Proof of concept of a new plasma complement Factor H from waste plasma fraction.

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Moss-produced human complement factor H with modified glycans has an extended half-life and improved biological activity.

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Emerging role of complement in COVID-19 and other respiratory virus diseases.

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