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

Abstract

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.

Identification and prevalence of CD8+ T‐cell responses directed against Epstein‐Barr virus‐encoded latent membrane protein 1 and latent membrane protein 2

“…25 In our view, therefore, sequence divergence is unlikely to have led to a significant underestimate of LMP-specific immunity. The present data indicating that the LMPs are only weakly immunogenic accord with the finding that the LMPs only induce detectable humoral responses in rare circumstances; thus anti-LMP1 antibodies have been detected in a subset of patients with HD or NPC but not in most healthy carriers, 23,31,32 while anti-LMP2 antibodies have only been described in NPC patients. 23,33,34 Furthermore, our recent studies have shown that LMP1 and LMP2 are also a poor source of epitopes for the CD4 ϩ T cell response.…”

Activation of DNA Methyltransferase 1 by EBV LMP1 Involves c-Jun NH2-Terminal Kinase Signaling

“…Using a more sensitive RT-PCR-based detection, several reports revealed much higher frequencies (>80%) of LMP1 expression (47,48). In addition, >70% of NPC patients' sera are positive for anti-LMP1 (49). Taken together, the positive rate for LMP1 in NPC is likely underestimated due to the sensitivity and specificity of the detection method.…”

Inhibition of oxidative phosphorylation underlies the antiproliferative and proapoptotic effects of mofarotene (Ro 40-8757) in Burkitt's lymphoma cells

“…Establishment and characterization of the HDE-14 LCL have been described elsewhere (Pomponi et al, 1996). BJAB cells transfected with the pIgLMP-1 plasmid and the vector alone (Xu et al, 2000) were kindly provided by Dr J Meneze´s (University of Montreal, Canada). Cell lines were cultured in RPMI 1640 supplemented with 10% heat-inactivated fetal calf serum, 100 U/ml penicillin, 100 mg/ml streptomycin, and 20 mm l-glutamine, and maintained in a humidified 5% CO 2 incubator at 371C.…”