DETECTION OF SKEWED T-CELL RECEPTOR V-BETA GENE USAGE IN THE PERIPHERAL-BLOOD OF PATIENTS WITH MULTIPLE-SCLEROSIS

The ex vivo analysis of the T-cell receptor V-beta (TCRBV) gene usage by circulating T lymphocytes in Multiple Sclerosis (MS) patients may c ontribute to understanding disease pathogenesis. In the present study, TCRBV gene usage was analyzed in freshly collected unstimulated perip heral blood mononuclear cells (PBMC) isolated from 40 MS patients and 20 healthy controls. Nine patients presented abnormal repertoires, wit h expansion of one or more TCRBV segments. Among these patients, six p resented expansion of TCRBV9 chain expression, three also having an ex pansion of TCRBV1, TCRBV11 and TCRBV22 segments. The most frequently o bserved TCRBV chain expansion, TCRBV9, was further analyzed and identi fied as polyclonal. Evaluation of clinical variables showed that media n disease duration was shorter in patients with TCRBV gene expression abnormalities. Longitudinal evaluation of five patients with a skewed repertoire showed regression of expanded TCRBV chains expression to no rmal values. These data indicate that certain MS patients have abnorma l TCRBV gene expression. Such abnormalities are caused by polyclonal e xpansions of T lymphocyte subpopulations that use the same TCRBV gene families, are unstable and preferentially observed early in the course of the disease. (C) 1398 Elsevier Science B.V. All rights reserved.