Effects of subcutaneous interleukin-2 therapy on CD4 subsets and in vitro cytokine production in HIV+ subjects.

HIV infection is characterized by the reduction of the CD4+, CD45RA+, CD26+, and CD28+ lymphocyte subsets and of the in vitro production of IL-2, IL-4, and interferon-gamma; on the contrary, chemokine production is usually increased. These abnormalities are only partially restored by antiretroviral chemotherapy. Therapy with interleukin-2 has been proposed to restore the functions of the immune system, but the mechanisms by which IL-2 exerts its activities are unknown. The aim of this study was to define the effects of rIL-2 administration on CD4+, CD45RA+, CD45R0+, and CD26+ lymphocytes and on the in vitro production of IL-2, IL-4, IL-10, IFN-gamma, RANTES, and sCD30 in HIV+ patients. 10 HIV+ patients with CD4 cell counts between 200 and 500 cells/mm3 were treated with six cycles of subcutaneous recombinant IL-2 administration, in combination with zidovudine and didanosine. This therapeutic regimen resulted in a remarkable increase in the number of CD4+ cells and in the prolonged reduction of the levels of viremia. CD45R01 cells were expanded during the first cycle of therapy, while CD45RA+/CD26+ cells predominated after the third cycle. At this time, the in vitro production of IL-2, IL-4, IFN-gamma, and sCD30 were significantly upregulated. These results demonstrate that rIL-2 in HIV+ patients induces the reconstitution of the CD4/CD45RA lymphocytes subtype. This expanded cell population recovered the ability to produce in vitro IL-2, IL-4, and IFN-gamma. These effects may be beneficial to HIV+ patients by improving their immune response to microorganisms or vaccines

Trans-Oral Brush Biopsies and Quantitative PCR for EBV DNA Detection and Screening of Nasopharyngeal Carcinoma

Objectives. To evaluate a newly developed noninvasive ambulatory, quantitative polymerase chain reaction (Q-PCR) Epstein-Barr virus (EBV) DNA detection and screening system (NP Screen) for nasopharyngeal carcinoma (NPC). Study Design. Correlation of the nasopharyngeal epithelial EBV-DNA levels and clinical findings by nasopharyngoscopy and final pathologic diagnosis of NPC with biopsy. Setting. Multicenter ENT/Oncology clinics in Hong Kong (Radiation Oncology Clinic at the Queen Elizabeth Hospital and Radiation Oncology Clinic and Head and Neck Clinic, Queen Mary Hospital, University of Hong Kong) and in Toronto, Canada (the Otolaryngology-Head and Neck Clinic at the Rouge Valley Health System and 2 large ENT practices in Toronto). Methods. A single-use trans-oral brush was used for rapid, nontraumatic nasopharyngeal (NP) epithelial cells DNA harvest in 600 Chinese patients, combined with a preservation and shipping kit for remote, real-time Q-PCR EBV DNA determinations. Results. All 600 patients had NP brushings using NP Screen in an ambulatory environment, and no adverse events or complications were recorded. A final 578 patients were included with sufficient amount of DNA for completion of the Q-PCR assay. Of these 578 patients, 94 were confirmed positive for NPC histologically. The study yielded a sensitivity of 98.9%, specificity of 99.3%, positive predictive value (PPV) of 96.9%, and negative predictive value (NPP) of 99.7% for NP Screen in detecting NPC. Endoscopy had a sensitivity of 94%, specificity 97.1%, PPV 85%, and NPP 98.9%. Conclusions. The trans-oral brushing system fulfills the characteristics of a noninvasive, sensitive, specific detection method suitable for routine, large-scale ambulatory NPC risk assessment for high-risk NPC populations. © American Academy of Otolaryngology-Head and Neck Surgery Foundation 2014.Link_to_subscribed_fulltex

Role of plasma EBV DNA levels in predicting recurrence of nasopharyngeal carcinoma in a western population

<p>Abstract</p> <p>Background</p> <p>Loco-regionally advanced nasopharyngeal carcinomas can be cured by the combination of chemotherapy and radiotherapy. In Eastern countries, plasma levels of viral Epstein-Barr deoxyribonucleic acid (DNA) are accurate in predicting recurrence, but few data are available in Western populations. The aim of this prospective study was to evaluate the relationship between viral Epstein-Barr DNA copy numbers in plasma and the response rate, progression-free survival and overall survival in a cohort of Western patients with stage IIb-IVb nasopharyngeal cancer.</p> <p>Methods</p> <p>We evaluated plasma samples from 36 consecutive patients treated with induction chemotherapy followed by chemoradiation. EBV copy numbers were determined after DNA extraction using real-time quantitative polymerase chain reaction. Survival curves were estimated using the Kaplan–Meier method.</p> <p>Results</p> <p>Circulating Epstein-Barr virus DNA levels were measured before treatment, at the end of concomitant chemo- and radiotherapy, and during the follow-up period. Pre-treatment levels significantly correlated with the initial stage and probability of relapse. Their increase was 100% specific and 71.3% sensitive in detecting loco-regional or metastatic recurrence (an overall accuracy of 94.4%). Three-year progression-free and overall survival were respectively 78.2% and 97.1%.</p> <p>Conclusions</p> <p>The results of this study confirm that patients from a Western country affected by loco-regionally advanced nasopharyngeal carcinoma have high plasma Epstein-Barr virus DNA levels at diagnosis. The monitoring of plasma levels is sensitive and highly specific in detecting disease recurrence and metastases.</p