Immunological Aspects of Polymyositis

Polymyositis is an acquired myopathy which is classified into three types: Type α ‘uncomplicated’ polymyositis; Type β, dermatomyositis and polymyositis associated with connective-tissue disorders; Type γ, polymyositis associated with neoplasia. The disorder may be due to lymphocyte-mediated hypersensitivity; the in vitro activity of lymphocytes from patients with the condition has therefore been studied. The degree of stimulation of these lymphocytes on incubation with whole muscle homogenate has been assessed by measuring their uptake of tritiated thymidine. Lymphocytes from patients with polymyositis showed a significantly higher response to muscle than did lymphocytes from patients with other diseases with and without muscle wasting. In polymyositis the index of response showed some correlation with the clinical activity of the disorder. Lymphocytes from none of the groups of patients responded to other antigens (collagen, encephalitogenic factor, liver, and kidney). The cytotoxic activity of lymphocytes has been studied by incubation with foetal muscle and other tissues in culture. Lymphocytes from patients with polymyositis appeared to be cytotoxic to muscle cultures; serum from these patients and lymphocytes from those with other disorders were not cytotoxic. Lymphocytes from patients with Type α (‘uncomplicated’) polymyositis were not cytotoxic to fibroblast and epithelial cultures but lymphocytes from those with Type γ polymyositis were so. Antilymphocytic antiserum appeared to prevent cytotoxic action by lymphocytes. There was some correlation between the degree of lymphocytic stimulation by muscle antigen and the cytotoxic activity of lymphocytes against muscle cultures. In a subsidiary project lymphocytes from patients with systemic sclerosis were studied. These lymphocytes showed a raised index of response to muscle antigen only when there was clinical evidence of myopathy; however, lymphocytes from all the patients were cytotoxic to cultures of all tissues. The evidence for an immunological pathogenesis in polymyositis is given and the significance of the present findings is discussed. The lymphocytic stimulation by muscle antigen and the cytotoxic activity against muscle cells appear to be specific. They suggest that in vivo sensitization has occurred to some component of muscle. Lymphocytic stimulation may reflect a secondary phenomenon. The relevance of in vitro cytotoxicity to the in vivo production of hypersensitivity lesions is uncertain. However, the findings taken together suggest that lymphocytes may be instrumental in the production of polymyositis. The classification of polymyositis is reviewed in the light of our results. Raynaud's phenomenon, arthralgia, and erythema may not always represent the multi-system involvement of Type β polymyositis.