Dynamics of complement activation in aHUS and how to monitor eculizumab therapy.

Claudio Tripodo, Federica Banterla, Francesco Tedesco, Marina Noris, Elisabetta Valoti, Serena Bettoni, Giuseppe Remuzzi, Piero Ruggenenti, Paolo Macor, Miriam Galbusera, Roberta Donadelli, Elena Bresin, Eliana Gotti, Alessandro Amore, Rosanna Coppo, Sara Gastoldi

Risultato della ricerca: Articlepeer review

224 Citazioni (Scopus)


Atypical hemolytic-uremic syndrome (aHUS) is associated with genetic complement abnormalities/anti-complement factor H antibodies, which paved the way to treatment with eculizumab. We studied 44 aHUS patients and their relatives to (1) test new assays of complement activation, (2) verify whether such abnormality occurs also in unaffected mutation carriers, and (3) search for a tool for eculizumab titration. An abnormal circulating complement profile (low C3, high C5a, or SC5b-9) was found in 47% to 64% of patients, irrespective of disease phase. Acute aHUS serum, but not serum from remission, caused wider C3 and C5b-9 deposits than control serum on unstimulated human microvascular endothelial cells (HMEC-1). In adenosine 5'-diphosphate-activated HMEC-1, also sera from 84% and 100% of patients in remission, and from all unaffected mutation carriers, induced excessive C3 and C5b-9 deposits. At variance, in most patients with C3 glomerulopathies/immune complex-associated membranoproliferative glomerulonephritis, serum-induced endothelial C5b-9 deposits were normal. In 8 eculizumab-treated aHUS patients, C3/SC5b-9 circulating levels did not change posteculizumab, whereas serum-induced endothelial C5b-9 deposits normalized after treatment, paralleled or even preceded remission, and guided drug dosing and timing. These results point to efficient complement inhibition on endothelium for aHUS treatment. C5b-9 endothelial deposits might help monitor eculizumab effectiveness, avoid drug overexposure, and save money considering the extremely high cost of the drug.
Lingua originaleEnglish
pagine (da-a)1715-1726
Numero di pagine12
Stato di pubblicazionePublished - 2014

All Science Journal Classification (ASJC) codes

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  • ???subjectarea.asjc.2400.2403???
  • ???subjectarea.asjc.2700.2720???
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