{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T09:33:16Z","timestamp":1776331996800,"version":"3.50.1"},"reference-count":0,"publisher":"Portland Press Ltd.","issue":"3","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[1997,3,15]]},"abstract":"<jats:p>The CD52 antigen is a lymphocyte glycoprotein with an extremely short polypeptide backbone and a single N-linked glycan, and it is attached to the cell membrane by a glycosylphosphatidylinositol (GPI) anchor. Treatment of rheumatoid arthritis patients with CAMPATH-1H, a humanized monoclonal antibody against CD52, resulted, in a small number of cases, in the appearance and persistence of CD52-negative T cells. Similarly, CD52-negative B cells emerged following in vitro treatment of a CD52-positive human B cell line with CAMPATH-1H. Both the B and T CD52-negative cells were also found to be defective in surface expression of other GPI-anchored proteins. Biochemical analysis revealed a severe defect in the synthesis of a mature GPI precursor in both the B and T cell lines. Therefore the phenotype of these CD52-negative B and T cells closely resembles that of lymphocytes from patients with paroxysmal nocturnal haemoglobinuria (PNH), in which the first step of the GPI-biosynthetic pathway, i.e. synthesis of GlcNAc-phosphatidylinositol, is blocked. In all cases studied to date, this defect maps to a mutation of the phosphatidylinositolglycan class A (PIG-A) structural gene. We therefore amplified the PIG-A gene from both the GPI-negative B and T cells by PCR and determined the nucleotide sequence. No differences from the wild-type sequence were detected; therefore a classical PNH mutation cannot be responsible for the GPI-biosynthesis defect in these cell lines. Significantly, the GPI-negative phenotype of the B cells was reversible upon separation of the positive and negative cells, resulting in a redistribution to a mixed population with either CD52-positive or -negative cells, whereas populations of 100% CD52-negative T cells were stably maintained during culture. Therefore, whereas the GPI-biosynthesis deficiency in the T cell lines may be due to a mutation in another gene required by the GPI-biosynthetic pathway, the reversible nature of this block in the B cell lines suggests a less direct cause, possibly an alteration in a regulatory factor. Overall, these data demonstrate that the PNH phenotype can be generated without a mutation in the PIG-A structural gene, and thereby identify a novel mechanism for the development of GPI deficiency.<\/jats:p>","DOI":"10.1042\/bj3220919","type":"journal-article","created":{"date-parts":[[2015,8,10]],"date-time":"2015-08-10T21:53:23Z","timestamp":1439243603000},"page":"919-925","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["Antibody selection against CD52 produces a paroxysmal nocturnal haemoglobinuria phenotype in human lymphocytes by a novel mechanism"],"prefix":"10.1042","volume":"322","author":[{"given":"Vanessa C.","family":"TAYLOR","sequence":"first","affiliation":[{"name":"Glaxo\u2013Wellcome Medical Research Laboratories, Stevenage, Herts., U.K."},{"name":"Laboratory of Cell Biology, Department of Biochemistry, Imperial College of Science, Technology and Medicine, London SW7 2AY, U.K."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"SIMS","sequence":"additional","affiliation":[{"name":"Glaxo\u2013Wellcome Medical Research Laboratories, Stevenage, Herts., U.K."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara","family":"BRETT","sequence":"additional","affiliation":[{"name":"Glaxo\u2013Wellcome Medical Research Laboratories, Stevenage, Herts., U.K."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark C.","family":"FIELD","sequence":"additional","affiliation":[{"name":"Laboratory of Cell Biology, Department of Biochemistry, Imperial College of Science, Technology and Medicine, London SW7 2AY, U.K."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"288","container-title":["Biochemical Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/portlandpress.com\/biochemj\/article-pdf\/322\/3\/919\/623516\/bj3220919.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/portlandpress.com\/biochemj\/article-pdf\/322\/3\/919\/623516\/bj3220919.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,11,24]],"date-time":"2021-11-24T00:27:40Z","timestamp":1637713660000},"score":1,"resource":{"primary":{"URL":"https:\/\/portlandpress.com\/biochemj\/article\/322\/3\/919\/33617\/Antibody-selection-against-CD52-produces-a"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1997,3,15]]},"references-count":0,"journal-issue":{"issue":"3","published-print":{"date-parts":[[1997,3,15]]}},"URL":"https:\/\/doi.org\/10.1042\/bj3220919","relation":{},"ISSN":["0264-6021","1470-8728"],"issn-type":[{"value":"0264-6021","type":"print"},{"value":"1470-8728","type":"electronic"}],"subject":[],"published":{"date-parts":[[1997,3,15]]}}}