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Current Pediatrics Reports

, Volume 7, Issue 1, pp 1–11 | Cite as

The Role of Complement in the Pathogenesis of HUS and the TMA Spectrum Disorders

  • Erin Jacobs
  • Carolina Ortiz
  • Christoph LichtEmail author
Renal (D Noone, Section Editor)
Part of the following topical collections:
  1. Renal

Abstract

Purpose of Review

This review aims to examine the current definitions of primary and secondary hemolytic uremic syndromes. Specifically, it seeks to determine which external conditions can result in secondary Thrombotic microangiopathy (TMA), which can trigger cases of primary atypical uremic syndromes (aHUS), and the role of complement in the pathogenesis of TMA spectrum disorders.

Recent Findings

Building on the growing insight about the pathogenic role of dysregulation of the alternative complement pathway in primary aHUS, the successful use of complement-blocking treatment in cases of thrombotic microangiopathy with coexisting conditions (secondary TMA), along with the identification of complement mutations in some of these cases, indicates a so far possibly under-appreciated pathogenic role for complement in diagnoses within the TMA spectrum.

Summary

Uncontrolled complement activity and pro-thrombotic environments represent a unifying pathogenic mechanism in aHUS and the TMA spectrum disorders and point towards shared diagnostic and therapeutic pathways.

Keywords

Thrombotic microangiopathy Atypical hemolytic uremic syndrome Complement system 

Abbreviations

ADAMTS13

A disintegrin and metalloproteinase with a thrombospondin type 1 motif member 13

AP

Alternative pathway (complement system)

aHUS

Atypical hemolytic uremic syndrome

CMV

Cytomegaloviruses

CP

Classical pathway (complement system)

DEAP-HUS

Deficiency of CFHR plasma proteins and autoantibody-positive form of _______hemolytic uremic syndrome

DGKE

Diacylglycerol kinase epsilon

ESRD

End-stage renal disease

FB

Factor B

FH

Factor H

FHR

Factor H–related protein

FI

Factor I

HELLP

Hemolysis, elevated liver enzymes, and low platelet count

HSCT

Hematopoietic stem cell transplantation

HUS

Hemolytic uremic syndrome

INF2

Inverted formin-2

LP

Lectin pathway (complement system)

MAC

Membrane attack complex

MAHA

Microangiopathic hemolytic anemia

MBL

Mannose-binding lectin

MCP

Membrane cofactor protein (CD46)

SCR

Short consensus repeat

STEC-HUS/eHUS

Shiga toxin–producing E. coli mediated HUS

Stx

Shiga toxin

THBD

Thrombomodulin (CD141)

TMA

Thrombotic microangiopathy

TTP

Thrombotic thrombocytopenic purpura

Notes

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Erin Jacobs
    • 1
  • Carolina Ortiz
    • 1
  • Christoph Licht
    • 1
    • 2
    • 3
    Email author
  1. 1.Cell Biology Program, Research InstituteThe Hospital for Sick ChildrenTorontoCanada
  2. 2.Department of PediatricsUniversity of TorontoTorontoCanada
  3. 3.Division of NephrologyThe Hospital for Sick ChildrenTorontoCanada

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