Nancy Klimas

Nancy G. Klimas, MD, is an American researcher and physician who is the Director at the Institute for Neuro Immune Medicine at Nova Southeastern University in Miami and Ft. Lauderdale, Florida. She is, also: Director of Clinical Immunology Research, Miami VAMC; Professor of Medicine, Department of Clinical Immunology, College of Osteopathic Medicine, Nova Southeastern University; Chair, Department of Clinical Immunology, College of Osteopathic Medicine, Nova Southeastern University; and Professor Emerita, University of Miami, School of Medicine.

Awards

• 2014, Rudy Perpich Senior Lectureship Award, presented to a distinguished CFS/FMS scientist, physician or healthcare worker awarded by IACFS/ME
• 2011, Nelson Gantz Outstanding Clinician Award awarded to a physician who emulates Nelson Gantz's clinical acumen, his passion for medicine, and his empathy for persons with CFS/FM awarded by IACFS/ME

2015 Institute of Medicine report

Dr. Klimas was one of the ME/CFS experts on the "Committee on the Diagnostic Criteria for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome" that was convened to produce the 2015 Institute of Medicine report.

Case definition authorships

Klimas is one of the authors of the 2011 case definition, International Consensus Criteria, as well as, one of the authors of the 2003 Canadian Consensus Criteria for ME/CFS, published as Myalgic Encephalomyelitis/Chronic Fatigue Syndrome:Clinical Working Case Definition,Diagnostic and Treatment Protocols

Chronic Fatigue Syndrome Advisory Committee

Dr. Klimas served as a voting member of the Chronic Fatigue Syndrome Advisory Committee for the U.S. Department of Health and Human Services from April 1, 2007 to April 1, 2011.

International Association for Chronic Fatigue Syndrome/Myalgic Encephalomyelitis

Dr. Klimas served as past President of the Board of Directors of the International Association for Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (IACFS/ME) from 2004-2009. She has been awarded the IACFS/ME Nelson Gantz Outstanding Clinician Award (in 2011) and the IACFS/ME Rudy Perpich Senior Lectureship Award (in 2014).

Notable studies

• 2017, Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Gulf War Illness patients exhibit increased humoral responses to the Herpesviruses-encoded dUTPase: Implications in disease pathophysiology: Herpesviruses in ME/CFS and Gulf War Illness

  Abstract - Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Gulf War Illness (GWI) are debilitating diseases with overlapping symptomology and there are currently no validated tests for definitive diagnosis of either syndrome. While there is evidence supporting the premise that some herpesviruses may act as possible triggers of ME/CFS, the involvement of herpesviruses in the pathophysiology of GWI has not been studied in spite of a higher prevalence of ME/CFS in these patients. We have previously demonstrated that the deoxyuridine triphosphate nucleotidohydrolases (dUTPase) encoded by Epstein-Barr virus (EBV), human herpesvirus-6 (HHV-6), and varicella-zoster virus (VZV) possess novel functions in innate and adaptive immunity. The results of this study demonstrate that a significant percentage of patients with ME/CFS (30.91-52.7%) and GWI (29.34%) are simultaneously producing antibodies against multiple human herpesviruses-encoded dUTPases and/or the human dUTPase when compared to controls (17.21%). GWI patients exhibited significantly higher levels of antibodies to the HHV-6 and human dUTPases than controls (p = 0.0053 and p = 0.0036, respectively), while the ME/CFS cohort had higher anti-EBV-dUTPase antibodies than in both GWI patients (p = 0.0008) and controls (p < 0.0001) as well as significantly higher anti-human dUTPase antibodies than in controls (p = 0.0241). These results suggest that screening of patients' sera for the presence of various combinations of anti-dUTPase antibodies could be used as potential biomarkers to help identify/distinguish patients with these syndromes and better direct treatment.

• 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.

• 2017, Multi-Site Clinical Assessment of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (MCAM): Design and Implementation of a Prospective/Retrospective Rolling Cohort Study

  Abstract - In the Multi-Site Clinical Assessment of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (MCAM), we relied on expert clinician diagnoses to enroll patients from 7 specialty clinics in the United States in order to perform a systematic collection of data on measures of myalgic encephalomyelitis (ME)/chronic fatigue syndrome (CFS). Healthy persons and those with other illnesses that share some features with ME/CFS were enrolled in comparison groups. The major objectives were to: 1) use standardized questionnaires to measure illness domains of ME/CFS and to evaluate patient heterogeneity overall and between clinics; 2) describe the course of illness, identify the measures that best correlate with meaningful clinical differences, and assess the performances of questionnaires as patient/person-reported outcome measures; 3) describe prescribed medications, orders for laboratory and other tests, and management tools used by expert clinicians to care for persons with ME/CFS; 4) collect biospecimens for future hypothesis testing and for evaluation of morning cortisol profiles; and 5) identify measures that best distinguish persons with ME/CFS from those in the comparison groups and detect subgroups of persons with ME/CFS who may have different underlying causes. Enrollment began in 2012 and is planned to continue in multiple stages through 2017. We present the MCAM methods in detail, along with an initial description of the 471 patients with ME/CFS who were enrolled in stage 1."

• 2017, Telephone-administered versus live group cognitive behavioral stress management for adults with CFS

  Abstract - Objective: Chronic fatigue syndrome (CFS) symptoms have been shown to be exacerbated by stress and ameliorated by group-based psychosocial interventions such as cognitive behavioral stress management (CBSM). Still, patients may have difficulty attending face-to-face groups. This study compared the effects of a telephone-delivered (T-CBSM) vs a live (L-CBSM) group on perceived stress and symptomology in adults with CFS. Methods: Intervention data from 100 patients with CFS (mean age 50years; 90% female) participating in T-CBSM (N=56) or L-CBSM (N=44) in previously conducted randomized clinical trials were obtained. Perceived Stress Scale (PSS) and the Centers for Disease Control and Prevention symptom checklist scores were compared with repeated measures analyses of variance in adjusted and unadjusted analyses. Results: Participants across groups showed no differences in most demographic and illness variables at study entry and had similar session attendance. Both conditions showed significant reductions in PSS scores, with L-CBSM showing a large effect (partial ε2=0.16) and T-CBSM a medium effect (partial ε2=0.095). For CFS symptom frequency and severity scores, L-CBSM reported large effect size improvements (partial ε2=0.19-0.23), while T-CBSM showed no significant changes over time. Conclusions: Two different formats for delivering group-based CBSM-live and telephone-showed reductions in perceived stress among patients with CFS. However, only the live format was associated with physical symptom improvements, with specific effects on post-exertional malaise, chills, fever, and restful sleep. The added value of the live group format is discussed, along with implications for future technology-facilitated group interventions in this population.

• 2016, Poor sleep quality is associated with greater circulating pro-inflammatory cytokines and severity and frequency of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) symptoms in women

  Abstract: Objective - Poor sleep quality has been linked to inflammatory processes and worse disease outcomes in the context of many chronic illnesses, but less is known in conditions such as chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME). This study examines the relationships between sleep quality, pro-inflammatory cytokines, and CFS/ME symptoms. Methods - Sixty women diagnosed with CFS/ME were assessed using the Pittsburgh Sleep Quality Index (PSQI), Fatigue Symptom Inventory (FSI) and Center for Disease Control and Prevention (CDC)-based CFS/ME symptom questionnaires. Circulating plasma pro-inflammatory cytokine levels were measured by ELISA. Multiple regression analyses examined associations between sleep, cytokines and symptoms, controlling for age, education, and body mass index. Results - Poor sleep quality (PSQI global score) was associated with greater pro-inflammatory cytokine levels: interleukin-1β (IL-1β) (β = 0.258, p = 0.043), IL-6 (β = 0.281, p = 0.033), and tumor necrosis factor-alpha (TNF-α) (β = 0.263, p = 0.044). Worse sleep quality related to greater fatigue severity (β = 0.395, p = 0.003) and fatigue-related interference with daily activities (β = 0.464, p < 0.001), and more severe and frequent CDC-defined core CFS/ME symptoms (β = 0.499, p < 0.001, and β = 0.556, p < 0.001, respectively). Conclusions - Results underscore the importance of managing sleep-related difficulties in this patient population. Further research is needed to identify the etiology of sleep disruptions in CFS/ME and mechanistic factors linking sleep quality to symptom severity and inflammatory processes."

• 2016, Illness progression in chronic fatigue syndrome: a shifting immune baseline
• 2016, Tracking post-infectious fatigue in clinic using routine Lab tests.

  Abstract: Background: While biomarkers for chronic fatigue syndrome (CFS) are beginning to emerge they typically require a highly specialized clinical laboratory. We hypothesized that subsets of commonly measured laboratory markers used in combination could support the diagnosis of post-infectious CFS (PI-CFS) in adolescents following infectious mononucleosis (IM) and help determine who might develop persistence of symptoms. Methods: Routine clinical laboratory markers were collected prospectively in 301 mono-spot positive adolescents, 4 % of whom developed CFS (n = 13). At 6, 12, and 24 months post-diagnosis with IM, 59 standard tests were performed including metabolic profiling, liver enzyme panel, hormone profiles, complete blood count (CBC), differential white blood count (WBC), salivary cortisol, and urinalysis....Results: Lower ACTH levels at 6 months post-IM diagnosis were highly predictive of CFS (AUC p = 0.02). ACTH levels in CFS overlapped with healthy controls at 12 months, but again showed a trend towards a deficiency at 24 months. Conversely, estradiol levels depart significantly from normal at 12 months only to recover at 24 months (AUC p = 0.02). Finally, relative neutrophil count showed a significant departure from normal at 24 months in CFS (AUC p = 0.01). Expression of these markers evolved differently over time between groups. Conclusions: Preliminary results suggest that serial assessment of stress and sex hormones as well as the relative proportion of innate immune cells measured using standard clinical laboratory tests may support the diagnosis of PI-CFS in adolescents with IM.

• 2016, Dr. Nancy Klimas, Dr. Irma Rey and several other researchers studied patients who developed gastroparesis following a viral history of flu-like symptoms or gastroenteritis. Nine at of the eleven patients with Idiopathic Gastroparesis studied (82 %) had active enterovirus infection on gastric biopsies. The study conclusion was that "antiviral and/or immune therapies against enterovirus seem to be favorable, as most of our patients had resolution of their gastroparesis symptoms after treatment. This is the first study to identify enterovirus as a possible infectious etiology of idiopathic gastroparesis.

Earlier studies

• Studies by Nancy Klimas for 2014 & 2015

• Studies by Nancy Klimas for 2012 & 2013

• Studies by Nancy Klimas for 2010 & 2011

• Studies by Nancy Klimas for 2008 & 2009

• Studies by Nancy Klimas for 2006 & 2007

• Studies by Nancy Klimas for 2004 & 2005

• Studies by Nancy Klimas for 2000 - 2003

• Studies by Nancy Klimas up to 2000

Interviews & talks

There are many videos on YouTube of Nancy Klimas speaking about her work.

• 2 Jun 2017, Speaker at the 12th Invest in ME International ME Conference on "Genetic Signature Study" - DVD available
• Dec 2, 2016, Episode 84 of ME/CFS Alert - Dr Nancy Klimas on ME/CFS Research, Treatment
• Dec 1, 2016 NBCDFW video interview and transcription
• 2014 ME/CFS Diagnosis and Name with Dr. Nancy Klimas
• 2014 ME/CFS Treatment Options Part 1 with Dr. Nancy Klimas
• 2014 ME/CFS Treatment Options Part 2 with Dr. Nancy Klimas
• ME/CFS and Exercise: VO2 Max Testing with Nancy Klimas M.D. PREVIEW
• 2011 ME/CFS Management A Pathogenesis Based Approach (sponsored by ANZMES)
• From Bedside to Bench and Back Again: Untangling the Mystery of Gulf War Illness and Chronic Fatigue Syndrome

Quotations

• "They experience a level of disability equal to that of patients with late-stage AIDS and patients undergoing chemotherapy"

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. Klimas, 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

Online presence

• PubMed - Nancy Klimas
• Nova Southeasterm University - Nancy Klimas

See also

• Dr. Gordon Broderick
• Dr. Mary Ann Fletcher
• Dr. Irma Rey
• Dr. Maria Vera
• Institute for Neuro Immune Medicine

National Academy of Medicine (NAM) - An American non-profit, non-governmental organization which provides expert advice to governmental agencies on issues relating to biomedical science, medicine and health. Formerly known as the Institute of Medicine (IOM).

myalgic encephalomyelitis (M.E.) - A disease often marked by neurological symptoms, but fatigue is sometimes a symptom as well. Some diagnostic criteria distinguish it from chronic fatigue syndrome, while other diagnostic criteria consider it to be a synonym for chronic fatigue syndrome. A defining characteristic of ME is post-exertional malaise (PEM), or post-exertional neuroimmune exhaustion (PENE), which is a notable exacerbation of symptoms brought on by small exertions. PEM can last for days or weeks. Symptoms can include cognitive impairments, muscle pain (myalgia), trouble remaining upright (orthostatic intolerance), sleep abnormalities, and gastro-intestinal impairments, among others. An estimated 25% of those suffering from ME are housebound or bedbound. The World Health Organization (WHO) classifies ME as a neurological disease.

antibodies Antibody/immunoglobulin refers to any of a large number of specific proteins produced by B cells that act against an antigen in an immune response.

antibodies Antibody/immunoglobulin refers to any of a large number of specific proteins produced by B cells that act against an antigen in an immune response.

serum The clear yellowish fluid that remains from blood plasma after clotting factors have been removed by clot formation. (Blood plasma is simply blood that has had its blood cells removed.)

myalgic encephalomyelitis (M.E.) - A disease often marked by neurological symptoms, but fatigue is sometimes a symptom as well. Some diagnostic criteria distinguish it from chronic fatigue syndrome, while other diagnostic criteria consider it to be a synonym for chronic fatigue syndrome. A defining characteristic of ME is post-exertional malaise (PEM), or post-exertional neuroimmune exhaustion (PENE), which is a notable exacerbation of symptoms brought on by small exertions. PEM can last for days or weeks. Symptoms can include cognitive impairments, muscle pain (myalgia), trouble remaining upright (orthostatic intolerance), sleep abnormalities, and gastro-intestinal impairments, among others. An estimated 25% of those suffering from ME are housebound or bedbound. The World Health Organization (WHO) classifies ME as a neurological disease.

cognition Thought processes, including attention, reasoning, and memory.

microbiome The full collection of microscopic organisms (especially bacteria and fungi) which are present in a particular environment, particularly inside the human body.

accuracy The "closeness of an observation to the true clinical state". With respect to diagnostic tests, "accuracy" means how specific and sensitive the test is.

stress Stress can by either physical or psychological, or both. Stress is either 1) a state of emotional or psychological strain or 2) the physical stress (pressure or tension) that a physical object such the human body is placed under, e.g., a stress test is a medical test that monitors the cardiovascular system during strenuous exercise.

Centers for Disease Control and Prevention (CDC) - The Centers for Disease Control and Prevention is a U.S. government agency dedicated to epidemiology and public health. It operates under the auspices of the Department of Health and Human Services.

post-exertional malaise (PEM) - A notable exacerbation of symptoms brought on by small physical or cognitive exertions. PEM may be referred to as a "crash" or "collapse" and can last for days or weeks. Symptoms can include cognitive impairments, muscle pain, trouble remaining upright (orthostatic intolerance), sleep abnormalities, and gastro-intestinal impairments, and others.

chronic illness any long-term illness, regardless of the severity. Chronic illnesses are typically incurable, requiring long-term management.

cytokine any class of immunoregulatory proteins secreted by cells, especially immune cells. Cytokines are small proteins important in cell signaling that modulate the immune system. (Learn more: me-pedia.org)

Centers for Disease Control and Prevention (CDC) - The Centers for Disease Control and Prevention is a U.S. government agency dedicated to epidemiology and public health. It operates under the auspices of the Department of Health and Human Services.

Centers for Disease Control and Prevention (CDC) - The Centers for Disease Control and Prevention is a U.S. government agency dedicated to epidemiology and public health. It operates under the auspices of the Department of Health and Human Services.

cytokine any class of immunoregulatory proteins secreted by cells, especially immune cells. Cytokines are small proteins important in cell signaling that modulate the immune system. (Learn more: me-pedia.org)

β β / Β. Greek letter beta (a symbol used in science), equivalent to "b".

α α / Α. Greek letter alpha or alfa (a symbol used in science), equivalent to "a".

etiology The cause of origin, especially of a disease.

enzyme a substance produced by a living organism which acts as a catalyst to bring about a specific biochemical reaction.

enterovirus A genus of RNA viruses which typically enter the body through the respiratory or gastrointestinal systems and sometimes spread to the central nervous system or other parts of the body, causing neurological, cardiac, and other damage. Since the first reports of myalgic encephalomyelitis (ME), enteroviruses have been suspected as a cause of ME. Enteroviruses have also been implicated as the cause of Type I diabetes, congestive heart failure, and other conditions. Enteroviruses include poliovirus, coxsackieviruses, and many others. New enteroviruses and new strains of existing enteroviruses are continuously being discovered. (Learn more: viralzone.expasy.org)

microbiome The full collection of microscopic organisms (especially bacteria and fungi) which are present in a particular environment, particularly inside the human body.

enterovirus A genus of RNA viruses which typically enter the body through the respiratory or gastrointestinal systems and sometimes spread to the central nervous system or other parts of the body, causing neurological, cardiac, and other damage. Since the first reports of myalgic encephalomyelitis (ME), enteroviruses have been suspected as a cause of ME. Enteroviruses have also been implicated as the cause of Type I diabetes, congestive heart failure, and other conditions. Enteroviruses include poliovirus, coxsackieviruses, and many others. New enteroviruses and new strains of existing enteroviruses are continuously being discovered. (Learn more: viralzone.expasy.org)

etiology The cause of origin, especially of a disease.