Infectious mononucleosis (IM) in childhood and adolescence increases risk of multiple sclerosis (MS), according to study results published in JAMA Network Open.

IM, which often results from Epstein-Barr virus (EBV), and high levels anti-EBV nuclear antigen 1(EBNA-1) antibodies are each linked with increased risk of MS, but there may be confounding factors, which may include common genetic factors. Previous studies have explored whether shared familial genetic and environmental factors could explain the connection of IM and MS. In the current study, researchers in Sweden examined the association of IM in childhood, adolescence and early adulthood with MS diagnosis in adulthood.

Data of individuals (n=2,492,980; 47.37% women) born in Sweden from 1958 to 1994 whose parents were alive in 1990 was included in the study. Researchers identified hospital-based MS diagnoses of the individuals and of their parents and first-degree relatives. They followed up with participants aged 20 years from 1978 to 2018 for a median 15.38 years.


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Women had increased risk of MS diagnosis ([Hazard Ratio (HR) 2.62]), as did those whose mothers were older at their birth (HR per older year of age 1.07), and those who were the oldest children.

Individuals who had IM in childhood (HR 1.98 [95% CI, 1.21-3.23]) or adolescence (3.00 [95% CI, 2.48-3.63]) were more likely to be diagnosed with MS compared with those who didn’t. Controlling for unmeasured shared family factors increased that association (HR 2.87 [95% CI, 1.44-5.74], HR 3.19 [95% CI, 2.29-4.46] respectively). Early adulthood IM held less of an association with diagnosis of MS (HR, 1.89; 95% CI 1.18-3.05), and that association was lost after controlling for unmeasured shared familial factors.

When the researchers excluded MS diagnoses at age 24 or younger, they found that increased risk of being diagnosed with MS was associated with IM in childhood and adolescence (HRs, 3.72 [95% CI, 1.44-9.56] and 3.96 [95% CI, 2.65-5.90]). When researchers defined possible onset of MS as first demyelinating disease of the central nervous system after age 20 and excluded individuals diagnosed with demyelinating disease prior to 20 years of age, IM in childhood and adolescence were linked with increased risk of MS diagnosis.

HRs were not impacted by exclusion of individuals born after 1987, between within-sibling analysis or within-full-sibling analysis, or exclusion of families with only 1 parent alive in 1990.

Study limitations include some exclusion of IM and MS diagnoses, possible selection bias, inability to assess MS onset prior to first MS diagnosis, and inability to adjust for vitamin D level, smoking level, and body mass index.

“The findings of this population–based cohort study suggest that IM in childhood and particularly adolescence is associated with a subsequent MS diagnosis, independent of shared familial factors. Therefore, greater susceptibility to infection is less likely to be the explanation,” the researchers concluded.

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures. 

Reference

Xu Y, Hiyoshi A, Smith KA, et al. Association of infectious mononucleosis in childhood and adolescence with risk for a subsequent multiple sclerosis diagnosis among siblings. JAMA Network Open. Published online October 11, 2021. doi: 10.1001/jamanetworkopen.2021.24932



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