Olivia Thomas Team

Our research focuses on how adaptive immune responses can damage the brain in neurological inflammatory diseases such as multiple sclerosis (MS). Additionally, we aim to understand the role of environmental pathogens as triggers of immune-mediated damage to the central nervous system (CNS).

MS is a chronic inflammatory demyelinating disease of the CNS, with affected individuals experiencing a wide array of symptoms such as vision disturbance, problems with mobility and cognitive deficits. Immune system damage to the myelin sheaths surrounding neurons lead to the formation of lesions in the brain and spinal cord and are responsible for the varied symptoms associated with the disease. The exact triggers for disease are unknown, however strong evidence supports a particular role for Epstein-Barr virus (EBV) in disease mechanisms. Evidence from previous studies suggests a key role for CD4+ T cell responses in the immunopathology of MS, and our work is trying to understand how T and B cells of the adaptive immune system generated in response to pathogens such as EBV may be damaging neuronal tissue in MS and other neurological diseases.

1. Understanding the role of T and B cell responses to EBV in MS development and progression

   The association of EBV with MS development has intrigued researchers for many years. However, despite strong epidemiological evidence and elevated antibody responses to certain viral proteins (Olsson et al. 2017 Nat Rev Neurol), there is currently no accepted mechanism. One hypothesis is molecular mimicry which occurs when adaptive immune responses to virus antigens can respond to proteins in the host’s tissues which have a similar structure. In 2023 our lab demonstrated that adaptive immune responses to EBNA1 from EBV can cross-react with the self-antigen alpha-crystallin B (CRYAB) (Thomas and Bronge et al. 2023 Sci Sdv), and our lab are investigating the role of adaptive immune responses as triggers for neuroinflammation and disease using a range of advanced immunological techniques.

2. Discovery of new autoantigens in neurological diseases

   Techniques to investigate autoreactive T cell responses vary in their efficiency and sensitivity, and often results are difficult to interpret due to the generally low frequency and avidity of autoreactive T cells in peripheral blood. Using a novel antigen-coupled bead technology previously developed by Hans Grönlund’s group (Bronge et al. 2019 Methods X), our lab previously discovered four new T cell autoantigens in MS (Bronge et al. 2022 Sci Adv) and we are now employing this method to investigate new targets of autoimmune attack in other neurological diseases.

Olivia Thomas, PhD, postdoc, olivia.thomas@ki.se

Olivia Thomas received her Ph.D. from the University of Birmingham in the United Kingdom with a focus on molecular mimicry between neuronal proteins and antigens from Epstein-Barr virus (EBV) in multiple sclerosis (MS) under the supervision of Dr Jill Brooks and Dr Graham Taylor. Between 2017 and 2019 she worked at the University of Oxford in the group of Professor Lars Fugger working on immunological mechanisms of MS. Following this, she joined the group of Professor Paul Moss and Dr Helen Parry at the Institute of Immunology and Immunotherapy at the University of Birmingham working on a project to identify perturbations in the immune system during immunotherapy for chronic lymphocytic leukaemia. In 2020, she joined the groups of Associate Professor Hans Grönlund and Professor Tomas Olsson where her current research focus is understanding how virus-specific T cell and antibody responses may cross-react with self-antigens and damage the central nervous system in neurological diseases.

Urszula Rykaczewska, PhD, postdoctoral researcher, urszula.rykaczewska@ki.se

Mattias Bronge, MD PhD, affiliated to research, mattias.bronge@ki.se

Marina Galešić, BSc, Erasmus internship student, marina.galesic@ki.se

Lorenzo De la Parra Soto , BSc,  Masters internship student, lorenzo.de.la.parra.soto@ki.se

Karolinska Neuroimmunology & Multiple Sclerosis Centre (KNIMS)

Our most recent publication (PMID: 37196088) gained global media attention receiving a top 5% overall Altmetric attention score and top 1% for articles of the same age (Altmetric score of 819 as of 2024-01-05). Over 100 media articles reported our work including:

• Karolinska Institutet pressrelease on 17^th May 2023: https://news.ki.se/new-study-explains-how-a-common-virus-can-cause-multiple-sclerosis
  Alternatively show the CMM press release?
• The Guardian, 17^th May 2023: https://www.theguardian.com/society/2023/may/17/common-viral-antibodies-could-trigger-ms-research-reveals

Medical News Today, 18^th May 2023: https://www.medicalnewstoday.com/articles/how-the-epstein-barr-virus-may-spur-the-progression-of-multiple-sclerosis?c=521321678804

Our lab contributes to science communication by translating complex research into accessible articles, published on platforms like The Conversation and The Science Breaker, thereby sharing insights and fostering public understanding of scientific advancements our field.

• “Multiple sclerosis: new evidence for the role of glandular fever virus” published online in The Conversation on 19^th May 2023: https://theconversation.com/multiple-sclerosis-new-evidence-for-the-role-of-glandular-fever-virus-205904
• “Korsreaktiva EBNA1-autoantikroppar riktar sig mot CRYAB vid MS” published online in Neurologi i Sverige on 21st September 2023: https://www.neurologiisverige.se/korsreaktiva-ebna1-autoantikroppar-riktar-sig-mot-cryab-vid-ms/
• “How the immune response to a common virus may target the brain in multiple sclerosis” published online in The Science Breaker on 20^th December 2023: https://doi.org/10.25250/thescbr.brk772

MS Forskningsfonden

NEURO Stockholm

Neurofonden

Gunvor och Josef Anérs Stiftelse

The impact of hybrid immunity on immune responses after SARS-CoV-2 vaccination in persons with multiple sclerosis treated with disease-modifying therapies.
Rabenstein M, Thomas OG, Carlin G, Khademi M, Högelin KA, Malmeström C, Axelsson M, Brandt AF, Gafvelin G, Grönlund H, Kockum I, Piehl F, Lycke J, Olsson T, Hessa T. Eur J Neurol. 2023 Dec;30(12):3789-3798. doi:10.1111/ene.16015. Epub 2023 Aug 24. PMID: 37522464.

Cross-reactive EBNA1 immunity targets alpha-crystallin B and is associated with multiple sclerosis.
Thomas OG*, Bronge M*, Tengvall K, Akpinar B, Nilsson OB, Holmgren E, Hessa T, Gafvelin G, Khademi M, Alfredsson L, Martin R, Guerreiro-Cacais AO, Grönlund H, Olsson T, Kockum I. Sci Adv. 2023 May 19;9(20):eadg3032. doi:10.1126/sciadv.adg3032. Epub 2023 May 17. PMID: 37196088; PMCID: PMC10191428.

Identification of four novel T cell autoantigens and personal autoreactive profiles in multiple sclerosis.
Bronge M, Högelin KA, Thomas OG, Ruhrmann S, Carvalho-Queiroz C, Nilsson OB, Kaiser A, Zeitelhofer M, Holmgren E, Linnerbauer M, Adzemovic MZ, Hellström C, Jelcic I, Liu H, Nilsson P, Hillert J, Brundin L, Fink K, Kockum I, Tengvall K, Martin R, Tegel H, Gräslund T, Al Nimer F, Guerreiro Cacais AO, Khademi M, Gafvelin G, Olsson T, Grönlund H. Sci Adv. 2022 Apr 29;8(17):eabn1823. doi: 10.1126/sciadv.abn1823. Epub 2022 Apr 27. PMID: 35476434; PMCID: PMC9045615.

Sensitive detection of antigen-specific T-cells using bead-bound antigen for in vitro re-stimulation.
Bronge M, Kaiser A, Carvalho-Queiroz C, Nilsson OB, Ruhrmann S, Holmgren E, Olsson T, Gafvelin G, Grönlund H. MethodsX. 2019 Jul 8;6:1635-1641. doi: 10.1016/j.mex.2019.07.004. PMID: 31367530; PMCID: PMC6651840.

Myelin oligodendrocyte glycoprotein revisited-sensitive detection of MOG-specific T-cells in multiple sclerosis.
Bronge M, Ruhrmann S, Carvalho-Queiroz C, Nilsson OB, Kaiser A, Holmgren E, Macrini C, Winklmeier S, Meinl E, Brundin L, Khademi M, Olsson T, Gafvelin G, Grönlund H. J Autoimmun. 2019 Aug;102:38-49. doi: 10.1016/j.jaut.2019.04.013. Epub 2019 May 1. PMID: 31054941.