| 1. |
- Andersson, Åsa, et al.
(författare)
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A genetic basis for shared autoimmunity in mouse models.
- 2005
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Ingår i: Autoimmunity. - : Informa UK Limited. - 0891-6934 .- 1607-842X. ; 38:3, s. 209-217
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Forskningsöversikt (refereegranskat)abstract
- Development of autoimmune disease is the result of activation of the immune system that subsequently leads to tissue destruction. Although the clinical outcome significantly differs between autoimmune diseases, some pathogenic pathways could be shared. During the recent years, intense efforts to find the genetic factors behind development of the complex and polygenic autoimmune diseases have been undertaken. The difficulties in addressing what genetic factors predispose for autoimmunity in humans underline the importance of animal models in the understanding of the general mechanisms behind the initiation of disease. Interestingly, it has been observed in studies of experimental models of autoimmune diseases, that many of the genetic linkages to disease development are located in the same genetic regions and potentially could be controlled by the same gene. Furthermore, comparison of the mouse/rat genetic regions with regions of association to human inflammatory diseases, also demonstrates some homologous loci between species. Some mouse strains can develop disease in more than one model for autoimmunity. This not only argues for some general mechanisms, but it also supports mechanisms related to the specific tissues attacked in the various autoimmune diseases. Here, we will discuss some aspects of shared autoimmunity in mouse models from a genetic point of view.
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| 2. |
- Baba, Akiyasu, et al.
(författare)
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Autoantibodies in atrial fibrillation: actor, biomaker or bystander?
- 2008
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Ingår i: Autoimmunity. - : Informa UK Limited. - 1607-842X .- 0891-6934. ; 41:6, s. 470-2
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Forskningsöversikt (refereegranskat)abstract
- Atrial fibrillation (AF) is one of the most common arrhythmias in patients with congestive heart failure, although the underlying mechanism has still to be determined. There is increasing evidence to suggest that autoimmunity may play an important role in the pathogenesis of AF. To date, at least three types of autoantibody have been found in AF: the anti-myosin heavy chain autoantibody, the anti-M2 muscarinic receptor autoantibody and the anti-heat shock protein autoantibody. The question is: are these autoantibodies actors, biomakers or merely bystanders? How much knowledge do we have?
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| 3. |
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| 4. |
- Christensen, Ulla Bjerre, et al.
(författare)
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Different islet protein expression profiles during spontaneous diabetes development vs. allograft rejection in BB-DP rats
- 2006
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Ingår i: Autoimmunity. - : Informa UK Limited. - 0891-6934 .- 1607-842X. ; 39:4, s. 315-321
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Tidskriftsartikel (refereegranskat)abstract
- Type 1 diabetes (T1D) is characterized by selective autoimmune destruction of the insulin producing beta-cells in the islets of Langerhans. When the beta-cells are destroyed exogenous administration of insulin is necessary for maintenance of glucose homeostasis. Allogeneic islet transplantation has been used as a means to circumvent the need for insulin administration and has in some cases been able to restore endogenous insulin production for years. However, long life immunosuppression is needed to prevent the graft from being rejected and destroyed. Changes in protein expression pattern during spontaneous diabetes development in the diabetes prone BioBreeding rat (BB-DP) have previously been described. In the present study, we have investigated if any of the changes seen in the protein expression pattern during spontaneous diabetes development are also present during allograft rejection of BB-DP rat islets. Two hundred neonatal islets were syngeneically transplanted under the kidney capsule of 30 day old BB-DP rats and removed prior to and at onset of diabetes. Allogeneically transplanted islets from BB-DP rats were removed before onset of allograft rejection and at maximal islet graft inflammation (rejection). The protein expression profiles of the transplants were visualised by two-dimensional gel (2-DG) electrophoresis, analysed and compared. In total, 2590 protein spots were visualised and of these 310 changed expression ( p < 0.01) in syngeneic islet transplants in the BB-DP rats from 7 days after transplantation until onset of diabetes. In BB-DP islets transplanted to WK rats 53 protein spots ( p < 0.01) showed changes in expression when comparing islet grafts removed 7 days after transplantation with islet grafts removed 12 days after transplantation where mononuclear cell infiltration is at its maximum. Only four protein spots (1%) were significantly changed in both syngeneic (autoimmune) and allogeneic islet destruction. When comparing protein expression changes in syngeneic BB-DP islet transplants from 37 days after transplantation to onset of diabetes with protein expression changes in allografts from day 7 to 12 after transplantation only three spot were found to commonly change expression in both situations. In conclusion, a large number of protein expression changes were detected in both autoimmune islet destruction and allogeneic islet rejection, only two overlaps were detected, suggesting that autoimmune islet destruction and allogeneic islet rejection may result from different target cell responses to signals induced by the cellular infiltrate. Whether this reflects activation of distinct signalling pathways in islet cells is currently unknown and need to be further investigated.
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| 5. |
- Daka, Bledar, 1976, et al.
(författare)
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Low agreement between radio binding assays in analyzing glutamic acid decarboxylase (GAD65Ab) autoantibodies in patients classified with type 2 diabetes.
- 2009
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Ingår i: Autoimmunity. - : Informa UK Limited. - 1607-842X .- 0891-6934. ; 42:6, s. 507-14
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Tidskriftsartikel (refereegranskat)abstract
- Autoantibodies against glutamic acid decarboxylase (GAD65Ab) are used in the classification of diabetes in adults. We assessed the concordance in GAD65 autoantibody levels within subjects between three different GAD65Ab radio binding assays (RBA). Plasma samples from 112 diabetes patients (median age 50 years) initially classified with type 2 diabetes was randomly selected from a local diabetes registry. Coded samples were analyzed with two RBA employing (35)S-labeled GAD65. The first used the pEx9 plasmid (pEx9 RBA), the second employed the pThGAD65 plasmid (pThGAD65 RBA) to label GAD65 by in vitro transcription translation. We also used a commercial kit employing plasmid pGAD17 labelled with (125)I (pGAD17 RBA). Subsequent analyses followed standard procedures. Two different cut-offs for GAD65Ab positivity were used in all three assays. We calculated the correlation, concordance, and agreement between the assays. The proportion of GAD65Ab positivity differed between assays when low cut-offs were used (pEx9 RBA 25%, pThGAD65 RBA 17.9%, and pGAD17 RBA 12.5%, respectively). When high cut-offs were applied, the concordance between the pEx9 RBA and the pThGAD65 RBA was 97.3 while their concordance to the pGAD17 RBA was lower (88.4 and 87.4, respectively). There was a low agreement between both pEx9 RBA and pGAD17 RBA (0.45, 95% CI 0.20-0.70) and between pThGAD65 RBA and pGAD17 RBA (0.43, 95% CI 0.18-0.68). We found discrepancies in determining the GAD65Ab positivity, which constitutes a problem when GAD65Ab are used clinically. Further methodological GAD65Ab assays studies are warranted.
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| 6. |
- Finke, Doreen, et al.
(författare)
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Endogenous type I interferon inducers in autoimmune diseases
- 2009
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Ingår i: Autoimmunity. - : Informa UK Limited. - 0891-6934 .- 1607-842X. ; 42:4, s. 349-352
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Forskningsöversikt (refereegranskat)abstract
- Type I interferon (IFN) is produced by the innate immune system in several autoimmune diseases, such as systemic lupus erythematosus (SLE), polymyositis, and systemic sclerosis. In these diseases, immune complex (IC)-containing DNA or RNA may act as endogenous IFN inducers. The abilities of these IC to reach the endosomes in the plasmacytoid dendritic cells (PDC) cause the intracellular toll-like receptor (TLR) to initiate a cascade of transcription factors--a critical step in triggering type I IFN production. A special configuration of the nucleic acid (NA), such as CpG-rich non-methylated DNA or GU-rich RNA, appears crucial. However, other components of the IC, like HMGB1, may also be necessary. Studies regarding the genetic background of autoimmune diseases suggest that variants of genes involved in both IFN production and response are associated with disease susceptibility. This knowledge is important for the development of new therapeutic strategies in autoimmune diseases.
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| 7. |
- Fu, Michael, 1963
(författare)
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Autoimmunity and idiopathic dilated cardiomyopathy: where we stand?
- 2008
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Ingår i: Autoimmunity. - : Informa UK Limited. - 1607-842X .- 0891-6934. ; 41:6, s. 415-8
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Forskningsöversikt (refereegranskat)abstract
- Idiopathic dilated cardiomyopathy (DCM) with its heterogeneous phenotype and genotype remains one of the leading causes of severe heart failure particularly in the younger. Even in the elderly, it appears around 15% of heart failure is due to DCM. Despite great improvements in heart failure therapy, prognoses remains poor. One of the most important reasons is that the present heart failure management is aimed mostly at restoration of neurohormonal balance, rather than targeting primary causes of the disease. As a matter of fact, a substantial subgroup of DCM and chronic heart failure is accompanied by autoimmune mechanism, in particular a wide spectrum of autoantibodies. For almost two decades, the autoimmune hypothesis has been considered a "fairy tale". Today, we have better understanding of autoimmune mechanism in DCM. This focused issue is aimed to summarize what has happened in the last two decades in the context of basic understanding of underlying mechanisms and clinical relevance.
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| 8. |
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| 9. |
- Goncalves, Isabel, et al.
(författare)
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Effects of simvastatin on circulating autoantibodies to oxidized LDL antigens : relation with immune stimulation markers
- 2009
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Ingår i: AUTOIMMUNITY. - : Informa UK Limited. - 0891-6934 .- 1607-842X. ; 42:3, s. 203-208
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Tidskriftsartikel (refereegranskat)abstract
- Statins exert a number of anti-inflammatory and immunomodulatory effects in vitro. However, the immunomodulatory effects in vivo are less clarified. In the present study, we investigated whether simvastatin treatment changed the levels of autoantibodies against specific oxidized LDL (oxLDL) antigens as well as their association with leukocyte activation markers. Eighty volunteers with mild-to-moderate hypercholesterolemia were randomized to either simvastatin 40mg or placebo for 6 weeks. Autoantibodies against apo B peptide antigens, C-reactive protein (CRP) and interleukin (IL)-6 in plasma were determined by ELISA. Subsets of circulating B and T cells were studied by flow cytometry. Simvastatin significantly reduced CRP by 26%, whereas IL-6 remained unchanged. Levels of IgG against the apo B peptide P-240 (amino acids 3586-3605) increased by 16% (p=0.03) in the simvastatin group whereas autoantibody levels to other apo B peptides did not change. At baseline and after 6 weeks, the P-240 IgG levels were significantly correlated with the number of CD57+CD28-CD8+T cells but not to other lymphocyte subsets or inflammatory markers. The P-240 IgG levels after 6 weeks simvastatin therapy was strongly correlated to the relative increase in CD57+CD28-CD8+T cells (p=0.003). Simvastatin treatment induced an increase in autoantibodies against an oxLDL antigen. The effect was related to an expansion of a CD8+T cell subset and may involve an immunostimulation by simvastatin.
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| 10. |
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