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Eculizumab-C5 complexes express a C5a neoepitope in vivo: Consequences for interpretation of patient complement analyses
Linnéuniversitetet, Fakulteten för Hälso- och livsvetenskap (FHL), Institutionen för kemi och biomedicin (KOB). Oslo Univ Hosp, Norway;Univ Oslo, Norway. (Linnaeus Ctr Biomat Chem, BMC)ORCID-id: 0000-0002-7192-5794
Oslo Univ Hosp, Norway.
Nordland Hosp, Norway.
Oslo Univ Hosp, Norway.
Vise andre og tillknytning
2017 (engelsk)Inngår i: Molecular Immunology, ISSN 0161-5890, E-ISSN 1872-9142, Vol. 89, s. 111-114Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

The complement system has obtained renewed clinical focus due to increasing number of patients treated with eculizumab, a monoclonal antibody inhibiting cleavage of C5 into C5a and C5b. The FDA approved indications are paroxysmal nocturnal haemoglobinuria and atypical haemolytic uremic syndrome, but many other diseases are candidates for complement inhibition. It has been postulated that eculizumab does not inhibit C5a formation in vivo, in contrast to what would be expected since it blocks C5 cleavage. We recently revealed that this finding was due to a false positive reaction in a C5a assay. In the present study, we identified expression of a neoepitope which was exposed on C5 after binding to eculizumab in vivo. By size exclusion chromatography of patient serum obtained before and after infusion of eculizumab, we document that the neoepitope was exposed in the fractions containing the eculizumab-C5 complexes, being positive in this actual C5a assay and negative in others. Furthermore, we confirmed that it was the eculizumab-C5 complexes that were detected in the C5a assay by adding an anti-IgG4 antibody as detection antibody. Competitive inhibition by anti-C5 antibodies localized the epitope to the C5a moiety of C5. Finally, acidification of C5, known to alter C5 conformation, induced a neoepitope reacting identical to the one we explored, in the C5a assays. These data are important for interpretation of complement analyses in patients treated with eculizumab.

sted, utgiver, år, opplag, sider
Elsevier, 2017. Vol. 89, s. 111-114
Emneord [en]
Complement, Eculizumab, C5, C5a, Neoepitope
HSV kategori
Forskningsprogram
Biomedicinsk vetenskap, Immunologi
Identifikatorer
URN: urn:nbn:se:lnu:diva-68145DOI: 10.1016/j.molimm.2017.05.021ISI: 000410014500012PubMedID: 28610663Scopus ID: 2-s2.0-85020486389OAI: oai:DiVA.org:lnu-68145DiVA, id: diva2:1146254
Konferanse
16th European Meeting on Complement in Human Disease (EMCHD), SEP 08-12, 2017, Copenhagen, DENMARK
Tilgjengelig fra: 2017-10-02 Laget: 2017-10-02 Sist oppdatert: 2019-09-06bibliografisk kontrollert

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