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

ABSTRACT

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.

KEYWORDS:

• Networks
• cytokines
• infectious mononucleosis
• chronic fatigue syndrome
• myalgic encephalomyelitis

Disclosure statement

No potential conflict of interest was reported by the author(s).

Acknowledgements

We thank the Comprehensive Metabolic Core of Northwestern University for excellent technical assistance with all of the cytokine assays.

Correction Statement

This article has been republished with minor changes. These changes do not impact the academic content of the article.

Additional information

Notes on contributors

Leonard A. Jason

Leonard A. Jason is professor of psychology and the Director of the Center for Community Research at DePaul University. He has been studying the epidemiology of ME/CFS since the early 1990s, and his work has included community-based adult and pediatric samples.

Joseph Cotler

Joseph Cotler earned his Ph.D. in Social Psychology from the University of Birmingham in England. He is currently researching cytokine expressions resulting from ME/CFS.

Mohammed F. Islam

Mohammed F. Islam has a background in experimental psychology with a focus on human cognition. He is currently studying the factors associated with the development of ME/CFS after infectious mononucleosis in college students.

Jacob Furst

Jacob Furst is a professor in the College of Computing and Digital Media and DePaul University. His research interests include medical informatics with applications of machine learning and data mining to medical image processing and computed vision.

Matthew Sorenson

Matthew Sorenson is a professor and the Assistant Dean for Graduate Education at Texas A&M. His research interests include immunological correlates of fatigue and pathogenesis in neurological disease. Additional interests include psychological stress, coping, and immunosenescence.

Ben Z. Katz

Dr Ben Z. Katz is a Professor of Pediatrics at the Northwestern University Feinberg School of Medicine and an Attending Physician in the Division of Infectious Diseases at the Ann & Robert H Lurie Children's Hospital of Chicago. He has been investigating epidemiology and prospective studies with the DePaul University group since 2002.