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Human herpesvirus (HHV)-6A or HHV-6B involvement in multiple sclerosis (MS) etiology has remained controversial mainly due to the lack of serological methods that can distinguish the two viruses. A novel multiplex serological assay measuring IgG reactivity against the immediate-early protein 1 from HHV-6A (IE1A) and HHV-6B (IE1B) was used in a MS cohort (8,742 persons with MS and 7,215 matched controls), and a pre-MS cohort (478 individuals and 476 matched controls) to investigate this further. The IgG response against IE1A was positively associated with MS (OR = 1.55, p = 9 × 10^-22), and increased risk of future MS (OR = 2.22, p = 2 × 10^-5). An interaction was observed between IE1A and Epstein-Barr virus (EBV) antibody responses for MS risk (attributable proportion = 0.24, p = 6 × 10^-6). In contrast, the IgG response against IE1B was negatively associated with MS (OR = 0.74, p = 6 × 10^-11). The association did not differ between MS subtypes or vary with severity of disease. The genetic control of HHV-6A/B antibody responses were located to the Human Leukocyte Antigen (HLA) region and the strongest association for IE1A was the DRB1^*13:01-DQA1^*01:03-DQB1^*06:03 haplotype while the main association for IE1B was DRB1^*13:02-DQA1^*01:02-DQB1^*06:04. In conclusion a role for HHV-6A in MS etiology is supported by an increased serological response against HHV-6A IE1 protein, an interaction with EBV, and an association to HLA genes.

BACKGROUND: Obesity early in life has been linked to increased risk of developing multiple sclerosis (MS). Leptin and insulin are both associated with obesity, making them suitable candidates for investigating this connection.

OBJECTIVE: To determine if leptin and insulin are risk factors for relapsing-remitting multiple sclerosis (RRMS).

METHODS: In this nested case-control study using blood samples from Swedish biobanks, we compared concentrations of leptin and insulin in 649 individuals who later developed RRMS with 649 controls matched for biobank, sex, age and date of sampling. Only pre-symptomatically drawn samples from individuals below the age of 40 years were included. Conditional logistic regression was performed on z-scored values to calculate odds ratios (ORs) with 95% confidence intervals (CIs).

RESULTS: A 1-unit leptin z-score increase was associated with increased risk of MS in individuals younger than 20 years (OR = 1.4, 95% CI = 1.1-1.9) and in all men (OR = 1.4, 95% CI = 1.0-2.0). In contrast, for women aged 30-39 years, there was a lower risk of MS with increased leptin levels (OR = 0.74, 95% CI = 0.54-1.0) when adjusting for insulin levels.

CONCLUSION: We show that the pro-inflammatory adipokine leptin is a risk factor for MS among young individuals.

Background: High 25-hydroxyvitamin D concentrations have been associated with a reduced risk of multiple sclerosis, with indications of a stronger effect among young individuals.

Objective: Investigate the 25-hydroxyvitamin D association with multiple sclerosis and test if this association is age dependent.

Methods: Prospectively drawn blood samples from individuals later developing relapsing-remitting multiple sclerosis and controls matched for biobank, sex, age and date of sampling, were analysed with liquid chromatography tandem mass spectrometry.

Results: High levels of 25-hydroxyvitamin D (top quintile) were associated with a reduced multiple sclerosis risk (odds ratio 0.68, 95% confidence interval 0.50-0.93).

Conclusion: These findings further support a role for vitamin D in MS aetiology.

Background and purpose: Infections with human herpesvirus 6A (HHV‐6A) and Epstein–Barr virus (EBV) have been linked to multiple sclerosis (MS) development. For EBV, late infection has been proposed as a risk factor, but serological support is lacking. The objective of this study was to investigate how age affects the EBV and HHV‐6A associated risks of developing MS.

Methods:  In this nested case–control study, Swedish biobanks were accessed to find pre‐symptomatically collected blood samples from 670 individuals who later developed relapsing MS and 670 matched controls. A bead‐based multiplex assay was used to determine serological response against EBV and HHV‐6A. Conditional logistic regression was used to calculate odds ratios and 95% confidence intervals.

Results: Seropositivity against EBV exhibited a pattern where associations switched from a decreased risk of developing MS in the group below 20 years of age to an increased risk amongst individuals aged 20–29 and 30–39 years (p for trend 0.020). The age of transition was estimated to be 18.8 years. In contrast, HHV‐6A was associated with increased MS risk in all age groups (total cohort odds ratio 2.1, 95% confidence interval 1.6–2.7).

Conclusions: This study suggests EBV infection after adolescence and age independent HHV‐6A infection as risk factors for MS.