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

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.