EMERGENCE OF CD52(-), GLYCOSYLPHOSPHATIDYLINOSITOL-ANCHOR-DEFICIENT LYMPHOCYTES IN RHEUMATOID-ARTHRITIS PATIENTS FOLLOWING CAMPATH-1H TREATMENT

CD52 is a glycosylphosphatidyl-inositol (GPI)-linked glycoprotein expr essed 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 pa tients treated with the humanized antibody Campath-1H in phase II clin ical trial, Whereas the majority of CD52(-) B cells had disappeared fr om the peripheral blood by 3 months post-treatment, both CD52(-) CD4() and CD8(+) T cells persisted in the circulation for at least 20 mont hs. In the two patients that were tested, the GPI-anchored surface mol ecules CD55 and CD59 were also absent on the CD52(-) cells, although e xpression of other cell surface transmembrane proteins (CD3, CD4 and C D2) was unaffected, The CD52(-) cells maintained a stable phenotype in vitro despite repeated re-stimulation in culture, Both CD52(-) and CD 52(+) clones, established from one of the patients, responded to a sim ilar 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 att ack against a GPI-anchored surface molecule can result in the selectio n of a GPI-anchor-deficient cell population, Despite the persistence o f CD52(-) T cells in the peripheral blood, no adverse reactions associ ated with the presence of these cells were noted in any of the patient s; in fact they responded with longer remission times after Campath-1H treatment than the other patients in the trial.