Development and implementation of natural killer cell simultaneous ADCC and direct killing assay

Assays to quantify natural killer (NK) cell killing efficacy have traditionally focused on assessing either direct killing or antibody dependent cell-mediated cytotoxicity (ADCC) independently. Due to the probability that immunotherapeutic interventions affect NK cell-mediated direct killing and NK cell-mediated ADCC differently, we developed an assay with the capacity to measure NK cell-mediated direct killing and ADCC simultaneously with cells from the same human donor. Specifically, this design allows for a single NK cell population to be split into several experimental conditions (e.g., direct killing, ADCC), thus controlling for potential confounders associated with human-to-human variation when assessing immunotherapy impacts. Our Natural Killer cell Simultaneous ADCC and Direct Killing Assay (NK-SADKA) allows researchers to reproducibly quantify both direct killing and ADCC by human NK cells. Furthermore, this optimized experimental design allows for concurrent analysis of the NK cells via flow cytometric immunophenotyping of NK cell populations which will facilitate the identification of relationships between NK cell phenotype and the subsequent killing potential. This assay will be valuable for assessing the broader impact(s) of immunotherapy strategies on both modes of NK cell killing

Long-term reduction of atrial tachyarrhythmia recurrences in patients paced for bradycardia-tachycardia syndrome

Background: Atrial tachyarrhythmias (AT) are considered progressive diseases. Several rhythm control therapies for treatment of AT have been proposed. Objectives: The Italian AT500 Registry was designed to prospectively study long-term AT evolution in patients paced for the brady-tachy form of sinus node disease (BT-SND). Methods: Three hundred forty-six BT-SND patients received an antitachycardia dual-chamber pace-maker and were followed-up for a minimum of 12 months (median 19 months). Prevention and antitachycardia pacing (ATP) features were enabled in all patients. Results: During the observation period, 224 (65%) patients were treated by antiarrhythmic drugs and 45 (13%) patients were cardioverted. Five patients suffered a stroke, 4 transient ischemic attack, 22 permanent AT, and 98 AT recurrences longer than 7 days. AT mean cycle length changed from 246 to 2 70 ms, and the percentage of patients with AT-related hospitalizations significantly decreased with an annual 28% relative reduction. AT burden and the percentage of patients with AT recurrences longer than 2 days remained constant with time in the overall population but decreased significantly in the subgroup of patients who did not develop permanent AT. High ATP efficacy was associated with an increasingly higher prevention of AT recurrences longer than 2 days. Conclusion: In a long-term observation of BT-SND patients, AT-related hospitalizations decreased significantly and mean AT cycle length increased significantly. The data suggest that rhythm control therapies induce inversion of AT progression. © 2005 Heart Rhythm Society. All rights reserved