Gene expression correlates of postinfective fatigue syndrome after infectious mononucleosis

Background. Infectious mononucleosis ( IM) commonly triggers a protracted postinfective fatigue syndrome ( PIFS) of unknown pathogenesis. Methods. Seven subjects with PIFS with 6 or more months of disabling symptoms and 8 matched control subjects who had recovered promptly from documented IM were studied. The expression of 30,000 genes was examined in the peripheral blood by microarray analysis in 65 longitudinally collected samples. Gene expression patterns associated with PIFS were sought by correlation with symptom factor scores. Results. Differential expression of 733 genes was identified when samples collected early during the illness and at the late ( recovered) time point were compared. Of these genes, 234 were found to be significantly correlated with the reported severity of the fatigue symptom factor, and 180 were found to be correlated with the musculoskeletal pain symptom factor. Validation by analysis of the longitudinal expression pattern revealed 35 genes for which changes in expression were consistent with the illness course. These genes included several that are involved in signal transduction pathways, metal ion binding, and ion channel activity. Conclusions. Gene expression correlates of the cardinal symptoms of PIFS after IM have been identified. Further studies of these gene products may help to elucidate the pathogenesis of PIFS.