Molecular size heterogeneity of immunoglobulins in health and disease.

The molecular size of serum IgG, IgA and IgM in patients with a variety of monoclonal and polyclonal immune disorders has been determined by a sensitive immunoblotting technique. IgM, IgA and IgG3 paraproteins from patients with B cell lymphoproliferative disorders frequently polymerize with IgA paraproteins demonstrating two polymeric series, the basic unit of the more dominant series being monomeric IgA, and the second consists of a basic unit having a molecular mass of approximately 70 kD heavier than monomeric IgA. The molecular nature of this heavier IgA moiety was shown to be IgA covalently bound with a single molecule of serum albumin or alpha 1 antitrypsin and this moiety was also observed in small quantities in sera from healthy subjects. IgM paraproteins, particularly from patients with malignant lymphoproliferative disorders, consisted of varying proportions of decamers, pentamers and monomers together with other low molecular weight IgM oligomers. Paraproteins from patients with benign conditions showed less tendency to exist in multiple molecular weight forms. Serum immunoglobulins from patients with polyclonal immune disorder also showed molecular sized heterogeneity. Significantly increased levels of dimeric IgA were observed in patients with alcoholic cirrhosis and Felty's syndrome, while low molecular weight IgM was commonly seen in patients with autoimmune disorders. In these latter disorders monomeric IgM correlated significantly with the serum IgM level suggesting a disorder of assembly of the IgM subunits during an ongoing IgM immune response. We have demonstrated considerable molecular size heterogeneity of serum immunoglobulins both in health and disease and have indicated some possible clinical associations.