Genes, environment, and safety monitoring in using registries

“For an MS registry to be useful, it should deliver a clinical tool for the day-to-day care of individual patients”, stated Prof. Tomas Olsson (Karolinska Institute, Sweden) at the beginning of his lecture. Compliance with entering data into the MS registry depends on the benefit for the clinician and the person with MS. Registries are a tool for quality assessment and development of MS care. Nationwide data obtained can be used for numerous research purposes.

The interface of the Swedish MS registry shows the “whole evolution of a certain patient”, Olsson continued, “such as the EDSS course and the different drugs given.” This has led to a widespread use of these rates in Sweden, with 17,397 of 20,500 current MS patients included (85% coverage). The data are used for research in genetics, neuroimmunology, epidemiology, post-marketing follow-up, and biobanks [1]. Subsequently, Prof. Olsson mentioned some selected examples of research projects using the Swedish MS registry as a platform. After the introduction of natalizumab and knowing the influence of JC virus on progressive multifocal leukoencephalopathy (PML) risk, he started the Immunomodulation and MS Epidemiology (IMSE) studies. “Since then, a lot of new drugs have come to the market, so post-marketing surveillance was warranted. Furthermore, several genetics, lifestyle, and environmental factors in MS (EIMS) studies are based on the Swedish data.”

Genetics, lifestyle, and environmental factors

The pathophysiological cascade of MS is characterised by many factors. “We need precise knowledge on causes of MS to provide prevention and more precise therapy. This has been a neglected area”, according to Prof. Olsson. This includes risk genes, lifestyle, and environmental factors, and the interactions between them [2]. Lifestyle and environmental factors have a modest influence (odd ratios of approximately 1.5-2), although their influence is mostly higher compared to the influence of non-HLA genes (ORs of approximately 1.1-1.2). Some factors act during adolescence and early adulthood, such as Epstein-Barr virus (EBV), obesity, brain concussion, and disturbed diurnal rhythm. Many factors interact with MS risk genes; all factors can be argued to act on the immune system.

Further research on the aetiology of MS is warranted to achieve prevention and more selective therapy. Perhaps there should be new emphasis on the adaptive immunity, including ways to define specificities and functions to auto-aggressive T and B cells. The combination of genetics and epidemiology may lead us into testable hypotheses, as exemplified by the interaction between smoking and HLA genes. Thus, combined studies are warranted. Upcoming genetics research should take environmental exposures into account; upcoming epidemiology research should take genetics into account.

1. Hillert J, Stawiarz L. Acta Neurol Scand. 2015;132:11-9.
2. Olsson T, et al. Nat Rev Neurol. 2017;13:25-36.

Posted on 8 November, 201922 March, 2021