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

Br J Haematol. 2001 Mar;112(4):969-71. doi: 10.1046/j.1365-2141.2001.02677.x.

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)-gamma, IL-6, IL-10, and tumour necrosis factor (TNF)-alpha], except transforming growth factor (TGF)-beta. Given the inhibitory activity of TGF-beta, its elevated levels may contribute to the selective pressure of Campath-1H, leading to the emergence of PNH-like lymphocytes.

Publication types

  • Case Reports

MeSH terms

  • Alemtuzumab
  • Antibodies, Monoclonal / administration & dosage*
  • Antibodies, Monoclonal, Humanized
  • Antibodies, Neoplasm / administration & dosage*
  • Case-Control Studies
  • Flow Cytometry
  • Hemoglobinuria, Paroxysmal / immunology*
  • Humans
  • Interferon-gamma / metabolism
  • Interleukin-10 / metabolism
  • Interleukin-13 / metabolism
  • Interleukin-2 / metabolism
  • Interleukin-4 / metabolism
  • Interleukin-6 / metabolism
  • Leukemia, Lymphocytic, Chronic, B-Cell / immunology*
  • Leukemia, Lymphocytic, Chronic, B-Cell / therapy*
  • Lymphocytes / immunology*
  • Lymphocytes / metabolism
  • Male
  • Membrane Proteins / genetics
  • Middle Aged
  • Phytohemagglutinins / pharmacology
  • Polymorphism, Single-Stranded Conformational
  • RNA, Messenger / analysis
  • Transforming Growth Factor beta / metabolism
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antibodies, Neoplasm
  • Interleukin-13
  • Interleukin-2
  • Interleukin-6
  • Membrane Proteins
  • Phytohemagglutinins
  • RNA, Messenger
  • Transforming Growth Factor beta
  • Tumor Necrosis Factor-alpha
  • phosphatidylinositol glycan-class A protein
  • Interleukin-10
  • Interleukin-4
  • Alemtuzumab
  • Interferon-gamma