Emergence of CD52 −, glycosyiphosphatidylinositol-anchor deficient lymphocytes in rheumatoid arthritis patients following Campath-1H treatment

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Abstract
CD52 is a glycosylphosphatidyl-inositol (GPI)-llnked 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 the 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 CD52+ 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-llnked 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.

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