Cytokine networks analysis uncovers further differences between those who develop myalgic encephalomyelitis/chronic fatigue syndrome following infectious mononucleosis

Background: We followed college students before, during, and after infectious mononucleosis (IM) for the development of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Aim: We used network analysis to study relationships between pre-illness cytokine data amongst three groups of participants: those 30 who went on to develop ME/CFS following IM (and met one case definition), those 18 who went on to develop severe ME/CFS (S-ME-CFS) following IM (and met greater than one case definition), and those 58 who recovered following IM (controls). Methods: We recruited 4501 college students; approximately 5% developed IM during their enrollment at university. Those who developed IM were evaluated at a 6-month follow-up to determine whether they recovered or met criteria for ME/CFS; those who met >1 set of criteria for ME/CFS were termed S-ME/CFS. Patterns of pre-illness cytokine networks were then classified according to the following characteristics: membership, modularity, Eigen centrality, Total centrality, and mean degree. Network statistics were compared across groups using a one-way analysis of variance (ANOVA). Results: Those with S-ME/CFS had a more interconnected network of cytokines, whereas recovered controls had more differentiated networks and more subgroupings of cytokine connections. Those with ME/CFS had a network that was denser than the controls, but less dense than those with severe ME/CFS. Conclusions: The distinct network differences between these three groups implies that there may be biological differences between our three groups of study participants at baseline.