| 1. |
- Albrecht, Inka, et al.
(författare)
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Development of autoantibodies against muscle-specific FHL1 in severe inflammatory myopathies
- 2015
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Ingår i: Journal of Clinical Investigation. - : AMER SOC CLINICAL INVESTIGATION INC. - 0021-9738 .- 1558-8238. ; 125:12, s. 4612-4624
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Tidskriftsartikel (refereegranskat)abstract
- Mutations of the gene encoding four-and-a-half LIM domain 1 (FHL1) are the causative factor of several X-linked hereditary myopathies that are collectively termed FHL1-related myopathies. These disorders are characterized by severe muscle dysfunction and damage. Here, we have shown that patients with idiopathic inflammatory myopathies (IIMs) develop autoimmunity to FHL1, which is a muscle-specific protein. Anti-FHL1 autoantibodies were detected in 25% of IIM patients, while patients with other autoimmune diseases or muscular dystrophies were largely anti-FHL1 negative. Anti-FHL1 reactivity was predictive for muscle atrophy, dysphagia, pronounced muscle fiber damage, and vasculitis. FHL1 showed an altered expression pattern, with focal accumulation in the muscle fibers of autoantibody-positive patients compared with a homogeneous expression in anti-FHL1-negative patients and healthy controls. We determined that FHL1 is a target of the cytotoxic protease granzyme B, indicating that the generation of FHL1 fragments may initiate FHL1 autoimmunity. Moreover, immunization of myositis-prone mice with FHL1 aggravated muscle weakness and increased mortality, suggesting a direct link between anti-FHL1 responses and muscle damage. Together, our findings provide evidence that FHL1 may be involved in the pathogenesis not only of genetic FHL1-related myopathies but also of autoimmune IIM. Importantly, these results indicate that anti-FHL1 autoantibodies in peripheral blood have promising potential as a biomarker to identify a subset of severe IIM.
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| 2. |
- Eriksson, D, et al.
(författare)
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Extended exome sequencing identifies BACH2 as a novel major risk locus for Addison's disease
- 2016
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 286:6, s. 595-608
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Autoimmune disease is one of the leading causes of morbidity and mortality worldwide. In Addison's disease, the adrenal glands are targeted by destructive autoimmunity. Despite being the most common cause of primary adrenal failure, little is known about its aetiology.METHODS: To understand the genetic background of Addison's disease, we utilized the extensively characterized patients of the Swedish Addison Registry. We developed an extended exome capture array comprising a selected set of 1853 genes and their potential regulatory elements, for the purpose of sequencing 479 patients with Addison's disease and 1394 controls.RESULTS: We identified BACH2 (rs62408233-A, OR = 2.01 (1.71-2.37), P = 1.66 × 10(-15) , MAF 0.46/0.29 in cases/controls) as a novel gene associated with Addison's disease development. We also confirmed the previously known associations with the HLA complex.CONCLUSION: Whilst BACH2 has been previously reported to associate with organ-specific autoimmune diseases co-inherited with Addison's disease, we have identified BACH2 as a major risk locus in Addison's disease, independent of concomitant autoimmune diseases. Our results may enable future research towards preventive disease treatment.
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| 3. |
- Skogar, O, et al.
(författare)
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"Effects of Tactile Touch on pain, sleep and health related quality of life in Parkinsons disease with chronic pain": A randomized, controlled and prospective study
- 2013
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Ingår i: European Journal of Integrative Medicine. - : Elsevier. - 1876-3820 .- 1876-3839. ; 5:2, s. 141-152
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Parkinsons disease (PD) is often associated with chronic PD related pain. Complementary medicine are widely used but randomized, controlled and prospective studies of the effects are sparse. less thanbrgreater than less thanbrgreater thanAims of the study: To compare the effects of Tactile Touch (TT) with Rest to Music (RTM) in PD patients with chronic pain and to describe effects within groups. less thanbrgreater than less thanbrgreater thanPatients and methods: A 34 week controlled randomized and prospective trial compared the effects of TT with RTM in 45 (29 TT and 16 RTM) patients with PD and chronic pain. The whole body tactile stimulation method was performed for each individual patient by the same therapist for 10 times during the first 8 weeks. The RTM group received the same therapy except for the tactile stimulation. Pharmacotherapy was kept unchanged. Participants were assessed at pre- and post-intervention for pain, sleep patterns and health related quality of life (HRQoL). less thanbrgreater than less thanbrgreater thanResults: Differences between TT and RTM groups were few. Total PDSS significantly improved within the TT but not in the RTM-group. No significant differences between groups were seen in pain parameters, although significant improvements were seen within the TT-group after the intervention period. There were significant improvements within both groups in HRQoL and between groups in the items physical role and social functioning 4 weeks after screening. less thanbrgreater than less thanbrgreater thanConclusions: No significant differences between the TT and RTM groups were seen. Only in single aspects did patients with PD and chronic pain have more benefit more from CAM therapy with TT in combination with RTM.
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