J Korean Med Sci.  2009 Dec;24(6):1015-1023. 10.3346/jkms.2009.24.6.1015.

Differential Immunohistological Features of Inflammatory Myopathies and Dysferlinopathy

Affiliations
  • 1Department of Neurology, Pusan National University School of Medicine, Yangsan, Korea. dskim@pusan.ac.kr
  • 2Department of Rheumatology, Pusan National University School of Medicine, Yangsan, Korea.
  • 3Department of Orthopedic Surgery, Pusan National University School of Medicine, Yangsan, Korea.
  • 4Department of Pathology, Pusan National University School of Medicine, Yangsan, Korea.
  • 5Medical Research Institute, Pusan National University School of Medicine, Yangsan, Korea.

Abstract

This study was performed in order to characterize the types of the infiltrating cells, and the expression profiles of major histocompatibility complex (MHC) class I and membrane attack complex (MAC) in patients with inflammatory myopathies and dysferlinopathy. Immunohistochemical stains were performed using monoclonal antibodies against several inflammatory cell types, MHC class I, and MAC in muscles from inflammatory myopathies and dysferlinopathy. There was significant difference in the types of infiltrating cells between polymyositis (PM), dermatomyositis (DM), and dysferlinopathy, including significantly high CD4+/CD8+ T cell ratio and B/T cell ratio in DM. In dysferlinopathy, CD4+ T cells were the most abundant and the proportions of infiltrating cell types were similar to those of DM. MHC class I was expressed in muscle fibers of PM and DM regardless of the presence of inflammatory infiltrates. MAC was expressed in necrotic fibers and vessels of PM and DM. One patient with early stage DM had a MAC deposits on endomysial capillaries. In dysferlinopathy, MAC deposit was also observed on the sarcolemma of nonnecrotic fibers. The analysis of inflammatory cells, MHC class I expressions and MAC deposits may help to differentiate dysferlinopathy from idiopathic inflammatory myopathy.

Keyword

Polymyositis; Dermatomyositis; Muscular Dystrophies; Major Histocompatibility Complex Class I; Complement Membrane Attack Complex

MeSH Terms

Adult
Aged
*Dermatomyositis/immunology/pathology
Female
Genes, MHC Class I
Humans
Male
*Membrane Proteins/genetics/immunology
Middle Aged
Muscle Fibers, Skeletal/cytology/immunology/pathology
*Muscle Proteins/genetics/immunology
*Muscular Dystrophies, Limb-Girdle/immunology/pathology
*Myositis/immunology/pathology
*Polymyositis/immunology/pathology
T-Lymphocytes/cytology/immunology/pathology
Young Adult

Figure

  • Fig. 1 Cellular composition of inflammatory infiltrates in polymyositis (patient 3, A-E), dermatomyositis (patient 10, F-J), and dysferlinopathy (patient 15, K-O). In polymyositis (PM), the inflammatory infiltrates are mainly observed in endomysial spaces, and CD8+ T cells are most abundant. In dermatomyositis (DM), there are two inflammatory infiltrates in perivascular areas. CD4+ T cells and macrophages are more frequent than others. In dysferlinopathy (DF), there are inflammatory infiltrates in perivascular areas. CD4+ T cells and macrophages are mainly observed as in DM. A few CD8+ T cell are also scattered in endomysial spaces, but they do not surround or invade a normal-appearing muscle fibers. H&E, hematoxylin and eosin stain; CD8, immunostaining for CD8+ T cells; CD4, immunostaining for CD4+ T cells; CD20, immunostaining for B cells; CD68, immunostaining for macrophages.

  • Fig. 2 Immunohistochemical localization of MHC class I in control, polymyositis, dermatomyositis, and dysferlinopathy. In control muscle (A), MHC class I reactivity is present on the endothelium, but staining of the sarcolemma is negative. In polymyositis (B-F) and dermatomyositis (G, H), the non-necrotic muscle fibers show marked sarcolemmal reactivity for MHC class I. In some patients with prominent inflammatory infiltrates (B, D), pronounced cytoplasmic staining is present in non-necrotic fiber as well as in necrotic fibers. In patients with dysferlinopathy (I-L), MHC class I is expressed in the extracellular matrix and endothelium, but not on the sarcolemma of muscle fibers.

  • Fig. 3 Immunohistochemical localization of MAC depositis. In PM (A) and DM (B), there are MAC depositis on vessel walls of arteriole and within necrotic muscle fibers. In dysferlinopathy (C, D), MAC deposits are found on the sarcolemma of nonnecrotic fibers as well as on vessel walls.

  • Fig. 4 In a patient with early stage DM (patient 10), MAC deposits are clearly observed on endomysial capillaries (A, B, arrows). In a patient with late stage DM (patient 12), there is no MAC deposit on capillaries (C, D, arrows).


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