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Principal Investigator: Jiandi Wan
Organization: UNIVERSITY OF CALIFORNIA AT DAVIS
Fiscal Year: 2024
Award: $224,955
Funding agency: National Institute of Allergy and Infectious Diseases
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex, debilitating disease with
inconclusive causes and no laboratory-based diagnostic tests. Oxygen tension (PO2)-regulated red blood cell
(RBC) capillary velocity has emerged recently as a new mechanism regulating cerebral capillary perfusion and
measures RBC responses to local hypoxia. Such intrinsic RBC responses to PO2 changes may change distinctly
under different pathological conditions and thus represent a new RBC-based approach for disease diagnosis.
Indeed, our preliminary results showed that RBCs collected from ME/CFS patients exhibited impaired velocity in
a microfluidic capillary in response to reduced PO2 and PO2-regulated RBC capillary velocity was improved
significantly when patients received craniocervical instability surgery, strongly suggesting that PO2-regualted
RBC capillary velocity may represent a new characteristic of ME/CFS that might be used to diagnose ME/CFS
and measure ME/CFS progression. Here, we extend our preliminary study and propose an interdisciplinary
approach combing microfluidics, machine learning and RBC cytokine assay to examine rigorously the accuracy
of PO2-regulated RBC capillary velocity as a new laboratory test for ME/CFS and investigate mechanistically the
roles of RBC cytokine signaling in ME/CFS.
Aim 1 will measure PO2-regulated RBC capillary velocity using RBCs from 96 participants and compare the
results of ME/CFS patients with age, gender and race-matched healthy controls. Furthermore, we will develop
machine-learning algorithms to establish a diagnostic classifier to validate PO2-regulated RBC capillary velocity
as a new laboratory test for ME/CFS and assess its feasibility to differentiate ME/CFS patients with different
disease severity. Mechanistically, we will examine hemoglobin-band 3 interactions in RBCs from ME/CFS
patients and examine their correlations with increased oxidative stress in ME/CFS.
Aim 2 will quantify the cytokine profile in RBCs from ME/CFS patients and compare them with age, gender and
race-matched healthy controls. Furthermore, we will alter the RBC cytokine profile and measure the
corresponding changes of PO2-regulated RBC capillary velocity to examine whether RBC cytokine profile plays
a role in the modulation of PO2-regulated RBC capillary velocity. These experiments will provide a previously
unrecognized RBC cytokine signaling in ME/CFS and add new insights to the immune dysregulation in ME/CFS.
Together, the proposed studies exploit new tools and technology to develop a new laboratory test for ME/CFS
and reveal mechanistims underlying PO2-regulated RBC capillary velocity in ME/CFS, which we believe will
directly improve the diagnosis and treatment of ME/CFS.
Terms: <Affect><Age><Assay><Binding><Bioassay><Biological Assay><Biology><Blood capillaries><Blood erythrocyte><COVID survivors><COVID-19 infection survivors><COVID-19 survivors><Cell membrane><Cerebrovascular Circulation><Cerebrum><Characteristics><Chronic Disease><Chronic Fatigue Disorder><Chronic Fatigue Syndrome><Chronic Fatigue and Immune Dysfunction Syndrome><Chronic Illness><Chronic Infectious Mononucleosis-Like Syndrome><Classification><Clinical Research><Clinical Study><Collaborations><Collecting Cell><Complex><Consumption><Cytokine Signal Transduction><Cytokine Signaling><Cytoplasmic Membrane><Development><Diagnosis><Diagnostic><Diagnostic tests><Disease><Disease Progression><Disorder><Erythrocytes><Erythrocytic><Exclusion><Exhibits><Gender><Goals><Hemoglobin><Human><Hyperemia><Hypoxia><Hypoxic><Immune><Immunes><Impairment><Laboratories><Long COVID><Long COVID-19><Long coronavirus disease><Long coronavirus disease 2019><ME/CFS><Machine Learning><Marrow erythrocyte><Measures><Microfluidics><Mission><Modern Man><Molecular><Molecular Interaction><Monitor><Myalgic Encephalomyelitis><NIH><National Institutes of Health><O element><O2 element><Operative Procedures><Operative Surgical Procedures><Oxidative Stress><Oxygen><Oxygen Deficiency><Participant><Pathologic><Patients><Perfusion><Persons><Phosphate Buffer><Phosphorylation><Plasma Membrane><Postviral Fatigue Syndrome><Property><Protein Phosphorylation><Race><Races><Red Blood Cells><Red Cell><Reporting><Research><Role><Royal Free Disease><SARS-CoV-2 survivors><Saline><Saline Solution><Severity of illness><Surgical><Surgical Interventions><Surgical Procedure><Symptoms><Systematics><Technology><Testing><Time><United States National Institutes of Health><Work><ages><blood corpuscles><blood flow in brain><brain blood circulation><brain blood flow><brain capillary><capillary><cerebral><cerebral blood flow><cerebral capillary><cerebral circulation><cerebrocirculation><cerebrovascular blood flow><chronic COVID><chronic COVID-19><chronic disorder><chronic novel coronavirus disease 2019><clinical diagnosis><cytokine><debilitating symptom><developmental><diagnostic approach><diagnostic strategy><diphosphoglycerate><disease diagnosis><disease severity><experience><experiment><experimental research><experimental study><experiments><improved><in vivo><insight><interdisciplinary approach><long haul COVID><long haul COVID-19><long haul coronavirus disease><long haul coronavirus disease 2019><long-hauler COVID><long-hauler COVID-19><long-hauler coronavirus disease 2019><long-hauler syndrome><long-term COVID><long-term COVID-19><long-term coronavirus disease><long-term coronavirus disease 2019><longterm COVID><longterm COVID-19><longterm coronavirus disease><longterm coronavirus disease 2019><machine based learning><machine learned algorithm><machine learning algorithm><machine learning based algorithm><multidisciplinary approach><multiphoton excitation microscopy><multiphoton microscopy><novel><pandemic><pandemic disease><persistent COVID-19><physical symptom><plasmalemma><post COVID syndrome><post COVID-19 syndrome><post acute COVID syndrome><post acute COVID-19><post acute COVID-19 syndrome><post acute SARS-CoV-2><post acute coronavirus disease 2019><post acute coronavirus disease 2019 syndrome><post acute coronavirus disease syndrome><post acute severe acute respiratory syndrome coronavirus 2><post coronavirus disease 2019 syndrome><post coronavirus disease syndrome><post-acute phases of COVID-19><power analysis><prolonged COVID-19 symptoms><racial><racial background><racial origin><recruit><response><response to therapy><response to treatment><social role><surgery><survive COVID-19><survive SARS-CoV-2><therapeutic response><therapy response><tool><treatment response><treatment responsiveness><µfluidic>