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Immunohistochemical markers MHC class I, MHC class II, ICAM-1, MAC and neonatal myosin heavy chain in muscle biopsies: Expression in healthy subjects, normal muscle biopsies and inflammatory myopathies
Linköping University, Department of Neuroscience and Locomotion, Neurology. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Molecular and Clinical Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences.
(English)Manuscript (preprint) (Other academic)
Abstract [en]

Although immunohistochemistry on muscle biopsies is widely used scientifically and clinically, information is limited regarding the expression in normal healthy subjects. In the present study we investigated the expression of relevant immune markers in a large material (n=58) of healthy subjects and compared with the expression in morphologically normal muscle biopsies (n=46) obtained from clinical routine. As a reference of inflammation, muscle biopsies from idiopathic inflammatmy myopathies (IIM) were used (n=22).

We found that the expression in healthy subjects was not significantly different from that in morphologically normal biopsies, although a few individuals with minimal morphological aberrations also showed higher expression of immune markers. The IIM group showed significantly higher expression of all markers. In brief, major histocompatibility complex (MHC) class I was nmmally not, or very weakly, expressed on muscle fibres, MHC class II was not expressed on capillary endothelial cells, whereas intercellular adhesion molecule (ICAM)-1 was constitutively expressed to a ce1tain degree on capillmy endothelial cells. The complement activation marker membrane attack complex (MAC) was merely absent in nonnal biopsies. Neonatal myosin heavy chain was normally present only in a very few regenerating fibres. A constructed grading scale was found useful, based on normal occun·ence as well as intensity and distribution of expression.

In conclusion we demonstrate the nmmal expression of MHC class I, MHC class II, ICAM-1, MAC and neonatal myosin as found in healthy subjects. The expression was similar in morphologically completely normal muscle biopsies obtained from clinical routine, justifyhtg the use of such biopsies as normal reference. Some caution is warranted for using biopsies with minimal morphological changes, since these showed increased expression of some inflammatory markers.

National Category
Medical and Health Sciences
URN: urn:nbn:se:liu:diva-81622OAI: diva2:553414
Available from: 2012-09-19 Created: 2012-09-19 Last updated: 2012-09-19Bibliographically 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.
Linköping University Medical Dissertations, ISSN 0345-0082 ; 760
National Category
Medical and Health Sciences
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)


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

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