Sonya Marshall-Gradisnik

Sonya M. Marshall-Gradisnik, BSc (Hons), PhD, is co-director (alongside Professor Donald Staines of the National Centre for Neuroimmunology and Emerging Diseases (NCNED) at Griffith University in Australia. Her expertise is in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis with particular focus on Natural Killer Cell function and signalling pathways, T regulatory and B cell phenotypes and cytokine production, and transcriptional profiling and gene expression. In her studies, she compares the changes of the different cells of the immune system in relation to the severity of the disease.

She is one of the authors of the 2011 case definition, International Consensus Criteria.

Marshall-Gradisnik is on the Board of Directors of the International Association for Chronic Fatigue Syndrome/Myalgic Encephalomyelitis.

Biomarker Patent
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 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."

Notable studies

 * 2016, Progressive brain changes in patients with chronic fatigue syndrome: A longitudinal MRI study"'Abstract: Purpose - To examine progressive brain changes associated with chronic fatigue syndrome (CFS). Materials and Methods - We investigated progressive brain changes with longitudinal MRI in 15 CFS and 10 normal controls (NCs) scanned twice 6 years apart on the same 1.5 Tesla (T) scanner. MR images yielded gray matter (GM) volumes, white matter (WM) volumes, and T1‐ and T2‐weighted signal intensities (T1w and T2w). Each participant was characterized with Bell disability scores, and somatic and neurological symptom scores. We tested for differences in longitudinal changes between CFS and NC groups, inter group differences between pooled CFS and pooled NC populations, and correlations between MRI and symptom scores using voxel based morphometry. The analysis methodologies were first optimized using simulated atrophy. Results We found a significant decrease in WM volumes in the left inferior fronto‐occipital fasciculus (IFOF) in CFS while in NCs it was unchanged (family wise error adjusted cluster level P value, P FWE < 0.05). This longitudinal finding was consolidated by the group comparisons which detected significantly decreased regional WM volumes in adjacent regions (P FWE < 0.05) and decreased GM and blood volumes in contralateral regions (P FWE < 0.05). Moreover, the regional GM and WM volumes and T2w in those areas showed significant correlations with CFS symptom scores (P FWE < 0.05). Conclusion - The results suggested that CFS is associated with IFOF WM deficits which continue to deteriorate at an abnormal rate.'"
 * 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, Novel characterisation of mast cell phenotypes from peripheral blood mononuclear cells in chronic fatigue syndrome/myalgic encephalomyelitis patients
 * 2016, Killer Cell Immunoglobulin-like Receptor Genotype and Haplotype Investigation of Natural Killer Cells from an Australian Population of Chronic Fatigue Syndrome/Myalgic Encephalomyelitis Patients
 * 2015, Cytokines in the Cerebrospinal Fluids of Patients with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis
 * 2015, Serum Immune Proteins in Moderate and Severe Chronic Fatigue Syndrome/Myalgic Encephalomyelitis Patients
 * 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, 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.'"
 * 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, 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, 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.'"
 * 2013, The role of clinical guidelines for chronic fatigue syndrome/myalgic encephalomyelitis in research settings. Abstract

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. Marshall-Gradisnik, 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

Clinic location
NCNED is located at Griffith University on the Gold Coast, in Queensland, Australia.

Talks & interviews

 * 2016, Australian scientists make breakthrough in Chronic Fatigue Syndrome testing
 * 2015, Speaker at the 10th Invest in ME International ME Conference DVD available(no speech title given)]
 * 2014, "Professor Sonya Marshall-Gradisnik, Australia's foremost expert on chronic fatigue syndrome" interviewed on ABC Gold Coast
 * 2014, Speaker at the 9th Invest in ME International ME Conference DVD available(no speech title given)]
 * 2012, Speaker at the 7th Invest in ME International ME Conference DVD available(no speech title given)]
 * 2012, Keynote address by Prof Sonya Marshall-Gradisnik at Emerge Australia (formerly ME/CFS Australia (Victoria)) Awareness Week

Online presence

 * PubMed - Sonya Marshall-Gradisnik
 * Griffith University - Sonya Marshall-Gradisnik
 * National Centre for Neuroimmunology and Emerging Diseases

Learn more

 * 2016, News Article - "Closer to a Full Understanding of chronic fatigue syndrome"
 * 2014, "Gold Coast’s Griffith University to lead way in the battle against chronic fatigue"