Ekua Weba Brenu, PhD, is a post-doctorate researcher at the School of Medical Science, Griffith University, Griffith Health Institute, and a Senior Research Fellow at the National Centre for Neuroimmunology and Emerging Diseases, Gold Coast, Queensland, Australia.
- 2011, Junior Investigator Award to encourage young CFS/FM researchers in recognition of their work awarded by IACFSME.
In 2015, Griffith University filed for a patent for a biological marker (Patent Publication number WO2016023077 A1) for the diagnosis and management of ME and CFS. Sonya Marshall-Gradisnik and Ekua Brenu are listed as the inventors. The patent application states: "The present invention resides broadly in the use of at least one miRNA as a biological marker for identifying or diagnosing a subject having CFS and/or ME." Very simply stated, microRNA (miRNA) are molecules involved in gene expression. They are different from mRNA which stands for messenger RNA. In 2016, Griffith University's Professor Donald Staines and Professor Sonya Marshall-Gradisnik announced that they have been awarded a $4-million grant to be administered during the next five years that will enable them to continue research into developing a diagnostic test for ME/CFS.
- 2016, Regulatory T, natural killer T and γδ T cells in multiple sclerosis and chronic fatigue syndrome/myalgic encephalomyelitis: a comparison.
"Results: We observed significant increase in Tregs in the CFS/ME group (p≤0.005) compared with the healthy controls group. Total γδ and γδ2 T cells were significantly reduced in the MS patients in comparison with the healthy controls group. Conversely, CD4+iNKT percentage of iNKT, was significantly increased in the CFS/ME group compared with healthy controls and double negative iNKT percentage of iNKT significantly decreased compared with the healthy controls group. Conclusion: This study has not identified immunological disturbances that are common in both MS and CFS/ME patients. However differential expression of cell types between the conditions investigated suggests different pathways of disease. These differences need to be explored in further studies."
- 2016, A Preliminary Comparative Assessment of the Role of CD8+ T Cells in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis and Multiple Sclerosis
- 2016, Pilot Study of Natural Killer Cells in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis and Multiple Sclerosis
- 2015, A Comparison of Cytokine Profiles of Chronic Fatigue Syndrome/Myalgic Encephalomyelitis and Multiple Sclerosis Patients
Abstract - "Background: Chronic Fatigue Syndrome, also known as Myalgic Encephalomyelitis (CFS/ME), is a debilitating condition that presents with a range of symptoms, including fatigue, cognitive dysfunction, muscular and joint pain, and may be immune-mediated. In particular, patients exhibit abnormal cytokine expression. Similarly, in Multiple Sclerosis (MS), patients display neuroimmunological symptoms, and abnormal cytokine expression, with some overlap in symptomology with CFS/ME. The purpose of this study was to compare Th1, Th2, Th17 cytokines, inflammatory cytokines and chemokines, in healthy controls, CFS/ME and MS patients. Methods: Serum samples were collected from healthy controls (n = 16, mean age = 50 ± 11.85 years), CFS/ME patients (n = 16, mean age = 49.88 ± 9.54 years) and MS patients (n = 11, mean age = 52.75 ± 12.81 years). The concentrations of 27 cytokines (IFN-γ, TNF-α, IL-12, IL-2, IL-1β, IL-4, IL-6, IL-10, IL-13, IL-5, IL-17, IL-1ra, IL-7, IL-8, IL-9, eotaxin, IP-10, MCP-1, MIP1α, MIP1β, PDGF-bb, RANTES, basic FGF, GCSF, GMCSF, VEGF and IL-15) were measured using a Bio-Plex Pro™ kit. Results: IFN-γ, IL-10 and IL-5 were significantly higher in the serum of both CFS/ME and MS patients compared to the healthy controls (p ≤ 0.041). However, only the MS patients had significantly elevated levels of IL-12, IL-1β, IL-4, IL-13, IL-6, IL-17, IL-1ra, IL-7, IL-9, eotaxin, IL-10, MIP1α, basic FGF, GCSF and VEGF compared to the CFS/ME patients and controls (p ≤ 0.04). There were no significant differences between groups for IL-8, MCP-1, MIP1β, RANTES, GMCSF, TNF-α, and IL-2. Conclusion: CFS/ME and MS patients both displayed abnormal cytokine levels, with dual expression of Th1 and Th2 cytokines. Further research into cytokines such as IFN-γ, IL-10 and IL-5, with the use of a specific CFS/ME case definition and sensitive cytokine assays, is required to improve the understanding of the pathophysiology of CFS/ME."
- 2015, Serum Immune Proteins in Moderate and Severe Chronic Fatigue Syndrome/Myalgic Encephalomyelitis Patients
- 2015, Characterisation of cell functions and receptors in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME)
"Conclusions: This study was the first to show significant differences in a number of receptors in NK, CD4+T and CD8+T cells in CFS/ME suggesting dysregulation in NK cell cytotoxic activity, receptor regulation and potentially cell adherence. Consistent with previous literature, our research suggests that CFS/ME patients have immunological dysregulation in the innate and adaptive immune cells. We have also highlighted significant differences in NK, CD4+T and CD8+T cells between moderate and severe CFS/ME patients, suggesting severity subgroups may have distinct immune perturbations and consequently aetiology. Further studies examining severity subgroups of CFS/ME patients may therefore contribute to the understanding of the pathomechanism associated with the illness."
- 2015, Examination of Single Nucleotide Polymorphisms (SNPs) in Transient Receptor Potential (TRP) Ion Channels in Chronic Fatigue Syndrome Patients
Abstract - "Background: The transient receptor potential (TRP) superfamily in humans comprises 27 cation channels with permeability to monovalent and divalent cations. These channels are widely expressed within humans on cells and tissues and have significant sensory and regulatory roles on most physiological functions. Chronic fatigue syndrome (CFS) is an unexplained disorder with multiple physiological impairments. Objectives: The purpose of this study was to determine the role of TRPs in CFS. Methods: The study comprised 115 CFS patients (age = 48.68 ± 1.06 years) and 90 nonfatigued controls (age = 46.48 ± 1.22 years). CFS patients were defined according to the 1994 Center for Disease Prevention and Control criteria for CFS. A total of 240 single nucleotide polymorphisms (SNPs) for 21 mammalian TRP ion channel genes (TRPA1, TRPC1, TRPC2, TRPC3, TRPC4, TRPC6, TRPC7, TRPM1, TRPM2, TRPM3, TRPM4, TRPM5, TRPM6, TRPM7, TRPM8, TRPV1, TRPV2, TRPV3, TRPV4, TRPV5, and TRPV6) were examined via the Agena Biosciences iPLEX Gold assay. Statistical analysis was performed using the PLINK analysis software. Results: Thirteen SNPs were significantly associated with CFS patients compared with the controls. Nine of these SNPs were associated with TRPM3 (rs12682832; P ≤ 0.003, rs11142508; P < 0.004, rs1160742; P < 0.08, rs4454352; P ≤ 0.013, rs1328153; P ≤ 0.013, rs3763619; P ≤ 0.014, rs7865858; P ≤ 0.021, rs1504401; P ≤ 0041, rs10115622; P ≤ 0.050), while the remainder were associated with TRPA1 (rs2383844; P ≤ 0.040, rs4738202; P ≤ 0.018) and TRPC4 (rs6650469; P ≤ 0.016, rs655207; P ≤ 0.018). Conclusion: The data from this pilot study suggest an association between TRP ion channels, predominantly TRPM3 and CFS. This and other TRPs identified may contribute to the etiology and pathomechanism of CFS."
- 2015, Longitudinal analysis of immune abnormalities in varying severities of Chronic Fatigue Syndrome/Myalgic Encephalomyelitis patients
"Conclusions: Severe CFS/ME patients differed from controls and moderate CFS/ME patients over time and expressed significant alterations in iNKT cell phenotypes, CD8+T cell markers, NK cell receptors and γδT cells at 6 months. This highlights the importance of further assessing these potential immune biomarkers longitudinally in both moderate and severe CFS/ME patients."
- 2015, Cytokines in the Cerebrospinal Fluids of Patients with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis
Abstract - Background: Chronic fatigue syndrome, also known as myalgic encephalomyelitis (CFS/ME) is a particularly difficult illness to identify. To aid in classifying patients for research as well as clinical care, potential cases may be evaluated according to clinical guidelines. Purpose: The purpose of this paper is to provide an overview of three sets of guidelines currently available: the Centers for Disease Control & Prevention (CDC) Toolkit; the International Association for Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (IACFS/ME) Primer; and the International Consensus Primer. Methods: These guidelines were examined and compared with respect to required symptoms, laboratory and investigative protocols, and exclusionary and comorbid conditions. The comparisons were also intended to evaluate the guidelines in light of new research that advances the clinical understanding of CFS/ME and assists in identifying patients. Results: Guidelines vary significantly in the symptoms and comorbidities considered in light of the differing symptom requirements of three case definitions. There is also no specification on how symptoms should be measured, contributing to the significant heterogeneity found in CFS/ME. Conclusions: Further revision of clinical guidelines, preferably based on a definition that is well-informed by current empirical studies, is recommended to ensure that guidelines are applied with consistency and understanding in both research and clinical settings.
- 2014, The Role of Adaptive and Innate Immune Cells in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis FULL TEXT
Abstract: "Perturbations in immune processes are a hallmark of a number of autoimmune and inflammatory disorders. Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is an inflammatory disorder with possible autoimmune correlates, characterized by reduced NK cell activity, elevations in regulatory T cells (Tregs) and dysregulation in cytokine levels. The purpose of this article is to examine innate and adaptive immune cell phenotypes and functional characteristics that have not been previously examined in CFS/ME patients. Thirty patients with CFS/ME and 25 non-fatigued controls were recruited for this study. Whole blood samples were collected from all participants for the assessment of cell phenotypes, functional properties, receptors, adhesion molecules, antigens and intracellular proteins using flow cytometric protocols. The cells investigated included NK cells, dendritic cells, neutrophils, B cells, T cells, γδT cells and Tregs. Significant changes were observed in B-cell subsets, Tregs, CD4+CD73+CD39+ T cells, cytotoxic activity, granzyme B, neutrophil antigens, TNF-α and IFN-γ in the CFS/ME patients in comparison with the non-fatigued controls. Alterations in B cells, Tregs, NK cells and neutrophils suggest significant impairments in immune regulation in CFS/ME and these may have similarities to a number of autoimmune disorders."
- 2014, Characterization of Natural Killer Cell Phenotypes in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (FULL TEXT)
Abstract - Objective: Natural Killer (NK) cells are classified into different phenotypes according to the expression of the surface markers CD56 and CD16. Each NK cell phenotype has a role in the immune response through cytotoxic activity or cytokine production. Reduced NK cell cytotoxic activity is a consistent finding in patients with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) and investigations into the potential causes of reduced NK cell cytotoxic activity have predominantly focused on total NK cells. The purpose of this study was to investigate and characterize four NK cell phenotypes in CFS/ME. Methods: Twenty nine CFS/ME patients (mean age ± SEM=48.28 ± 2.63) meeting the 1994 Fukuda definition and 27 healthy controls (mean age ± SEM=49.15 ± 2.51) were included in this study. Flow cytometric protocols identified CD56bright CD16-/dim, CD56dimCD16-, CD56dimCD16+ or CD56-CD16+ NK cells for the measurement of surface markers including adhesion molecules CD2, CD18, CD11a, CD11b and CD11c, natural cytotoxicity receptors, Killer Immunoglobulin Like Receptors, signalling lymphocytic activation molecules and cell maturation (CD57). Following stimulation, NK cell phenotype expression of CD107a and CD107b was measured as a marker for degranulation. Intracellular staining measured lytic proteins including perforin, Granzyme A and Granzyme B in the four NK cell phenotypes. Results: In the CFS/ME group, CD56brightCD16-/dim NK cell co-expression of adhesion molecules CD2 and CD18 was significantly reduced. Granzyme B was significantly decreased in CD56dimCD16+ and CD56-CD16+ NK cells from CFS/ME patients. CD57 expression on CD56dimCD16+ NK cells from CFS/ME patients was significantly increased. Conclusion: This is the first study to characterize four NK cell phenotypes in CFS/ME by investigating surface and intracellular molecules necessary for NK cell effector function. The data suggests that a combination of impairments in CD56dimCD16+ NK cells from CFS/ME patients may contribute to reduced cytotoxic activity of this phenotype.
- 2014, Analysis of the Relationship between Immune Dysfunction and Symptom Severity in Patients with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) FULL TEXT
Abstract - "Objective: Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) is a disabling illness, characterised by persistent, debilitating fatigue and a multitude of symptoms. Immunological alterations are prominent in CFS/ME cases, however little is known about the relationship between CFS/ME severity and the extent of immunological dysfunction. The purpose of this study was to assess innate and adaptive immune cell phenotypes and function of two groups of CFS/ME patients, bedridden (severe) and mobile (moderate). Methods: CFS/ME participants were defined using the Centres for Disease Prevention and Control (1994 CDC) Criteria for CFS/ME. Participants were grouped into healthy controls (n=22, age=40.14 ± 2.38), moderate/ mobile (n=23; age=42.52 ± 2.63) and severe/bedridden (n=18; age=39.56 ± 1.51) CFS/ME patients. Flow cytometric protocols were used to examine neutrophil, monocyte, dendritic cells (DCs), iNKT, Treg, B, γδ and CD8+ T cell phenotypes, NK cytotoxic activity and receptors. Results: The present data found that CFS/ME patients demonstrated significant decreases in NK cytotoxic activity, transitional and regulatory B cells, γδ1T cells, KIR2DL1/DS1, CD94+ and KIR2DL2/L3. Significant increases in CD56-CD16+NKs, CD56dimCD16- and CD56brightCD16-/dim NKs, DCs, iNKT phenotypes, memory and naive B cells were also shown in CFS/ME participants. Severe CFS/ME patients demonstrated increased CD14-CD16+ DCs, memory and naïve B cells, total iNKT, iNKT cell and NK phenotypes compared to moderate CFS/ME patients. Conclusion: This study is the first to determine alterations in NK, iNKT, B, DC and γδ T cell phenotypes in both moderate and severe CFS/ME patients. Immunological alterations are present in innate and adaptive immune cells and sometimes, immune deregulation appears worse in CFS/ME patients with more severe symptoms. It may be appropriate for CFS/ME patient severity subgroups to be distinguished in both clinical and research settings to extricate further immunological pathologies that may not have been previously reported.
- 2012, Longitudinal investigation of natural killer cells and cytokines in chronic fatigue syndrome/myalgic encephalomyelitis
- 2012, Cytotoxic lymphocyte microRNAs as prospective biomarkers for Chronic Fatigue Syndrome/Myalgic Encephalomyelitis
Talks & interviews
- 2013, The 2nd International Symposium for Chronic Fatique Syndrome/Myalgic Encephalomyelitis Presented: "Immune dysregulation in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis"
- Ramos, S; Brenu, E; Broadley, S; Kwiatek, R; Ng, J; Nguyen, T; Freeman, S; Staines, D; Marshall-Gradisnik, S (20 March 2016), "Regulatory T, natural killer T and γδ T cells in multiple sclerosis and chronic fatigue syndrome/myalgic encephalomyelitis: a comparison", Asian Pac J Allergy Immunol, doi:10.12932/AP0733
- Brenu, EW; Broadley, S; Nguyen, T; Johnston, S; Ramos, S; Staines, D; Marshall-Gradisnik, S (2016-01-04), "A Preliminary Comparative Assessment of the Role of CD8+ T Cells in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis and Multiple Sclerosis", Journal of Immunology Research, 2016: –9064529, doi:10.1155/2016/9064529
- Huth, TK; Brenu, EW; Ramos, S; Nguyen, T; Broadley, S; Staines, D; Marshall-Gradisnik, S (Jan 2016), "Pilot Study of Natural Killer Cells in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis and Multiple Sclerosis", Scand J Immunol, 83(1): 44-51, PMID 26381393, doi:10.1111/sji.12388
- Wong, Naomi; Nguyen, Thao; Brenu, Ekua Weba; Broadley, Simon; Staines, Donald; Marshall-Gradisnik, Sonya (2015), "A Comparison of Cytokine Profiles of Chronic Fatigue Syndrome/Myalgic Encephalomyelitis and Multiple Sclerosis Patients", International Journal of Clinical Medicine, 6 (10): 769-783, doi:10.4236/ijcm.2015.610103
- Hardcastle, SL; Brenu, EW; Johnston, S; Nguyen, T; Huth, T; Wong, N; Ramos, S; Staines, DR; Marshall-Gradisnik, SM (2015), "Serum Immune Proteins in Moderate and Severe Chronic Fatigue Syndrome/Myalgic Encephalomyelitis Patients", International Journal of Medical Sciences, 12 (10): 764-772, doi:10.7150/ijms.12399
- Hardcastle, SL; Brenu, EW; Johnston, S; Nguyen, T; Huth, T; Wong, N; Ramos, S; Staines, DR; Marshall-Gradisnik, SM (2015), "Characterisation of cell functions and receptors in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME)", BMC Immunology, 16 (35), doi:10.1186/s12865-015-0101-4
- Marshall-Gradisnik, Sonya M.; Smith, Peter; Brenu, Ekua W.; Nilius, Bernd; Ramos, Sandra B.; Staines, Donald R. (2015), "Examination of Single Nucleotide Polymorphisms (SNPs) in Transient Receptor Potential (TRP) Ion Channels in Chronic Fatigue Syndrome Patients", Immunology and Immunogenetics Insights, 2015 (7): 1-6, doi:10.4137/III.S25147
- Hardcastle, Sharni Lee; Brenu, Ekua Weba; Johnston, Samantha; Nguyen, Thao; Huth, Teilah; Ramos, Sandra; Staines, Donald; Marshall-Gradisnik, Sonya (2015), "Longitudinal analysis of immune abnormalities in varying severities of Chronic Fatigue Syndrome/Myalgic Encephalomyelitis patients", Journal of Translational Medicine, 13 (299), doi:10.1186/s12967-015-0653-3
- Peterson, D; Brenu, EW; Gottschalk, G; Ramos, Sandra B; Nguyen, T; Staines, D; Marshall-Gradisnik, S (2015), "Cytokines in the Cerebrospinal Fluids of Patients with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis", Mediators of Inflammation, 2015, doi:10.1155/2015/929720
- Johnston, S. C.; Brenu, E. W.; Staines, D. R.; Marshall-Gradisnik, S. M. (2014), "The role of clinical guidelines for chronic fatigue syndrome/myalgic encephalomyelitis in research settings", Fatigue: Biomedicine, Health & Behavior, 2 (1): 28-39, doi:10.1080/21641846.2013.860779
- Brenu, EW; Huth, TK; Hardcastle, SL; Fuller, K; Kaur, M; Johnston, S; Ramos, S; Staines, D; Marshall-Gradisnik, S (2014), "The Role of adaptive and innate immune cells in chronic fatigue syndrome/myalgic encephalomyelitis", International Immunology, 26 (4): 233-42, PMID 24343819, doi:10.1093/intimm/dxt068
- Huth, Teilah K.; Brenu, Ekua; Nguyen, Thao; Hardcastle, Sharni L.; Johnston, Samantha; Ramos, Sandra; Staines, Donald R.; Marshall-Gradisnik, Sonya M. (2014), "Characterization of Natural Killer Cell Phenotypes in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis", Journal of Clinical & Cellular Immunology, 5 (3), doi:10.4172/2155-9899.1000223
- Hardcastle, Sharni Lee; Brenu, Ekua Weba; Johnston, Samantha; Nguyen, Thao; Huth, Teilah; Kaur, Manprit; Ramos, Sandra; Salajegheh, Ali; Staines, Donald R; Marshall-Gradisnik, Sonya (2014), "Analysis of the Relationship between Immune Dysfunction and Symptom Severity in Patients with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME)", Journal of Clinical & Cellular Immunology, 5 (190), doi:10.4172/2155-9899.1000190
- Brenu, Ekua W; van Driel, Mieke L; Staines, Donald R; Ashton, Kevin J; Hardcastle, Sharni L; Keane, James; Tajouri, Lotti; Peterson, Daniel; Ramos, Sandra B; Marshall-Gradisnik, Sonya M (2012), "Longitudinal investigation of natural killer cells and cytokines in chronic fatigue syndrome/myalgic encephalomyelitis", Journal of Translational Medicine, 10: 88, doi:10.1186/1479-5876-10-88
- Brenu, EW; Ashton, KJ; van Driel, M; Staines, D; Peterson, D; Atkinson, GM; Marshall-Gradisnik, S (2012), "Cytotoxic lymphocyte microRNAs as prospective biomarkers for Chronic Fatigue Syndrome/Myalgic Encephalomyelitis.", Journal of Affective Disorders, 141 (2-3): 261-9, doi:10.1016/j.jad.2012.03.037