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The Molecule Immunopathologic Study of DYSFERLINOPATHY

Author: GuoHua
Tutor: LiNa
School: Hebei Medical University
Course: Neurology
Keywords: Dysferlinopathy Inflammatory myopathies Muscle biopsy Immunohistochemical staining Inflammatory mechanisms
CLC: R746
Type: Master's thesis
Year: 2007
Downloads: 29
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Abstract

Objective: Dysferlinopathy the dysferlin gene mutations lead to a group characterized by progressive muscle weakness inherited myopathy. Dysferlin skeletal muscle a muscle cell membrane repair transmembrane protein. Diverse and complex, Dysferlin gene mutations in type no significant mutational hotspots, phenotypic heterogeneity of individuals. Currently found dysferlinopathy three clinical phenotypes: limb-girdle muscular dystrophy 2B (limb-girdle muscular dystrophy 2B; LGMD2B), Myoshi muscular dystrophy (Miyoshi muscular dystrophy; MMD) and tibialis anterior group myopathy (Distal anterior compartment myopathy ). They have a common skeletal pathological manifestations: varying degrees of muscle cell degeneration, necrosis, regeneration, and inflammatory cell infiltration. Molecular pathology: the anti-dysferlin monoclonal antibody immunohistochemical staining, the complete absence of dysferlin protein in the muscle cell membrane. Clinical and histopathological LGMD2B and polymyositis (polymyositis, PM) performance has a certain similarity, sometimes difficult to identify, dysferlin monoclonal antibody immunohistochemical staining to identify the key. This study investigated the the dysferlin protein function and related proteins; Dysferlinopathy inflammatory reaction mechanisms and the relationship with inflammatory myopathies. Improve the molecular pathology the diagnosis dysferlinopathy the awareness, diagnosis and differential diagnosis of difficult cases should be positive immunohistochemical staining, pathological diagnosis, and to explore the treatment method. Method: based on anti-dysferlin monoclonal antibodies to immunohistochemical staining, the muscle cell membrane dysferlin protein is completely missing the 8 patients selected for the case group typing diagnosis according to the initial involvement of the lesion, proximal lower limb muscles first involved patients attending for LGMD2B ; distal lower extremities after a group of muscles, MMD the gastrocnemius was first affected patients diagnosed as; first involved muscle group muscle of the distal lower extremities of Distal the anterior compartment myopathy. The control group of patients with inflammatory myopathies, seven cases including polymyositis, dermatomyositis, and inclusion body myositis patients were diagnosed according to international diagnostic criteria. The two groups of patients with skeletal muscle at the same time anti-CD4 T cells, CD8 T cells, MHC-Ⅰ molecule monoclonal antibody immunohistochemical staining, light microscope to observe the type of inflammatory cell infiltration, distribution characteristics, and quantitative analysis, the two sample t-test processing data. Observed MHC-Ⅰ the positive myocytes distribution characteristics, the extent and distribution of inflammatory cells. The two groups were compared, explore dysferlinopathy inflammatory reaction mechanisms proposed diagnosis and differential diagnosis and to explore effective treatment. Results: 1 patient group selected eight patients, which LGMD2B3; MMD5 cases, none of Distal is anterior and compartment myopathy. The average age of onset is 16-46 years of age, duration of 5-16 years. 1 patient had a positive family history. Creatine kinase levels were increased all dysferlinopathy patient's numerical changes in the 2283-11000U / L.. EMG: LGMD2B are myogenic changes; MMD patients with early visible neurogenic changes, late presentation myogenic changes, the remaining three cases showed myogenic changes. Skeletal muscle staining pathological analysis: all patients in case group showed changes in muscular dystrophy: varying degrees of muscle cell degeneration, necrosis and regeneration. Active inflammatory response (acid phosphatase staining), including two cases of most muscle cells have been replaced by fat tissue, the inflammatory response is not obvious. Control group: PM muscle cell degeneration and necrosis obvious, was part of the focal distribution, a large number of inflammatory cell infiltration; DM visible beam Week atrophy, necrotic cells and inflammatory cells were mainly distributed in the the atrophy fiber bundle weeks and perivascular. IBM visible edge of vacuoles, Congo red staining amyloid deposition. Molecular pathology: anti-dysferlin monoclonal immunohistochemical staining, skeletal muscle cell membrane of the case group dysferlin protein is completely missing, dysferlin protein expression in the normal control group. 2 cases and control groups of anti-CD4 T cells, CD8 T cells, MHC-Ⅰ molecule monoclonal antibody immunohistochemical staining, pathological analysis. Random observations from three different horizons, the case group patients were almost no expression of CD8 T cells, a small amount of CD4 T cells express distribution within the extracellular matrix around blood vessels and degeneration, necrotic muscle cells. PM and IBM control group mainly CD8 T cells express distribution in the endomysium, degeneration and necrosis of muscle cells and blood vessels around; DM CD4 T cells express mainly distributed in the fiber bundle weeks atrophy and perivascular. T-cells, CD8 T cell counts of Dysferlinopathy, significantly less than the PM, two-sample t-test analysis of the data, P lt; 0.05 was statistically significant. The two groups of patients showed enhanced expression of MHC-Ⅰ molecule in skeletal muscle cell membrane. Dysferlinopathy patients in five cases only in the perivascular, degeneration and necrosis of the muscle cell membrane expression of the remaining three cases at the same time in morphologically normal muscle cell membrane expression, expression of MHC-1-positive muscle cells accounted for eight cases the ratio of the total number of muscle cells in the same field of vision lt; 25% around much accumulation of inflammatory cells, and some were focal distribution. MHC-Ⅰ positive expression control group distribution: PM and IBM are distributed in morphologically normal, degeneration and necrosis of the muscle cell membrane and perivascular; DM located in the cell membrane and perivascular bundle weeks atrophic, the lowest proportion of positive expression in 50% -75%. Conclusion: a muscle cell degeneration and necrosis Dysferlinopathy histopathological features similar to polymyositis, difficult to identify. 2 Dysferlinopathy inflammatory cells than T cells, almost no CD8 T cell infiltration; surface of skeletal muscle cells up-regulated expression of MHC-I expression levels as inflammatory myopathies obvious. 3 Dysferlin protein deficient dysferlinopathy muscle cell degeneration and necrosis of the key factors, secondary inflammatory response in dysferlinopathy muscle cell degeneration and necrosis process, but do not initiate action with. The inflammatory reaction mechanisms of 4 Dysferlinopathy unlike polymyositis.

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