RESUMEN
The phenotypes of B lineage cells that produce oligoclonal IgG in multiple sclerosis have not been unequivocally determined. Here, we utilized single-cell RNA-seq data of intrathecal B lineage cells in combination with mass spectrometry of intrathecally synthesized IgG to identify its cellular source. We found that the intrathecally produced IgG matched a larger fraction of clonally expanded antibody-secreting cells compared to singletons. The IgG was traced back to two clonally related clusters of antibody-secreting cells, one comprising highly proliferating cells, and the other consisting of more differentiated cells expressing genes associated with immunoglobulin synthesis. These findings suggest some degree of heterogeneity among cells that produce oligoclonal IgG in multiple sclerosis.
RESUMEN
BACKGROUND AND OBJECTIVES: To prospectively investigate the long-term relationship between body mass index (BMI) in adolescents and young adults and risk for multiple sclerosis (MS) at the population level. METHODS: We used data from the population-based compulsory Norwegian tuberculosis screening program during 1963 to 1975, including objectively measured height and weight from ≈85% of all eligible citizens. This was combined with data from the Norwegian MS registry and biobank up to November 2020. BMI was standardized according to age and sex, and risk for MS was calculated with Cox proportional hazard models. RESULTS: During 30,829,506 years of follow-up, we found 1,409 cases of MS among 648,734 participants in eligible age groups (14-34 years). Overall, obesity was associated with increased MS risk (hazard ratio [HR] 1.53 [95% confidence interval (CI) 1.25-1.88]), and the risk was similar in men (HR 1.4 [95% CI 0.95-2.06] and women (HR 1.59 [95% CI 1.25-2.02]). Risk was highest for the youngest age groups (age 14-16: HR 1.73 [95% CI 1.19-2.53]; 17-19: HR 1.61 [95% CI 1.08-2.39]; 20-24: HR 1.56 [95% CI 1.04-2.36]) and was no longer present for those >30 years of age. DISCUSSION: High BMI in individuals 14 to 24 years of age was associated with increased MS risk later in life in both male and female individuals.