Emergence of CD52-, phosphatidylinositolglycan-anchor-deficient T lymphocytes after in vivo application of Campath-1H for refractory B-cell non-Hodgkin lymphoma.
CD52 is a phosphatidylinositolglycan (PIG)-anchored glycoprotein (PIG-AP) expressed on normal T and B lymphocytes, monocytes, and the majority of B-cell non-Hodgkin lymphomas. We observed the emergence of CD52- T cells in 3 patients after intravenous treatment with the humanized anti-CD52 monoclonal antibody Campath-1H for refractory B-cell lymphoma and could identify the underlaying mechanism. In addition to the absence of CD52, the PIG-AP CD48 and CD59 were not detectable on the CD52- T cells in 2 patients. PIG-AP-deficient T-cell clones from both patients were established. Analysis of the mRNA of the PIG-A gene showed an abnormal size in the T-cell clones from 1 of these patients, suggesting that a mutation in the PIG-A gene was the cause of the expression defect of PIG-AP. An escape from an immune attack directed against PIG-AP+ hematopoiesis has been hypothesized as the cause of the occurrence of PIG-AP-deficient cells in paroxysmal nocturnal hemoglobinuria (PNH) and aplastic anemia. Our results support the hypothesis that an attack against the PIG-AP CD52 might lead to the expansion of a PIG-anchor-deficient cell population with the phenotypic and molecular characteristics of PNH cells.
Hertenstein
B
B
Department of Internal Medicine III, University of Ulm, Germany.
Wagner
B
B
Bunjes
D
D
Duncker
C
C
Raghavachar
A
A
Arnold
R
R
Heimpel
H
H
Schrezenmeier
H
H
D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D015703:Antigens, CD / Q000378:metabolism*; D000951:Antigens, Neoplasm; D001483:Base Sequence; D017252:CD3 Complex / Q000032:analysis; D000074301:CD52 Antigen; D017931:DNA Primers / Q000737:chemistry; D005434:Flow Cytometry; D006023:Glycoproteins; D017261:Glycosylphosphatidylinositols / Q000378:metabolism*; D006801:Humans; D016130:Immunophenotyping; D007167:Immunotherapy; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000628:therapy*; D008969:Molecular Sequence Data; D016176:T-Lymphocyte Subsets / Q000473:pathology*
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000951:Antigens, Neoplasm; D017252:CD3 Complex; D000074301:CD52 Antigen; C000613862:CD52 protein, human; D017931:DNA Primers; D006023:Glycoproteins; D017261:Glycosylphosphatidylinositols