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