The immunopathogenic mechanisms of a number of immune mediated disease and/or diseases characterized by abnormalities of immune function were investigated. B cells from patients with common variable immunodeficiency (CVI) were studied and shown to respond normally to low molecular weight B cell growth factor (LMW-BCGF), but abnormally or not at all to high molecular weight (HMW)-BCGF despite the ability to express receptors for HMW-BCGF). This abnormality is compatible with a post receptor signal transduction defect. Indeed, our data suggest that overprodution of an arachidonic acid metabolite such as PGE or one of the leukotrienes may be playing an inhibitory role in the normal signal transduction occurring with HMW-BCGF. Studies in systemic lupus erythematosus (SLE) indicate that T cells of patients who have disease flares with production of IgG antibody produced a factor which enhances IgG production and inhibits IgM production in vitro. We have extended our studies on the hypereosinophilic syndrome (HES) and have recently had the opportunity to investigate a large family cohort of patients with hereditary HES. They will serve as a valuable model for study of this interesting syndrome. We have demonstrated the presence of antineutrophil antibodies in patients with Wegener's granulomatosis, lymphomatoid granulomatosis, polyarteritis nodosa, and SLE. In some cases, the titer of anti-neutrophil IgG correlates with disease activity. Finally, we have continued our studies of idiopathic dilated cardiomyopathy and preliminary analysis of data indicate that this disease is responsive to immunosuppressive therapy.
