Presentation format:Oral or Poster presentation
Title:Evaluation of FcR CD16A of NK cells in patients with Chronic Fatigue Syndrome
Authors:Isabel Barao1, Ph.D.,Stephen Anderson2, Ph.D., Daniel Peterson3, M.D., Dorothy Hudig1, Ph.D
Institutional Affiliations:1University of Nevada, Reno, School of Medicine, Reno, NV, USA;2National Institutes of Health, National Cancer Institute, Frederick, MD, USA; 3Sierra Internal Medicine, Incline Village, USA
Key Words:CD16A, ADCC, NK cells, CFS
Objective:Natural killer (NK) cytotoxicity of chronic fatigue syndrome (CFS) patients is decreased, as reported bymultiple laboratories. This observation led us to ask if the patientsâ€™ NK cells also lack antibody-dependent cell mediatedcytotoxicity (ADCC). NK cells use the IgGFcR CD16A to mediate ADCC. We postulate that there are low levels of CD16A in the NK cells of CFS patients that may reduce their ADCC activity and contribute to their susceptibility to viral infections. Setting: To assess potentialADCC effectors, we examined the peripheral blood NK cells of 11 CFS patients from a Lake Tahoe cohort that met the Fukudastandards for CFS and had low SF-36fatigue scores. FourCFS patients represent two families with CFS proband and CFS child pairs. Healthy controls were age- and gender-matched. Methods:We stained peripheralblood cells with monoclonal antibodies for CD16A (clone 3G8), for CD3 to discriminate NK cells from CD3pos T cells, for CD56 a marker of NK cells, and for perforin the critical pore-forming molecule that kills cells during ADCC, and then assessed the cells by flowcytometry using LSR II. Results:We found that the percentages of NK cells expressing CD16A were slightly lower for CFS patients, 86.0+/-11.5% vs. controls 93.0+/-6.6% (P=0.08). The median fluorescent indices (MFIs), that indicate the amount of a protein per NK cell, were also lower for the CD16A of CFS patients,i.e.72% of the control levels, 9342+/-3233 vs. control 12929+/-4425, though not statistically significant (P<0.17).Of note, within the two CFS families, the CFS patientshad remarkable low CD16A levels, indicating that low CD16A in CFS may be affected as a dominant genetic trait. Intracellular staining for perforin in the CD16Apos cells was similar for patients and controls. Interpretation: The data, while consistent with our hypothesis, strongly indicate that a larger sampling of CFS patients vs. controls is required to determine if there are significant differences in CD16A that can later be correlated with in vitro ADCC activity. In addition, a genetic bias in AA158 F over V allelic variants of CD16A might add to impairment, since the F allele confers reduced ADCC.