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The expression of adhesion molecules in muscle biopsies: the LFA-1/VLA-4 ratio in polymyositis
Linköping University, Department of Neuroscience and Locomotion, Neurology. Linköping University, Faculty of Health Sciences.
Department of Neurology, County Hospital in Örebro, Sweden.
Linköping University, Department of Neuroscience and Locomotion, Neurology. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Biomedicine and Surgery, Clinical Chemistry. Linköping University, Faculty of Health Sciences.
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2003 (English)In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 107, no 2, 134-141 p.Article in journal (Refereed) Published
Abstract [en]

Objectives– The expression of three pairs of adhesion receptors and ligands was examined in 22 consecutive muscle biopsies showing morphological signs of inflammation.

Material and methods– The following groups were studied: patients with polymyositis (PM) (n=7), patients with myositis that did not fulfil criteria for PM, i.e. suspected PM (n=5), patients with other diseases, with no clinical signs of inflammatory myopathy (n=6), and a small group of non-PM inflammatory myopathies (n=4). The endothelial expression of ICAM-1, VCAM-1 and E-selectin was evaluated, as was the cellular expression of LFA-1, VLA-4 and SLex. In addition, the expression of MHC class I and II was studied.

Results– The ratio between the number of cells expressing LFA-1 and VLA-4 showed significant differences between the groups, with the lowest values in PM.

Conclusion– The LFA-1/VLA-4 ratio should be suitable for diagnostic purposes. Our findings also indicate that the VLA-4/VCAM-1 system is important for chronic T cell inflammation in muscle, in line with findings in other “hidden” organs like joints and the central nervous system.

Place, publisher, year, edition, pages
2003. Vol. 107, no 2, 134-141 p.
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-26433DOI: 10.1034/j.1600-0404.2003.02062.xLocal ID: 10976OAI: oai:DiVA.org:liu-26433DiVA: diva2:246982
Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2017-12-13Bibliographically approved
In thesis
1. Immunohistological studies on muscle biopsies: clinical and pathogenetic aspects on inflammatory myopathies
Open this publication in new window or tab >>Immunohistological studies on muscle biopsies: clinical and pathogenetic aspects on inflammatory myopathies
2002 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Inflammatory myopathies constitute a heterogeneous group of disorders comprising polymyositis (PM), dermatomyositis (DM), inclusion body myositis (IBM), as well as overlap syndromes where inflammatory myopathy is associated with different inflammatory systemic diseases, e.g, Sjögren's syndrome. Immunohistochemical methods are increasingly used in the diagnostic evaluation of muscle biopsies, as well as in the search for pathogenetic mechanisms in neuromuscular diseases. The aim of the present thesis was to evaluate immunological markers in the context of diagnostic use and pathogenetic mechanisms in patients with inflammatory myopathies (IM).

In the first paper, the expression of inflammatory markers was investigated in muscle biopsies from 58 healthy subjects, since no large studies on normal expression have been reported previously. MHC class I stained capillaries but not muscle fibres. No capillary or muscle fibre staining was found of MHC class II, complement activation marker MAC, or the regeneration marker neonatal myosin heavy chain, whereas the adhesion molecule ICAM-I was constitutively expressed on capillary endothelial cells. The expression was similar in morphologically completely normal muscle biopsies obtained from clinical routine, justifying the use of such biopsies as normal reference, although some caution is warranted because of individuals with higher expression of inflammatory markers.

Adhesion molecules regulate cell to cell interactions, e.g. they are involved in recruiting cells into inflammatory lesions in muscles. In a group of consecutive patients (n=22) with inflammatory infiltrates pairs of adhesion molecules were examined on infiltrating cells and vascular endothelial cells. VLA-4, known to be important in chronic inflammation, was found to be expressed mostly on infiltrating cells in definite PM, whereas LFA-1 was expressed in all types of IM. These findings suggest a diagnostic potential of the LFA-1/VLA-4 ratio, and a role for VLA-4/VCAM-1 in the pathogenesis of PM.

In a large study of patients (n=48) with primary Sjögren's syndrome (pSS), we described muscle histology and immunohistochemical findings in relation to muscle pain (n=36), a common complaint of patients with pSS. Morphological changes, as perivascular inflammation was common in pSS. A surprisingly high proportion of patients displayed IBM-Iike changes, such as rimmed vacuoles, inflammation and atrophic fibres. Immunohistochemically, MHC class I and MAC showed increased expression, but no single finding showed any relation to muscle pain. MAC expression indicates a role for complement activation in pSS associated myositis.

The finding of IBM-Iike changes in pSS, resulted in a subsequent comparative study of cytoplasmic and vacuolar proteins in classical IBM and pSS. Although more frequently found in IBM, the same vacuolar proteins were found in muscle biopsies from patients with pSS. Clinical symptoms differed between IBM and pSS associated myositis, indicating that these diseases represent different entities. The similarity in histological findings suggests that non-specific mechanisms may operate and lead to the same end result. We therefore propose that vacuolar myositis in pSS should be regarded as a separate entity, different from classical IBM and suggest the term aIBM (autoimmune associated) for patients with IBM-Iike changes and associated autoimmune disease.

Place, publisher, year, edition, pages
Linköping: Linköpings universitet, 2002. 90 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 760
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-26662 (URN)11228 (Local ID)91-7373-200-1 (ISBN)11228 (Archive number)11228 (OAI)
Public defence
2002-12-07, Berzeliussalen, Hälsouniversitet, Linköping, 10:15 (Swedish)
Opponent
Note

2002

Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2012-09-19Bibliographically approved

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Lindvall, BjörnHenriksson, Karl-GöstaErnerudh, Jan

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