Benign monoclonal gammopathy: a reassessment of the problem.

Disease associations of clonally restricted serum immunoglobulin (Ig) abnormalities were examined using methods for detecting and characterizing homogeneous Ig that are approximately forty times more sensitive than either cellulose acetate zone electrophoresis or immunoelectrophoresis. Medical records of three hundred five patients with clonally-restricted serum immunoglobulins, including 100 monoclonal gammopathies, and 205 immune complex/oligoclonal patterns were reviewed to obtain the attending physician's discharge diagnosis. Our data confirm lymphoproliferative disorders as the most frequent cause of monoclonal gammopathy (63% of our cases). However, in contrast to earlier reports, we found little evidence to support an association between monoclonal gammopathy and non-reticular malignancy. This does not mean our patients with these disorders had normal serum immunoglobulin patterns; rather, their qualitative abnormalities were, for the most part, not monoclonal. Instead, patients with these diseases had a high incidence of serum immune complexes and their antibody excess sequelae, oligoclonal patterns. Oligoclonal responses are noteworthy because Ig products of the individual clones do not always achieve equivalent serum concentrations, nor are the various clonal products synchronized with respect to the time at which they attain peak concentration. This creates a number of problems for laboratories attempting to characterize such abnormalities; 1) some analytical methods may only be capable of detecting the dominant clone of an oligoclonal pattern, and 2) analysis of a single specimen may yield erroneous results because the unique waxing and waning kinetic pattern of oligoclonal responses may preclude identification of all components at a single time point. We conclude that benign "monoclonal" gammopathies and circulating immune complex/oligoclonal Ig abnormalities occur in the same clinical situations and may be synonymous. The sensitivity of an individual laboratory's analytical methods would then determine which name is applied.