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.

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

Likewise, she was one of the experts on the "Committee on the Diagnostic Criteria for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome" that was convened for the 2015 Institute of Medicine report.

Klimas served as past President of the Board of Directors of the International Association for Chronic Fatigue Syndrome/Myalgic Encephalomyelitis from 2004-2009. She was a voting member of the Health and Human Services's CFSAC committee from 04/01/07-04/01/11.

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

Notable studies

 * 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.
 * 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.'"
 * 2014, Stress management skills, cortisol awakening response, and post-exertional malaise in Chronic Fatigue Syndrome
 * 2012, Minimum data elements for research reports on CFS. Full text "Abstract: 'Chronic fatigue syndrome (CFS) is a debilitating condition that has received increasing attention from researchers in the past decade. However, it has become difficult to compare data collected in different laboratories due to the variability in basic information regarding descriptions of sampling methods, patient characteristics, and clinical assessments. The issue of variability in CFS research was recently highlighted at the NIH's 2011 State of the Knowledge of CFS meeting prompting researchers to consider the critical information that should be included in CFS research reports. To address this problem, we present our consensus on the minimum data elements that should be included in all CFS research reports, along with additional elements that are currently being evaluated in specific research studies that show promise as important patient descriptors for subgrouping of CFS. These recommendations are intended to improve the consistency of reported methods and the interpretability of reported results. Adherence to minimum standards and increased reporting consistency will allow for better comparisons among published CFS articles, provide guidance for future research and foster the generation of knowledge that can directly benefit the patient.'"
 * 2012, Biomarkers for chronic fatigue.
 * 2012, Cytokine expression profiles of immune imbalance in post-mononucleosis chronic fatigue
 * 2010, Plasma neuropeptide Y: a biomarker for symptom severity in chronic fatigue syndrome
 * 2010, A Formal Analysis of Cytokine Networks in Chronic Fatigue Syndrome Full Text
 * 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.'"
 * 2003, Identification of ambiguities in the 1994 chronic fatigue syndrome research case definition and recommendations for resolution
 * 2003, Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Clinical Working Case Definition, Diagnostic and Treatment Protocols"'Abstract - Recent years have brought growing recognition of the need for clinical criteria for myalgic encephalomyelitis (ME), which is also called chronic fatigue syndrome (CFS). An Expert Subcommittee of Health Canada established the Terms of Reference, and selected an Expert Medical Consensus Panel representing treating physicians, teaching faculty and researchers. A Consensus Workshop was held on March 30 to April 1,2001 to culminate the review process and establish consensus for a clinical working case definition, diagnostic protocols and treatment protocols. We present a systematic clinical working case definition that encourages a diagnosis based on characteristic patterns of symptom clusters, which reflect specific areas of pathogenesis. Diagnostic and treatment protocols, and a short overview of research are given to facilitate a comprehensive and integrated approach to this illness. Throughout this paper, “myalgic encephalomyelitis” and “chronic fatigue syndrome” are used interchangeably and this illness is referred to as “ME/CFS.”"
 * 2001, Cytokine and Other Immunologic Markers in Chronic Fatigue Syndrome and Their Relation to Neuropsychological Factors
 * 2000, Comparative Analysis of Lymphocytes in Lymph Nodes and Peripheral Blood of Patients with Chronic Fatigue Syndrome"'Abstract - Blood and lymph node samples were obtained from patients with chronic fatigue syndrome (CFS) who had volunteered to undergo a lymph node biopsy while participating in a phase 1 clinical trial of a novel immunomodulatory therapy. The surface marker phenotypes of the peripheral blood and lymph node samples were examined using four-color flow cytometry and compared to published proportions of cells in peripheral blood and lymph nodes from control individuals. While a greater proportion of T lymphocytes from both lymph nodes and peripheral blood of control subjects are immunologically “naive” (CD45RA+), the proportions of lymphocytes with a “memory” phenotype predominate in lymph nodes and peripheral blood of CFS patients. CFS has been proposed to be a disease of autoimmune etiology and in this respect it is interesting to note that decreased proportions of CD45RA+ T (“naive”) cells are also seen in the peripheral blood of patients with autoimmune diseases.'"
 * 2000, Chronic Fatigue Syndrome: Evidence Supporting the Hypothesis of a Behaviorally-Activated Neuromodulator of Fatigue "Abstract - Chronic Fatigue Syndrome (CFS) is a disorder characterized by a prolonged, debilitating fatigue of unknown etiology. In addition, patients with CFS frequently report enhanced fatigue symptoms following even mild physical exertion, and their tolerance for physical exercise is limited relative to healthy individuals. The physiological mechanisms underlying the excessive fatigue and weakness common to this disorder remain an issue of scientific debate. Collectively, the available data suggest that fatigue in CFS is not due to any neuromuscular dysfunction, per se, but possibly is caused or influenced by some centrally acting mediator that is released during behavioral activities that require physical or mental exertion. In addition to persistent fatigue, there is growing evidence that many CFS patients exhibit alterations in hypothalamic-pituitary-adrenal (HPA) axis and autonomic function, including the inability to maintain the blood pressure response to orthostatic challenge. When an individual engages in mental or physical behavioral activation, there is a release of numerous centrally acting neuromodulators, some of which have been postulated to influence fatigue. This paper examines the evidence supporting a common pathway through which these centrally-mediated psychological and autonomic abnormalities may be linked. It is hypothesized that as a consequence of behavioral activation there is an abnormality in neuromodulator release or action in individuals with CFS, and that this abnormal neuromodulator activity results in increased fatigue. Furthermore, it is postulated that the CNS initiates a counter-regulatory mechanism to reduce the activity of those systems responsible for the production of the neuromodulator; and that the consequence of this counter-regulatory maneuver is the prevailing dysregulation of the autonomic and HPA axes and other dysfunctional cardiovascular and immunological sequelae."
 * 2000, Clinical and Immunologic Effects of Autologous Lymph Node Cell Transplant in Chronic Fatigue Syndrome"'Abstract - An open labeled, phase 1, safety and feasibility study using lymph node extraction, ex vivo lymph node cell expansion, followed by autologous cell reinfusion was evaluated as a potential immunomodulatory treatment strategy in patients with chronic fatigue syndrome (CFS). The experimental therapy utilized the cells of the lymph node, activated and grown in culture with defined media, interleukin-2 (IL-2) and anti-CD3 to activate and enhance cellular immunological functions. This procedure was designed to change the cytokine pattern of the lymph node lymphocytes to favor expression of T-helper (Th)l-type over Th2-type cytokines. The mixed population of ex vivo immune-enhanced cells were reinfused into the donor, who was carefully monitored for adverse events and possible clinical benefit. There were no adverse events. There were significant improvements in clinical status in association with a significant decrease in Th2-type cytokine production."
 * 2000, Immunotherapy of Chronic Fatigue Syndrome: Therapeutic Interventions Aimed at Modulating the Th1/Th2 Cytokine Expression Balance"'Abstract - Based on the postulates of viral and autoimmune etiologies of CFS, several interventions have been designed and tested by different research groups around the world, including the United States, Sweden, United Kingdom, Italy, and Japan. This review addresses those interventions aimed at altering the balance of certain cytokines, the mediators of immune responses. Patients with CFS who show evidence of activation of the immune system have poor immune cell function and a predominance of what is called a T-helper (Th)2-type cytokine response when their lymphocytes are activated. A Th2-type response, which is characterized by production of cytokines such as interleukin (IL)−4, −5, and −10, favors the function of B lymphocytes, the cellular factories of immunoglobulins. A predominance of a Th2-type response is therefore consistent with pathologies, such as autoimmunity and atopy, which are based on inappropriate production of immunoglobulins. Many of the CFS therapies discussed decrease the Th2-type predominance seen at baseline in CFS patients, thereby allowing a greater predominance of a Thl-type response, which favors the function of macrophages and natural killer cells. The function of the latter cells, which have the natural ability of directly destroying invading microbes and cancer cells, is defective in untreated CFS patients. Typical Thl-type cytokines include IL-2 and interferon-gamma, and some of the therapies induce their production. The interventions discussed in this review cover a wide spectrum of therapeutic tools ranging from lymph node cell immunotherapy, herbal products, and small molecules to vaccines. Despite the controversies on the etiology of CFS, immunotherapy research is useful and necessary.''"
 * 1996, Interindividual Immune Status Variation Patterns in Patients with Chronic Fatigue Syndrome: Association with Gender and the Tumor Necrosis Factor System Abstract - "Changes in soluble immune mediator levels in association with the chronic fatigue syndrome (CFS) usually occur within normal ranges and are apparent mainly as changes in the skewness of population distributions. The latter finding undermines the usefulness of cytokine levels as clinical tools at the individual level as has been seen in sepsis syndrome where a similar overlap occurs. Nonetheless, changes in cytokine levels at the population level can contribute to an understanding of the disease process. For example, we reported previously that significant proportions of CFS patients showed elevated serum levels of either soluble tumor necrosis factor-receptor I (sTNF-RI, sCD120a) or TNF-a as compared to controls. The latter results could reflect different disease processes or extremes of a common disease process. Using sera collected over a five-year period, we have now studied an extended cohort of 108 CFS patients and our results are consistent with a common graded disease process. When we assessed the effect of gender on the distributions of serum levels of immune mediators, levels of sTNF-RI, sTNF-RII (sCD 12Ob), sIL-6R (sCDl26), and sICAM-1 were found to be consistently higher among males than females and among CFS patients as compared to controls regardless of gender. Moreover, differences in soluble immune mediator levels between CFS and control individuals were more clearly defined when restricting the analysis to the female gender. These observations are consistent with endocrine influences on immunological changes."
 * 1995, Physical symptoms of chronic fatigue syndrome are exacerbated by the stress of Hurricane Andrew
 * 1995, Relationships of Cognitive Difficulties to Immune Measures, Depression and Illness Burden in Chronic Fatigue Syndrome - Abstract
 * 1994, Dysregulated expression of tumor necrosis factor in chronic fatigue syndrome: interrelations with cellular sources and patterns of soluble immune mediator expression"'ABSTRACT: Among a group of 70 individuals who met the criteria established by the Centers for Disease Control and Prevention (Atlanta) for chronic fatigue syndrome (CFS), 12%-28% had serum levels exceeding 95% of control values for tumor necrosis factor (TNF) alpha, TNF-beta, interleukin (IL) 1 alpha, IL-2, soluble IL-2 receptor (sIL-2R), or neopterin; overall, 60% of patients had elevated levels of one or more of the nine soluble immune mediators tested. Nevertheless, only the distributions for circulating levels of TNF-alpha and TNF-beta differed significantly in the two populations. In patients with CFS--but not in controls--serum levels of TNF-alpha, IL-1 alpha, IL-4, and sIL-2R correlated significantly with one another and (in the 10 cases analyzed) with relative amounts (as compared to beta-globin or beta-actin) of the only mRNAs detectable by reverse transcriptase-coupled polymerase chain reaction in peripheral-blood mononuclear cells: TNF-beta, unspliced and spliced; IL-1 beta, lymphocyte fraction; and IL-6 (in order of appearance). These findings point to polycellular activation and may be relevant to the etiology and nosology of CFS.'"

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


 * 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