Biological and molecular characterization of PNH-like lymphocytes emergingafter Campath-1H therapy

Campath-1H, an anti-CD52 monoclonal antibody, is therapeutically active in lymphoproliferative and autoimmune diseases. After Campath-1H therapy, lymp hocytes with a paroxysmal nocturnal haemoglobinuria (PNH) phenotype have be en reported to emerge. We characterized a PNH-like lymphocyte population em erging after Campath-1H therapy, in a patient with fludarabine refractory B -cell chronic lymphocytic leukaemia (B-CLL). We demonstrated a reduction in PIG-A mRNA levels compared with controls, and of all cytokines tested [int erleukin (IL)-4, IL-13, IL-2, interferon(IFN)-gamma, IL-6, IL-10, and tumou r necrosis factor (TNF)-alpha], except transforming growth factor (TGF)-bet a, Given the inhibitory activity of TGF-beta, its elevated levels may contr ibute to the selective pressure of Campath-1H, leading to the emergence of PNH-like lymphocytes.