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Danielsson, Olof
Publications (10 of 13) Show all publications
Albrecht, I., Wick, C., Hallgren, A., Tjarnlund, A., Nagaraju, K., Andrade, F., . . . Lundberg, I. E. (2015). Development of autoantibodies against muscle-specific FHL1 in severe inflammatory myopathies. Journal of Clinical Investigation, 125(12), 4612-4624
Open this publication in new window or tab >>Development of autoantibodies against muscle-specific FHL1 in severe inflammatory myopathies
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2015 (English)In: Journal of Clinical Investigation, ISSN 0021-9738, E-ISSN 1558-8238, Vol. 125, no 12, p. 4612-4624Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
AMER SOC CLINICAL INVESTIGATION INC, 2015
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-123783 (URN)10.1172/JCI81031 (DOI)000365831300026 ()26551678 (PubMedID)
Note

Funding Agencies|Swedish Research Council; Ragnar Soderberg Foundation; Karolinska Institutet; Borje Dahlin Foundation; Swedish Rheumatism Association; King Gustaf V 80-year Foundation; Stockholm County Council; Karolinska Institutet on medical training and clinical research (ALF); Swedish Strategic Foundation (PRIMI); Torsten Soderberg Foundation

Available from: 2016-01-11 Created: 2016-01-11 Last updated: 2017-11-30
Danielsson, O., Lindvall, B., Gati, I. & Ernerudh, J. (2013). Classification and Diagnostic Investigation in Inflammatory Myopathies: A Study of 99 Patients. Journal of Rheumatology, 40(7), 1173-1182
Open this publication in new window or tab >>Classification and Diagnostic Investigation in Inflammatory Myopathies: A Study of 99 Patients
2013 (English)In: Journal of Rheumatology, ISSN 0315-162X, E-ISSN 1499-2752, Vol. 40, no 7, p. 1173-1182Article in journal (Refereed) Published
Abstract [en]

Objective. Insights into the pathogenesis of inflammatory myopathies have led to new diagnostic methods. The aims of our study were (1) to evaluate the consequences of using the classification of Amato/European Neuromuscular Centre Workshop (ENMC), compared to that of Bohan and Peter; and (2) to evaluate any diagnostic benefit in using an extended pathological investigation. less thanbrgreater than less thanbrgreater thanMethods. From a consecutive retrospective database, we evaluated 99 patients for classification. Patients with inclusion body myositis (IBM) were classified according to Griggs, et al. In addition to routine stainings and immunohistochemistry, a multilevel serial sectioning procedure was performed on paraffin-embedded material, to identify scarce pathological findings. less thanbrgreater than less thanbrgreater thanResults. Classification according to Bohan and Peter could be performed for 83 of the 99 patients, whereas only 60 patients met the Amato/ENMC criteria, the latter resulting in the following diagnostic groups: IBM (n = 18), nonspecific myositis (n = 14), polymyositis (n = 12), dermatomyositis (n = 10), dermatomyositis sine dermatitis (n = 5), and immune-mediated necrotizing myopathy (n = 1). Most of the Amato/ENMC diagnostic groups harbored patients from several of the Bohan and Peter groups, which included a substantial group lacking proximal muscle weakness. The serial sectioning procedure was essential for classification of 9 patients (15%), and led to a more specific diagnosis for 13 patients (22%) according to Amato/ENMC. less thanbrgreater than less thanbrgreater thanConclusion. The classification of Amato/ENMC was more restrictive, forming groups based on clinical criteria and specified myopathological findings, which clearly differed from the groups of the Bohan and Peter classification. An extended pathological investigation increased the diagnostic yield of a muscle biopsy and highlights the quantity and specificity of certain pathological findings.

Place, publisher, year, edition, pages
Journal of Rheumatology, 2013
Keywords
INFLAMMATORY MYOPATHIES, IDIOPATHIC INFLAMMATORY MYOPATHIES, POLYMYOSITIS, DERMATOMYOSITIS, INCLUSION BODY MYOSITIS
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-96992 (URN)10.3899/jrheum.120804 (DOI)000321993800023 ()
Note

Funding Agencies|University Hospital Linkoping||County Council of Ostergotland||

Available from: 2013-09-02 Created: 2013-09-02 Last updated: 2017-12-06
Dezsi, L., Danielsson, O., Gati, I., Timea Varga, E. & Vecsei, L. (2013). Inclusion body myositis - a rarely recognized disorder. Ideggyogyaszati Szemle - Clinical Neuroscience, 66(3-4), 89-101
Open this publication in new window or tab >>Inclusion body myositis - a rarely recognized disorder
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2013 (Hungarian)In: Ideggyogyaszati Szemle - Clinical Neuroscience, ISSN 0019-1442, Vol. 66, no 3-4, p. 89-101Article, review/survey (Refereed) Published
Abstract [en]

Inclusion body myositis is the most common disabling inflammatory myopathy in the elderly. It is more frequent in men and after the age of 50 years. Inflammatory and degenerative features coexist. There is a T-cell mediated autoimmunity driven by in situ clonally expanded cytotoxic CD8-positive T-cells invading non-necrotic muscle fibres expressing MHC-I antigen. The hallmarks of degeneration are the deposition of protein aggregates and the formation of vesicles. The course of the disease is slow and the diagnosis is usually set after several years. The muscle weakness and wasting is assymetric, affecting predominantly distal muscles of the upper extremity and proximal muscles of the legs. The signs and clinical course can be characteristic, but the diagnosis is established by muscle biopsy. less thanbrgreater than less thanbrgreater thanThere is currently no evidence based effective treatment for sIBM. Prednisone, azathioprine, methotrexate, cyclosporine and IFN-beta failed. Oxandrolon did not improve symptoms. Treatment with intravenous immunglobuline (IVIG) induced in some patients a transient improvement of swallowing and of muscle strenght, but the overall study results were negative. less thanbrgreater than less thanbrgreater thanA T-cell depleting monoclonal antibody (alemtuzumab), in a small uncontrolled study slowed down disease progression for a six-month period. Repeated muscle biopsies showed the reduction of T-cells in the muscle and the suppression of some degeneration associated molecules. An effective therapeutic mean should act on both aspects of the pathomechanism, on the inflammatory and the degenerative processes as well.

Place, publisher, year, edition, pages
Budapest, Hungary: Literatura Medica Kiado, 2013
Keywords
sIBM, inflammation, degenerative process, amyloid precursor protein, endoplasmic reticulum, immunosuppressive treatment
National Category
Physiology
Identifiers
urn:nbn:se:liu:diva-92707 (URN)000317633400002 ()
Available from: 2013-05-16 Created: 2013-05-16 Last updated: 2018-01-11Bibliographically approved
Klingstedt, T., Blechschmidt, C., Nogalska, A., Prokop, S., Häggqvist, B., Danielsson, O., . . . Nilsson, K. P. (2013). Luminescent Conjugated Oligothiophenes for Sensitive Fluorescent Assignment of Protein Inclusion Bodies. ChemBioChem (Print), 14(5), 607-616
Open this publication in new window or tab >>Luminescent Conjugated Oligothiophenes for Sensitive Fluorescent Assignment of Protein Inclusion Bodies
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2013 (English)In: ChemBioChem (Print), ISSN 1439-4227, E-ISSN 1439-7633, Vol. 14, no 5, p. 607-616Article in journal (Refereed) Published
Abstract [en]

Small hydrophobic ligands identifying intracellular protein deposits are of great interest, as protein inclusion bodies are the pathological hallmark of several degenerative diseases. Here we report that fluorescent amyloid ligands, termed luminescent conjugated oligothiophenes (LCOs), rapidly and with high sensitivity detect protein inclusion bodies in skeletal muscle tissue from patients with sporadic inclusion body myositis (s-IBM). LCOs having a conjugated backbone of at least five thiophene units emitted strong fluorescence upon binding, and showed co-localization with proteins reported to accumulate in s-IBM protein inclusion bodies. Compared with conventional amyloid ligands, LCOs identified a larger fraction of immunopositive inclusion bodies. When the conjugated thiophene backbone was extended with terminal carboxyl groups, the LCO revealed striking spectral differences between distinct protein inclusion bodies. We conclude that 1) LCOs are sensitive, rapid and powerful tools for identifying protein inclusion bodies and 2) LCOs identify a wider range of protein inclusion bodies than conventional amyloid ligands.

Place, publisher, year, edition, pages
Wiley-VCH Verlag Berlin, 2013
Keywords
amyloid beta-peptides, biosensors, fluorescent probes, luminescent conjugated oligothiophene, protein inclusion body
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-91341 (URN)10.1002/cbic.201200731 (DOI)000316285600010 ()
Note

Funding Agencies|Swedish Foundation for Strategic Research||European Research Council (ERC)||EU||

Available from: 2013-04-23 Created: 2013-04-22 Last updated: 2017-12-06Bibliographically approved
Ingre, C., Pinto, S., Birve, A., Press, R., Danielsson, O., de Carvalho, M., . . . Andersen, P. M. (2013). No association between VAPB mutations and familial or sporadic ALS in Sweden, Portugal and Iceland. AMYOTROPHIC LATERAL SCLEROSIS AND FRONTOTEMPORAL DEGENERATION, 14(7-8), 620-627
Open this publication in new window or tab >>No association between VAPB mutations and familial or sporadic ALS in Sweden, Portugal and Iceland
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2013 (English)In: AMYOTROPHIC LATERAL SCLEROSIS AND FRONTOTEMPORAL DEGENERATION, ISSN 2167-8421, Vol. 14, no 7-8, p. 620-627Article in journal (Refereed) Published
Abstract [en]

Linkage analysis in Brazilian families with amyotrophic lateral sclerosis (ALS) revealed that a missense mutation p. Pro56Ser in a conserved gene VAMP-associated protein type B and C (VAPB) cosegregates with disease. Blood samples were studied from 973 Swedish, 126 Portuguese and 19 Icelandic ALS patients, and from 644 control subjects. We identified five VAPB mutations, two of which are novel, in 14 Swedish ALS patients and in nine control individuals from Sweden and Portugal. The 14 patients with VAPB mutations all carried a diagnosis of sporadic ALS. Mutations were also found in healthy adult relatives. The p. Asp130Glu VAPB mutation was also found in two patients from an Icelandic ALS family, but the mutation did not cosegregate with disease. All patients were instead found to be heterozygous for a p.Gly93Ser SOD1 mutation. There were no clinical differences between them, suggesting that the p. Asp130Glu VAPB mutation is unrelated to the disease process. less thanbrgreater than less thanbrgreater thanIn conclusion, the VAPB mutations were as frequent in control individuals as in patients. This observation, in combination with the finding of several healthy relatives carrying the VAPB mutations and no ancestors with ALS disease, suggests that it is unlikely that these VAPB mutations are pathogenic.

Place, publisher, year, edition, pages
Informa Healthcare, 2013
Keywords
ALS, risk factor, VAPB, SOD1, oligomutant
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-102382 (URN)10.3109/21678421.2013.822515 (DOI)000326626500021 ()
Note

Funding Agencies|Swedish Brain Power Consortium||Bertil Hallsten Foundation||Swedish Brain Research Foundation||Swedish Research Council||Umea University||Ulla-Carin Lindquist Foundation||Swedish Association for the Neurologically Disabled (NHR)||

Available from: 2013-12-09 Created: 2013-12-09 Last updated: 2013-12-09
Gati, I., Merkli, H., Pal, E. & Danielsson, O. (2012). External Ophthalmoplegia Associated With Hashimotos Thyroiditis and Recovered on Corticosteroid Treatment. The American journal of surgery, 344(2), 151-152
Open this publication in new window or tab >>External Ophthalmoplegia Associated With Hashimotos Thyroiditis and Recovered on Corticosteroid Treatment
2012 (English)In: The American journal of surgery, ISSN 0002-9629, E-ISSN 1538-2990, Vol. 344, no 2, p. 151-152Article in journal (Refereed) Published
Abstract [en]

Five-year follow-up of a young male patient is presented. Total external ophthalmoplegia developed 1 week after an upper respiratory tract infection. After 3 years of the course, hyperthyreosis and clinical signs of thyroid-associated ophthalmopathy occurred. Hashimotos thyroiditis and ultrastructural signs of mitochondrial damage of striated muscle were found by histological investigations. The paresis of the external ocular muscles recovered after long-term corticosteroid treatment. On the basis of clinical symptoms and histological results, the authors supposed that an immunological reaction had caused mitochondrial damage in the striated muscles, which also resulted in thyroiditis. This case history points that autoimmune mechanism more frequently might participate in the pathogenesis of chronic external ophthalmoplegia, and the symptoms might precede organ-specific or perhaps systemic autoimmune disorders.

Place, publisher, year, edition, pages
Lippincott, Williams and Wilkins, 2012
Keywords
External ophthalmoplegia, Hashimotos thyroiditis, Corticosteroid treatment
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-81506 (URN)10.1097/MAJ.0b013e31824d4d93 (DOI)000306966300015 ()
Available from: 2012-09-18 Created: 2012-09-18 Last updated: 2017-12-07
Gati, I., Danielsson, O., Gunnarsson, C., Vrethem, M., Häggqvist, B., Fredriksson, B.-A. & Landtblom, A.-M. (2012). Letter: Bent Spine Syndrome: A Phenotype of Dysferlinopathy or a Symptomatic DYSF Gene Mutation Carrier [Letter to the editor]. European Neurology, 67(5), 300-302
Open this publication in new window or tab >>Letter: Bent Spine Syndrome: A Phenotype of Dysferlinopathy or a Symptomatic DYSF Gene Mutation Carrier
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2012 (English)In: European Neurology, ISSN 0014-3022, E-ISSN 1421-9913, Vol. 67, no 5, p. 300-302Article in journal, Letter (Other academic) Published
Abstract [en]

n/a

Place, publisher, year, edition, pages
Karger, 2012
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-77740 (URN)10.1159/000336265 (DOI)000303444900009 ()
Available from: 2012-05-28 Created: 2012-05-28 Last updated: 2017-12-07
Danielsson, O., Gati, I., Lindvall, B. & Ernerudh, J. (2011). CLASSIFICATION AND VALUE OF EXTENDED PATHOLOGICAL WORK UP OF 99 CONSECUTIVE PATIENTS WITH MORPHOLOGICAL FINDINGS OF INFLAMMATORY MYOPATHY in EUROPEAN JOURNAL OF NEUROLOGY, vol 18, issue SI, pp 49-49. In: EUROPEAN JOURNAL OF NEUROLOGY: (pp. 49-49). Wiley-Blackwell, 18(SI)
Open this publication in new window or tab >>CLASSIFICATION AND VALUE OF EXTENDED PATHOLOGICAL WORK UP OF 99 CONSECUTIVE PATIENTS WITH MORPHOLOGICAL FINDINGS OF INFLAMMATORY MYOPATHY in EUROPEAN JOURNAL OF NEUROLOGY, vol 18, issue SI, pp 49-49
2011 (English)In: EUROPEAN JOURNAL OF NEUROLOGY, Wiley-Blackwell , 2011, Vol. 18, no SI, p. 49-49Conference paper, Published paper (Refereed)
Abstract [en]

n/a

Place, publisher, year, edition, pages
Wiley-Blackwell, 2011
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-71077 (URN)000294806600103 ()
Available from: 2011-09-30 Created: 2011-09-30 Last updated: 2013-11-07
Gati, I., Danielsson, O., Vrethem, M., Lindehammar, H., Lindvall, B., Häggqvist, B., . . . Landtblom, A.-M. (2011). SENSORY ATAXIC NEUROPATHY WITH DYSARTHRIA/DYSPHAGIA AND OPHTHALMOPLEGIA (SANDO) - CASE HISTORIES in EUROPEAN JOURNAL OF NEUROLOGY, vol 18, issue SI, pp 282-282. In: EUROPEAN JOURNAL OF NEUROLOGY (pp. 282-282). Wiley-Blackwell, 18(SI)
Open this publication in new window or tab >>SENSORY ATAXIC NEUROPATHY WITH DYSARTHRIA/DYSPHAGIA AND OPHTHALMOPLEGIA (SANDO) - CASE HISTORIES in EUROPEAN JOURNAL OF NEUROLOGY, vol 18, issue SI, pp 282-282
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2011 (English)In: EUROPEAN JOURNAL OF NEUROLOGY, Wiley-Blackwell , 2011, Vol. 18, no SI, p. 282-282Conference paper, Published paper (Refereed)
Abstract [en]

n/a

Place, publisher, year, edition, pages
Wiley-Blackwell, 2011
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-71080 (URN)000294806600516 ()
Available from: 2011-09-30 Created: 2011-09-30 Last updated: 2012-04-03
Gati, I., Danielsson, O., Betmark, T., Ernerudh, J., Öllinger, K. & Dizdar (Dizdar Segrell), N. (2010). Culturing of diagnostic muscle biopsies as spheroid-like structures: a pilot study of morphology and viability. Neurological Research, 32(6), 650-655
Open this publication in new window or tab >>Culturing of diagnostic muscle biopsies as spheroid-like structures: a pilot study of morphology and viability
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2010 (English)In: Neurological Research, ISSN 0161-6412, E-ISSN 1743-1328, Vol. 32, no 6, p. 650-655Article in journal (Refereed) Published
Abstract [en]

Objective: The aim of this study was to establish three-dimensional cultures originating from muscle biopsies and evaluate the viability and morphology. Method: Muscle biopsies from patients with suspected neuromuscular disorders were obtained and established as primary muscle tissue cultures. Tissue pieces, 1-2 mm of diameters, were placed in culture medium and subjected to sporadic stirring to prevent attachment and outgrowth as monolayer cells. Morphology and ability to attach to the surface were investigated by light microscopy. Viability was evaluated by Tc-99m-tetrofosmin uptake. After 1 month, histology was evaluated by light microscopy and immunocytochemistry. The findings of a healthy muscle and a dystrophic muscle were compared. Results: Initially, the tissue pieces were unshaped but formed spheroid-like structures during the culture period. For dystrophic muscle, attachment capacity to the surface was initially potent and decreased during the culture period, whereas control muscle showed weak attachment from the start that increased during the culture period. The uptake of Tc-99m-tetrofosmin increased in control muscle, while it decreased in dystrophic muscle, during the culture period. The histological investigation demonstrated larger destruction of myofiber, weaker satellite cell activation and reduced myofiber regeneration in the dystrophic muscle as compared to the control muscle. Conclusion: The cellular components of the muscle tissue can survive and proliferate as spheroid-like primary cultures. The cellular composition resembles the in vivo condition, which allows studies of degeneration of the original fibers, and activation and proliferation of the satellite cells. The culture system may provide better understanding of the degeneration and regeneration processes in different muscle disorders and allow investigations of pharmacological interventions.

Place, publisher, year, edition, pages
Forefront Publishing Group, 2010
Keywords
Muscle biopsy; primary tissue culture; spheroid-like structure
National Category
Engineering and Technology
Identifiers
urn:nbn:se:liu:diva-58289 (URN)10.1179/016164109X12464612122579 (DOI)000279001300013 ()
Available from: 2010-08-10 Created: 2010-08-09 Last updated: 2018-01-12
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