Alterations in CD30+ T Cells in Monoclonal Gammopathy of Undetermined Significance

Monoclonal gammopathy of unknown significance (MGUS) is a monoclonal B cell expansion characterized by high levels of circulating monoclonal antibody that affects 3% of individuals over the age of 70. Although this is considered benign, a high percentage of MGUS patients develop a debilitating peripheral autoimmune neuropathy and have a significantly increased risk for progression to multiple myeloma. Here we show that the relative numbers of the CD30+ T cell subset and levels of CD30 expression are elevated in activated lymphocytes from normal aged individuals (≥60 years) and in MGUS patients, when compared to younger controls. PBL from MGUS patients and age-matched controls produced comparable levels of IL-6 when activated with anti-CD3 plus IL-2, and costimulation with a soluble form of CD30 ligand (sCD30L/CD8α) augmented anti-CD3 inducible IL-6 production similarly in both groups. However, MGUS PBL also produced measurable IL-6 when activated with sCD30L/CD8α alone. This capability was associated with the unique presence of CD30+ T cells in the peripheral blood of MGUS patients. Furthermore, a higher percentage of activated MGUS T cells express CD30 when activated by incubation with idiotype-expressing autologous serum (68 ± 13) than those activated by anti-CD3 plus IL-2 (43 ± 7). These results indicate that quantitative alterations in CD30+ T cells accompany aging and MGUS and that these cells may contribute to the chronic activation of B cells though the production of IL-6.