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The Journal of Immunology, 2000, 164: 2815-2822.
Copyright © 2000 by The American Association of Immunologists

Analysis and Significance of Anti-Latent Membrane Protein-1 Antibodies in the Sera of Patients with EBV-Associated Diseases

Jingwu Xu*, Ali Ahmad*, Mario D’Addario*, Laurent Knafo*, James F. Jones{dagger}, U. Prasad{ddagger}, R. Dolcetti§, E. Vaccher§ and José Menezes*

* Laboratory of Immunovirology, Pediatric Research Center and Department of Microbiology and Immunology, University of Montreal and Ste.-Justine Hospital, Montreal, Quebec, Canada; {dagger} Department of Pediatrics, National Jewish Center for Immunology and Respiratory Medicine, Denver, CO; {ddagger} Department of Otorhinolaryngology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia; and § Divisions of Experimental Oncology, and Medical Oncology and AIDS, Centro di Riferimento Oncologico, Aviano (PN), Italy

Anti-latent membrane protein-1 (LMP-1) is an EBV-encoded type III integral membrane protein with oncogenic potential that is expressed most consistently in various EBV-associated malignancies. Unlike many other EBV proteins, LMP-1 Abs have rarely been demonstrated in EBV-associated disease conditions. We established a high level LMP-1-expressing cell clone and used it for the detection, quantitation, and characterization of these Abs in various human sera in immunoblots and ELISA. Our results demonstrate that, in contrast to the commonly held notion, LMP-1 induces significant humoral immune responses in EBV-associated malignant conditions especially in nasopharyngeal carcinoma (NPC) patients in whom >70% sera are positive for these Abs, and their titers correlate with the clinical condition of the tumors. Interestingly, anti-LMP-1 Abs of IgA isotype were found only in NPC patients. These Abs were absent from the sera of infectious mononucleosis and chronic EBV infection patients, whereas a small fraction (~5%) of the healthy, EBV-seropositive individuals were positive for them; however, their OD values were much lower than those of NPC patients. These studies demonstrate, for the first time, the potential significance of LMP-1-specific Abs for the diagnosis and prognosis of EBV-associated malignancies, especially of NPC.




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