Exposure to infant siblings during early life and risk of multiple sclerosis

摘要

Context The 'hygiene hypothesis' has implicated sibship as a marker of infection load during early life and suggests exposure or re-exposure to infections can influence the developing immune system. Viral infection has been implicated in the pathogenesis of multiple sclerosis (MS).\ud\udObjectives To evaluate whether exposure to infant siblings in early life is associated with the risk of MS . To explore the possible mechanism for any apparent protective effect, including altered Epstein-Barr virus (EBV) infection patterns. \ud\udDesign, setting and patients Population-based case-control study in Tasmania, Australia from 1999 to 2001 based on 136 cases of MRI-confirmed MS and 272 community controls, matched on sex and year of birth. \ud\udMain Outcome Measure Risk of MS and serum EBV IgG response by duration of contact with younger siblings aged less than 2 years in the first 6 years of life. \ud\udResults Increasing duration of contact with a younger sibling aged less than 2 years in the first 6 years of life was associated with reduced MS risk (Adjusted Odds Ratios: Less than 1 infant-years, 1:00 [reference]; 1 to 3 infant-years, 0.59 [ 95%CI, 0.34-1.02]; 3 to 5 infant-years, 0.47 [ 95%CI, 0.23, 1.02]; 5 or more infant-years, 0.23 [ 95%CI, 0.07, 0.72]; test for trend p = 0.002). A history of exposure to infant siblings was associated with a reduced IgG response to EBV among controls. Controls with at least one infant-year contact had a reduced risk of infectious mononucleosis (AOR 0.44 [ 95% CI, 0.21,0.92]) and a reduced risk of very high composite EBV IgG titres (AOR 0.33 [ 95% CI, 0.11,0.98 ]) compared to other controls. The inverse association between higher infant contact and MS was independent of EBV IgG titre. \ud\udConclusion Higher infant sibling exposure in the first six years of life was associated with a reduced risk of MS, possibly by altering childhood infection patterns and related immune responses.