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Bakker, Jaap A.

Bouts, Antonia H. M.

de Kar, Nicole C. A. J. van

Dorresteijn, Eiske M.

Goertz, Joop

Gracchi, Valentina

Jeronimus-Klaasen, Annelies

Keijzer-Veen, Mandy G.

Roos, Anja

van den Heuvel, Lambert P.

van der Molen, Renate G

van der Velden, Thea J. A. M.

van Wijk, Joanna A. E.

Volokhina, Elena B.

Westra, Dineke

English

PubMed

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

van der Molen, Renate G.

van der Velden, Thea J A M

Bouts, Antonia H M

van Wijk, Joanna A E

van Den Heuvel, Lambert P.

van de Kar, Nicole C A J

Utrecht University Repository

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

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. Serological profiles (C3, FH, FI, AP activity, C3d, C3bBbP, C3b/c, TCC, alpha FH) 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. 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. 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

NARCIS 

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

Volokhina, Elena B

Dorresteijn, Eiske M

Keijzer-Veen, Mandy G

Bakker, Jaap A

van den Heuvel, Lambert P

University of Groningen Research Database

University of Groningen

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.Serological profiles (C3, FH, FI, AP activity, C3d, C3bBbP, C3b/c, TCC, alpha FH) 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.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.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.</p

ARTS repository - University of Groningen

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

Springer - Publisher Connector

Westra, D.

Volokhina, E.B.

Molen, R.G. van der

Velden, T.J.A.M. van der

Jeronimus-Klaasen, A.

Goertz, J.H.C.

Gracchi, V.

Dorresteijn, E.M.

Bouts, A.H.

Keijzer-Veen, M.G.

Wijk, J.A. van

Bakker, J.A.

Roos, A. de

Heuvel, L.P.W.J. van den

Kar, N.C.A.J. van de

Radboud Repository

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

https://research.vumc.nl/en/publications/1563a5ce-1576-4f0e-8891-377156930e89

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

Abstract

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Utrecht University Repository

NARCIS

NARCIS

University of Groningen Research Database

University of Groningen

ARTS repository - University of Groningen

Springer - Publisher Connector

Springer - Publisher Connector

Radboud Repository