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- Ahlgren, Kerstin. M, et al.
(författare)
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Diabetes mellitus in dog - : No evidence for a type-1-like phenotype
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Aims/hypothesis Diabetes mellitus (DM) is one of the most common endocrine disorders in dogs, and is commonly proposed to be of autoimmune origin. Although the clinical symptoms of human type 1 diabetes (T1D) and canine DM are similar, the aetiologies may differ. The aim of this study was to investigate if autoimmune aetiology resembling human T1D is as prevalent in dogs as previously reported. Methods Sera from 121 diabetic dogs representing 38 different breeds were tested for islet cell antibodies (ICA) and GAD65 autoantibodies (GADA) and compared with sera from 133 healthy dogs from 40 breeds. ICA was detected by indirect immunofluorescence using both canine and human frozen sections. GADA was detected by in vitro transcription and translation (ITT) of human and canine GAD65, followed by immunoprecipitation. Results None of the canine sera analyzed tested positive for ICA on sections of frozen canine or human ICA pancreas. However, serum from one diabetic dog was weakly positive in the canine GADA assay and serum from one healthy dog was weakly positive in the human GADA assay. Conclusions/interpretations Based on sera from 121 diabetic dogs from 38 different breeds were tested for humoral autoreactivity using four different assays, contrary to previous observations, we find no support for an autoimmune aetiology in canine diabetes.
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| 3. |
- de Oliveira, Felipe, 1984-, et al.
(författare)
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Autoimmunity detection via proximity assays
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Since autoantibodies are recognized as valuable biomarkers for clinical diagnostics and prognostics in autoimmune diseases such as Stiff Person Syndrome (SPS) and Type 1 diabetes, detection of such markers at improved sensitivity and specificity could be of significant interest. In addition, as proximity assays have been shown to offer highly sensitive and specific detection of multiple proteins, the technique could be expanded to applications for autoimmunity detection. In the present study, we have applied the newly developed proximity ligation assay with rolling circle amplification (PLARCA), and proximity extension assay (PEA) for the detection of GADA, autoantibodies specific for glutamic acid decarboxylase 65 (GAD65). Through the use of oligonucleotide conjugated autoantigen GAD65 and anti-human antibodies, as proximity probes, we were able to apply these proximity assays to detect GADA in a set of SPS patient samples. In summary, we have applied and established both PLARCA and PEA, as a proof of concept, for the use of the specific and sensitive autoimmune detection.
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| 5. |
- Hägerkvist, Robert, 1976-
(författare)
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Anti-Diabetic and Beta-Cell Protective Actions of Imatinib Mesylate
- 2006
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Type 1 diabetes is a disease resulting from the progressive immune-mediated destruction of insulin producing β-cells. In order to understand more about diabetes we need to understand the mechanisms governing β-cell death.The leukemia drug Gleevec is a tyrosine kinase inhibitor that targets c-Abl. Surprisingly, Gleevec also counteracts Type 2 diabetes and acts as a cell death inhibiting agent, via inhibition c-Abl. Since both Type 1 and Type 2 diabetes are characterized by an increased β-cell death, and the role of c-Abl is unknown in β-cells, we wanted to investigate the following:1.Does Gleevec act via inhibition of c-Abl in β-cells?2.Can Gleevec treatment prevent beta-cell death and diabetes? 3.Which downstream signaling pathways are affected by Gleevec?In paper I, in order to determine whether Gleevec acts by inhibiting c-Abl, we used RNA-interference. Interestingly, siRNA against c-Abl produced by recombinant Dicer mediate almost complete and non-toxic silencing of c-Abl mRNA in dispersed islet cells and conferred protection from streptozotocin and cytokines.In paper II we show that Gleevec protects β-cells from nitric oxide, pro-inflammatory cytokines and streptozotocin in vitro and that Gleevec can prevent diabetes development in the NOD mouse and the streptozotocin-injected mouse. We also present the hypothesis that Gleevec induces a state resembling ischemic preconditioning.Paper III presents an additional mechanism by which Gleevec might improve β-cell survival, i.e. via the inhibition of the downstream stress-activated protein kinase c-Jun N-terminal kinase (JNK), the activity of which has been implicated in β-cell death signaling pathways. In paper IV we explore the interactions between the adaptor protein Shb and c-Abl. We presently show an association between Shb-c-Abl and that Shb is a substrate for the c-Abl kinase that might regulate stress-induced c-Abl activity.
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| 6. |
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| 7. |
- Lernmark, Åke, et al.
(författare)
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Immunology of β-Cell Destruction
- 2015. - 2nd
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Ingår i: Islets of Langerhans. - 9789400766853 ; , s. 1047-1080
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 8. |
- Lernmark, Åke, et al.
(författare)
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Molecular Biology of β-Cell Destruction
- 2003
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Ingår i: Type 1 Diabetes: Etiology and Treatment. (Contemporay Endocrinology). - 9780896039315 ; , s. 71-71
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 9. |
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| 10. |
- Lind, Alexander, et al.
(författare)
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Immunocyte single cell analysis of vaccine-induced narcolepsy
- 2021
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Ingår i: European Journal of Immunology. - : John Wiley & Sons. - 0014-2980 .- 1521-4141. ; 51:1, s. 247-249
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Increased incidence of narcolepsy type 1 (NT1) was observed following Pandemrix®-vaccination, initiated as a preventive measure against the 2009 Influenza pandemic. Here, single cell analysis was conducted to suggest a lower number of CD8+CD27+ T cells among these patients. These findings provide understanding into the autoimmune pathogenesis of NT1.
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