Treatment Avenues in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Split-gender Pharmacogenomic Study of Gene-expression Modules

Authors

Mary G. Jeffrey, Institute for Neuro-Immune Medicine, Nova Southeastern University, Ft. Lauderdale, FL, USA; College of Psychology, Nova Southeastern University, Ft. Lauderdale, FL, USA.
Lubov Nathanson, Institute for Neuro-Immune Medicine, Nova Southeastern University, Ft. Lauderdale, FL, USA; Department of Clinical Immunology, Nova Southeastern University, Ft. Lauderdale, FL, USA.
Kristina Aenlle, Institute for Neuro-Immune Medicine, Nova Southeastern University, Ft. Lauderdale, FL, USA; Department of Clinical Immunology, Nova Southeastern University, Ft. Lauderdale, FL, USA; Miami Veterans Affairs Medical Center, Miami, FL, USA.
Zachary M. Barnes, Institute for Neuro-Immune Medicine, Nova Southeastern University, Ft. Lauderdale, FL, USA; Miami Veterans Affairs Medical Center, Miami, FL, USA; Miller School of Medicine, University of Miami, Miami, FL, USA; Diabetes Research Institute, University of Miami, Miami, FL, USA.
Mirza Baig, Institute for Neuro-Immune Medicine, Nova Southeastern University, Ft. Lauderdale, FL, USA.
Gordon Broderick, Rochester Regional HealthFollow
Nancy G. Klimas, Institute for Neuro-Immune Medicine, Nova Southeastern University, Ft. Lauderdale, FL, USA; College of Psychology, Nova Southeastern University, Ft. Lauderdale, FL, USA; Department of Clinical Immunology, Nova Southeastern University, Ft. Lauderdale, FL, USA.
Mary Ann Fletcher, Institute for Neuro-Immune Medicine, Nova Southeastern University, Ft. Lauderdale, FL, USA; Department of Clinical Immunology, Nova Southeastern University, Ft. Lauderdale, FL, USA; Miami Veterans Affairs Medical Center, Miami, FL, USA.
Travis J. Craddock, Institute for Neuro-Immune Medicine, Nova Southeastern University, Ft. Lauderdale, FL, USA; College of Psychology, Nova Southeastern University, Ft. Lauderdale, FL, USA; Department of Clinical Immunology, Nova Southeastern University, Ft. Lauderdale, FL, USA; Department of Computer Science, Nova Southeastern University, Ft. Lauderdale, FL, USA.

Department

Research

Document Type

Article

Publication Title

Clinical Therapeutics

Abstract

PURPOSE: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating multisymptom illness impacting up to 1 million people in the United States. As the pathogenesis and etiology of this complex condition are unclear, prospective treatments are limited. Identifying US Food and Drug Administration-approved drugs that may be repositioned as treatments for ME/CFS may offer a rapid and cost-effective solution. METHODS: Here we used gene-expression data from 33 patients with Fukuda-defined ME/CFS (23 females, 10 males) and 21 healthy demographically comparable controls (15 females, 6 males) to identify differential expression of predefined gene-module sets based on nonparametric statistics. Differentially expressed gene modules were then annotated via over-representation analysis using the Consensus Pathway database. Differentially expressed modules were then regressed onto measures of fatigue and cross-referenced with drug atlas and pharmacogenomics databases to identify putative treatment agents. FINDINGS: The top 1% of modules identified in males indicated small effect sizes in modules associated with immune regulation and mitochondrial dysfunction. In females, modules identified included those related to immune factors and cardiac/blood factors, returning effect sizes ranging from very small to intermediate (0.147 < Cohen δ < 0.532). Regression analysis indicated that B-cell receptors, T-cell receptors, tumor necrosis factor α, transforming growth factor β, and metabolic and cardiac modules were strongly correlated with multiple composite measures of fatigue. Cross-referencing identified genes with pharmacogenomics data indicated immunosuppressants as potential treatments of ME/CFS symptoms. IMPLICATIONS: The findings from our analysis suggest that ME/CFS symptoms are perpetuated by immune dysregulation that may be approached via immune modulation-based treatment strategies.

First Page

815

Last Page

835.e6

DOI

10.1016/j.clinthera.2019.01.011

Volume

41

Issue

5

Publication Date

5-1-2019

Medical Subject Headings

Case-Control Studies; Fatigue Syndrome, Chronic (drug therapy, genetics); Female; Gene Regulatory Networks; Humans; Immunologic Factors (immunology); Male; Pharmacogenomic Testing

PubMed ID

30851951

Recommended Citation

Jeffrey, M. G., Nathanson, L., Aenlle, K., Barnes, Z. M., Baig, M., Broderick, G., Klimas, N. G., Fletcher, M. A., & Craddock, T. J. (2019). Treatment Avenues in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Split-gender Pharmacogenomic Study of Gene-expression Modules. Clinical Therapeutics, 41 (5), 815-835.e6. https://doi.org/10.1016/j.clinthera.2019.01.011