Susan M. Levine, MD, works with ME/CFS patients at her medical office in New York City, New York, United States. She is currently the chair of the Chronic Fatigue Syndrome Advisory Committee (CFSAC) which advises the U.S. Department of Health and Human Services. Her CFSAC term runs from 10 May 2014 to 10 May 2017. She was a voting member of the committee for the term 10 May 2010 to 10 May 2014.
- 2017, Fecal metagenomic profiles in subgroups of patients with myalgic encephalomyelitis/chronic fatigue syndrome (FULL TEXT)
Abstract - Background: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is characterized by unexplained persistent fatigue, commonly accompanied by cognitive dysfunction, sleeping disturbances, orthostatic intolerance, fever, lymphadenopathy, and irritable bowel syndrome (IBS). The extent to which the gastrointestinal microbiome and peripheral inflammation are associated with ME/CFS remains unclear. We pursued rigorous clinical characterization, fecal bacterial metagenomics, and plasma immune molecule analyses in 50 ME/CFS patients and 50 healthy controls frequency-matched for age, sex, race/ethnicity, geographic site, and season of sampling. Results: Topological analysis revealed associations between IBS co-morbidity, body mass index, fecal bacterial composition, and bacterial metabolic pathways but not plasma immune molecules. IBS co-morbidity was the strongest driving factor in the separation of topological networks based on bacterial profiles and metabolic pathways. Predictive selection models based on bacterial profiles supported findings from topological analyses indicating that ME/CFS subgroups, defined by IBS status, could be distinguished from control subjects with high predictive accuracy. Bacterial taxa predictive of ME/CFS patients with IBS were distinct from taxa associated with ME/CFS patients without IBS. Increased abundance of unclassified Alistipes and decreased Faecalibacterium emerged as the top biomarkers of ME/CFS with IBS; while increased unclassified Bacteroides abundance and decreased Bacteroides vulgatus were the top biomarkers of ME/CFS without IBS. Despite findings of differences in bacterial taxa and metabolic pathways defining ME/CFS subgroups, decreased metabolic pathways associated with unsaturated fatty acid biosynthesis and increased atrazine degradation pathways were independent of IBS co-morbidity. Increased vitamin B6 biosynthesis/salvage and pyrimidine ribonucleoside degradation were the top metabolic pathways in ME/CFS without IBS as well as in the total ME/CFS cohort. In ME/CFS subgroups, symptom severity measures including pain, fatigue, and reduced motivation were correlated with the abundance of distinct bacterial taxa and metabolic pathways. Conclusions: Independent of IBS, ME/CFS is associated with dysbiosis and distinct bacterial metabolic disturbances that may influence disease severity. However, our findings indicate that dysbiotic features that are uniquely ME/CFS-associated may be masked by disturbances arising from the high prevalence of IBS co-morbidity in ME/CFS. These insights may enable more accurate diagnosis and lead to insights that inform the development of specific therapeutic strategies in ME/CFS subgroups.
- 2016, Reduced diversity and altered composition of the gut microbiome in individuals with myalgic encephalomyelitis/chronic fatigue syndrome
- 2015, Findings from a clinical and laboratory database developed for discovery of pathogenic mechanisms in myalgic encephalomyelitis/chronic fatigue syndrome. Abstract
- 2015, Chronic fatigue syndrome and co-morbid and consequent conditions: evidence from a multi-site clinical epidemiology study. Abstract
- 2015, Distinct plasma immune signatures in ME/CFS are present early in the course of illness FULL TEXT
"Abstract: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is an unexplained incapacitating illness that may affect up to 4 million people in the United States alone. There are no validated laboratory tests for diagnosis or management despite global efforts to find biomarkers of disease. We considered the possibility that inability to identify such biomarkers reflected variations in diagnostic criteria and laboratory methods as well as the timing of sample collection during the course of the illness. Accordingly, we leveraged two large, multicenter cohort studies of ME/CFS to assess the relationship of immune signatures with diagnosis, illness duration, and other clinical variables. Controls were frequency-matched on key variables known to affect immune status, including season of sampling and geographic site, in addition to age and sex. We report here distinct alterations in plasma immune signatures early in the course of ME/CFS (n = 52) relative to healthy controls (n = 348) that are not present in subjects with longer duration of illness (n = 246). Analyses based on disease duration revealed that early ME/CFS cases had a prominent activation of both pro- and anti-inflammatory cytokines as well as dissociation of intercytokine regulatory networks. We found a stronger correlation of cytokine alterations with illness duration than with measures of illness severity, suggesting that the immunopathology of ME/CFS is not static. These findings have critical implications for discovery of interventional strategies and early diagnosis of ME/CFS."
- 2004, Immunologic Aspects of Chronic Fatigue Syndrome: Report on a Research Symposium Convened by The CFIDS Association of America and Co-Sponsored by the US Centers for Disease Control and Prevention and the National Institutes of Health
"Abstract - Chronic fatigue syndrome (CFS) is a serious health concern affecting over 800,000 Americans of all ages, races, socioeconomic groups and genders. The etiology and pathophysiology of CFS are unknown, yet studies have suggested an involvement of the immune system. A symposium was organized in October 2001 to explore the possibility of an association between immune dysfunction and CFS, with special emphasis on the interactions between immune dysfunction and other abnormalities noted in the neuroendocrine and autonomic nervous systems of individuals with CFS. This paper represents the consensus of the panel of experts who participated in this meeting. Data suggest that persons with CFS manifest changes in immune responses that fall outside normative ranges, but current research does not provide definitive evidence on whether these immune abnormalities are a cause or result of the illness. It has become clear that CFS cannot be understood based on single measurements of immune, endocrine, cardiovascular, or autonomic nervous system dysfunction. This panel encourages a new emphasis on multidisciplinary research into CFS."
- 2001, Prevalence of IgM and IgG Antibody to HHV-6 and HHV-8 and Results of Plasma PCR to HHV-6 and HHV-7 in a Group of CFS Patients and Healthy Donors
"Abstract - Human herpes virus-6 (HHV-6) is a beta herpes virus that was first described in 1986 and which occurs in the form of at least two variants, A and B. Healthy donors in the general population are carriers for mainly the B variant, in whom 90% harbor the DNA of this type in their peripheral blood mononuclear cells (PBMNC). A higher prevalence of this virus has been detected by testing of plasma and PBMNCs by IFA, ELISA and by the nested PCR technique, in addition to direct culture for HHV-6 in certain groups of immunesuppressed patients such as those with multiple sclerosis and HIV. It has also been isolated to a greater degree using these techniques from patients who meet the case definition for the chronic fatigue syndrome (CFS). We determined IgG and IgM antibody titers to HHV-6; IgG to HHV-8 and performed PCR testing for HHV-6 on the plasma of 46 patients with CFS and on 7 healthy donors (HD). We also performed PCR testing for HHV-7 on 15 CFS patients and on 4 HD(s). We found a higher prevalence of IgM antibody in CFS patients 23/36 (50%) versus 2/7 (28.5%) of HD. The prevalence of IgG antibody to HHV-8 was zero among both CFS patients and HD. Three out of forty six (6.5%) of CFS patients demonstrated a positive plasma by PCR to HHV-6 compared to zero out of 7 HD(s). Finally, four out of fifteen (26.7%) CFS patients and zero out of four HD(s) demonstrated a positive plasma PCR to HHV-7. Our results were influenced by the presence of various subpopulations of CFS patients among our study group, in addition to our reliance on the results of single specimens as opposed to a series of multiple samples over time in individual subjects, and by methodological variability (decreasing our yield because of diminished viral shedding in cell-free samples or increasing it compared to other research groups who failed to co-culture the PBMNCs with indicator cells, e.g., PHA-stimulated human cord blood cells or human fibroblasts for short-term culture [15 day]). Nevertheless, it is clear that the study of plasma and perhaps other tissue samples, such as cerebral spinal fluid and gastric mucosa from patients with CFS in better defined subgroups, as well as defined population of HDs using a variety of methodological techniques will increase our knowledge about the role of HHV-6 in this complex disorder."
- 2001, Prevalence in the Cerebrospinal Fluid of the Following Infectious Agents in a Cohort of 12 CFS Subjects: Human Herpes Virus-6 and 8; Chlamydia Species; Mycoplasma Species; EBV; CMV; and Coxsackievirus
"Abstract - Over the last decade a wide variety of infectious agents has been associated with the chronic fatigue syndrome (CFS) as potential etiologies for this disorder by researchers from all over the world. Many of these agents are neurotrophic and have been linked previously to other diseases involving the central nervous system (CNS). Human herpes virus-6 (HHV-6), especially the B variant, has been found in autopsy specimens of patients who suffered from multiple sclerosis. Because patients with CFS manifest a wide range of symptoms involving the CNS as shown by abnormalities on brain MRIs, SPECT scans of the brain and results of tilt table testing we sought to determine the prevalence of HHV-6, HHV-8, Epstein-Barr virus (EBV), cytomegalovirus (CMV), Mycoplasma species, Chlamydia species, and Coxsackie virus in the spinal fluid of a group of 12 patients with CFS. Although we intended to search mainly for evidence of actively replicating HHV-6, a virus that has been associated by several researchers with this disorder, we found evidence of HHV-8, Chlamydia species, CMV and Coxsackie virus in 6/12 samples. Attempts were made to correlate the clinical presentations of each of these patients, especially the neurological exams and results of objective testing of the CNS, with the particular infectious agent isolated. It was also surprising to obtain such a relatively high yield of infectious agents on cell free specimens of spinal fluid that had not been centrifuged. Future research in spinal fluid analysis, in addition to testing tissue samples by polymerase chain reaction (PCR) and other direct viral isolation techniques will be important in characterizing subpopulations of CFS patients, especially those with involvement of the CNS."
- 1999, Borna Disease Virus Proteins in Patients with CFS
"Summary - Bornavirus is a member of a newly recognized virus family, Bornaviridae, and is neurotropic for a wide range of animal species, including birds, rodents, horses, and humans. Although little is known about its mode of transmission and it has not been clearly linked to any human disease, an association between borna viruses and neuro-psychiatric disorders has been suggested. Several researchers have also isolated this organism from patients who meet the clinical criteria for the Chronic Fatigue Syndrome (CFS). However, due to non-standardization of assay protocols, lack of a large study population and the possibility of contamination in certain laboratory settings, the true prevalence of Bornaviral proteins and their possible role in the pathogenesis of at least a subgroup of CFS patients remains undefined. We analyzed the serum immune reactivity to Borna Disease Virus (BDV) in 77 CFS patients and in 33 healthy normal controls using an ELISA based assay of 3 different recombinant BDV proteins. Of the 6 samples that displayed immunoreactivity to 2 or more BDV proteins, 5 were from patients (83.3%). Two samples, both from CFS patients, displayed immunoreactivity to 3 BDV proteins."
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Talks & interviews
- 20 Apr 2017, Solve ME/CFS Initiative Webinar - "A 360° Approach to Solve ME/CFS"
- 17 Mar 2016, Solve ME/CFS Initiative Webinar - "The Future of ME/CFS"
Open Letter to The Lancet
Two open letters to the editor of The Lancet urged the editor to commission a fully independent review of the PACE trial, which the journal had published in 2011. In 2016, Dr. Levine, along with 41 colleagues in the ME/CFS field, signed the second letter.
- 10 February 2016, An open letter to The Lancet, again - Virology blog
- Nagy-Szakal, Dorottya; Williams, Brent L.; Mishra, Nischay; Che, Xiaoyu; Lee, Bohyun; Bateman, Lucinda; Klimas, Nancy G.; Komaroff, Anthony L.; Levine, Susan; Montoya, Jose G.; Peterson, Daniel L.; Ramanan, Devi; Jain, Komal; Eddy, Meredith L.; Hornig, Mady; Lipkin, W. Ian (2017), "Fecal metagenomic profiles in subgroups of patients with myalgic encephalomyelitis/chronic fatigue syndrome", Microbiome, 5 (44), doi:10.1186/s40168-017-0261-y
- Giloteaux, L.; Goodrich, J. K.; Walters, W. A.; Levine, S. M.; Ley, R.; Hanson, M. R. (2016), "Reduced diversity and altered composition of the gut microbiome in individuals with myalgic encephalomyelitis/chronic fatigue syndrome.", Microbiome, 4 (1): 30, PMID 27338587, doi:10.1186/s40168-016-0171-4
- Klimas, N.G.; Ironson, G.; Carter, A.; Balbin, E.; Bateman, L.; Felsenstein, D.; Levine, S.; Peterson, D.; Chiu, K.; Allen, A.; Cunningham, K.; Gottschalk, C.G.; Fletcher, M; Hornig, M.; Canning, C.; Komaroff, A.L. (2015), "Findings from a clinical and laboratory database developed for discovery of pathogenic mechanisms in myalgic encephalomyelitis/chronic fatigue syndrome", Fatigue: Biomedicine, Health & Behavior, 3 (2): 75-96, doi:10.1080/21641846.2015.1023652
- Bateman, L.; Darakjy, S.; Klimas, N.; Peterson, D.; Levine, S.M.; Allen, A.; Carlson, S.A.; Balbin, E.G.; Gottschalk, G.; March, D. (2015), "Chronic fatigue syndrome and co-morbid and consequent conditions: evidence from a multi-site clinical epidemiology study", Fatigue: Biomedicine, Health & Behavior, 3 (1): 1-15, doi:10.1080/21641846.2014.978109
- Hornig, M; Montoya, JG; Klimas, NG; Levine, SM; Felsenstein, D; Bateman, L; Peterson, DL; Gottschalk, CG; Schultz, AF; Che, X; Eddy, ML; Komaroff, AL; Lipkin, WI (2015), "Distinct plasma immune signatures in ME/CFS are present early in the course of illness", Science Advances, 1 (1), doi:10.1126/sciadv.1400121
- Gerrity, T.R.; Papanicolaou, D.A.; Amsterdam, J.D.; Bingham, S.; Grossman, A.; Hedrick, T.; Herberman, R.B.; Krueger, G.; Levine, S.; Mohagheghpour, N.; Moore, R.C.; Oleske, J.M.; Snell, C.R.; CFIDS Association of America (2004), "Immunologic Aspects of Chronic Fatigue Syndrome: Report on a Research Symposium Convened by The CFIDS Association of America and Co-Sponsored by the US Centers for Disease Control and Prevention and the National Institutes of Health", Neuroimmunomodulation, 11: 351–357, PMID 15467349, doi:10.1159/000080144
- Susan Levine, Helen Eastman & Dharam V. Ablashi. (2001). Prevalence of IgM and IgG Antibody to HHV-6 and HHV-8 and Results of Plasma PCR to HHV-6 and HHV-7 in a Group of CFS Patients and Healthy Donors. Journal of Chronic Fatigue Syndrome, Vol. 9, Iss. 1-2, pp. 31-40. http://dx.doi.org/10.1300/J092v09n01_04
- Susan Levine. (2001). Prevalence in the Cerebrospinal Fluid of the Following Infectious Agents in a Cohort of 12 CFS Subjects: Human Herpes Virus-6 and 8; Chlamydia Species; Mycoplasma Species; EBV; CMV; and Coxsackievirus. Journal of Chronic Fatigue Syndrome, Vol. 9, Iss. 1-2, pp. 41-51. http://dx.doi.org/10.1300/J092v09n01_05
- Susan Levine. (1999). Borna Disease Virus Proteins in Patients with CFS. Journal of Chronic Fatigue Syndrome, Vol. 5, Iss. 3-4, pp. 199-206. http://dx.doi.org/10.1300/J092v05n03_17