Suppression of polyclonal immunoglobulin production by M-proteins shows isotype specificity

Monoclonal gammopathies are B cell neoplasms that are characterized by the presence of monoclonal immunoglobulins (M-proteins) in the serum. By an unk nown mechanism, the normal polyclonal immunoglobulin levels are frequently reduced in sera of these patients. To assess the role of M-protein isotype in this effect, we used serum protein electrophoresis to quantitate monoclo nal and polyclonal immunoglobulins in patients and we used serum immunofixa tion electrophoresis to determine their M-protein isotype. When divided int o populations of 30 patients with IgG M-proteins (mean 2.5 g/dl) and 19 pat ients with IgM or IgA M-proteins (mean 2.6 g/dl), the mean polyclonal immun oglobulin level was significantly lower in the IgG M-protein population (0. 4 g/dl) than the IgM/IgA population (0.8 g/dl). Patients with IgG M-protein s also had significantly lower polyclonal immunoglobulin levels when compar ed separately with the patients with either IgA or IgM paraproteins. Since the polyclonal immunoglobulin fraction is comprised mostly of IgG, these re sults give the first direct indication that IgG M-proteins have a greater s uppressive effect on polyclonal IgG levels than do M-proteins of other isot ypes. These findings suggest that an isotype-specific feedback mechanism co uld be involved in the normal regulation of serum IgG levels.