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


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.


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.


Thrombotic microangiopathy Atypical hemolytic uremic syndrome Complement system 



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


Alternative pathway (complement system)


Atypical hemolytic uremic syndrome




Classical pathway (complement system)


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


Diacylglycerol kinase epsilon


End-stage renal disease


Factor B


Factor H


Factor H–related protein


Factor I


Hemolysis, elevated liver enzymes, and low platelet count


Hematopoietic stem cell transplantation


Hemolytic uremic syndrome


Inverted formin-2


Lectin pathway (complement system)


Membrane attack complex


Microangiopathic hemolytic anemia


Mannose-binding lectin


Membrane cofactor protein (CD46)


Short consensus repeat


Shiga toxin–producing E. coli mediated HUS


Shiga toxin


Thrombomodulin (CD141)


Thrombotic microangiopathy


Thrombotic thrombocytopenic purpura


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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Copyright information

© 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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