Comparative Analysis of Immunodeficiency in Patients with Monoclonal Gammopathy of Undetermined Significance and Patients with Untreated Multiple Myeloma

Abstract
The objectives of this study were firstly, to compare the immunophenotype of patients with monoclonal gammopathy of undetermined significance (MGUS) with that of patients with newly diagnosed, untreated multiple myeloma (Unt. MM). Our second objective was to determine which variables might distinguish patients with MGUS and early MM. The CD4/CD8 ratio in both patient groups differed significantly from normal as a result of a decrease in the proportion of CD4+ cells. Similarly, surface immunoglobulin-positive (Ig+) B cells were significantly reduced in both groups. Also, some impairment of Ig secretion was observed. An in vitro specificity study of B cells showed an enriched proportion of B cells specific for tetanus toxoid (which may be indicative of enrichment for memory B cells) in both MGUS and Unt. MM patients. Further to this, in MM patients but not in MGUS patients, there was an enriched proportion of B cells specific for determinants on the F(ab'')2 fragment of Ig. This suggests an anomalous auto-immune reactivity to polyclonal Ig molecules. In one of the two patients studied, who progressed from MGUS to MM, disease progression was accompanied by an increase in this anti-Ig reactivity. In both patients there was a decrease in CD4/CD8 ratio.