Studies of immunoregulation in patients with juvenile dermatomyositis

Juvenile dermatomyositis (JDM) is a rare, inflammatory disease of children. The aetiology and pathogenesis of the disease are unknown, although it is believed to be autoimmune in origin. The target antigens on affected tissues have not been identified and initial experiments failed to demonstrate significant differences between the proliferative responses of control and patient peripheral blood lymphocytes (PBL) to skeletal muscle antigens. In addition, autoantibodies with specificity for skeletal muscle or endothelial cell antigens were not detected by immunofluorescence. In the absence of detectable antigen specific responses to tissues in these patients, studies of immunoregulation were undertaken to determine whether defective lymphocyte function was contributing to the persistence of tissue damage. Such studies have not previously been undertaken in JDM patients. In vitro experiments compared cooperation between mononuclear cells from the peripheral blood of 14 JDM and 8 adult polymyositis (PM) patients with appropriate normal controls. Mitogen stimulation experiments showed anergic proliferative responses (30-50% of controls) by adult patients' cells in response to T cell mitogens. In contrast, JDM patients' cells showed no significant differences in proliferative response to T cell mitogens but did show significantly elevated (p<0.01) spontaneous IgM production and significantly reduced (p<0.01) IgM production in response to pokeweed mitogen, compared to controls. Coculture experiments indicated a defect at the level of the T cell in JDM patients. Analysis of T cell function in JDM patients was further investigated employing autologous stimulation as a model system. Significantly reduced proliferation, compared to controls, was measured (p<0.01) and, more significantly, four patients, in contrast to controls, were unable to generate suppressor T cells. These results could partially be explained by inability of JDM T cell populations to produce and respond to IL-2. These results were independent of corticosteroid therapy. A JDM serum factor, identified as an IgG antibody, was observed to inhibit autologous stimulation. Further study indicated that this effect was due to inhibition of responses to IL-2, although the antibody did not appear to directly bind IL-2 or the IL-2 receptor. Although experiments indicated that the antibody might have specificity for Human Lymphocyte Antigen class II determinants, this could not be confirmed. The activity of NK cells in the peripheral blood of 18 JDM patients was found to be significantly less than that of controls (p<0.01). Sequential measurements showed that this was a consistent finding, not associated with corticosteroid therapy, disease severity or lymphopaenia. The activity of LAK cells from 15 JDM patients was also significantly less than controls (p