Siblings reduce multiple sclerosis risk by preventing delayed primary Epstein-Barr virus infection

Area of Science:

• Epidemiology
• Virology
• Neurology

Background:

• Delayed Epstein-Barr virus (EBV) infection is strongly linked to the development of multiple sclerosis (MS).
• Siblings can offer protection against infectious mononucleosis (IM) by potentially preventing delayed primary EBV infection.
• The protective effect of siblings against IM increases with the number of siblings and decreases with age difference.

Purpose of the Study:

• To investigate the hypothesis that sibling constellation influences MS risk by mirroring the risk of infectious mononucleosis (IM).
• To indirectly test the role of primary EBV infection timing in MS development.

Main Methods:

• Retrospective cohort study using Danish nationwide registers.
• Followed individuals born 1971-2018 for diagnoses of IM and MS.
• Analyzed relative risks (hazard ratios) of IM and MS based on sibship constellation using Cox regression.

Main Results:

• Hazard ratios for IM and MS as a function of sibship constellation were similar (P=0.19).
• Having siblings, especially younger ones, was associated with reduced risk of both IM and MS.
• Maximum protection was observed with a 0-2 year younger sibling (HR=0.80 for MS), while a 0-2 year older sibling offered less protection (HR=0.91 for MS).

Conclusions:

• Sibling exposure, particularly to younger siblings, may protect against MS by promoting early EBV infection.
• Findings support the hypothesis that delayed EBV infection is a prerequisite for MS development.
• Early EBV vaccination before adolescence could potentially prevent MS, pending further research into immune mechanisms.