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Mol Neurobiol. 2018 Oct 8. doi: 10.1007/s12035-018-1354-8. [Epub ahead of print]

Immunosignature Analysis of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS).

Author information

1
Günther Analytics, Vancouver, BC, Canada.
2
British Columbia Centre for Disease Control, Vancouver, BC, Canada.
3
School of Population and Public Health, University of British Columbia, Vancouver, BC, Canada.
4
Biodesign Institute, Arizona State University, Phoenix, AZ, USA.
5
Department of Oncology and Medical Physics, Haukeland University Hospital, Bergen, Norway.
6
Sidra Medical and Research Centre, Doha, Qatar.
7
Centre for Health Evaluation and Outcome Sciences, St. Paul's Hospital, Vancouver, BC, Canada.
8
British Columbia Centre for Disease Control, Vancouver, BC, Canada. david.patrick@ubc.ca.
9
School of Population and Public Health, University of British Columbia, Vancouver, BC, Canada. david.patrick@ubc.ca.

Abstract

A random-sequence peptide microarray can interrogate serum antibodies in a broad, unbiased fashion to generate disease-specific immunosignatures. This approach has been applied to cancer detection, diagnosis of infections, and interrogation of vaccine response. We hypothesized that there is an immunosignature specific to ME/CFS and that this could aid in the diagnosis. We studied two subject groups meeting the Canadian Consensus Definition of ME/CFS. ME/CFS (n = 25) and matched control (n = 25) sera were obtained from a Canadian study. ME/CFS (n = 25) sera were obtained from phase 1/2 Norwegian trials (NCT01156909). Sera from six healthy controls from the USA were included in the analysis. Canadian cases and controls were tested for a disease immunosignature. By combining results from unsupervised and supervised analyses, a candidate immunosignature with 654 peptides was able to differentiate ME/CFS from controls. The immunosignature was tested and further refined using the Norwegian and USA samples. This resulted in a 256-peptide immunosignature with the ability to separate ME/CFS cases from controls in the international data sets. We were able to identify a 256-peptide signature that separates ME/CFS samples from healthy controls, suggesting that the hit-and-run hypothesis of immune dysfunction merits further investigation. By extending testing of both our signature and one previously reported in the literature to larger cohorts, and further interrogating the specific peptides we and others have identified, we may deepen our understanding of the origins of ME/CFS and work towards a clinically meaningful diagnostic biomarker.

KEYWORDS:

Diagnosis; Immunosignatures; Myalgic encephalomyelitis/chronic fatigue syndrome; Peptides

PMID:
30298340
DOI:
10.1007/s12035-018-1354-8

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