Journal of IiMER University in Australia. Abstract: Impaired calcium mobilization and dysregulation of transient receptor potential melastatin 3 ion channels in natural killer cells from chronic fatigue syndrome/myalgic encephalomyelitis. Staines, D.R1,2., Nguyen, T., 1,2 , Johnston, S1,2., Smith, P 2 and Marshall-Gradisnik, S1,2 1. School of Medical Science, Griffith University, Gold Coast, Australia 2. The National Centre for Neuroimmunology and Emerging Diseases, Menzies Health Institute Queensland, Griffith University, Gold Coast, Australia. Chronic Fatigue Syndrome/ Myalgic Encephalomyelitis (CFS/ME) is disorder with hallmarks of varying changes in immune cells and molecular related mechanisms. Transient receptor potential melastatin subfamily 3 (TRPM3) ion channels play a role in calcium (Ca2+) cell signalling. Reduced TRPM3 protein expression has been identified in chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) patients. However, the significance of TRPM3 and association with intracellular Ca2+ mobilization has yet to be determined. Ca2+ flux, TRPM3 and NK cytotoxicity activity was measured under various stimulants, including pregnenolone sulphate (PregS), thapsigargin (TG), 2‐aminoethoxydiphenyl borate (2APB) and ionomycin on CD56dimCD16+NK cells and CD56brightCD16dim/– isolated NK cells. Unstimulated CD56brightCD16dim/– NK cells showed significantly reduced TRPM3 receptors in CFS/ME compared with healthy controls (HC). PregS‐stimulated CD56dimCD16+ NK cells increased TRPM3 expression significantly in CFS/ME, but this was not associated with a significant increase in Ca2+flux and NK cell lysis. TG‐stimulated CD56dimCD16+ NK cells significantly increased NK cell lysis prior to PregS stimulation in CFS/ME patients compared with HC. Differential expression of TRPM3 and Ca2+ flux between NK cell subtypes may provide evidence for their role in the pathomechanism involving NK cell cytotoxicity in CFS/ME. Professor Nancy Klimas Director, Institute for Neuro Immune Medicine, Nova Southeastern University Director, 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 Professor Emerita, University of Miami, School of Medicine Nancy Klimas, MD, has more than 30 years of professional experience and www.investinme.org Page 69 of 82

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