PT  - JOURNAL ARTICLE
AU  - Anna Karin Hedström
AU  - Nicole Brenner
AU  - Julia Butt
AU  - Jan Hillert
AU  - Tim Waterboer
AU  - Tomas Olsson
AU  - Lars Alfredsson
TI  - Overweight/obesity in young adulthood interacts with aspects of EBV infection in MS etiology
AID  - 10.1212/NXI.0000000000000912
DP  - 2021 Jan 01
TA  - Neurology - Neuroimmunology Neuroinflammation
PG  - e912
VI  - 8
IP  - 1
4099  - http://nn.neurology.org/content/8/1/e912.short
4100  - http://nn.neurology.org/content/8/1/e912.full
SO  - Neurol Neuroimmunol Neuroinflamm2021 Jan 01; 8
AB  - Objective 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.Methods 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.Results 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.Conclusions 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.BMI=body mass index; EBV=Epstein-Barr virus; EIMS=Epidemiological Investigation of Multiple Sclerosis; EIRA=Epidemiological Investigation of Rheumatoid Arthritis; EPNA-1=Epstein-Barr nuclear antigen 1; GEMS=Genes and Environment in Multiple Sclerosis; HLA=human leukocyte antigen; IM=infectious mononucleosis; MFI=median flourescence intensity