Emergence of CD52-, glycosylphosphatidylinositol-anchor-deficient lymphocytes in rheumatoid arthritis patients following Campath-1H treatment.
CD52 is a glycosylphosphatidyl-inositol (GPI)-linked glycoprotein expressed at high levels on normal T and B lymphocytes and at lower levels on monocytes, while being absent on granulocytes and bone marrow stem cell precursors. The emergence of CD52- lymphocytes of both T and B cell lineages was observed in three out of 25 rheumatoid arthritis patients treated with teh humanized antibody Campath-1H in phase II clinical trial. Whereas the majority of CD52- B cells had disappeared from the peripheral blood by 3 months post-treatment, both CD52- CD4+ and CD8+ T cells persisted in the circulation for at least 20 months. In the two patients that were tested, the GPI-anchored surface molecules CD55 and CD59 were also absent on the CD52- cells, although expression of other cell surface transmembrane, proteins (CD3, CD4 and CD2) was unaffected. The CD52- cells maintained a stable phenotype in vitro despite repeated re-stimulation in culture. Both CD52- and C52+ clones, established from one of the patients, responded to a similar extent to several T cell mitogens, as assessed by proliferation, suggesting that a general defect in expression of GPI-linked molecules does not impair T cell activation. These data show that an immune attack against a GPI-anchored surface molecule can result in the selection of a GPI-anchor-deficient cell population. Despite the persistence of CD52- T cells in the peripheral blood, no adverse reactions associated with the presence of these cells were noted in any of the patients; in fact they responded with longer remission times after Campath-1H treatment than the other patients in the trial.
Brett
S J
SJ
Molecular Immunology Group, Wellcome Research Laboratories, Kent, UK.
Baxter
G
G
Cooper
H
H
Rowan
W
W
Regan
T
T
Tite
J
J
Rapson
N
N
D000328:Adult; D000074323:Alemtuzumab; D000911:Antibodies, Monoclonal / Q000494:pharmacology* / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm / Q000494:pharmacology* / Q000627:therapeutic use; D015703:Antigens, CD / Q000096:biosynthesis*; D000951:Antigens, Neoplasm; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000737:chemistry; D000074301:CD52 Antigen; D018414:CD8-Positive T-Lymphocytes / Q000737:chemistry; D002478:Cells, Cultured; D005260:Female; D006023:Glycoproteins; D006801:Humans; D008213:Lymphocyte Activation; D016131:Lymphocyte Subsets / Q000276:immunology; D008214:Lymphocytes / Q000737:chemistry* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D013997:Time Factors
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D015703:Antigens, CD; D000951:Antigens, Neoplasm; D000074301:CD52 Antigen; C000613862:CD52 protein, human; D006023:Glycoproteins; D000074323:Alemtuzumab