Biological and molecular characterization of PNH-like lymphocytes emerging after Campath-1H therapy.
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.
Fracchiolla
N S
NS
Dipartimento di Ematologia, Ospedale Maggiore Policlinico IRCCS, Vis F. Sforza 35, 20122-Milan, Italy.
Barcellini
W
W
Bianchi
P
P
Motta
M
M
Fermo
E
E
Cortelezzi
A
A
D000074323:Alemtuzumab; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm / Q000008:administration & dosage*; D016022:Case-Control Studies; D005434:Flow Cytometry; D006457:Hemoglobinuria, Paroxysmal / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D018793:Interleukin-13 / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000276:immunology* / Q000628:therapy*; D008214:Lymphocytes / Q000276:immunology* / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D010835:Phytohemagglutinins / Q000494:pharmacology; D018807:Polymorphism, Single-Stranded Conformational; D012333:RNA, Messenger / Q000032:analysis; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D018793:Interleukin-13; D007376:Interleukin-2; D015850:Interleukin-6; D008565:Membrane Proteins; D010835:Phytohemagglutinins; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; C080086:phosphatidylinositol glycan-class A protein; D016753:Interleukin-10; D015847:Interleukin-4; D000074323:Alemtuzumab; D007371:Interferon-gamma