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

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

*Corresponding author voor dit werk

    OnderzoeksoutputAcademicpeer review

    49 Citaten (Scopus)
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    Samenvatting

    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.

    Originele taal-2English
    Pagina's (van-tot)297-309
    Aantal pagina's13
    TijdschriftPediatric Nephrology
    Volume32
    Nummer van het tijdschrift2
    DOI's
    StatusPublished - feb.-2017

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