| 1001. |
- Nilsson, Bo, et al.
(författare)
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Complement Diagnostics : Concepts, Indications, and Practical Guidelines
- 2012
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Ingår i: Clinical & Developmental Immunology. - : Hindawi Limited. - 1740-2522 .- 1740-2530.
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Forskningsöversikt (refereegranskat)abstract
- Aberrations in the complement system have been shown to be direct or indirect pathophysiological mechanisms in a number of diseases and pathological conditions such as autoimmune disease, infections, cancer, allogeneic and xenogeneic transplantation, and inflammation. Complement analyses have been performed on these conditions in both prospective and retrospective studies and significant differences have been found between groups of patients, but in many diseases, it has not been possible to make predictions for individual patients because of the lack of sensitivity and specificity of many of the assays used. The basic indications for serological diagnostic complement analysis today may be divided into three major categories: (a) acquired and inherited complement deficiencies; (b) disorders with complement activation; (c) inherited and acquired C1INH deficiencies. Here, we summarize indications, techniques, and interpretations for basic complement analyses and present an algorithm, which we follow in our routine laboratory.
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| 1002. |
- Nilsson, Bo, et al.
(författare)
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Control of IBMIR (Instant Blood-Mediated Inflammatory Reaction) to improve islets of Langerhans engraftement
- 2011
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Ingår i: Current Opinion in Organ Transplantation. - 1087-2418 .- 1531-7013. ; 16:6, s. 620-626
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Forskningsöversikt (refereegranskat)abstract
- Purpose of review Transplantation of islets of Langerhans is an emerging treatment procedure for patients with severe type 1 diabetes, but despite recent progress the procedure is associated with massive tissue loss caused by an inflammatory reaction termed instant blood-mediated inflammatory reaction (IBMIR). This reactioninvolves activation of the complement and coagulation cascades, ultimately resulting in clot formation and infiltration of leukocytes into the islets, which leadsto disruption of islet integrity and islet destruction. Recent findings In this review we discuss basic mechanisms underlying the IBMIR and emerging strategies for therapeutic regulation of the IBMIR. These include the use ofselective inhibitors of the coagulation and complement systems, different procedures to coat the surface of the islets as well as the development ofcomposite islet-endothelial cell grafts. Summary The IBMIR is a major cause of tissue loss in clinical islet transplantation, and most likely in other cell therapies in which cells are exposed to blood. Thus, it is an obvious target for therapeutic intervention. Due to its complexity, it is necessary to use different strategies to control the IBMIR.
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| 1003. |
- Nilsson, Bo, et al.
(författare)
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Distinctive expression of neoantigenic C3(D) epitopes on bound C3 following activation and binding to different target surfaces in normal and pathological human sera
- 1989
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Ingår i: Molecular Immunology. - : Elsevier BV. - 0161-5890 .- 1872-9142. ; 26:4, s. 383-390
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Tidskriftsartikel (refereegranskat)abstract
- Binding of C3 to sheep erythrocytes in a serum-free milieu (EAC14oxy2, EAC142) has previously been shown to mimic the antigenic change that occurs upon denaturation of C3 in sodium dodecyl sulphate (SDS), whereby neoantigenic C3(D) epitopes are exposed. The present paper deals with C3 bound to various target surfaces which are known to modulate the functional properties of C3 in different ways. Bound C3 fragments on serum-treated human aggregated gammaglobulin, zymosan, rabbit and sheep erythrocytes, and on circulating immune complexes isolated from sera of patients with rheumatoid arthritis and systemic lupus erythematosus, were shown to be mainly in the iC3b form. By RIAs, employing polyclonal antibodies, the range of C3(D) antigenic epitopes of 125I-labelled SDS denatured C3 expressed by the particle-bound iC3b was monitored. The physiologically bound iC3b on all tested particles expressed wide ranges of C3(D) epitopes and each type of particle-bound C3 exposed its individual range. By competition ELISA specific C3(D)α epitopes were monitored, employing monoclonal antibodies. A distinct difference in the expression of these epitopes was observed in iC3b bound to various test particles in the presence of normal serum and in iC3b present on circulating immune complexes from pathological sera. Considering that the neoantigenic C3(D) epitopes have been shown to be associated with different functions of C3, the distinctive antigenic expression of each type of serum-treated particle might reflect different functional forms of the protein.
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| 1004. |
- Nilsson, Bo, et al.
(författare)
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How COVID-19 and other pathological conditions and medical treatments activate our intravascular innate immune system
- 2023
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Ingår i: Frontiers in Immunology. - : Frontiers Media S.A.. - 1664-3224. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- COVID-19 has been shown to have a multifaceted impact on the immune system. In a recently published article in Front Immunol, we show that the intravascular innate immune system (IIIS) is strongly activated in severe COVID-19 with ARDS and appears to be one of the causes leading to severe COVID-19. In this article, we describe the IIIS and its physiological function, but also the strong pro-inflammatory effects that are observed in COVID-19 and in various other pathological conditions and treatments such as during ischemia reperfusion injury and in treatments where biomaterials come in direct contact with blood in, e.g., extracorporeal and intravasal treatments. In the present article, we describe how the IIIS, a complex network of plasma proteins and blood cells, constitute the acute innate immune response of the blood and discuss the effects that the IIIS induces in pathological disorders and treatments in modern medicine.
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| 1005. |
- Nilsson, Bo, et al.
(författare)
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How the Innate Immune System of the Blood Contributes to Systemic Pathology in COVID-19-Induced ARDS and Provides Potential Targets for Treatment
- 2022
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Ingår i: Frontiers in Immunology. - : Frontiers Media S.A.. - 1664-3224. ; 13
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Forskningsöversikt (refereegranskat)abstract
- Most SARS-CoV-2 infected patients experience influenza-like symptoms of low or moderate severity. But, already in 2020 early during the pandemic it became obvious that many patients had a high incidence of thrombotic complications, which prompted treatment with high doses of low-molecular-weight heparin (LMWH; typically 150-300IU/kg) to prevent thrombosis. In some patients, the disease aggravated after approximately 10 days and turned into a full-blown acute respiratory distress syndrome (ARDS)-like pulmonary inflammation with endothelialitis, thrombosis and vascular angiogenesis, which often lead to intensive care treatment with ventilator support. This stage of the disease is characterized by dysregulation of cytokines and chemokines, in particular with high IL-6 levels, and also by reduced oxygen saturation, high risk of thrombosis, and signs of severe pulmonary damage with ground glass opacities. The direct link between SARS-CoV-2 and the COVID-19-associated lung injury is not clear. Indirect evidence speaks in favor of a thromboinflammatory reaction, which may be initiated by the virus itself and by infected damaged and/or apoptotic cells. We and others have demonstrated that life-threatening COVID-19 ARDS is associated with a strong activation of the intravascular innate immune system (IIIS). In support of this notion is that activation of the complement and kallikrein/kinin (KK) systems predict survival, the necessity for usage of mechanical ventilation, acute kidney injury and, in the case of MBL, also coagulation system activation with thromboembolism. The general properties of the IIIS can easily be translated into mechanisms of COVID-19 pathophysiology. The prognostic value of complement and KKsystem biomarkers demonstrate that pharmaceuticals, which are licensed or have passed the phase I trial stage are promising candidate drugs for treatment of COVID-19. Examples of such compounds include complement inhibitors AMY-101 and eculizumab (targeting C3 and C5, respectively) as well as kallikrein inhibitors ecallantide and lanadelumab and the bradykinin receptor (BKR) 2 antagonist icatibant. In this conceptual review we discuss the activation, crosstalk and the therapeutic options that are available for regulation of the IIIS.
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| 1006. |
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| 1007. |
- Nilsson, Bo, et al.
(författare)
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The role and regulation of complement activation as part of the thromboinflammation elicited in cell therapies
- 2014
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Ingår i: Molecular Immunology. - : Elsevier BV. - 0161-5890 .- 1872-9142. ; 61:2, s. 185-190
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Forskningsöversikt (refereegranskat)abstract
- Cell therapies in which the cells come into direct contact with blood and other body fluids are emerging treatment procedures for patients with various diseases, such as diabetes mellitus, liver insufficiency, and graft-versus-host disease. However, despite recent progress, these procedures are associated with tissue loss caused by thromboinflammatory reactions. These deleterious reactions involve the activation of the complement and coagulation cascades and platelet and leukocyte activation, ultimately resulting in clot formation and damage to the implanted cells. In this concept review, we discuss the basic mechanisms underlying the thrombininflammatory process, with special reference to the engagement of complement and emerging strategies for the therapeutic regulation of these reactions that include the use of selective systemic inhibitors and various procedures to coat the surfaces of the cells. The coating procedures may also be applied to other treatment modalities in which similar mechanisms are involved, including whole organ transplantation, treatment with biomaterials in contact with blood, and extracorporeal procedures. (C) 2014 Published by Elsevier Ltd.
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| 1008. |
- Nilsson, Bo, et al.
(författare)
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The tick-over theory revisited : Is C3 a contact-activated protein?
- 2012
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Ingår i: Immunobiology. - : Elsevier BV. - 0171-2985 .- 1878-3279. ; 217:11, s. 1106-1110
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Forskningsöversikt (refereegranskat)abstract
- The tick-over theory was first introduced in the 1970s to explain the presence of the initial C3b molecules, which are able to trigger complement activation by the alternative pathway in human plasma under physiological conditions. After the identification of the thioester, the predominant hypothesis has been that this bond is hydrolyzed at a slow but constant rate by nucleophilic attack by H2O, leading to the generation of C3(H2O). Here we put forward the hypothesis that the rate of hydrolysis of C3 to C3(H2O) may be greatly accelerated by the interaction between C3 and a number of biological and artificial interfaces, including gas bubbles, biomaterial surfaces and different lipid surfaces and complexes. We therefore propose that C3 should preferentially be regarded as a contact activated protein rather than a target for passive, random hydrolysis in the fluid phase. (C) 2012 Elsevier GmbH. All rights reserved.
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| 1009. |
- Nilsson, Christina, et al.
(författare)
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Self reported fear of childbirth and its association with women´s birth experience and mode of delivery : a longitudinal population-based study
- 2012
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Ingår i: Women and Birth. - : Elsevier BV. - 1871-5192 .- 1878-1799. ; 25:3, s. 114-121
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Tidskriftsartikel (refereegranskat)abstract
- ObjectiveTo explore fear of childbirth (FOC) during pregnancy and one year after birth and its association to birth experience and mode of delivery.DesignA longitudinal population-based study.PopulationPregnant women who were listed for a routine ultrasound at three hospitals in the middle-north part of Sweden.MethodDifferences between women who reported FOC and who did not were calculated using risk ratios with a 95% confidence interval. In order to explain which factors were most strongly associated to suffer from FOC during pregnancy and one year after childbirth, multivariate logistic regression analyses were used.ResultsFOC during pregnancy in multiparous women was associated with a previous negative birth experience (RR 5.1, CI 2.5–10.4) and a previous emergency caesarean section (RR 2.5, CI 1.2–5.4). Associated factors for FOC one year after childbirth were: a negative birth experience (RR 10.3, CI 5.1–20.7), fear of childbirth during pregnancy (RR 7.1, CI 4.4–11.7), emergency caesarean section (RR 2.4, CI 1.2–4.5) and primiparity (RR 1.9, CI 1.2–3.1).ConclusionFOC was associated with negative birth experiences. Women still perceived the birth experience as negative a year after the event. Women's perception of the overall birth experience as negative seems to be more important for explaining subsequent FOC than mode of delivery. Maternity care should focus on women's experiences of childbirth. Staff at antenatal clinics should ask multiparous women about their previous experience of childbirth. So that FOC is minimized, research on factors that create a positive birth experience for women is required.
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| 1010. |
- Nilsson, Evalill, et al.
(författare)
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A Human, Organization, and Technology Perspective on Patients' Experiences of a Chat-Based and Automated Medical History-Taking Service in Primary Health Care : Interview Study Among Primary Care Patients
- 2021
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Ingår i: Journal of Medical Internet Research. - : JMIR Publications. - 1438-8871. ; 23:10
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Tidskriftsartikel (refereegranskat)abstract
- Background: The use of e-visits in health care is progressing rapidly worldwide. To date, studies on the advantages and disadvantages of e-consultations in the form of chat services for all inquiries in primary care have focused on the perspective of health care professionals (HCPs) rather than those of end users (patients). Objective: This study aims to explore patients' experiences using a chat-based and automated medical history-taking service in regular, tax-based, not-for-profit primary care in Sweden. Methods: Overall, 25 individual interviews were conducted with patients in the catchment areas of 5 primary care centers (PCCs) in Sweden that tested a chat-based and automated medical history-taking service for all types of patient inquiries. The semistructured interviews were transcribed verbatim before content analysis using inductive and deductive strategies, the latter including an unconstrained matrix of human, organization, and technology perspectives. Results: The service provided an easily managed way for patients to make written contact with HCPs, which was considered beneficial for some patients and issues but less suitable for others (acute or more complex cases). The automated medical history-taking service was perceived as having potential but still derived from what HCPs need to know and how they address and communicate health and health care issues. Technical skills were not considered as necessary for a mobile phone chat as for handling a computer; however, patients still expressed concern for people with less digital literacy. The opportunity to take one's time and reflect on one's situation before answering questions from the HCPs was found to reduce stress and prevent errors, and patients speculated that it might be the same for the HCPs on the other end of the system. Patients appreciated the ability to have a conversation from almost anywhere, even from places not suitable for telephone calls. The asynchronicity of the chat service allowed the patients to take more control of the conversation and initiate a chat at any time at their own convenience; however, it could also lead to lengthy conversations where a single issue in the worst cases could take days to close. The opportunity to upload photographs made some visits to the PCC redundant, which would otherwise have been necessary if the ordinary telephone service had been used, saving patients both time and money. Conclusions: Patients generally had a positive attitude toward e-visits in primary care and were generally pleased with the prospects of the digital tool tested, somewhat more with the actual chat than with the automated history-taking system preceding the chat. Although patients expect their PCC to offer a range of different means of communication, the human, organization, and technology analysis revealed a need for more extensive (end) user experience design in the further development of the chat service.
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