Obesity interacts with infectious mononucleosis in risk of multiple sclerosis.

The possible interaction between adolescent obesity and past infectious mononucleosis (IM) was investigated with regard to multiple sclerosis (MS) risk. This report is based on two population-based case-control studies, one with incident cases (1780 cases, 3885 controls) and one with prevalent cases (4502 cases, 4039 controls). Subjects were categorized based on adolescent body mass index (BMI) and past IM and compared with regard to occurrence of MS by calculating odds ratios with 95% confidence intervals (CIs) employing logistic regression. A potential interaction between adolescent BMI and past IM was evaluated by calculating the attributable proportion due to interaction. Regardless of human leukocyte antigen (HLA) status, a substantial interaction was observed between adolescent obesity and past IM with regard to MS risk. The interaction was most evident when IM after the age of 10 was considered (attributable proportion due to interaction 0.8, 95% CI 0.6-1.0 in the incident study, and attributable proportion due to interaction 0.7, 95% CI 0.5-1.0 in the prevalent study). In the incident study, the odds ratio of MS was 14.7 (95% CI 5.9-36.6) amongst subjects with adolescent obesity and past IM after the age of 10, compared with subjects with none of these exposures. The corresponding odds ratio in the prevalent study was 13.2 (95% CI 5.2-33.6). An obese state both impacts the cellular immune response to infections and induces a state of chronic immune-mediated inflammation which may contribute to explain our finding of an interaction between adolescent BMI and past IM. Measures taken against adolescent obesity may thus be a preventive strategy against MS.

Hedström AK ，Lima Bomfim I ，Hillert J ，Olsson T ，Alfredsson L ... -  《-》

Overweight/obesity in young adulthood interacts with aspects of EBV infection in MS etiology.

Because obesity affects the cellular immune response to infections, we aimed to investigate whether high body mass index (BMI) in young adulthood and high Epstein-Barr nuclear antigen 1 (EBNA-1) antibody levels interact with regard to MS risk. We also aimed at exploring potential 3-way interactions between BMI at age 20 years, aspects of Epstein-Barr virus (EBV) infection (high EBNA-1 antibody levels and infectious mononucleosis [IM] history, respectively) and the human leukocyte antigen (HLA)-DRB1*15:01 allele. Using Swedish population-based case-control studies (5,460 cases and 7,275 controls), we assessed MS risk in relation to interactions between overweight/obesity at age 20 years, IM history, EBNA-1 levels, and HLA-DRB1*15:01 status by calculating ORs with 95% CIs using logistic regression. Potential interactions were evaluated on the additive scale. Overweight/obesity, compared with normal weight, interacted significantly with high (>50th percentile) EBNA-1 antibody levels (attributable proportion due to interaction 0.2, 95% CI 0.1-0.4). The strength of the interaction increased with higher category of EBNA-1 antibody levels. Furthermore, 3-way interactions were present between HLA-DRB1*15:01, overweight/obesity at age 20 years, and each aspect of EBV infection. With regard to MS risk, overweight/obesity in young adulthood acts synergistically with both aspects of EBV infection, predominantly among those with a genetic susceptibility to the disease. The obese state both induces a chronic immune-mediated inflammation and affects the cellular immune response to infections, which may contribute to explain our findings.

Hedström AK ，Brenner N ，Butt J ，Hillert J ，Waterboer T ，Olsson T ，Alfredsson L ... -  《-》

Smoking and Epstein-Barr virus infection in multiple sclerosis development.

Hedström AK ，Huang J ，Brenner N ，Butt J ，Hillert J ，Waterboer T ，Kockum I ，Olsson T ，Alfredsson L ... -  《-》

Interaction between adolescent obesity and HLA risk genes in the etiology of multiple sclerosis.

Hedström AK ，Lima Bomfim I ，Barcellos L ，Gianfrancesco M ，Schaefer C ，Kockum I ，Olsson T ，Alfredsson L ... -  《-》

Season of infectious mononucleosis and risk of multiple sclerosis at different latitudes; the EnvIMS Study.

Lossius A ，Riise T ，Pugliatti M ，Bjørnevik K ，Casetta I ，Drulovic J ，Granieri E ，Kampman MT ，Landtblom AM ，Lauer K ，Magalhaes S ，Myhr KM ，Pekmezovic T ，Wesnes K ，Wolfson C ，Holmøy T ... -  《-》