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Open Access 01-02-2017 | Original Article

Serological and genetic complement alterations in infection-induced and complement-mediated hemolytic uremic syndrome

Authors: Dineke Westra, Elena B. Volokhina, Renate G. van der Molen, Thea J. A. M. van der Velden, Annelies Jeronimus-Klaasen, Joop Goertz, Valentina Gracchi, Eiske M. Dorresteijn, Antonia H. M. Bouts, Mandy G. Keijzer-Veen, Joanna A. E. van Wijk, Jaap A. Bakker, Anja Roos, Lambert P. van den Heuvel, Nicole C. A. J. van de Kar

Published in: Pediatric Nephrology | Issue 2/2017

Abstract

Background

The role of complement in the atypical form of hemolytic uremic syndrome (aHUS) has been investigated extensively in recent years. As the HUS-associated bacteria Shiga-toxin-producing Escherichia coli (STEC) can evade the complement system, we hypothesized that complement dysregulation is also important in infection-induced HUS.

Methods

Serological profiles (C3, FH, FI, AP activity, C3d, C3bBbP, C3b/c, TCC, αFH) and genetic profiles (CFH, CFI, CD46, CFB, C3) of the alternative complement pathway were prospectively determined in the acute and convalescent phase of disease in children newly diagnosed with STEC-HUS or aHUS. Serological profiles were compared with those of 90 age-matched controls.

Results

Thirty-seven patients were studied (26 STEC-HUS, 11 aHUS). In 39 % of them, including 28 % of STEC-HUS patients, we identified a genetic and/or acquired complement abnormality. In all patient groups, the levels of investigated alternative pathway (AP) activation markers were elevated in the acute phase and normalized in remission. The levels were significantly higher in aHUS than in STEC-HUS patients.

Conclusions

In both infection-induced HUS and aHUS patients, complement is activated in the acute phase of the disease but not during remission. The C3d/C3 ratio displayed the best discrepancy between acute and convalescent phase and between STEC-HUS and aHUS and might therefore be used as a biomarker in disease diagnosis and monitoring. The presence of aberrations in the alternative complement pathway in STEC-HUS patients was remarkable, as well.

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Title: Serological and genetic complement alterations in infection-induced and complement-mediated hemolytic uremic syndrome
Authors: Dineke Westra
Elena B. Volokhina
Renate G. van der Molen
Thea J. A. M. van der Velden
Annelies Jeronimus-Klaasen
Joop Goertz
Valentina Gracchi
Eiske M. Dorresteijn
Antonia H. M. Bouts
Mandy G. Keijzer-Veen
Joanna A. E. van Wijk
Jaap A. Bakker
Anja Roos
Lambert P. van den Heuvel
Nicole C. A. J. van de Kar
Publication date: 01-02-2017
Publisher: Springer Berlin Heidelberg
Published in: Pediatric Nephrology / Issue 2/2017
Print ISSN: 0931-041X
Electronic ISSN: 1432-198X
DOI: https://doi.org/10.1007/s00467-016-3496-0

At a glance: The STEP trials

Springer Medicine

Serological and genetic complement alterations in infection-induced and complement-mediated hemolytic uremic syndrome

Abstract

Background

Methods

Results

Conclusions

At a glance: The STEP trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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