Spontaneous aggregation of native immunoglobulins in hypoalbuminemic serum

We have previously demonstrated that isolated IgG, when added to buffer or serum, undergoes aggregation during incubation at 37°C. The addition of albumin inhibits aggregation. The present studies were designed to determine whether endogenous immunoglobulins in normal serum, present in low-normal concentration, would likewise aggregate in the presence of hypoalbuminemia. Albumin was removed from normal serum by absorption with Affi-gel Blue. Following incubation at 37°C, high molecular weight IgG, IgM and IgA were detectable by density gradient ultracentrifugation. Reconstituting the samples with albumin prior to incubation prevented the formation of immunoglobulin aggregates. These data suggest that immunoglobulin aggregation might also occur in vivo in a variety of pathological conditions associated with hypoalbuminemia and/or hypergammaglobulinemia and might be incorrectly assumed to represent antigen-antibody complexes.