uu.seUppsala University Publications
Change search
Link to record
Permanent link

Direct link
BETA
Alternative names
Publications (10 of 171) Show all publications
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
Show others...
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 SA, 2019
Keywords
C1q, immunoassays, plasma, CSF, SLE, nephritis
National Category
Rheumatology and Autoimmunity Immunology in the medical area
Identifiers
urn:nbn:se:uu:diva-376814 (URN)10.3389/fimmu.2019.00007 (DOI)000456846400001 ()
Funder
Swedish Research Council, 2016-2075-5.1Swedish Research Council, 2016-04519
Available from: 2019-02-19 Created: 2019-02-19 Last updated: 2019-02-19Bibliographically approved
Seisenbaeva, G. A., Fromell, K., Vinogradov, V. V., Terekhov, A. N., Pakhomov, A. V., Nilsson, B., . . . Kessler, V. G. (2018). Author Correction: Dispersion of TiO2 nanoparticles improves burn wound healing and tissue regeneration through specific interaction with blood serum proteins. Scientific Reports, 8, Article ID 4416.
Open this publication in new window or tab >>Author Correction: Dispersion of TiO2 nanoparticles improves burn wound healing and tissue regeneration through specific interaction with blood serum proteins
Show others...
2018 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, article id 4416Article in journal (Other academic) Published
National Category
Biochemistry and Molecular Biology
Identifiers
urn:nbn:se:uu:diva-352922 (URN)10.1038/s41598-018-22717-8 (DOI)000426827000001 ()29520072 (PubMedID)
Funder
Swedish Research Council, 2014-3938
Note

WoS title: "Dispersion of TiO2 nanoparticles improves burn wound healing and tissue regeneration through specific interaction with blood serum proteins (vol 7, 15448, 2017)".

Correction to: Scientific Reports, 2017, vol. 7, Article number: 15448.

DOI: 10.1038/s41598-017-15792-w

Available from: 2018-06-08 Created: 2018-06-08 Last updated: 2018-06-08Bibliographically approved
Huber-Lang, M., Nilsson Ekdahl, K., Wiegner, R., Fromell, K. & Nilsson, B. (2018). Auxiliary activation of the complement system and its importance for the pathophysiology of clinical conditions. Seminars in Immunopathology, 40(1), 87-102
Open this publication in new window or tab >>Auxiliary activation of the complement system and its importance for the pathophysiology of clinical conditions
Show others...
2018 (English)In: Seminars in Immunopathology, ISSN 1863-2297, E-ISSN 1863-2300, Vol. 40, no 1, p. 87-102Article, review/survey (Refereed) Published
Abstract [en]

Activation and regulation of the cascade systems of the blood (the complement system, the coagulation/contact activation/kallikrein system, and the fibrinolytic system) occurs via activation of zymogen molecules to specific active proteolytic enzymes. Despite the fact that the generated proteases are all present together in the blood, under physiological conditions, the activity of the generated proteases is controlled by endogenous protease inhibitors. Consequently, there is remarkable little crosstalk between the different systems in the fluid phase. This concept review article aims at identifying and describing conditions where the strict system-related control is circumvented. These include clinical settings where massive amounts of proteolytic enzymes are released from tissues, e.g., during pancreatitis or post-traumatic tissue damage, resulting in consumption of the natural substrates of the specific proteases and the available protease inhibitor. Another example of cascade system dysregulation is disseminated intravascular coagulation, with canonical activation of all cascade systems of the blood, also leading to specific substrate and protease inhibitor elimination. The present review explains basic concepts in protease biochemistry of importance to understand clinical conditions with extensive protease activation.

Keywords
Complement system, Proteases, Protease inhibitors, Trauma
National Category
Immunology in the medical area
Identifiers
urn:nbn:se:uu:diva-350204 (URN)10.1007/s00281-017-0646-9 (DOI)000424058800008 ()28900700 (PubMedID)
Funder
German Research Foundation (DFG)Swedish Research Council, 2016-01060; 2016-04519EU, FP7, Seventh Framework Programme, 602699
Available from: 2018-05-08 Created: 2018-05-08 Last updated: 2018-05-08Bibliographically approved
Nilsson Ekdahl, K., Davoodpour, P., Ekstrand-Hammarström, B., Fromell, K., Hamad, O. A., Hong, J., . . . Nilsson, B. (2018). Contact (kallikrein/kinin) system activation in whole human blood induced by low concentrations of α-Fe2O3 nanoparticles.. Nanomedicine: Nanotechnology, Biology and Medicine, 14(3), 735-744
Open this publication in new window or tab >>Contact (kallikrein/kinin) system activation in whole human blood induced by low concentrations of α-Fe2O3 nanoparticles.
Show others...
2018 (English)In: Nanomedicine: Nanotechnology, Biology and Medicine, ISSN 1549-9634, E-ISSN 1549-9642, Vol. 14, no 3, p. 735-744Article in journal (Refereed) Published
Abstract [en]

Iron-oxide nanoparticles (NPs) generated by environmental events are likely to represent health problems. alpha-Fe2O3 NPs were synthesized, characterized and tested in a model for toxicity utilizing human whole blood without added anticoagulant. MALDI-TOF of the corona was performed and activation markers for plasma cascade systems (complement, contact and coagulation systems), platelet consumption and release of growth factors, MPO, and chemokine/cytokines from blood cells were analyzed. The coronas formed on the pristine alpha-Fe2O3 NPs contained contact system proteins and they induced massive activation of the contact (kinin/kallikrein) system, as well as thrombin generation, platelet activation, and release of two pro-angiogeneic growth factors: platelet-derived growth factor and vascular endothelial growth factor, whereas complement activation was unaffected. The alpha-Fe2O3 NPs exhibited a noticeable toxicity, with kinin/kallikrein activation, which may be associated with hypotension and long-term angiogenesis in vivo, with implications for cancer, arteriosclerosis and pulmonary disease.

Place, publisher, year, edition, pages
Elsevier, 2018
Keywords
α-Fe2O3, NPsContact/kallikrein system, Innate immunity
National Category
Immunology in the medical area Nano Technology
Identifiers
urn:nbn:se:uu:diva-343471 (URN)10.1016/j.nano.2017.12.008 (DOI)000429528900010 ()
Funder
Swedish Research Council, 2014-3938 2016-2075-5.1 2016-01060 2016-04519EU, FP7, Seventh Framework Programme, 602699AFA Insurance
Note

Joint and equal contribution to senior authorship by Kristina N. Ekdahl, Padideh Davoodpour and Bo Nilsson

Available from: 2018-02-27 Created: 2018-02-27 Last updated: 2018-06-08Bibliographically approved
Fromell, K., Johansson, U., Dührkop, C., Adler, A., Usterud, E., Hamad, O. A., . . . Nilsson, B. (2018). Generation of an alternative pathway convertase by contact-activated C3 is dependent on the conformation of C3. Paper presented at 27th International Complement Workshop (ICW), SEP 16-20, 2018, Santa Fe, New Mexico, USA.. Molecular Immunology, 102, 193-193
Open this publication in new window or tab >>Generation of an alternative pathway convertase by contact-activated C3 is dependent on the conformation of C3
Show others...
2018 (English)In: Molecular Immunology, ISSN 0161-5890, E-ISSN 1872-9142, Vol. 102, p. 193-193Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
PERGAMON-ELSEVIER SCIENCE LTD, 2018
Keywords
Complement C3
National Category
Immunology Biochemistry and Molecular Biology
Identifiers
urn:nbn:se:uu:diva-365114 (URN)10.1016/j.molimm.2018.06.167 (DOI)000445313600163 ()
Conference
27th International Complement Workshop (ICW), SEP 16-20, 2018, Santa Fe, New Mexico, USA.
Available from: 2018-11-15 Created: 2018-11-15 Last updated: 2018-11-15Bibliographically approved
Nilsson Ekdahl, K., Persson, B., Mohlin, C., Sandholm, K., Skattum, L. & Nilsson, B. (2018). Interpretation of Serological Complement Biomarkers in Disease. Frontiers in Immunology, 9, Article ID 2237.
Open this publication in new window or tab >>Interpretation of Serological Complement Biomarkers in Disease
Show others...
2018 (English)In: Frontiers in Immunology, ISSN 1664-3224, E-ISSN 1664-3224, Vol. 9, article id 2237Article, review/survey (Refereed) Published
Abstract [en]

Complement systemaberrations have been identified as pathophysiological mechanisms in a number of diseases and pathological conditions either directly or indirectly. Examples of such conditions include infections, inflammation, autoimmune disease, as well as allogeneic and xenogenic transplantation. Both prospective and retrospective studies have demonstrated significant complement-related differences between patient groups and controls. However, due to the low degree of specificity and sensitivity of some of the assays used, it is not always possible to make predictions regarding the complement status of individual patients. Today, there are three main indications for determination of a patient's complement status: (1) complement deficiencies (acquired or inherited); (2) disorders with aberrant complement activation; and (3) C1 inhibitor deficiencies (acquired or inherited). An additional indication is to monitor patients on complement-regulating drugs, an indication which may be expected to increase in the near future since there is now a number of such drugs either under development, already in clinical trials or in clinical use. Available techniques to study complement include quantification of: (1) individual components; (2) activation products, (3) function, and (4) autoantibodies to complement proteins. In this review, we summarize the appropriate indications, techniques, and interpretations of basic serological complement analyses, exemplified by a number of clinical disorders.

Place, publisher, year, edition, pages
Frontiers Media S.A., 2018
Keywords
complement, deficiency, activation products, functional test, complement regulatory drugs
National Category
Immunology in the medical area Immunology
Identifiers
urn:nbn:se:uu:diva-369948 (URN)10.3389/fimmu.2018.02237 (DOI)000448107500001 ()30405598 (PubMedID)
Funder
Swedish Research Council, 2016-2075-5.1Swedish Research Council, 2016-04519
Available from: 2018-12-18 Created: 2018-12-18 Last updated: 2018-12-18Bibliographically approved
Mohlin, C., Petrus-Reurer, S., Lanner, F., Sandholm, K., Nilsson, P., Nilsson, B. & Nilsson Ekdahl, K. (2018). Is the polarized secretion of complement factor H of importance in age-related macular degeneration?. Paper presented at Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO), APR 29-MAY 03, 2018, Honolulu, HI. Investigative Ophthalmology and Visual Science, 59(9)
Open this publication in new window or tab >>Is the polarized secretion of complement factor H of importance in age-related macular degeneration?
Show others...
2018 (English)In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 59, no 9Article in journal, Meeting abstract (Other academic) Published
National Category
Ophthalmology
Identifiers
urn:nbn:se:uu:diva-366392 (URN)000442932806149 ()
Conference
Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO), APR 29-MAY 03, 2018, Honolulu, HI
Funder
Swedish Research Council
Available from: 2018-11-21 Created: 2018-11-21 Last updated: 2018-11-21Bibliographically approved
van Griensven, M., Ricklin, D., Denk, S., Halbgebauer, R., Braun, C. K., Schultze, A., . . . Huber-Lang, M. S. (2018). PROTECTIVE EFFECTS OF THE COMPLEMENT INHIBITOR COMPSTATIN CP40 IN HEMORRHAGIC SHOCK. Paper presented at 41st Annual Conference on Shock, JUN 09-12, 2018, Scottsdale, AZ. Shock, 49(6, Suppl. 1), 117-118, Article ID P183.
Open this publication in new window or tab >>PROTECTIVE EFFECTS OF THE COMPLEMENT INHIBITOR COMPSTATIN CP40 IN HEMORRHAGIC SHOCK
Show others...
2018 (English)In: Shock, ISSN 1073-2322, E-ISSN 1540-0514, Vol. 49, no 6, Suppl. 1, p. 117-118, article id P183Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
LIPPINCOTT WILLIAMS & WILKINS, 2018
National Category
Cell and Molecular Biology
Identifiers
urn:nbn:se:uu:diva-365172 (URN)10.1097/SHK.0000000000001158 (DOI)000441343800253 ()
Conference
41st Annual Conference on Shock, JUN 09-12, 2018, Scottsdale, AZ
Available from: 2018-11-12 Created: 2018-11-12 Last updated: 2018-11-12Bibliographically approved
Reis, E. S., Berger, N., Wang, X., Koutsogiannaki, S., Doot, R. K., Gumas, J. T., . . . Lambris, J. D. (2018). Safety profile after prolonged C3 inhibition. Clinical Immunology, 197, 96-106
Open this publication in new window or tab >>Safety profile after prolonged C3 inhibition
Show others...
2018 (English)In: Clinical Immunology, ISSN 1521-6616, E-ISSN 1521-7035, Vol. 197, p. 96-106Article in journal (Refereed) Published
Abstract [en]

The central component of the complement cascade, C3, is involved in various biological functions, including opsonization of foreign bodies, clearance of waste material, activation of immune cells, and triggering of pathways controlling development. Given its broad role in immune responses, particularly in phagocytosis and the clearance of microbes, a deficiency in complement C3 in humans is often associated with multiple bacterial infections. Interestingly, an increased susceptibility to infections appears to occur mainly in the first two years of life and then wanes throughout adulthood. In view of the well-established connection between C3 deficiency and infections, therapeutic inhibition of complement at the level of C3 is often considered with caution or disregarded. We therefore set out to investigate the immune and biochemical profile of non-human primates under prolonged treatment with the C3 inhibitor compstatin (Cp40 analog). Cynomolgus monkeys were dosed subcutaneously with Cp40, resulting in systemic inhibition of C3, for 1 week, 2 weeks, or 3 months. Plasma concentrations of both C3 and Cp40 were measured periodically and complete saturation of plasma C3 was confirmed. No differences in hematological, biochemical, or immunological parameters were identified in the blood or tissues of animals treated with Cp40 when compared to those injected with vehicle alone. Further, skin wounds showed no signs of infection in those treated with Cp40. In fact, Cp40 treatment was associated with a trend toward accelerated wound healing when compared with the control group. In addition, a biodistribution study in a rhesus monkey indicated that the distribution of Cp40 in the body is associated with the presence of C3, concentrating in organs that accumulate blood and produce C3. Overall, our data suggest that systemic C3 inhibition in healthy adult non-human primates is not associated with a weakened immune system or susceptibility to infections.

Keywords
Complement, C3, Compstatin, Cp40, AMY-101, Inflammation, Infection, Non-human primate
National Category
Immunology in the medical area Immunology
Identifiers
urn:nbn:se:uu:diva-373239 (URN)10.1016/j.clim.2018.09.004 (DOI)000454372500013 ()30217791 (PubMedID)
Funder
EU, FP7, Seventh Framework Programme, 602699 DIREKT
Available from: 2019-01-14 Created: 2019-01-14 Last updated: 2019-01-14Bibliographically approved
Knabl, L., Berktold, M., Hamad, O. A., Fromell, K., Chatterjee, S., Speth, C., . . . Orth-Holler, D. (2018). Shiga toxin 2a binds antithrombin and heparin, but does not directly activate platelets. International Journal of Medical Microbiology, 308(7), 969-976
Open this publication in new window or tab >>Shiga toxin 2a binds antithrombin and heparin, but does not directly activate platelets
Show others...
2018 (English)In: International Journal of Medical Microbiology, ISSN 1438-4221, E-ISSN 1618-0607, Vol. 308, no 7, p. 969-976Article in journal (Refereed) Published
Abstract [en]

Escherichia coli-induced hemolytic uremic syndrome (eHUS) is a life-threatening complication of infection with Shiga toxin (Stx), in particular Stx2a-producing Escherichia coli. Enhanced coagulation activation with formation of microthrombi seems to be a key event in development of eHUS. Platelet activation has been postulated as a possible, but controversially debated mechanism. The present study investigated the effect of Stx2a on plasmatic coagulation and platelets. Binding studies were initially performed with ELISA and co-immunoprecipitation and supported by quartz crystal microbalance with dissipation monitoring (QCM-D). Antithrombin (AT) activity was measured using the automated BCS XP (R) system. ROTEM (R) was used for functional coagulation testing. Platelet binding and activation was studied with FACS and light-transmission aggregometry. We found binding of Stx2a to AT, an important inhibitor of blood coagulation, but only a mild albeit significant reduction of AT activity against FXa in the presence of Stx2a. QCM-D analysis also showed binding of Stx2a to heparin and an impaired binding of AT to Stx2a-bound heparin. ROTEM (R) using Stx2a-treated platelet-poor plasma revealed a significant, but only moderate shortening of clotting time. Neither binding nor activation of platelets by Stx2a could be demonstrated. In summary, data of this study suggest that Stx2a binds to AT, but does not induce major effects on plasmatic coagulation. In addition, no interaction with platelets occurred. The well-known non-beneficial administration of heparin in eHUS patients could be explained by the interaction of Stx2a with heparin.

Keywords
Stx2a, Hemolytic uremic syndrome, Plasmatic coagulation, Antithrombin
National Category
Cell and Molecular Biology
Identifiers
urn:nbn:se:uu:diva-369763 (URN)10.1016/j.ijmm.2018.07.008 (DOI)000448628100027 ()30064820 (PubMedID)
Available from: 2018-12-17 Created: 2018-12-17 Last updated: 2018-12-17Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0003-0057-2730

Search in DiVA

Show all publications