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Sandholm, Kerstin
Publikasjoner (10 av 30) Visa alla publikasjoner
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.
Åpne denne publikasjonen i ny fane eller vindu >>Evaluation of a Novel Immunoassay for Quantification of C1q for Clinical Diagnostic Use
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2019 (engelsk)Inngår i: Frontiers in Immunology, ISSN 1664-3224, E-ISSN 1664-3224, Vol. 10, artikkel-id 7Artikkel i tidsskrift (Fagfellevurdert) 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.

sted, utgiver, år, opplag, sider
Frontiers Media S.A., 2019
Emneord
C1q, immunoassays, plasma, CSF, SLE, nephritis
HSV kategori
Forskningsprogram
Biomedicinsk vetenskap, Immunologi
Identifikatorer
urn:nbn:se:lnu:diva-80277 (URN)10.3389/fimmu.2019.00007 (DOI)000456846400001 ()2-s2.0-85061243783 (Scopus ID)
Tilgjengelig fra: 2019-02-07 Laget: 2019-02-07 Sist oppdatert: 2019-08-29bibliografisk kontrollert
Mohlin, C., Sandholm, K., Kvanta, A., Nilsson Ekdahl, K. & Johansson, K. (2018). A model to study complement involvement in experimental retinal degeneration.. Upsala Journal of Medical Sciences, 123(1), 28-42
Åpne denne publikasjonen i ny fane eller vindu >>A model to study complement involvement in experimental retinal degeneration.
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2018 (engelsk)Inngår i: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 123, nr 1, s. 28-42Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

BACKGROUND: The complement system (CS) plays a role in the pathogenesis of a number of ocular diseases, including diabetic retinopathy (DR), glaucoma, uveitis, and age-related macular degeneration (AMD). Given that many of the complex eye-related degenerative diseases have limited treatment opportunities, we aimed to mimic the in vivo retinal degenerative process by developing a relevant co-culture system.

METHOD AND MATERIALS: The adult porcine retina was co-cultured with the spontaneously arising human retinal pigment epithelial cells-19 (ARPE-19).

RESULTS: Inflammatory activity was found after culture and included migrating microglial cells, gliosis, cell death, and CS activation (demonstrated by a minor increase in the secreted anaphylotoxin C3a in co-culture). CS components, including C1q, C3, C4, soluble C5b-9, and the C5a receptor, were expressed in the retina and/or ARPE cells after culture. C1q, C3, and CS regulators such as C4 binding protein (C4BP), factor H (CFH), and factor I (CFI) were secreted after culture.

DISCUSSION: Thus, our research indicates that this co-culturing system may be useful for investigations of the CS and its involvement in experimental neurodegenerative diseases.

sted, utgiver, år, opplag, sider
Taylor & Francis, 2018
Emneord
AMD, RPE, complement system, ocular diseases, retina
HSV kategori
Forskningsprogram
Biomedicinsk vetenskap, Immunologi
Identifikatorer
urn:nbn:se:lnu:diva-71489 (URN)10.1080/03009734.2018.1431744 (DOI)000428060300004 ()29436895 (PubMedID)2-s2.0-85041902488 (Scopus ID)
Tilgjengelig fra: 2018-03-12 Laget: 2018-03-12 Sist oppdatert: 2019-08-29bibliografisk kontrollert
Labriere, C., Kondori, N., Caous, J. S., Boomgaren, M., Sandholm, K., Nilsson Ekdahl, K., . . . Svenson, J. (2018). Development and evaluation of cationic amphiphilic antimicrobial 2,5-diketopiperazines. Paper presented at 7th International Meeting on Antimicrobial Peptides, AUG 25-27, 2017, Univ Copenhagen, Copenhagen, DENMARK. Journal of Peptide Science, 24(7), Article ID UNSP e3090.
Åpne denne publikasjonen i ny fane eller vindu >>Development and evaluation of cationic amphiphilic antimicrobial 2,5-diketopiperazines
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2018 (engelsk)Inngår i: Journal of Peptide Science, ISSN 1075-2617, E-ISSN 1099-1387, Vol. 24, nr 7, artikkel-id UNSP e3090Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Both pathogenic bacteria and fungi are developing resistance to common antimicrobial treatment at an alarming rate. To counteract this development, it is of essence to develop new classes of antimicrobial agents. One such class is antimicrobial peptides, most of which are derived from the innate immune system. In this study, a series of novel 2,5-diketopiperazines were designed, synthesized, and evaluated for their antimicrobial abilities. The compounds were designed to probe the pharmacophore dictated for short linear mimics of antimicrobial cationic peptides, and as such, the compounds contain a range of cationic and hydrophobic functionalities. Several of the prepared compounds displayed high antimicrobial activities toward bacteria and also against human pathogenic fungi. Of particular interest was the high activity toward fungal strains with an inherent increased resistance toward conventional antifungal agents. The most effective compounds displayed inhibition of Candida glabrata and Candida krusei growth at concentrations between 4 and 8 mu g/mL, which is comparable to commercial antifungal agents in use. Structure activity relationship studies revealed a similar dependence on cationic charge and the volume of the hydrophobic bulk as for linear cationic antimicrobial peptides. Finally, the hemolytic activity of selected compounds was evaluated, which revealed a potential to produce active compounds with attenuation of unwanted hemolysis. The findings highlight the potential of cyclic cationic amphiphilic peptidomimetics as a class of promising compounds for the treatment of infections caused by microorganisms with an increased resistance to conventional antimicrobial agents.

sted, utgiver, år, opplag, sider
John Wiley & Sons, 2018
Emneord
2, 5-diketopiperazine, antifungal agents, antimicrobial, Candida krusei, MRSA, structure-activity relationship
HSV kategori
Forskningsprogram
Naturvetenskap, Biomedicinsk vetenskap
Identifikatorer
urn:nbn:se:lnu:diva-77499 (URN)10.1002/psc.3090 (DOI)000440144700005 ()29845683 (PubMedID)2-s2.0-85047664224 (Scopus ID)
Konferanse
7th International Meeting on Antimicrobial Peptides, AUG 25-27, 2017, Univ Copenhagen, Copenhagen, DENMARK
Tilgjengelig fra: 2018-08-31 Laget: 2018-08-31 Sist oppdatert: 2019-08-29bibliografisk kontrollert
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.
Åpne denne publikasjonen i ny fane eller vindu >>Interpretation of Serological Complement Biomarkers in Disease
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2018 (engelsk)Inngår i: Frontiers in Immunology, ISSN 1664-3224, E-ISSN 1664-3224, Vol. 9, artikkel-id 2237Artikkel, forskningsoversikt (Fagfellevurdert) 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.

sted, utgiver, år, opplag, sider
Frontiers Media S.A., 2018
Emneord
complement, deficiency, activation products, functional test, complement regulatory drugs
HSV kategori
Forskningsprogram
Biomedicinsk vetenskap, Immunologi
Identifikatorer
urn:nbn:se:lnu:diva-78739 (URN)10.3389/fimmu.2018.02237 (DOI)000448107500001 ()2-s2.0-85055834488 (Scopus ID)
Tilgjengelig fra: 2018-11-08 Laget: 2018-11-08 Sist oppdatert: 2019-08-29bibliografisk kontrollert
Mohlin, C., Petrus-Reurer, S., Lanner, F., Sandholm, K., Nilsson, P. H., 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)
Åpne denne publikasjonen i ny fane eller vindu >>Is the polarized secretion of complement factor H of importance in age-related macular degeneration?
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2018 (engelsk)Inngår i: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 59, nr 9Artikkel i tidsskrift, Meeting abstract (Annet vitenskapelig) Published
sted, utgiver, år, opplag, sider
ASSOC RESEARCH VISION OPHTHALMOLOGY INC, 2018
HSV kategori
Forskningsprogram
Naturvetenskap, Optometri
Identifikatorer
urn:nbn:se:lnu:diva-78425 (URN)000442932806149 ()
Konferanse
Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO), APR 29-MAY 03, 2018, Honolulu, HI
Tilgjengelig fra: 2018-10-22 Laget: 2018-10-22 Sist oppdatert: 2018-11-16bibliografisk kontrollert
Mohlin, C., Petrus-Reurer, S., Lanner, F., Sandholm, K., Kvanta, A., Nilsson, B. & Nilsson Ekdahl, K. (2017). Complement system proteins in human embryonic stem cell-derived retinal pigment epithelial cells co-cultured with or without porcine retina. Paper presented at 16th European Meeting on Complement in Human Disease (EMCHD), SEP 08-12, 2017, Copenhagen, DENMARK. Molecular Immunology, 89, 162-163
Åpne denne publikasjonen i ny fane eller vindu >>Complement system proteins in human embryonic stem cell-derived retinal pigment epithelial cells co-cultured with or without porcine retina
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2017 (engelsk)Inngår i: Molecular Immunology, ISSN 0161-5890, E-ISSN 1872-9142, Vol. 89, s. 162-163Artikkel i tidsskrift, Meeting abstract (Annet vitenskapelig) Published
HSV kategori
Forskningsprogram
Biomedicinsk vetenskap, Immunologi
Identifikatorer
urn:nbn:se:lnu:diva-68148 (URN)10.1016/j.molimm.2017.06.132 (DOI)000410014500107 ()
Konferanse
16th European Meeting on Complement in Human Disease (EMCHD), SEP 08-12, 2017, Copenhagen, DENMARK
Tilgjengelig fra: 2017-10-02 Laget: 2017-10-02 Sist oppdatert: 2018-11-16bibliografisk kontrollert
Mohlin, C., Sandholm, K., Nilsson Ekdahl, K. & Nilsson, B. (2017). The link between morphology and complement in ocular disease. Paper presented at 16th European Meeting on Complement in Human Disease (EMCHD), SEP 08-12, 2017, Copenhagen, DENMARK. Molecular Immunology, 89, 84-99
Åpne denne publikasjonen i ny fane eller vindu >>The link between morphology and complement in ocular disease
2017 (engelsk)Inngår i: Molecular Immunology, ISSN 0161-5890, E-ISSN 1872-9142, Vol. 89, s. 84-99Artikkel, forskningsoversikt (Fagfellevurdert) Published
Abstract [en]

The complement system is a vital component of the immune-priveliged human eye that is always active at a low-grade level, preventing harmful intraocular injuries caused by accumulation of turnover products and controlling pathogens to preserve eye homeostasis and vision. The complement system is a double-edged sword that is essential for protection but may also become harmful and contribute to eye pathology. Here, we review the evidence for the involvement of complement system dysregulation in age-related macular degeneration, glaucoma, uveitis, and neuromyelitis optica, highlighting the relationship between morphogical changes and complement system protein expression and regulation in these diseases. The potential benefits of complement inhibition in age-related macular degeneration, glaucoma, uveitis, and neuromyelitis optica are abundant, as are those of further research to improve our understanding of complement-mediated injury in these diseases.

sted, utgiver, år, opplag, sider
Elsevier, 2017
Emneord
Complement, Eye, Morphology, Age-related macular degeneration, Glaucoma, Uveitis, Neuromyelitis optica
HSV kategori
Forskningsprogram
Biomedicinsk vetenskap, Immunologi
Identifikatorer
urn:nbn:se:lnu:diva-71382 (URN)10.1016/j.molimm.2017.05.028 (DOI)000410014500010 ()28622910 (PubMedID)2-s2.0-85020678968 (Scopus ID)
Konferanse
16th European Meeting on Complement in Human Disease (EMCHD), SEP 08-12, 2017, Copenhagen, DENMARK
Tilgjengelig fra: 2018-03-05 Laget: 2018-03-05 Sist oppdatert: 2019-08-29bibliografisk kontrollert
Lindblom, R. P. F., Aeinehband, S., Ström, M., Al Nimer, F., Sandholm, K., Khademi, M., . . . Nilsson Ekdahl, K. (2016). Complement receptor 2 is increased in cerebrospinal fluid of multiple sclerosis patients and regulates C3 function. Clinical Immunology, 166, 89-95
Åpne denne publikasjonen i ny fane eller vindu >>Complement receptor 2 is increased in cerebrospinal fluid of multiple sclerosis patients and regulates C3 function
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2016 (engelsk)Inngår i: Clinical Immunology, ISSN 1521-6616, E-ISSN 1521-7035, Vol. 166, s. 89-95Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Besides its vital role in immunity, the complement system also contributes to the shaping of the synaptic circuitry of the brain. We recently described that soluble Complement Receptor 2 (sCR2) is part of the nerve injury response in rodents. We here study CR2 in context of multiple sclerosis (MS) and explore the molecular effects of CR2 on C3 activation.

Significant increases in sCR2 levels were evident in cerebrospinal fluid (CSF) from both patients with relapsing-remitting MS (n = 33; 6.2 ng/mL) and secondary-progressive MS (n = 9; 7.0 ng/mL) as compared to controls (n = 18; 4.1 ng/mL). Furthermore, CSF sCR2 levels correlated significantly both with CSF C3 and C1q as well as to a disease severity measure. In vitro, sCR2 inhibited the cleavage and down regulation of C3b to iC3b, suggesting that it exerts a modulatory role in complement activation downstream of C3.

These results propose a novel function for CR2/sCR2 in human neuroinflammatory conditions.

HSV kategori
Forskningsprogram
Biomedicinsk vetenskap, Immunologi
Identifikatorer
urn:nbn:se:lnu:diva-52309 (URN)10.1016/j.clim.2016.04.003 (DOI)000378011500010 ()27085202 (PubMedID)2-s2.0-84963963835 (Scopus ID)
Tilgjengelig fra: 2016-04-28 Laget: 2016-04-28 Sist oppdatert: 2018-11-16bibliografisk kontrollert
Huang, S., Engberg, A. E., Jonsson, N., Sandholm, K., Nicholls, I. A., Mollnes, T. E., . . . Nilsson Ekdahl, K. (2016). Reciprocal relationship between contact and complement system activation on artificial polymers exposed to whole human blood.. Biomaterials, 77, 111-119
Åpne denne publikasjonen i ny fane eller vindu >>Reciprocal relationship between contact and complement system activation on artificial polymers exposed to whole human blood.
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2016 (engelsk)Inngår i: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 77, s. 111-119Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

BACKGROUND: Inappropriate and uncontrolled activation of the cascade systems in the blood is a driving force in adverse inflammatory and thrombotic reactions elicited by biomaterials, but limited data are available on the activation of the contact system by polymers and the present study was undertaken to investigate these mechanisms in established models.

METHODS: Polymer particles were incubated in (1) EDTA-plasma (10 mM) to monitor the adsorption of 20 selected proteins; (2) lepirudin-anticoagulated plasma to evaluate contact system activation, monitored by the formation of complexes between the generated proteases factor[F]XIIa, FXIa and kallikrein and the serpins C1-inhibitor [C1INH] and antithrombin [AT]; (3) lepirudin-anticoagulated whole blood to determine cytokine release.

RESULTS: Strong negative correlations were found between 10 cytokines and the ratio of deposited FXII/C1INH, generated FXIIa-C1INH complexes, and kallikrein-C1INH complexes. Formation of FXIIa-C1INH complexes correlated negatively with the amount of C3a and positively with deposited IgG.

CONCLUSIONS: A reciprocal relationship was found between activation of the contact system and the complement system induced by the polymers studied here. The ratios of FXII/C1INH or C4/C4BP, adsorbed from EDTA-plasma are useful surrogate markers for cytokine release and inflammatory response to materials intended for blood contact.

sted, utgiver, år, opplag, sider
Elsevier, 2016
Emneord
Biomaterials, Complement system, Contact system, FXII, In vitro screening
HSV kategori
Forskningsprogram
Kemi, Biokemi
Identifikatorer
urn:nbn:se:lnu:diva-47390 (URN)10.1016/j.biomaterials.2015.10.067 (DOI)000367118200010 ()26584351 (PubMedID)2-s2.0-84949221849 (Scopus ID)
Tilgjengelig fra: 2015-11-24 Laget: 2015-11-24 Sist oppdatert: 2018-11-16bibliografisk kontrollert
Kozarcanin, H., Lood, C., Munthe-Fog, L., Sandholm, K., Hamad, O. A., Bengtsson, A. A., . . . Nilsson, B. (2016). The lectin complement pathway serine proteases (MASPs) represent a possible crossroad between the coagulation and complement systems in thromboinflammation. Journal of Thrombosis and Haemostasis, 14(3), 531-545
Åpne denne publikasjonen i ny fane eller vindu >>The lectin complement pathway serine proteases (MASPs) represent a possible crossroad between the coagulation and complement systems in thromboinflammation
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2016 (engelsk)Inngår i: Journal of Thrombosis and Haemostasis, ISSN 1538-7933, E-ISSN 1538-7836, Vol. 14, nr 3, s. 531-545Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

The lectin pathway's MASP-1/2 activates coagulation factors but the trigger of the activation is unknown. MASP-1/2 activation was assessed by quantifying complexes between MASPs and antithrombin/C1-inhibitor. Activated platelets and fibrin were demonstrated to activate MASP-1 and MASP-2 both invitro and invivo. These findings may represent a crossroad between the complement and the coagulation systems. Summary Background The activated forms of the complement lectin pathway (LP) proteases MASP-1 and MASP-2 are able to cleave the coagulation factors prothrombin, fibrinogen, factor XIII and thrombin-activatable fibrinolysis inhibitor invitro. In vivo studies also show that MASP-1 is involved in thrombogenesis. Objectives To clarify the not yet identified mechanisms involved in triggering activation of the LP during thrombotic reactions. Methods Novel sandwich-ELISAs for detection of complexes between MASP-1 or MASP-2 and the serpins C1 inhibitor (C1-INH) or antithrombin (AT), were used to specifically detect and quantify the activated forms of MASP-1 and MASP-2. Results Activated platelets were shown by flow cytometry to bind Ficolin-1, -2 and -3 but not MBL, which was associated with activation of MASP-1 and MASP-2. We also demonstrated that fibrin and the plasmin-generated fibrin fragment DD in plasma, bind and activate MASP-1 and MASP-2. As demonstrated by the ELISA and SDS-PAGE/Western blotting, the fibrin-associated activation was reflected in a specific inactivation by AT during clotting without the assistance of heparin. In all other cases the MASPs were, as previously reported, inactivated by C1-INH. In systemic lupus erythematosus patients with thrombotic disease and in polytrauma patients, the levels of activated MASP-1 and MASP-2 in complex with both AT and C1-INH were associated with markers of thrombotic disease and contact/coagulation system activation. Conclusions MASP-1 and MASP-2 are activated during blood clotting. This activation is triggered by activated platelets and by the generation of fibrin during thrombotic reactions invitro and invivo, and may represent a novel activation/amplification mechanism in thromboinflammation.

Emneord
blood coagulation, complement pathway, mannose-binding lectin, fibrin, mannose-binding protein-associated serine proteases, platelet activation
HSV kategori
Forskningsprogram
Naturvetenskap, Biomedicinsk vetenskap
Identifikatorer
urn:nbn:se:lnu:diva-52120 (URN)10.1111/jth.13208 (DOI)000372525100015 ()26614707 (PubMedID)2-s2.0-84960100143 (Scopus ID)
Tilgjengelig fra: 2016-04-18 Laget: 2016-04-18 Sist oppdatert: 2018-11-16bibliografisk kontrollert
Organisasjoner