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Multiple Sclerosis (MS), a complex autoimmune disorder affecting mainly young adults, with a higher prevalence in women. Its diverse symptoms and inherent progression complexity hinder early detection and personalized prognostic evaluations. This proposal aspires to enhance health outcomes, elucidate MS’s intricate mechanisms, and reduce neurological disabilities through innovative, transformative methodologies.The objective is to develop advanced predictive models by harnessing extensive multimodal data, facilitating early detection, and personalized interventions. The project is organized in 6 different but interconnected tasks and will run for 5 years. We will integrate clinical, lifestyle, and ´omics´ data. By targeting the prodromal phase of MS, we aspire to devise impactful intervention strategies and project disease progression, with Artificial Intelligence (AI) serving as the cornerstone for analyzing data. We will test the MS prediction among first degree relatives. We will also identify biomarkers for MS risk and severity and genetic factors associated with MS severity. A special focus will be on role of sex hormones.Employing advanced analytical techniques, network theories, autoencoders and deep learning, we will probe the multifaceted nature of MS using one of the world’s leading MS-specific databases. This will contribute to more comprehensive and individualized MS treatment approaches.

Research problem and specific questions: The labour market is currently undergoing a substantial transformation. The nature of work and the way it is conceptualized is evolving in unprecedented ways. Work is increasingly becoming more remote, complex, and inter-connected whilst employees are expected to be more autonomous and efficient at work, whilst learning and adapting to the new technologies at the same time. Multiple sclerosis (MS) is the most common neurological disease-causing disability in young adults. In the past 20 years, treatment strategies have become increasingly effective. However, most people with MS (PwMS) experience limitations in respect to their work capacity and many are forced to exit the labour market once the disease progresses and substantial disabilities appear. It is uncertain how the changing dynamics of the labour market are impacting the work of PwMS and whether these changes can differ depending on the labour market attachment and the timing of disease onset and progression. Therefore, this project aims to study the impact of the described labour market changes in relation to individuals with MS and disease progression in light of the recently developed highly effective treatments.  Data and method and Plan for project realisation: Different research strategies will be used: Microdata linked from several Swedish registers including all people of working age diagnosed with MS, about 14 000 individuals and matched population references, will be used to explore factors associated with entering the labour market, remaining in paid work long term, and exiting from the workforce. In the second part, survey information collected from over 4000 responders in 2021, linked to register information will be used. Here we will focus on strategies used in relation to work and further deepen the understanding of how MS has influenced their work life. In the third part, individual and focus group interviews including PwMS and employers will be used to contrast our findings with the experiences of the work-life challenges related to new ways of working in combination with experienced physical or cognitive limitations both from a patient and an employer perspective.  Societal relevance and utilisation: This interdisciplinary project will generate new, relevant, and updated knowledge of working outcomes of PwMS given the transformation of the modern labour market and treatment advances for MS.

Background: Multiple sclerosis (MS) predominantly affects women, and the clinical onset of MS often occurs during child-bearing age. Clinicians recommend discontinuation of disease-modifying therapies (DMTs) before conception unless the risk of disease worsening outweighs the risk to the fetus. New high-efficacy DMTs such as rituximab, a chimeric monoclonal B-cell-depleting anti-CD20 antibody, are frequently used off-label for the treatment of MS in Sweden. Objective: There is a lack of evidence on the influence of DMTs including anti-CD20-antibodies on the infant´s immune system and their responses to vaccination during the first months after birth. Purpose: To fill the knowledge gaps regarding the impact of the mother´s DMT on a newborn´s humoral immune system. Aims: To investigate the association between mother´s exposure to DMTs pre-pregnancy and infant´s 1) successful B-cell production 2) vaccine response and 3) risk of infections within the first year. Setting: a) Retrospective cohort study with infants born between 2012 and 2022 to mothers with MS treated with DMTs. The infants´humoral immune system will be assessed by analyzing markers of successful B-cell production in newborn dried-blood spot samples. b) Prospective cohort study, recruiting between 2024 och 2025. Vaccine responses and infection rates in infants to mothers with rituximab will be compared to mothers with other DMTs prior to pregnancy.