Laboratory findings in patients treated with complement factor C3 inhibitor pegcetacoplan

作者：Langemeijer SMC, Langereis JD, Avest MT, Duineveld C, van de Logt AE, De Kat Angelino CM, van Deelen A, Michels MAHM, Gloerich J, Sprenkeler EGG, van der Molen RG, van de Kar NCAJ, Jacobs JFM · 发表于：Clinical chemistry and laboratory medicine · 年份：2026 · DOI：10.1515/cclm-2025-1270 · 研究领域：C3 glomerulopathy、complement factor C3、complement inhibition、paroxysmal nocturnal hemoglobinuria、pegcetacoplan、properdin

OBJECTIVES: Complement inhibitor pegcetacoplan binds to C3 and its activation product C3b. Pegcetacoplan has been approved for the treatment of paroxysmal nocturnal hemoglobinuria. Because pegcetacoplan exerts broad inhibition of the complement cascade its efficacy is also investigated in numerous other diseases caused by complement dysregulation, such as C3 glomerulopathy. Pegcetacoplan causes a number of counterintuitive changes in laboratory results. METHODS: In-depth complement analysis in two patients with PNH and three patients with C3 glomerulopathy, all treated with pegcetacoplan. RESULTS: C3 levels increase up to 300 % above reference levels. In vitro testing showed that this is not a turbidimetric artifact in the C3 immunoassay due to pegcetacoplan-C3 complex formation but appears to be caused by increased half-life of C3 bound to pegcetacoplan. Unbiased mass spectrometric plasma proteome analysis confirmed the dramatic pegcetacoplan-induced increase in circulating C3. Surprisingly, also a three-fold increase of properdin was observed during pegcetacoplan treatment. Serum protein electrophoresis showed an additional band in all patients after pegcetacoplan exposure. This C3-band does not migrate at its expected position because of changes in the mass and charge of C3 bound to pegcetacoplan and should therefore not be misinterpreted as an M-protein. Both in vitro experiments and real clinical practice laboratory results demonstrated that pegcetacoplan completely bl...