Significance of circulating T-cell clones in Sezary syndrome

Identification of malignant Sezary cells by T-cell receptor (TCR) clonality studies is routinely used for the diagnosis of Sezary syndrome, but T-cell clones expressed in a single patient have never been accurately characterized. We previously reported that CD158k expression delineates Sezary syndrome malignant cells, and, more recently, we identified vimentin at the surface membranes of Sezary cells and normal activated lymphocytes. In the present study, T-cell clones from 13 pa-tients with Sezary syndrome were identified by immunoscopy and further characterized in the blood according to their TCR V beta, CD158k, and vimentin cell-surface expression. We found in most patients a unique malignant T-cell clone that co-expressed CD158k and vimentin and that, when patients were tested, was also present in the skin. However, in some patients we detected the presence of a nonmalignant circulating clone expressing high amounts of vimentin and lacking CD1 58k. These results indicate that clonal expansion may originate from circulating malignant and nonmalignant CD4(+) T cell populations in patients with Sezary syndrome. Identification of the malignant cells in Sezary syndrome cannot be achieved by T-cell clonality studies or by TCR V beta monoclonal antibody (mAb) analysis alone; it also relies on CD1 58k phenotyping.