Knut Tore Lappegård1, Terje Enebakk2, Hilde Thunhaug2, Judith Krey Ludviksen3, Tom Eirik Mollnes4, Anders Hovland5. 1. Coronary Care Unit, Division of Internal Medicine, Nordland Hospital, Bodø, Norway; Institute of Clinical Medicine, University of Tromsø, Tromsø, Norway. Electronic address: knut.tore.lappegard@gmail.com. 2. Dialysis Unit, Division of Internal Medicine, Nordland Hospital, Bodø, Norway. 3. Research Laboratory, Nordland Hospital, Bodø, Norway. 4. Research Laboratory, Nordland Hospital, Bodø, Norway; Institute of Clinical Medicine, Faculty of Health Sciences, K.G. Jebsen TREC, University of Tromsø, Tromsø, Norway; Centre of Molecular Inflammation Research, Norwegian University of Science and Technology, Trondheim, Norway; Department of Immunology, Oslo University Hospital Rikshospitalet, Oslo, Norway; K.J. Jebsen Inflammation Research Centre, University of Oslo, Oslo, Norway. 5. Coronary Care Unit, Division of Internal Medicine, Nordland Hospital, Bodø, Norway; Institute of Clinical Medicine, University of Tromsø, Tromsø, Norway.
Abstract
BACKGROUND: Low-density lipoprotein (LDL) apheresis is an extracorporeal treatment modality used in high-risk coronary patients. It may, however, induce complement activation and downstream inflammation due to bio-incompatibility. OBJECTIVE: We explored changes in soluble inflammatory markers when changing from LDL apheresis to the novel PCSK9 inhibitor evolocumab. METHODS: Three patients with familial hypercholesterolemia participated. Blood samples (EDTA plasma) for complement activation and markers of inflammation were obtained before (baseline) and after LDL apheresis week at 0 and before biweekly administration of evolocumab at weeks 1, 3, 5, and 7. Complement activation was measured by ELISA and cytokines by multiplex technology. RESULTS: Complement activation products C3a and Bb were both significantly higher after LDL apheresis compared to baseline (P = .01), returned to baseline levels before administration of evolocumab and remained low through week 7. C4d was unchanged during LDL apheresis, whereas TCC was slightly higher after apheresis compared to baseline and week 7 without statistical difference. MCP-1 was higher after LDL apheresis compared to baseline (P = .04), returned to baseline levels before administration of evolocumab and remained low through week 7. There were minor changes for other cytokines including TNF, IFN-γ, MIP-1α, MIP-1β, with some higher and some lower after apheresis; however, none of these changes were statistically significant. Fibrinogen and CRP were lower after LDL apheresis and had returned to levels comparable to baseline at week 7, statistically significant however only for fibrinogen. CONCLUSIONS: LDL apheresis activated the alternative complement system significantly as reflected by an increase in C3a and Bb. PCSK9 inhibition did not affect complement or cytokines during 7 weeks follow-up. Copyright Â
BACKGROUND: Low-density lipoprotein (LDL) apheresis is an extracorporeal treatment modality used in high-risk coronary patients. It may, however, induce complement activation and downstream inflammation due to bio-incompatibility. OBJECTIVE: We explored changes in soluble inflammatory markers when changing from LDL apheresis to the novel PCSK9 inhibitor evolocumab. METHODS: Three patients with familial hypercholesterolemia participated. Blood samples (EDTA plasma) for complement activation and markers of inflammation were obtained before (baseline) and after LDL apheresis week at 0 and before biweekly administration of evolocumab at weeks 1, 3, 5, and 7. Complement activation was measured by ELISA and cytokines by multiplex technology. RESULTS: Complement activation products C3a and Bb were both significantly higher after LDL apheresis compared to baseline (P = .01), returned to baseline levels before administration of evolocumab and remained low through week 7. C4d was unchanged during LDL apheresis, whereas TCC was slightly higher after apheresis compared to baseline and week 7 without statistical difference. MCP-1 was higher after LDL apheresis compared to baseline (P = .04), returned to baseline levels before administration of evolocumab and remained low through week 7. There were minor changes for other cytokines including TNF, IFN-γ, MIP-1α, MIP-1β, with some higher and some lower after apheresis; however, none of these changes were statistically significant. Fibrinogen and CRP were lower after LDL apheresis and had returned to levels comparable to baseline at week 7, statistically significant however only for fibrinogen. CONCLUSIONS: LDL apheresis activated the alternative complement system significantly as reflected by an increase in C3a and Bb. PCSK9 inhibition did not affect complement or cytokines during 7 weeks follow-up. Copyright Â
Authors: Felix Poppelaars; Bernardo Faria; Mariana Gaya da Costa; Casper F M Franssen; Willem J van Son; Stefan P Berger; Mohamed R Daha; Marc A Seelen Journal: Front Immunol Date: 2018-01-25 Impact factor: 7.561