Sharni Hardcastle

Source: ResearchGate

Sharni Lee Hardcastle, BBioMedSc (Hons1) PhD, is a researcher and Immunology Lecturer at National Centre for Neuroimmunology and Emerging Diseases, Griffith University, School of Medical Science, Brisbane, Queensland, Australia.

Awards

• 2016, Junior Investigator Award to encourage young CFS/FM researchers in recognition of their work awarded by IACFSME.
• 2013, Gold Coast Women in Business Award - Empowering Young Women’s Award In recognition of significant leadership potential and outstanding qualities and performance.
• 2010, Award: Co-Author of Best Poster at the International Science Symposium for CFS/ME

Notable studies

• 2017, Impaired calcium mobilization in natural killer cells from chronic fatigue syndrome/myalgic encephalomyelitis patients is associated with transient receptor potential melastatin 3 ion channels FREE ACCESS/FULL TEXT
• 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, 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."

• 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

Talks & interviews

• 2014, International Student Research Forum, Denmark. Sharni Hardcastle represented National Centre for Neuroimmunology and Emerging Diseases and gave both an oral and poster presentation about her CFS/ME research.
• 2013, The 2nd International Symposium for Chronic Fatique Syndrome/Myalgic Encephalomyelitis Presented: "The immunological profile of Chronic Fatigue Syndrome/Myalgic Encephalomyelitis"

Online presence

• PubMed
• Twitter
• Facebook
• Website
• ResearchGate

Learn more

• National Centre for Neuroimmunology and Emerging Diseases Website

See also

• National Centre for Neuroimmunology and Emerging Diseases
• Donald Staines
• Sonya Marshall-Gradisnik

T cell A type of white blood cell which is mostly produced or matured in the thymus gland (hence T-cell) and is involved in the adaptive immune response on a cellular level. Also known as a T lymphocyte. (Learn more: www.youtube.com)

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.

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)

B cell B lymphocyte, or a type of white blood cell, which is involved in the immune response by secreting antibodies to ward off infections. In mammals, they are mostly matured in the bone marrow.

B cell B lymphocyte, or a type of white blood cell, which is involved in the immune response by secreting antibodies to ward off infections. In mammals, they are mostly matured in the bone marrow.

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

γ γ / Γ. Greek letter gamma/gamme (a symbol used in science), third letter of the Greek alphabet. Equivalent to the letter "g".

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.

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)

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.)