IMMUNOHISTOCHEMICAL ANALYSIS OF PERFORIN AND GRANZYME-A IN INFLAMMATORY MYOPATHIES

Perforin (PF) and granzyme A (GA) are candidates suspected of being cy tolytic proteins of the granules of cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells. We analysed PF and GA in muscles from pati ents with inflammatory myopathies. Five Gases of polymyositis (PM), tw o cases of inclusion body myositis (IBM), and five cases of dermatomyo sitis (DM) were studied immunohistochemically using anti-PF and GA ant ibodies raised against each synthetic peptide of human PF and mouse GA , together with a panel of monoclonal antibodies reactive for lymphocy te subsets. In PM and IBM, PF positive cells were colocalized with GA positive cells and occasionally invaded into the non-necrotic muscle f ibres. The percentage of PF positive cells among the endomysial CD8 po sitive cell population was 9.9% (PM) and 12.5% (IBM), and the majority of the endomysial CD8 positive cells were alpha/beta T cells. In cont rast, in DM, both PF and GA positive cells were very few in all cases. Only few inflammatory cells were CD16(+) or CD57(+) NK cells among th ese diseases. Our results suggest that PF and GA are secreted mainly f rom alpha/beta T cells, and may play a key role in muscle fibre damage in at least some PM and IBM, but not in DM.