The objective of this proposal is to gain a better understanding of the factors regulating immunoglobulin production in individuals with immune- mediated neurologic disorders. A method is proposed for measuring human IgG synthesis rates in vivo, in order to test the hypothesis that plasmapheresis and intravenous immunoglobulin infusion have immune- modulating effects on IgG production. This method relies on the intravenous administration and biosynthetic incorporation of L-(1-13C) leucine into newly synthesized IgG. The increment of L(1-13C) leucine in IgG is determined by mass spectrometer. Potential advantages of this method are that patients can be studied under non-steady state conditions, studies can be repeated after short intervals, and there is no exposure to radioisotopes. To establish the reliability of the IgG synthetic rate. In addition, rates of IgG synthesis during a """"""""flooding dose"""""""" and a """"""""tracer dose"""""""" leucine infusion protocol will be compared. IgG synthesis will then be studied in patients with myasthenia gravis or inflammatory demyelinating polyneuropathy to investigate the immune-modulating effects of 2 therapies in wide use for these disorders: intravenous immunoglobulin, and plasmapheresis. The hypothesis that there is an increase in IgG production following plasmapheresis will be tested. The hypothesis that intravenous immunoglobulin infusion suppresses IgG production will be tested. If plasmapheresis is found to increase the rate of IgG synthesis, the potential for suppressing this effect by IgG repletion using intravenous immunoglobulin will be tested. These studies will provide a method for investigating the effect of immune-modulating treatments on IgG synthesis in individuals with autoimmune disease.
