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Updated: Dec 21, 2025
Separation of Immune Cell Subpopulations in Peripheral Blood Samples from Children with Infectious Mononucleosis
Published on: September 7, 2022
Intrathecal immunoreactivity in people with or without previous infectious mononucleosis
Daniel Jons1,2, Henrik Zetterberg3,4,5,6, Clas Malmeström1,2
1Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Objectives:
The risk of developing multiple sclerosis (MS) increases (OR: 3.1) after infectious mononucleosis (IM). However, the nature of this link is obscure. We tested the hypothesis that IM might incur long-term sequelae, including low-key inflammatory activity, with characteristics of an MS endophenotype (or presymptomatic trait) and that assays of MS-relevant cyto-/chemokines in the cerebrospinal fluid (CSF) post-IM may show a trend in this direction.
Materials And Methods:
We selected seven CSF cytokines (IL-1b, IL-6, YKL-40, TNF-alpha) or chemokines (IL-8, CCL2, IP-10), representing pro-inflammatory factors previously associated with MS. We assayed the CSF levels of these seven cyto-/chemokines in healthy individuals with a median follow-up time of 10 years after serologically confirmed IM (post-IM group, n = 22), and in healthy controls without a history of IM (n = 19). A group of MS patients (n = 23) were included as reference.
Results:
The CSF levels of IP-10, YKL-40, and CCL-2 were higher in the post-IM group than in our IM unexposed controls (P = .021, .049, .028). Seven of seven cyto-/chemokine assays showed a trend in the predicted direction (P of binomial ratio = .008). However, this trend was non-significant in a multivariate test (P = .22). A power analysis indicated that similar studies including a larger cohort would be numerically realistic.
Conclusions:
These results do not reject the hypothesis that the established epidemiological association between IM and MS results from a stepwise inflammatory propagation from IM sequelae to an MS endophenotype (or presymptomatic trait) in a proportion of IM patients, pending confirmation with adequate power.
Insights
Infectious mononucleosis (IM) may trigger long-term inflammation, potentially leading to multiple sclerosis (MS) endophenotypes. Cerebrospinal fluid analysis post-IM showed elevated inflammatory markers, suggesting a link requiring further investigation.
Area of Science:
- Neuroimmunology
- Infectious Disease Immunology
- Biomarker Discovery
Background:
- Infectious mononucleosis (IM) is linked to an increased risk of multiple sclerosis (MS).
- The precise biological mechanisms underlying this association remain unclear.
- Investigating long-term inflammatory sequelae of IM is crucial for understanding MS pathogenesis.
Purpose of the Study:
- To test the hypothesis that IM can cause long-term inflammatory activity resembling an MS endophenotype.
- To analyze cerebrospinal fluid (CSF) cyto-/chemokine levels in individuals post-IM.
- To explore potential presymptomatic MS traits following IM.
Main Methods:
- Assayed seven MS-relevant CSF cyto-/chemokines (IL-1b, IL-6, YKL-40, TNF-alpha, IL-8, CCL2, IP-10).
- Compared CSF levels in individuals 10 years post-IM (n=22) with controls without IM history (n=19).
- Included an MS patient group (n=23) as a reference.
Main Results:
- CSF levels of IP-10, YKL-40, and CCL-2 were significantly higher in the post-IM group compared to controls.
- A trend towards elevated levels of all seven assayed cyto-/chemokines was observed in the post-IM group.
- The observed trend, while directionally consistent, did not reach statistical significance in multivariate analysis.
Conclusions:
- The findings do not refute the hypothesis linking IM sequelae to MS endophenotypes.
- A stepwise inflammatory process from IM to an MS presymptomatic trait is plausible in a subset of patients.
- Larger cohort studies are needed to confirm these preliminary findings with adequate statistical power.
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