CD5+ B cells in Graves' disease: correlation with disease activity.

In the present paper the distribution of peripheral blood CD5+/CD19+ (CD5+B) and CD5-/CD19+ (CD5-B) B-lymphocytes in Graves' disease (GD) patients is analyzed in order to correlate them with disease activity, interleukin-2 (IL-2) and IL-6 binding to T and B cells as well as with anti-thyrotropin (TSH) receptor antibodies and the thyroid hormone serum levels. The combination of flow cytometry and 3-color immunofluorescence revealed a remarkable increase in the absolute numbers of CD5+ B cells in hyperthyroid-untreated GD patients (218 +/- 137 x 10(6)/l vs. 66 +/- 69 x 10(6)/l in healthy subjects, p < 0.01) that gradually fell to normal values once hyperthyroidism had been controlled by methimazole. However, relative numbers of CD5+ B cells persisted at a relatively stable but increased level in GD patients in long term remission of an average of 3.1 years. This was also confirmed in a follow-up study of a group of 12 newly diagnosed patients during the first 90 days of anti-thyroid drug therapy with methimazole. No correlation was observed between either CD5+ B cells or CD5- B cells and the serum levels of pathogenic anti-TSH receptor antibodies. Increased numbers of CD5+ B cells were related to the increased free thyroxine and total triiodothyronine serum levels. In addition, a strong correlation between both the absolute levels of B cells binding to exogenous IL-2 and IL-6 and the absolute number of CD5+ B cells in hyperthyroid GD patients (LR = 0.798, p < 0.001; LR = 0.569, p < 0.01, respectively) was observed. These results suggest that CD5+ B cells in GD are partly regulated by thyroid hormone serum levels as well as by IL-2 and IL-6 binding to B cells. Nevertheless, they are not involved, at least directly, in the production of anti-TSH receptor antibodies.