Griffith University Media release, by Louise Durack, 9 June 2016: Chronic Fatigue Syndrome cell discovery may hold key to treatment:
Chronic Fatigue Syndrome researchers have discovered a cell receptor which could be a key contributing factor to CFS, providing a much clearer picture of how to tackle the debilitating illness.
Researchers from Griffith University’s National Centre for Neuroimmunology and Emerging Diseases at the Menzies Health Institute Queensland, have identified significant impairments in the cellular function of people with CFS.
CFS – sometimes known as ME (myalgic encephalomyelitis) – is a complex illness characterised by impaired memory and concentration, metabolic, cardiac, gut and immune dysfunction and debilitating muscle pain and fatigue on exertion (also known as neuroimmune exhaustion).
Published in Biological Research the study reveals a receptor not previously identified on particular immune cells.
“TRPM3 receptors have been identified on these particular immune cells, not only in healthy people for the first time, but also have been shown to be significantly reduced in CFS/ME patients,” says Professor Sonya Marshall-Gradisnik who is leading the study.
Importance of receptors
“These receptors are important as they move calcium inside the cell. Interestingly in this study we also reported a significant reduction of calcium inside these cells from CFS/ME patients.
“The discovery means that we now have a potentially key contributing factor in the cause of this condition. This discovery also fits with our previous research showing that changes in genes and cell function are involved in vital cell signalling pathways found in all cell types.”
“These findings contribute to our knowledge of the clinical presentation of this condition and provide a sound basis for further research,” says Professor Don Staines. “We are now much closer to having a complete understanding of CFS.”
In another recent publication Clinical Therapeutics, NCNED researchers have shown that few therapeutic interventions are currently effective in CFS/ME.
“This is a very complex illness and it is likely that no single intervention will counter all effects of the pathology. We need to have concentrated efforts on further research to discover appropriate treatments which are effective,” Professor Staines says.
In the coming weeks these novel research findings are being presented by NCNED researchers at international clinical and research conferences in London and the Federation of America Societies For Experiential Biology (FASEB), Lisbon.
Research article abstract:
Background:
Transient receptor potential melastatin 3 (TRPM3) cation channels are ubiquitously expressed by multiple cells and have an important regulatory role in calcium-dependent cell signalling to help maintain cellular homeostasis. TRPM3 protein expression has yet to be determined on Natural Killer (NK) cells and B lymphocytes.
Multiple single nucleotide polymorphisms have been reported in TRPM3 genes from isolated peripheral blood mononuclear cells, NK and B cells in Chronic fatigue syndrome/Myalgic encephalomyelitis (CFS/ME) patients and have been proposed to correlate with illness presentation. The object of the study was to assess TRPM3 surface expression on NK and B lymphocytes from healthy controls, followed by a comparative investigation examining TRPM3 surface expression, and cytoplasmic and mitochondrial calcium influx in CD19+ B cells, CD56bright and CD56dim cell populations from CFS/ME patients.
Results:
TRPM3 cell surface expression was identified for NK and B lymphocytes in healthy controls (CD56bright TRPM3 35.72 % ± 7.37; CD56dim 5.74 % ± 2.00; B lymphocytes 2.05 % ± 0.19, respectively). There was a significant reduction of TRPM3 surface expression on CD19+ B cells (1.56 ± 0.191) and CD56bright NK cells (17.37 % ± 5.34) in CFS/ME compared with healthy controls. Anti-CD21 and anti-IgM conjugated biotin was cross-linked with streptavidin,and subsequently treatment with thapsigargin. This showed a significant reduction in cytoplasmic calcium ion concentration in CD19+ B lymphocytes. CD56bright NK cells also had a significant decrease in cytoplasmic calcium in the presence of 2-APB and thapsigargin in CFS/ME patients.
Conclusions:
The results from this preliminary investigation identify, for the first time, TRPM3 surface expression on both NK and B lymphocytes in healthy controls. We also report for the first time, significant reduction in TRPM3 cell surface expression in NK and B lymphocytes, as well as decreased intracellular calcium within specific conditions in CFS/ME patients. This warrants further examination of these pathways to elucidate whether TRPM3 and impaired calcium mobilisation has a role in CFS/ME.
Novel identification and characterisation of Transient receptor potential melastatin 3 ion channels on Natural Killer cells and B lymphocytes: effects on cell signalling in Chronic fatigue syndrome/Myalgic encephalomyelitis patients, by T. Nguyen, D. Staines, B. Nilius, P. Smith and S. Marshall-Gradisnik in Biological Research 2016 49:27 [Published: 31 May 2016]
