Browsing by Subject "COMPLEMENT ACTIVATION"

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  • Koskela, Sirpa; Mäkelä, Satu; Strandin, Tomas; Vaheri, Antti; Outinen, Tuula; Joutsi-Korhonen, Lotta; Pörsti, Ilkka; Mustonen, Jukka; Laine, Outi (2021)
    Puumala hantavirus (PUUV) causes a hemorrhagic fever with renal syndrome (HFRS), also called nephropathia epidemica (NE), which is mainly endemic in Europe and Russia. The clinical features include a low platelet count, altered coagulation, endothelial activation, and acute kidney injury (AKI). Multiple connections between coagulation pathways and inflammatory mediators, as well as complement and kallikrein-kinin systems, have been reported. The bleeding symptoms are usually mild. PUUV-infected patients also have an increased risk for disseminated intravascular coagulation (DIC) and thrombosis.
  • Lokki, A. Inkeri; Haapio, Mikko; Heikkinen-Eloranta, Jenni (2020)
    Preeclampsia is a pregnancy-specific disorder affecting ca 3% of all pregnant women. Preeclampsia is the source of severe pregnancy complications. Later life consequences for mother and infant include increased risk of cardiovascular disease. Preeclampsia is caused by the dysfunction of the endothelium with subsequent activation of complement and coagulation systems. HELLP syndrome is considered to be an extreme complication of preeclampsia but it can also present independently. Diagnostic symptoms in HELLP syndrome are Hemolysis, Elevated Liver enzymes, and Low Platelets. Similar phenotype is present in thrombotic microangiopathies (TMAs) and HELLP syndrome is considered part of the TMA spectrum. Here, we present a case of severe preeclampsia and HELLP syndrome, which exacerbated rapidly and eventually led to need of intensive care, plasma exchange, and hemodialysis. The patient showed signs of hemolysis, disturbance in the coagulation, and organ damage in liver and kidneys. After comprehensive laboratory testing and supportive care, the symptoms did not subside and treatment with complement C5 inhibitor eculizumab was started. Thereafter, the patient started to recover. The patient had pregnancy-induced aHUS. Earlier initiation of eculizumab treatment may potentially shorten and mitigate the disease and hypothetically decrease future health risks of preeclamptic women.
  • Kari, Otto K.; Ndika, Joseph; Parkkila, Petteri; Louna, Antti; Lajunen, Tatu; Puustinen, Anne; Viitala, Tapani; Alenius, Harri; Urtti, Arto (2020)
    Methodological constraints have limited our ability to study protein corona formation, slowing nanomedicine development and their successful translation into the clinic. We determined hard and soft corona structural properties along with the corresponding proteomic compositions on liposomes in a label-free workflow: surface plasmon resonance and a custom biosensor for in situ structure determination on liposomes and corona separation, and proteomics using sensitive nanoliquid chromatography tandem mass spectrometry with open-source bioinformatics platforms. Undiluted human plasma under dynamic flow conditions was used for in vivo relevance. Proof-of-concept is presented with a regular liposome formulation and two light-triggered indocyanine green (ICG) liposome formulations in preclinical development. We observed formulation-dependent differences in corona structure (thickness, protein-to-lipid ratio, and surface mass density) and protein enrichment. Liposomal lipids induced the enrichment of stealth-mediating apolipoproteins in the hard coronas regardless of pegylation, and their preferential enrichment in the soft corona of the pegylated liposome formulation with ICG was observed. This suggests that the soft corona of loosely interacting proteins contributes to the stealth properties as a component of the biological identity modulated by nanomaterial surface properties. The workflow addresses significant methodological gaps in biocorona research by providing truly complementary hard and soft corona compositions with corresponding in situ structural parameters for the first time. It has been designed into a convenient and easily reproducible single-experiment format suited for preclinical development of lipid nanomedicines.
  • Lokki, A. Inkeri; Heikkinen-Eloranta, Jenni K.; Laivuori, Hannele (2018)
    Pregnancy is an immunological challenge to the mother. The fetal tissues including the placenta must be protected from activation of the maternal immune system. On the other hand, the placental tissue sheds into the maternal circulation and must be adequately identified and phagocytized by the maternal immune system. During a healthy pregnancy, numerous immunosuppressive processes take place that allow the allograft fetus to thrive under exposure to humoral and cellular components of the maternal immune system. Breakdown of immune tolerance may result in sterile inflammation and cause adverse pregnancy outcomes such as preeclampsia, a vascular disease of the pregnancy with unpredictable course and symptoms from several organs. Immunological incompatibility between mother and fetus is strongly indicated in preeclampsia. Recently, genetic factors linking immunological pathways to predisposition to preeclampsia have been identified. In this mini-review genetic variation in immunological factors are discussed in the context of preeclampsia. Specifically, we explore immunogenetic and immunomodulary mechanisms contributing to loss of tolerance, inflammation, and autoimmunity in preeclampsia.