RNA-seq analysis of gene expression, viral pathogen, and B-cell/T-cell receptor signatures in complex chronic disease
Open accessAbstract
Background: Chronic fatigue syndrome (CFS) remains poorly understood. Although infections are speculated to trigger the syndrome, a specific infectious agent and underlying pathophysiological mechanism remain elusive. In a previous study, we described similar clinical phenotypes in CFS patients and alternatively diagnosed chronic Lyme syndrome (ADCLS) patients—individuals diagnosed with Lyme disease by testing from private Lyme specialty laboratories but who test negative by reference 2-tiered serologic analysis. Methods: Here, we performed blinded RNA-seq analysis of whole blood collected from 25 adults diagnosed with CFS and 13 ADCLS patients, comparing these cases to 25 matched controls and 11 patients with well-controlled systemic lupus erythematosus (SLE). Samples were collected at patient enrollment and not during acute symptom flares. RNA-seq data were used to study host gene expression, B-cell/T-cell receptor profiles (BCR/TCR), and potential viral infections. Results: No differentially expressed genes (DEGs) were found to be significant when CFS or ADCLS cases were compared to controls. Forty-two DEGs were found when SLE cases were compared to controls, consistent with activation of interferon signaling pathways associated with SLE disease. BCR/TCR repertoire analysis did not show significant differences between CFS and controls or ADCLS and controls. Finally, viral sequences corresponding to anelloviruses, human pegivirus 1, herpesviruses, and papillomaviruses were detected in RNA-seq data, but proportions were similar (P = .73) across all genus-level taxonomic categories. Conclusions: Our observations do not support a theory of transcriptionally mediated immune cell dysregulation in CFS and ADCLS, at least outside of periods of acute symptom flares.
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Morris, M. C., Cooney, K. E., Sedghamiz, H., Abreu, M., Collado, F., Balbin, E. G., Craddock, T. J. A., Klimas, N. G., Broderick, G., & Fletcher, M. A. (2019) · Clinical Therapeutics · doi:10.1016/j.clinthera.2019.03.002 · Cited by 14 · see citing works
- Authors
- Bouquet, J., Gardy, J. L., Brown, S., Pfeil, J., Miller, R. R., Morshed, M., Avina-Zubieta, A., Shojania, K., McCabe, M., Parker, S., Uyaguari, M., Federman, S., Tang, P., Steiner, T., Otterstater, M., Holt, R., Moore, R., Chiu, C. Y., Patrick, D. M., & for the Complex Chronic Disease Study Group
- Affiliations
- Department of Laboratory Medicine, University of California, San Francisco
- University of British Columbia (CA)
- BC Cancer Agency (CA)
- University of California, San Francisco (US)
- Department of Medicine, Division of Rheumatology, University of British Columbia
- BC Centre for Disease Control (CA)
- Centre for Advancing Health Outcomes (CA)
- Sidra Medical and Research Center (QA)
- Department of Medicine, Division of Infectious Diseases, University of British Columbia, Vancouver, Canada
- Canada’s Michael Smith Genome Sciences Centre, BC Cancer Agency
- Corresponding author
- Chiu, Charles Y.
- ORCID
- Venue
- Clinical Infectious Diseases
- Publisher
- Oxford University Press (OUP)
- Published
- 2017-01-18
- Volume
- 64
- Issue
- 4
- Pages
- 476-481
- ISSN
- 1058-4838 (ISSN-L)
- 1537-6591
- PMC
- PMC5850034
- OpenAlex
- W2587139687
- Cited by
- 25
- References
- 40
- Citations by year
- 2025: 3 · 2024: 2 · 2023: 4 · 2022: 2 · 2021: 4 · 2020: 2 · 2019: 3 · 2018: 4 · 2017: 1
- FWCI
- 2.25
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Clinical Infectious Diseases (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by-nc-nd)
- Funders
- National Institutes of Health (R01-HL105704)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Fibromyalgia and Chronic Fatigue Syndrome Research
- Health Sciences › Medicine › Neurology › Long-Term Effects of COVID-19
- Life Sciences › Immunology and Microbiology › Parasitology › Vector-borne infectious diseases
- Keywords
- chronic fatigue syndrome, chronic Lyme disease, systemic lupus erythematosus, host gene expression, B cell receptor repertoire, T cell receptor repertoire, viral infection, anelloviruses, herpesvirus, papillomavirus, interferon signaling, immune dysregulation
- MeSH terms
- Amino Acid Sequence, B-Lymphocytes, Chronic Disease, Disease Susceptibility, Female, Humans, Lyme Disease, Male, Phenotype, Receptors, Antigen, B-Cell, Receptors, Antigen, T-Cell, T-Lymphocytes, Virus Diseases, Fatigue Syndrome, Chronic, Gene Expression, Case-Control Studies, Genetic Predisposition to Disease, Amino Acid Motifs, Gene Expression Profiling, Host-Pathogen Interactions, Metagenome, Metagenomics, High-Throughput Nucleotide Sequencing
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