| 11. |
- Lindvall, Björn, 1952-
(författare)
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Immunohistological studies on muscle biopsies : clinical and pathogenetic aspects on inflammatory myopathies
- 2002
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- 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.
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| 13. |
- Minde, Jan, et al.
(författare)
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A novel NGFB point mutation : a phenotype study of heterozygous patients
- 2009
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Ingår i: Journal of Neurology, Neurosurgery and Psychiatry. - : BMJ Publishing Group Ltd. - 0022-3050 .- 1468-330X. ; 80:2, s. 188-195
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: A family with neurological findings similar to hereditary sensory and autonomic neuropathy type V having a point mutation in the nerve growth factor beta (NGFB) gene was recently described. The homozygous genotype gives disabling symptoms. The purpose of the present study was to evaluate the symptoms in heterozygous patients. METHODS: 26 patients heterozygous for the NGFB mutation (12 men, mean age 50 (13-90) years) were examined clinically and answered a health status questionnaire, including the Michigan Neuropathy Screening Instrument (MNSI). 28 relatives (15 men, mean age 44 (15-86) years) without the mutation served as controls in the clinical examination part. 23 of the heterozygotes were examined neurophysiologically and six heterozygous patients underwent a sural nerve biopsy. RESULTS: The heterozygous phenotype ranged from eight patients with Charcot arthropathy starting in adult age and associated with variable symptoms of neuropathy but without complete insensitivity to pain, anhidrosis or mental retardation, to 10 symptom free patients. There was no difference in MNSI between the young heterozygous cases (<55 years old) and the controls. Six of 23 heterozygous patients had impaired cutaneous thermal perception and 11 of 23 had signs of carpal tunnel syndrome. Sural nerve biopsies showed a moderate reduction of both small myelinated (Adelta) and unmyelinated (C) fibres. No apparent correlation of small fibre reduction to symptoms was found. CONCLUSIONS: The NGFB mutation in its heterozygous form results in a milder disease than in homozygotes, with a variable clinical picture, ranging from asymptomatic cases to those with Charcot arthropathy appearing in adult age. Particularly age, but perhaps lifestyle factors also, may influence the development of clinical polyneuropathy.
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