Purpose:To compare the performance of three PCR assays in measuring circulating Epstein-Barr virus (EBV). DNA levels in nasopharyngeal carcinoma patients and to confirm its prognostic significance. Experimental Design: Plasma from 58 newly diagnosed nasopharyngeal carcinoma patients were collected before, during, and every 3 to 6 months after radiotherapy. EBV DNA levels were determined by real-time quantitative PCR using primer/probe sets for polymerase-1 (Pol-1), latent membrane protein 2 (Lmp2), and BamHI-W. Pretreatment levels from the three assays were correlated with each other and serial measurements from the Pol-1 assay were correlated with clinical variables. Results: Pol-1 was more accurate than BamHI-W in predicting EBV DNA concentrations in cell lines. Of the three assays, BamHI-W yielded the highest concentrations followed by Pol-1 in plasmas (n = 23). The correlation coefficient was 0.99 (P < 0.0001) for Pol-1 and Lmp2, 0.66 (P < 0.0001) for Pol-1 and BamHI-W, and 0.55 (P < 0.0001) for BamHI-W and Lmp2.Elevated pretreatment DNA levels as detected by Pol-1 were correlated with advanced nodal stage (P = 0.04) and overall stage (P = 0.028). There was no correlation between pretreatment EBV DNA levels and freedom-from-relapse or overall survival; however, there was a significant correlation between posttreatment levels and these variables. The 2-year freedom-from-relapse and overall survival rates were 92% and 94% for patients with undetectable, and 37% and 55% for those with detectable, posttreatment levels (P < 0.0001 and P < 0.002). Conclusions:The three PCR assays yielded similar results in detecting EBV DNA in plasmas. The Pol-1-detected posttreatment EBV DNA level was the strongest predictor for treatment outcomes.

In this expanded study, we were able to replicate the prognostic significance of OPN using a predefined cut off point in an independent patient group and demonstrated that plasma OPN is an independent prognostic marker for HNSCC.

Intravenous immunoglobulin (IVIG) provides replacement therapy in immunodeficiency and immunomodulatory therapy in inflammatory and autoimmune diseases. This paper describes the immune mechanisms underlying six major non-primary immunodeficiency pediatric diseases and the diverse immunomodulatory functions of IVIG therapy. In Kawasaki disease, IVIG plays a major, proven, and effective role in decreasing aneurysm formation, which represents an aberrant inflammatory response to an infectious trigger in a genetically predisposed individual. In immune thrombocytopenia, IVIG targets the underlying increased platelet destruction and decreased platelet production. Although theoretically promising, IVIG shows no clear clinical benefit in the prophylaxis and treatment of neonatal sepsis. Limitations in research design combined with the unique neonatal immunologic environment offer explanations for this finding. Inflammation from aberrant immune activation underlies the myelinotoxic effects of Guillain-Barré syndrome. HIV-1 exerts a broad range of immunologic effects and was found to decrease serious bacterial infections in the pre-highly active anti-retroviral therapy (HAART) era, although its practical relevance in the post-HAART era has waned. Clinical and experimental data support the role of immune mechanisms in the pathogenesis of childhood epilepsy. IVIG exerts anti-epileptic effects through targeting upregulated cytokine pathways and antibodies thought to contribute to epilepsy. Applications in six additional pediatric diseases including pediatric asthma, atopic dermatitis, cystic fibrosis, pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS), autism, and transplantation will also be briefly reviewed. From autoimmunity to immunodeficiency, a dynamic immunologic basis underlies major pediatric diseases and highlights the broad potential of IVIG therapy.