The aim of our study was to address the question of whether muscle fibers express major histocompatibility complex (MHC) class II in inflammatory myopathies. For this purpose we performed a systematic study of MHC class II antigen expression on muscle fiber membranes in muscle tissue from polymyositis and dermatomyositis patients in various stages of disease activity. Thirty-two patients with classical clinical signs of myositis were divided into subgroups depending on duration of clinical signs of myositis and presence or absence of inflammatory infiltrates in muscle tissue. Immunohistochemistry as well as double-immunofluorescence stainings were used to identify the presence of MHC class II in muscle tissue. MHC class I was included for comparison. Quantification of positive staining was performed using an image analysis system in addition to evaluation by manual microscopic scoring and laser confocal microscopy. It was demonstrated that a significant proportion of skeletal muscle fibers in inflammatory myopathies express MHC class II as well as MHC class I and that MHC antigen expression is independent of the inflammatory cell infiltration. Furthermore, there were no differences in staining pattern between polymyositis and dermatomyositis patients. Our results indicate that MHC class II and MHC class I molecules may be involved in initiating and maintaining the pathological condition in myositis rather than only being a consequence of a preceding local inflammation.

Objective. To address the hypothesis that endothelial cells and/or muscle fibers are primary targets in the disease process by analysis of muscle tissue from patients with polymyositis (PM) and dermatomyositis (DM).Methods. We included patients with laboratory signs and clinical symptoms typical of myositis, but without detectable infiltration of clusters of inflammatory cells in their muscle biopsy samples. An immunohistochemical technique was applied to identify CD3, CD68, lymphocyte function-associated antigen 1␣, CD11b, very late activation antigen 4, endothelium 4, interleukin-1␣ (IL-1␣), intercellular adhesion molecule 1, vascular cell adhesion molecule 1, IgG, IgM, IgA, and HLA-A/B/C in muscle tissue. Fiber type was defined by ATPase staining.Results. IL-1␣ expression was detected in endothelial cells of capillaries to a greater extent in patients than in controls, and class I major histocompatibility complex (MHC) expression was significantly increased in muscle fibers. We also observed that class I MHC expression was mainly confined to type II muscle fibers.Conclusion. Our findings imply that defined molecular changes of blood vessels and muscle fibers are both independent of adjacent inflammatory infiltrates and could thus be primary events in the development of myositis. Moreover, both IL-1␣ and class I MHC molecules might be important for the development of clinical symptoms in PM and DM patients.

Objectives: To determine whether muscle weakness is correlated with inflammation, expression of interleukin 1a (IL1a) and major histocompatibility complex (MHC) class I and II antigens on muscle fibres. Methods: Biopsy specimens from clinically symptomatic (proximal muscles) and asymptomatic (all distal but two proximal) muscles in eight patients with polymyositis, three patients with dermatomyositis and six healthy controls were analysed by immunohistochemistry for the presence of T cells and macrophages, and expression of IL1a and of MHC class I and II antigens. Results were evaluated by conventional light microscopy and by computerised image analysis. Results: Inflammatory infiltrates with T cells and macrophages were observed to an equal degree in both symptomatic and asymptomatic muscle. The numbers of capillaries with IL1a expression were significantly higher (p,0.05) in the symptomatic and asymptomatic muscles of patients than in controls. The total IL1a expression per tissue section assessed by computerised image analysis was significantly higher in symptomatic muscles but not in asymptomatic muscles compared with that in controls. Neither the number of IL1a-positive capillaries nor the total IL1a expression differed significantly between symptomatic and asymptomatic muscles. Expression of MHC class I and II antigens on muscle fibres was detected in both symptomatic and asymptomatic muscles but rarely in healthy controls. Conclusions: Presence of inflammatory infiltrates, T cells and macrophages, and expression of MHC class I and II antigens and of IL1a on muscle fibres were independent of clinical symptoms, and were present to an equal degree in both proximal and distal muscles. Thus, other factors seem to determine the development of clinical symptoms. One such factor could be variations in physical demands.

Objective. To investigate T cell receptor (TCR) expression in 3 different compartments that could be involved in patients with myositis: muscle, lung, and peripheral blood.Methods. Nine patients with polymyositis (PM), dermatomyositis, or inclusion body myositis underwent bronchoscopy and bronchoalveolar lavage (BAL) as well as muscle biopsy and blood sampling. A panel of 19 monoclonal antibodies specific for TCR V ␤ (BV) and V ␣ (AV) were used to characterize the TCR profile in CD4؉ and CD8؉ T cell populations in BAL fluid and peripheral blood by flow cytometry. Muscle biopsy tissues were analyzed by immunohistochemistry. Patients were also typed for HLA-DRB1 and DRB3 alleles.Results. A total of 17 T cell expansions were detected in BAL fluid, 6 in the CD4؉ T cell population and 11 in the CD8؉ T cell population. Four T cell expansions were detected in peripheral blood. A selective TCR V usage was found in muscle. Two PM patients, both of whom had BAL fluid BV3؉ T cell expansions in the CD4 population and in whom BV3 was also a prominent TCR V segment in muscle tissue, shared the HLA-DRB1*03 allele. These 2 patients were the only ones who were positive for anti-Jo-1 antibody.Conclusion. We found a restricted accumulation of T lymphocytes expressing selected TCR V-gene segments in the target organ compartments (i.e., lung and muscle). The occurrence of shared TCR gene segment usage in muscle and lungs could suggest common target antigens in these organs.