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Nilsson Ekdahl, KristinaORCID iD iconorcid.org/0000-0001-7888-1571
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Publications (10 of 226) Show all publications
Azuma, T., Matsushita, T., Manivel, V. A., Nilsson Ekdahl, K., Nilsson, B., Teramura, Y. & Takai, M. (2020). Poly(2-aminoethyl methacrylate)-based polyampholyte brush surface with carboxylic groups to improve blood compatibility. Journal of Biomaterials Science. Polymer Edition, 1-15
Open this publication in new window or tab >>Poly(2-aminoethyl methacrylate)-based polyampholyte brush surface with carboxylic groups to improve blood compatibility
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2020 (English)In: Journal of Biomaterials Science. Polymer Edition, ISSN 0920-5063, E-ISSN 1568-5624, p. 1-15Article in journal (Refereed) Published
Abstract [en]

Zwitterionic material-based polymer brush significantly prevents protein adsorption and cell adhesion, which leads to the blood compatibility. However, zwitterionic polymer itself is difficult to be modified further, for the blood compatibility since the charged balance is impaired after the modification. In this research, chemically modifiable mixed charge polymer brush is designed, without impairing its characteristics. Condensed mixed charge polymer brush will work like zwitterionic material because neighbouring opposite charge is reported to be important in the zwitterionic material. Cationic polymer brush with primary amine group, which is based on 2-aminoethyl methacrylate (AEMA), was prepared and modified by succinic anhydride to obtain carboxylic group induced poly(AEMA). The ratio of primary amine group and carboxylic group was optimized to obtain the polyampholyte brush. The blood compatibility was evaluated by measuring coagulation/complement activation, protein adsorption and cell adhesion induced by the polymer. Our designed cationic-based polyampholyte brush prevented coagulation/complement activation comparable to poly(2-methacryloyloxyethyl phosphorylcholine) brush, based on intra-monomer interaction, because condensed mix charge works like zwitterion.

Place, publisher, year, edition, pages
Taylor & Francis Group, 2020
Keywords
Mixed-charge polymer, complement activation, coagulation related activation, polymer brush, zwitterion
National Category
Biochemistry and Molecular Biology
Research subject
Biomedical Sciences, Immunology
Identifiers
urn:nbn:se:lnu:diva-91180 (URN)10.1080/09205063.2019.1710900 (DOI)000506501000001 ()31888410 (PubMedID)
Available from: 2020-01-23 Created: 2020-01-23 Last updated: 2020-01-23
Nilsson Ekdahl, K., Fromell, K., Mohlin, C., Teramura, Y. & Nilsson, B. (2019). A human whole-blood model to study the activation of innate immunity system triggered by nanoparticles as a demonstrator for toxicity. Science and Technology of Advanced Materials, 20(1), 688-698
Open this publication in new window or tab >>A human whole-blood model to study the activation of innate immunity system triggered by nanoparticles as a demonstrator for toxicity
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2019 (English)In: Science and Technology of Advanced Materials, ISSN 1468-6996, E-ISSN 1878-5514, Vol. 20, no 1, p. 688-698Article, review/survey (Refereed) Published
Abstract [en]

In this review article, we focus on activation of the soluble components of the innate immune system triggered by nonbiological compounds and stress variances in activation due to the difference in size between nanoparticles (NPs) and larger particles or bulk material of the same chemical and physical composition. We then discuss the impact of the so-called protein corona which is formed on the surface of NPs when they come in contact with blood or other body fluids. For example, NPs which bind inert proteins, proteins which are prone to activate the contact system (e.g., factor XII), which may lead to clotting and fibrin formation or the complement system (e.g., IgG or C3), which may result in inflammation and vascular damage. Furthermore, we describe a whole blood model which we have developed to monitor activation and interaction between different components of innate immunity: blood protein cascade systems, platelets, leukocytes, cytokine generation, which are induced by NPs. Finally, we describe our own studies on innate immunity system activation induced by three fundamentally different species of NPs (two types of engineered NPs and diesel NPs) as demonstrator of the utility of an initial determination of the composition of the protein corona formed on NPs exposed to ethylenediaminetetraacetic acid (EDTA) plasma and subsequent analysis in our whole blood model. [GRAPHICS] .

Place, publisher, year, edition, pages
Taylor & Francis Group, 2019
Keywords
Coagulation system, complement system, contact, kallikrein system, inflammation, innate immunity, nanoparticles, protein corona, screening, toxicity, whole blood model
National Category
Immunology
Research subject
Biomedical Sciences, Immunology
Identifiers
urn:nbn:se:lnu:diva-86907 (URN)10.1080/14686996.2019.1625721 (DOI)000472611100001 ()31275460 (PubMedID)2-s2.0-85067849252 (Scopus ID)
Available from: 2019-07-18 Created: 2019-07-18 Last updated: 2019-08-29Bibliographically approved
Zhao, F., Afonso, S., Lindner, S., Hartmann, A., Loeschmann, I., Nilsson, B., . . . Skerka, C. (2019). C3-Glomerulopathy Autoantibodies Mediate Distinct Effects on Complement C3-and C5-Convertases. Frontiers in Immunology, 10, 1-14, Article ID 1030.
Open this publication in new window or tab >>C3-Glomerulopathy Autoantibodies Mediate Distinct Effects on Complement C3-and C5-Convertases
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2019 (English)In: Frontiers in Immunology, ISSN 1664-3224, E-ISSN 1664-3224, Vol. 10, p. 1-14, article id 1030Article in journal (Refereed) Published
Abstract [en]

C3 glomerulopathy (C3G) is a severe kidney disease, which is caused by defective regulation of the alternative complement pathway. Disease pathogenesis is heterogeneous and is caused by both autoimmune and genetic factors. Here we characterized IgG autoantibodies derived from 33 patients with autoimmune C3 glomerulopathy. Serum antibodies from all 33 patients as well as purified IgGs bound to the in vitro assembled C3-convertase. Noteworthy, two groups of antibodies were identified: group 1 with strong (12 patients) and group 2 with weak binding C3-convertase autoantibodies (22 patients). C3Nef, as evaluated in a standard C3Nef assay, was identified in serum from 19 patients, which included patients from group 1 as well as group 2. The C3-convertase binding profile was independent of C3Nef. Group 1 antibodies, but not the group 2 antibodies stabilized the C3-convertase, and protected the enzyme from dissociation by Factor H. Also, only group 1 antibodies induced C3a release. However, both group 1 and group 2 autoantibodies bound to the C5-convertase and induced C5a generation, which was inhibited by monoclonal anti-C5 antibody Eculizumab in vitro. In summary, group 1 antibodies are composed of C3Nef and C5Nef antibodies and likely over-activate the complement system, as seen in hemolytic assays. Group 2 antibodies show predominantly C5Nef like activities and stabilize the C5 but not the C3-convertase. Altogether, these different profiles not only reveal a heterogeneity of the autoimmune forms of C3G (MPGN), they also show that in diagnosis of C3G not all autoimmune forms are identified and thus more vigorous autoantibody testing should be performed.

Place, publisher, year, edition, pages
Frontiers Media S.A., 2019
Keywords
C3 glomerulopathy, C3NeF, C5Nef, complement, Eculizumab
National Category
Immunology
Research subject
Biomedical Sciences, Immunology
Identifiers
urn:nbn:se:lnu:diva-85855 (URN)10.3389/fimmu.2019.01030 (DOI)000470171700001 ()2-s2.0-85068447901 (Scopus ID)
Available from: 2019-06-25 Created: 2019-06-25 Last updated: 2019-08-29Bibliographically approved
Tjernberg, A. R., Woksepp, H., Sandholm, K., Johansson, M., Dahle, C., Ludvigsson, J. F., . . . Nilsson Ekdahl, K. (2019). Celiac disease and complement activation in response to Streptococcus pneumoniae. European Journal of Pediatrics
Open this publication in new window or tab >>Celiac disease and complement activation in response to Streptococcus pneumoniae
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2019 (English)In: European Journal of Pediatrics, ISSN 0340-6199, E-ISSN 1432-1076Article in journal (Refereed) Epub ahead of print
Abstract [en]

Individuals with celiac disease (CD) are at increased risk of invasive pneumococcal disease (IPD). The aim of this study was to explore whether the complement response to Streptococcus pneumoniae differed according to CD status, and could serve as an explanation for the excess risk of IPD in CD. Twenty-two children with CD and 18 controls, born 1999-2008, were included at Kalmar County Hospital, Sweden. The degree of complement activation was evaluated by comparing levels of activation products C3a and sC5b-9 in plasma incubated for 30 min with Streptococcus pneumoniae and in non-incubated plasma. Complement analyses were performed with enzyme-linked immunosorbent assay (ELISA). Pneumococcal stimulation caused a statistically significant increase in C3a as well as sC5b-9 in both children with CD and controls but there was no difference in response between the groups. After incubation, C3a increased on average 4.6 times and sC5b-9 22 times in both the CD and the control group (p = 0.497 and p = 0.724 respectively). Conclusion: Complement response to Streptococcus pneumoniae seems to be similar in children with and without CD and is thus unlikely to contribute to the increased susceptibility to invasive pneumococcal disease in CD.

Place, publisher, year, edition, pages
Springer, 2019
Keywords
Coeliac, Pneumococcal, Infection, Innate immunity, MBL
National Category
Immunology
Research subject
Biomedical Sciences, Immunology
Identifiers
urn:nbn:se:lnu:diva-90197 (URN)10.1007/s00431-019-03490-w (DOI)000494392200001 ()31691001 (PubMedID)
Available from: 2019-11-21 Created: 2019-11-21 Last updated: 2019-11-21
Mohebnasab, M., Eriksson, O., Persson, B., Sandholm, K., Mohlin, C., Huber-Lang, M., . . . Nilsson, B. (2019). Current and Future Approaches for Monitoring Responses to Anti-complement Therapeutics. Frontiers in Immunology, 10, 1-13, Article ID 2539.
Open this publication in new window or tab >>Current and Future Approaches for Monitoring Responses to Anti-complement Therapeutics
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2019 (English)In: Frontiers in Immunology, ISSN 1664-3224, E-ISSN 1664-3224, Vol. 10, p. 1-13, article id 2539Article, review/survey (Refereed) Published
Abstract [en]

Aberrations in complement system functions have been identified as either direct or indirect pathophysiological mechanisms in many diseases and pathological conditions, such as infections, autoimmune diseases, inflammation, malignancies, and allogeneic transplantation. Currently available techniques to study complement include quantification of (a) individual complement components, (b) complement activation products, and (c) molecular mechanisms/function. An emerging area of major interest in translational studies aims to study and monitor patients on complement regulatory drugs for efficacy as well as adverse events. This area is progressing rapidly with several anti-complement therapeutics under development, in clinical trials, or already in clinical use. In this review, we summarized the appropriate indications, techniques, and interpretations of basic complement analyses, exemplified by a number of clinical disorders.

Place, publisher, year, edition, pages
Frontiers Media S.A., 2019
Keywords
clinical trial, laboratory investigation, immunoassays, functional assays, CV%
National Category
Immunology
Research subject
Biomedical Sciences, Immunology
Identifiers
urn:nbn:se:lnu:diva-90506 (URN)10.3389/fimmu.2019.02539 (DOI)000498927000001 ()31787968 (PubMedID)
Available from: 2019-12-12 Created: 2019-12-12 Last updated: 2019-12-12Bibliographically approved
Sandholm, K., Carlsson, H., Persson, B., Skattum, L., Tjernberg, I., Nilsson, B. & Nilsson Ekdahl, K. (2019). Discrepancies in plasma levels of complement components measured by a newly introduced commercially available magnetic bead technique compared to presently available clinical reference intervals [Letter to the editor]. Scandinavian Journal of Immunology, Article ID e12831.
Open this publication in new window or tab >>Discrepancies in plasma levels of complement components measured by a newly introduced commercially available magnetic bead technique compared to presently available clinical reference intervals
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2019 (English)In: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, article id e12831Article in journal, Letter (Refereed) Epub ahead of print
Place, publisher, year, edition, pages
John Wiley & Sons, 2019
National Category
Immunology
Research subject
Biomedical Sciences, Immunology
Identifiers
urn:nbn:se:lnu:diva-90503 (URN)10.1111/sji.12831 (DOI)000497171700001 ()31536648 (PubMedID)
Available from: 2019-12-13 Created: 2019-12-13 Last updated: 2019-12-13
Sandholm, K., Persson, B., Skattum, L., Eggertsen, G., Nyman, D., Gunnarsson, I., . . . Nilsson Ekdahl, K. (2019). Evaluation of a Novel Immunoassay for Quantification of C1q for Clinical Diagnostic Use. Frontiers in Immunology, 10, Article ID 7.
Open this publication in new window or tab >>Evaluation of a Novel Immunoassay for Quantification of C1q for Clinical Diagnostic Use
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2019 (English)In: Frontiers in Immunology, ISSN 1664-3224, E-ISSN 1664-3224, Vol. 10, article id 7Article in journal (Refereed) Published
Abstract [en]

Objectives: C1q is a valuable biomarker of disease activity in systemic lupus erythematosus (SLE). The "gold standard" assay, rocket immunoelectrophoresis (RIE), is time-consuming, and thus a shift to soluble immune precipitation techniques such as nephelometry has occurred. However, quantification of C1q with these techniques has been questioned as a result of the antibody binding properties of C1q. In the present work, we have compared results using various techniques (RIE, nephelometry, and ELISA) and have developed and validated a new magnetic bead-based sandwich immunoassay (MBSI). Methods: C1q was quantified by nephelometry and the new sandwich immunoassay in 45 serum samples analyzed using RIE. C1q was also assessed in plasma using RIE and sandwich immunoassay in samples from SLE patients with nephritis (n = 69), SLE patients without nephritis (n = 310) as classified by BILAG score, and matched controls (n = 322). In addition, cerebrospinal fluid (CSF) samples from 31 patients, previously analyzed with ELISA, were also analyzed with the MBSI to test the behavior of this new assay in the lower detection range. Results: We found a strong correlation between the new MBSI, RIE, and ELISA, but not with nephelometry. The MBSI demonstrated lower levels of C1q in SLE patients than in matched controls (p < 0.0001), and patients with nephritis had lower levels than patients without nephritis (p < 0.01). Similarily, RIE showed significant differences between the patient groups (p < 0.0001). An association was also found between the levels of C1q and the SLE disease activity index (SLEDAI). Furthermore, there was good correlation between the values obtained by MBSI and ELISA, in both serum (r = 0.960) and CSF (r = 0.786), underscoring the ability of both techniques to measure low concentrations of C1q with high accuracy. Conclusion: The sandwich immunoassay correlated well with RIE, but soluble immune precipitation techniques, such as nephelometry, did not appear suitable alternatives, since C1q itself, and possibly anti-C1q antibodies, interfered with the measurements. The new sandwich immunoassay is therefore a good replacement for RIE in monitoring SLE disease activity.

Place, publisher, year, edition, pages
Frontiers Media S.A., 2019
Keywords
C1q, immunoassays, plasma, CSF, SLE, nephritis
National Category
Immunology Rheumatology and Autoimmunity
Research subject
Biomedical Sciences, Immunology
Identifiers
urn:nbn:se:lnu:diva-80277 (URN)10.3389/fimmu.2019.00007 (DOI)000456846400001 ()2-s2.0-85061243783 (Scopus ID)
Available from: 2019-02-07 Created: 2019-02-07 Last updated: 2019-11-12Bibliographically approved
Gustafson, E., Hamad, O. A., Deckmyn, H., Barbu, A., Nilsson Ekdahl, K. & Nilsson, B. (2019). Exposure of von Willebrand Factor on Isolated Hepatocytes Promotes Tethering of Platelets to the Cell Surface. Transplantation, 103(8), 1630-1638
Open this publication in new window or tab >>Exposure of von Willebrand Factor on Isolated Hepatocytes Promotes Tethering of Platelets to the Cell Surface
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2019 (English)In: Transplantation, ISSN 0041-1337, E-ISSN 1534-6080, Vol. 103, no 8, p. 1630-1638Article in journal (Refereed) Published
Abstract [en]

Background. Hepatocyte transplantation (Hctx) is a potentially attractive method for the treatment of acute liver failure and liver-based metabolic disorders. Unfortunately, the procedure is hampered by the instant blood-mediated inflammatory reaction (IBMIR), a thromboinflammatory response elicited by the vascular innate immune system, causing activation of the coagulation and complement systems and clearance of transplanted cells. Observations have also revealed platelets adhered to the surface of the hepatocytes (Hc). To establish Hctx as a clinical treatment, all factors that trigger IBMIR need to be identified and controlled. This work explores the expression of von Willebrand factor (VWF) on isolated Hc resulting in tethering of platelets. Methods. VWF on Hc was studied by flow cytometry, confocal microscopy, immunoblot, and real-time polymerase chain reaction. Interaction between Hc and platelets was studied in a Chandler loop model. Adhesion of platelets to the hepatocyte surface was demonstrated by flow cytometry and confocal microscopy. Results. Isolated Hc constitutively express VWF on their cell surface and mRNA for VWF was found in the cells. Hc and platelets, independently of coagulation formed complexes, were shown by antibody blocking studies to be dependent on hepatocyte-associated VWF and platelet-bound glycoprotein Ib alpha. Conclusions. VWF on isolated Hc causes, in contact with blood, adhesion of platelets, which thereby forms an ideal surface for coagulation. This phenomenon needs to be considered in hepatocyte-based reconstitution therapy and possibly even in other settings of cell transplantation.

Place, publisher, year, edition, pages
Wolters Kluwer, 2019
National Category
Immunology
Research subject
Biomedical Sciences, Immunology
Identifiers
urn:nbn:se:lnu:diva-88831 (URN)10.1097/TP.0000000000002707 (DOI)000480691100024 ()30896677 (PubMedID)
Available from: 2019-08-29 Created: 2019-08-29 Last updated: 2019-08-29Bibliographically approved
Nilsson Ekdahl, K., Mohlin, C., Adler, A., Aman, A., Manivel, V. A., Sandholm, K., . . . Nilsson, B. (2019). Is generation of C-3(H2O) necessary for activation of the alternative pathway in real life?. Paper presented at 17th European Meeting on Complement in Human Disease (EMCHD), 2019, Madrid, SPAIN. Molecular Immunology, 114, 353-361
Open this publication in new window or tab >>Is generation of C-3(H2O) necessary for activation of the alternative pathway in real life?
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2019 (English)In: Molecular Immunology, ISSN 0161-5890, E-ISSN 1872-9142, Vol. 114, p. 353-361Article in journal (Refereed) Published
Abstract [en]

In the alternative pathway (AP) an amplification loop is formed, which is strictly controlled by various fluid-phase and cell-bound regulators resulting in a state of homeostasis. Generation of the "C3b-like" C3(H2O) has been described as essential for AP activation, since it conveniently explains how the initial fluid-phase AP convertase of the amplification loop is generated. Also, the AP has a status of being an unspecific pathway despite thorough regulation at different surfaces. During complement attack in pathological conditions and inflammation, large amounts of C3b are formed by the classical/lectin pathway (CP/LP) convertases. After the discovery of LP's recognition molecules and its tight interaction with the AP, it is increasingly likely that the AP acts in vivo mainly as a powerful amplification mechanism of complement activation that is triggered by previously generated C3b molecules initiated by the binding of specific recognition molecules. Also in many pathological conditions caused by a dysregulated AP amplification loop such as paroxysmal nocturnal hemoglobulinuria (PNH) and atypical hemolytic uremic syndrome (aHUS), C3b is available due to minute LP and CP activation and/or generated by non-complement proteases. Therefore, C3(H2O) generation in vivo may be less important for AP activation during specific attack or dysregulated homeostasis, but may be an important ligand for C3 receptors in cell-cell interactions and a source of C3 for the intracellular complement reservoir.

Place, publisher, year, edition, pages
Elsevier, 2019
Keywords
Complement system, C-3(H2O), Conformation, Analysis, Proteases, Alternative pathway
National Category
Immunology
Research subject
Biomedical Sciences, Immunology
Identifiers
urn:nbn:se:lnu:diva-89867 (URN)10.1016/j.molimm.2019.07.032 (DOI)000490625600041 ()31446306 (PubMedID)
Conference
17th European Meeting on Complement in Human Disease (EMCHD), 2019, Madrid, SPAIN
Available from: 2019-10-31 Created: 2019-10-31 Last updated: 2019-10-31Bibliographically approved
Noiri, M., Asawa, K., Okada, N., Kodama, T., Murayama, Y., Inoue, Y., . . . Teramura, Y. (2019). Modification of human MSC surface with oligopeptide-PEG-lipids for selective binding to activated endothelium. Journal of Biomedical Materials Research. Part A, 107(8), 1779-1792
Open this publication in new window or tab >>Modification of human MSC surface with oligopeptide-PEG-lipids for selective binding to activated endothelium
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2019 (English)In: Journal of Biomedical Materials Research. Part A, ISSN 1549-3296, E-ISSN 1552-4965, Vol. 107, no 8, p. 1779-1792Article in journal (Refereed) Published
Abstract [en]

Promising cell therapies using mesenchymal stem cells (MSCs) is proposed for stroke patients. Therefore, we aimed to efficiently accumulate human MSC (hMSC) to damaged brain area to improve the therapeutic effect using poly(ethylene glycol) (PEG)-conjugated phospholipid (PEG-lipid) carrying an oligopeptide as a ligand, specific for E-selectin which is upregulated on activated endothelial cells under hypoxia-like stroke. Here we synthesized E-selectin-binding oligopeptide (ES-bp) conjugated with PEG spacer having different molecular weights from 1 to 40 kDa. We found that ES-bp can be immobilized onto the hMSC surface through PEG-lipid without influence on cell growth and differentiation into adipocytes and osteocytes, respectively. It is also possible to control the immobilization of ES-bp on hMSC surface (<10(8) ES-bp per cell). Immobilized ES-bp can be continuously immobilized at the outside of cell membrane when PEG-lipids with PEG 5 and 40 kDa were used. In addition, the modified hMSC can specifically attach onto E-selectin-immobilized surface as a model surface of activated endothelium in human blood, indicating the sufficient number of immobilized ES-bp onto hMSC. Thus, this technique is one of the candidates for hMSC accumulation to cerebral infarction area. (c) 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 1779-1792, 2019.

Place, publisher, year, edition, pages
John Wiley & Sons, 2019
Keywords
cell surface modification, E-selectin, mesenchymal stem cell (MSC), poly(ethylene glycol)-conjugated phospholipid (PEG-lipid), stroke
National Category
Biochemistry and Molecular Biology
Research subject
Natural Science, Biomedical Sciences
Identifiers
urn:nbn:se:lnu:diva-86883 (URN)10.1002/jbm.a.36697 (DOI)000471813900020 ()30983125 (PubMedID)2-s2.0-85067416608 (Scopus ID)
Available from: 2019-07-18 Created: 2019-07-18 Last updated: 2019-08-29Bibliographically approved
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ORCID iD: ORCID iD iconorcid.org/0000-0001-7888-1571

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