Biocompatibility in low-density lipoprotein apheresis and plasma separation
AuthorHardersen, Randolf Inge
Introduction: Low-density lipoprotein (LDL) apheresis is used for the removal of LDL in selected patients and is also used for other medical indications. This thesis aimed to systematically study how different LDL apheresis systems affected the immune system in a biocompatibility perspective under in vivo and ex vivo conditions.
Methods: Whole blood adsorption, dextran sulfate plasma adsorption, and double filtration plasma LDL apheresis systems were studied using a human whole blood model differentiating the effect of the lipoprotein apheresis and plasma separation columns, also describing temporal changes.
Results: The in vivo study showed equal complement activation with all devices. Cytokines were consistently either increased, decreased, or unchanged. The ex vivo studies showed that the whole blood system was inert with regard to complement activation. The whole blood system reduced cytokine concentration and the plasma separation column can be a barrier to the reduction of eotaxin. Differences in temporal concentration changes were revealed for PDGF-BB and IP10. CD11b expression was complement factor 5 (C5) dependent and a possible C5 dependence for granulocyte-platelet conjugates formation was indicated.
Conclusion: There are marked differences in how the three LDL apheresis systems affect the immune system. Low-density lipoprotein apheresis can modulate the immune system which possibly can be beneficial for the patient when used for medical indications other than LDL lowering. The results underline the importance of testing LDL apheresis systems independently for each medical indication they are used, other than the removal of lipoproteins, and to take temporal changes into account when developing treatment regimes.
Paper I: Hovland, A., Hardersen, R., Sexton, J., Mollnes, T.E. & Lappegard, K.T. (2009). Different inflammatory responses induced by three LDL-lowering apheresis columns. Journal of Clinical Apheresis, 24(6), 247-253. Also available at https://doi.org/10.1002/jca.20223.
Paper II: Hovland, A., Hardersen, R., Nielsen, E.W., Enebakk, T., Christiansen, D., Ludviksen, J.K. Mollnes, T.E. & Lappegard, K.T. (2012). Complement profile and activation mechanisms by different LDL apheresis systems. Acta Biomaterialia, 8(6), 2288-2296. Also available at https://doi.org/10.1016/j.actbio.2012.02.017.
Paper III: Hardersen, R., Enebakk, T., Christiansen, D., Ludviksen J.K., Mollnes, T.E., Lappegard, K.T. & Hovland, A. (2020). Comparison of cytokine changes in three different lipoprotein apheresis systems in an ex vivo whole blood model. Journal of Clinical Apheresis, 35(2), 104-116. Also available at https://doi.org/10.1002/jca.21765. Accepted manuscript version available in Munin at https://hdl.handle.net/10037/17432.
Paper IV: Hardersen, R., Enebakk, T., Christiansen, D., Bergseth, G., Brekke, O.L., Mollnes, T.E. Lappegard, K.T. & Hovland, A. (2018). Granulocyte and monocyte CD11b expression during plasma separation is dependent on complement factor 5 (C5) - an ex vivo study with blood from a C5-deficient individual. Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), 126(4), 342-352. Also available at https://doi.org/10.1111/apm.12821. Accepted manuscript version available in Munin at https://hdl.handle.net/10037/14970.
PublisherUiT The Arctic University of Norway
UiT Norges arktiske universitet
The following license file are associated with this item: