Neutrophils express CD52 and exhibit complement-mediated lysis in the presence of alemtuzumab.
Neutropenia is a recognized adverse event in patients treated with the humanized anti-CD52 monoclonal antibody alemtuzumab. However, as it is widely believed that neutrophils do not express CD52, the etiology of alemtuzumab-associated neutropenia is unclear. We have found that neutrophils express both mRNA coding for CD52 and the protein itself on the cell surface. We confirmed cell-surface expression using 3 different anti-CD52 antibodies, and note that neutrophils express lower levels of CD52 than lymphocytes and eosinophils. Further, incubation of alemtuzumab with neutrophils results in dose-dependent, complement-mediated lysis in the presence of both heterologous and autologous complement. These data offer an explanation for the etiology of alemtuzumab-associated neutropenia. In a climate of increased use of alemtuzumab in leukemia and other disease states, as well as in transplantation, these data highlight the need for increased vigilance of emerging neutropenia in patients treated with alemtuzumab.
Ambrose
Lyn R
LR
Department of Immunology, Division of Medicine, Imperial College London, London, United Kingdom. lynambrose@googlemail.com
Morel
Anne-Sophie
AS
Warrens
Anthony N
AN
D000074323:Alemtuzumab; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm / Q000494:pharmacology*; D015703:Antigens, CD / Q000378:metabolism*; D000951:Antigens, Neoplasm / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D000074301:CD52 Antigen; D003165:Complement System Proteins / Q000378:metabolism*; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D004804:Eosinophils / Q000378:metabolism; D005434:Flow Cytometry; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D009504:Neutrophils / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D015703:Antigens, CD; D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D000074301:CD52 Antigen; C000613862:CD52 protein, human; D006023:Glycoproteins; D012333:RNA, Messenger; D000074323:Alemtuzumab; D003165:Complement System Proteins