M. Ronald Glaser, Ph.D, is a professor in the Department of Cancer Biology and Genetics and Director of the Institute for Behavioral Medicine Research at the College of Medicine, The Ohio State University, Columbus, Ohio. His main research interests are tumor virology/stress and immunology.
Dr. Glaser advocates that a possible subset of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) could be from viral reactivation following a stressful event. In 2012, Dr Glaser and his team announced work on a possible diagnostic biomarker for CFS that involves the detection of EBV-encoded DNA polymerase and EBV-encoded dUTPase, two proteins that are produced early in the process of Epstein-Barr virus reactivation.
Chronic Fatigue Syndrome Advisory Committee
2001 CDC Case Definition Workshop
In 2001, the CDC held a three-day workshop on Issues Related to the Chronic Fatigue Syndrome (CFS) Research Case Definition. Dr Glaser was one of the invited participants. During the workshop, Dr Glaser gave the presentation: "Immune Modulation by Latent Herpesvirus Proteins."
- 2012, Antibody to Epstein-Barr Virus Deoxyuridine Triphosphate Nucleotidohydrolase and Deoxyribonucleotide Polymerase in a Chronic Fatigue Syndrome Subset (FULL TEXT)
Abstract - "Background: A defined diagnostic panel differentiated patients who had been diagnosed with chronic fatigue syndrome (CFS), based upon Fukuda/Carruthers criteria. This diagnostic panel identified an Epstein-Barr virus (EBV) subset of patients (6), excluding for the first time other similar “clinical” conditions such as cytomegalovirus (CMV), human herpesvirus 6 (HHV6), babesiosis, ehrlichiosis, borreliosis, Mycoplasma pneumoniae, Chlamydia pneumoniae, and adult rheumatic fever, which may be mistakenly called CFS. CFS patients were treated with valacyclovir (14.3 mg/kg q6h) for ≥12 months. Each patient improved, based upon the Functional Activity Appraisal: Energy Index Score Healthcare Worker Assessment (EIPS), which is a validated (FSS-9), item scale with high degree of internal consistency measured by Cronbach's alpha. Methods: Antibody to EBV viral capsid antigen (VCA) IgM, EBV Diffuse Early Antigen EA(D), and neutralizing antibodies against EBV-encoded DNA polymerase and EBV-encoded dUTPase were assayed serially approximately every three months for 13–16 months from sera obtained from patients with CFS (6) and from sera obtained from twenty patients who had no history of CFS. Results: Antibodies to EBV EA(D) and neutralizing antibodies against the encoded-proteins EBV DNA polymerase and deoxyuridine triphosphate nucleotidohydrolase (dUTPase) were present in the EBV subset CFS patients. Of the sera samples obtained from patients with CFS 93.9% were positive for EA(D), while 31.6% of the control patients were positive for EBV EA(D). Serum samples were positive for neutralizing antibodies against the EBV-encoded dUTPase (23/52; 44.2%) and DNA polymerase (41/52; 78.8%) in EBV subset CFS patients, but negative in sera of controls. Conclusions: There is prolonged elevated antibody level against the encoded proteins EBV dUTPase and EBV DNA polymerase in a subset of CFS patients, suggesting that this antibody panel could be used to identify these patients, if these preliminary findings are corroborated by studies with a larger number of EBV subset CFS patients.
- 2005, Stress-associated changes in the steady state expression of latent Epstein-Barr Virus: Implications for Chronic Fatigue Syndrome and Cancer
Abstract - "Antibodies to several Epstein-Barr virus (EBV)-encoded enzymes are observed in patients with different EBV-associated diseases. The reason for these antibody patterns and the role these proteins might play in the pathophysiology of disease, separate from their role in virus replication, is unknown. In this series of studies, we found that purified EBV deoxyuridine triphosphate nucleotidohydrolase (dUTPase) can inhibit the replication of human peripheral blood mononuclear cells in vitro and upregulate the production of TNF-alpha, IL-1beta, IL-6, IL-8, and IL-10. It also enhanced the ability of natural killer cells to lyse target cells. The EBV dUTPase also significantly inhibited the replication of mitogen-stimulated lymphocytes and the synthesis of IFN-gamma by cells isolated from lymph nodes and spleens obtained from mice inoculated with the protein. It also produced sickness behaviors known to be induced by some of the cytokines that were studied in the in vitro experiments. These symptoms include an increase in body temperature, a decrease in body mass and in physical activity. The data provide a new perspective on how an early nonstructural EBV-encoded protein can cause immune dysregulation and produce clinical symptoms observed in patients with chronic fatigue syndrome (CFS) separate from its role in virus replication and may serve as a new approach to help identify one of the etiological agents for CFS. The data also provide additional insight into the pathophysiology of EBV infection, inflammation, and cancer."
- 1998, Stress-associated immune modulation: relevance to viral infections and chronic fatigue syndrome.
Abstract - "The frequent association of an active viral infection with the symptoms of CFS led researchers to hypothesize that chronic fatigue syndrome (CFS) is induced by a virus. Results of these studies indicated that despite clinical support for this hypothesis, there were no clear data linking viruses to CFS. In this overview, we will explore the interrelation of the immune, endocrine, and central nervous systems, and the possibility that stress and/or the reactivation/replication of a latent virus (such as Epstein Barr virus) could modulate the immune system to induce CFS. Relevant research conducted in the developing field of psychoneuroimmunology will be reviewed, with a particular focus on cytokine synthesis, natural killer (NK) cell activity, and T-lymphocyte function, as they relate to CFS."
- 1986, Stress depresses interferon production by leukocytes concomitant with a decrease in natural killer cell activity.
Abstract - "The quantity of interferon (IFN) produced by concanavalin A stimulated leukocytes obtained from 40 medical students during examinations was significantly lower when compared with IFN levels produced by peripheral blood leukocytes taken 6 wks earlier (baseline). Three assays measuring natural killer cells also showed significant decrements during examinations when compared with baseline samples. Data on the Brief Symptom Inventory documented the significantly greater distress associated with examinations in comparison with baseline samples. Implications for immunosuppressive disorders and stress-associated illnesses are discussed."
Talks & interviews
- 2013, "Dr. Ronald Glaser - Chronic Fatigue Syndrome and the Pathophysiology of EBV Infection " by Cort Johnson
- HHS.gov (2009), May 27 & 28, 2009 CFSAC Meeting (PDF) (Roster)
- HHS.gov (2010), October 12 & 13, 2010 CFSAC Meeting (PDF) (Roster)
- Lerner, AM; Ariza, ME; Williams, M; Jason, L; Beqaj, S; Fitzgerald, JT; Lemeshow, S; Glaser, R (2012), "Antibody to Epstein-Barr Virus Deoxyuridine Triphosphate Nucleotidohydrolase and Deoxyribonucleotide Polymerase in a Chronic Fatigue Syndrome Subset", PLoS ONE, 7 (11): e47891, doi:10.1371/journal.pone.0047891
- Glaser, R.; Padgett, D.A.; Litsky, M.L.; Baiocchi, R.A.; Yang, E.V.; Chen, M.; Yeh, P-E.; Klimas, N.G.; Marshall, G.D.; Whiteside, T.; Herberman, R.; Kiecolt-Glaser, J.K.; Williams, M.V. (2005), "Stress-associated changes in the steady state expression of latent Epstein-Barr Virus: Implications for Chronic Fatigue Syndrome and Cancer", Brain, Behavior and Immunity, 19 (2): 91-103, PMID 15664781, doi:10.1016/j.bbi.2004.09.001
- Glaser, R; Kiecolt-Glaser, JK (1998), "Stress-associated immune modulation: relevance to viral infections and chronic fatigue syndrome.", The American Journal of Medicine, 105(3A): 35S-42S, PMID 9790480
- Glaser, Ronald; Rice, John; Speicher, Carl E.; Stout, Julie C.; Kiecolt-Glaser, Janice K. (Oct 1986), "Stress depresses interferon production by leukocytes concomitant with a decrease in natural killer cell activity.", Behavioral Neuroscience, 100(5): 675-678, doi:10.1037/0735-7044.100.5.675