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

Abstract

Campath-1H, an anti-CD52 monoclonal antibody, is therapeutically active in lymphoproliferative and autoimmune diseases. After Campath-1H therapy, lymphocytes with a paroxysmal nocturnal haemoglobinuria (PNH) phenotype have been reported to emerge. We characterized a PNH-like lymphocyte population emerging 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 [interleukin (IL)-4, IL-13, IL-2, interferon(IFN)-γ, IL-6, IL-10, and tumour necrosis factor (TNF)-α], except transforming growth factor (TGF)-β. Given the inhibitory activity of TGF-β, its elevated levels may contribute to the selective pressure of Campath-1H, leading to the emergence of PNH-like lymphocytes.