The immunopathogenic mechanisms of a number of immune mediated diseases 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 abnormally is compatible with a post receptor signal transduction defect. Indeed, our data suggest that overproduction 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. Use of the lipoxygenase inhibitors ketoprofen or hydrocortisone have resulted in markedly enhanced production of antigen specific antibody 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 hypereosinophilia. They will serve as a valuable model for study of this interesting syndrome. We have demonstrated the presence of antineutrophil cytoplasmic antibodies (ANCA) in patients with the Wegener's granulomatosis, lymphomatoid granulomatosis, polyarteritis nodosa, and systemic lupus erythematosus (SLE). In some cases, the ANCA IgG correlated with disease activity. The data indicate that ANCA is a sensitive and specific marker for Wegener's granulomatosis. Finally, we have continued our studies of idiopathic dilated cardiomyopathy and have demonstrated that this disease is responsive to immunosuppressive therapy.
