MULTIPLE ANTIGENS ARE ALTERED ON T-LYMPHOCYTE AND B-LYMPHOCYTE FROM PERIPHERAL-BLOOD AND SPLEEN OF PATIENTS WITH WISKOTT-ALDRICH SYNDROME

The gene for Wiskott-Aldrich syndrome (CAS) has been recently identifi ed and cloned, but our knowledge of downstream events affected in WAS is limited to a few leucocyte cell surface molecules. To identify cell surface molecules whose abnormal expression could contribute to the f unctional impairment observed in WAS B and T lymphocytes, we studied t he expression of a large panel of antigens on peripheral blood lymphoi d cells (PBLC) and on isolated lymphocyte subpopulations from the sple en of WAS patients. WAS T lymphocytes from peripheral blood express in creased levels of the activation antigens 4F2, CD49d, CD49e, CD53 and the activation/memory marker CD45RO. In the spleen, however, WAS patie nts have more CD45RA CD4(+) and CD8(+) T lymphocytes than normal indiv iduals, suggesting the selective accumulation of presumably naive cell s in the WAS spleen. Interestingly, the naive phenotype of the lymphoc ytes that seem to accumulate in the WAS spleen is confirmed by the abs ence of increased expression of several activation antigens on their s urface, and this correlated with their increased expression of CD43. T hese lymphocyte abnormalities were accompanied by an abnormal distribu tion of lymphocyte subsets within the spleen architecture, in particul ar by the lack of well developed germianl centres and T cell areas. We also found abnormal expression of CD43 and other sialyated proteins s uch as CDw75 and CD76, whose expression requires the action of specifi c sialyltransferases. This study shows that the combined impairment in cellular and humoral immunity observed in WAS is the result of multip le molecular abnormalities on the surface of WAS lymphocytes, that in turn might result in recirculation/migration anomalies.