Rikard Holmdahl

About me

I have an unusual background as I entered medical school on the basis of several years work in hard metal industry. I studied on evenings and succeed to be accepted at medical school at Uppsala University 1977. During the medical courses I became interested in basic research and in particular in immunology and why autoimmune diseases developed. I joined the immunology department led by Hans Wigzell 1981 and completed my PhD 1985. I completed my MD 1987 and was appointed as a docent 1987, everything at Uppsala University.  After a short clinical residency career, and some shorter postdoc experiences in US, I was appointed as an associate professor at the Swedish Medical Research Council 1990. I was appointed as a full professor at Lund University 1993 and, happily for me, my entire research group joined in the move to Lund – together we formed the Medical Inflammation Research (MIR) unit at Lund University.

At Lund University we built a platform for genetic analysis of animal models for autoimmune diseases. We were the first to positionally clone genetic polymorphism causing autoimmune diseases, the first discovery was a single nucleotide polymorphism at the Ncf1 gene causing susceptibility to autoimmune diseases in rat models. This polymorphism could later be shown to of major importance also in human autoimmune diseases and contributed to change the view on redox regulation, lack of oxidation could enhance autoimmunity. We have continued to positional clone genes and our current research is based on several of the genes that have been identified, making the focus on relevant targets for regulation of autoimmune diseases more relevant.

In 2008 I was recruited to Karolinska Institute and was located as a professor and head of the section for medial inflammation research. We moved our research group from Lund to Stockholm. On the basis of our basic research we continued to also develop some more applied projects with the aim to enhance the diagnostic tests and developing vaccines to prevent autoimmune diseases. We have continued our genetic research with a strong focus on redox regulation in autoimmunity but we are also looking at the other side of the coin, how redox regulation could help protection against cancer.

To be research leader also requires administrative and economic responsibilities as all research need to be self-financed and be adjusted into a university organisation. Besides this, its and important scientific responsibility, also at the international level, to defend scientific standards.  But the beauty of science is still very strongly alive for me, to have the golden opportunity to make new discoveries and discuss research results with my younger coworkers and collegues.

Ranked no 2 in Sweden in Immunology (2022 edition for the ranking of top 1000 scientists) and no 245 in the world (https://research.com/scientists-rankings/immunology).

20 selected publications

1. Michaëlsson E, Malmström V, Reis S, Burkhardt H, Engström Å, Holmdahl R: T cell recognition of carbohydrates on type II collagen. J Exp Med 30, 745-749. 1994.
2. Sundvall M, Jirholt J, Yang H-T, Jansson L, Engström Å, Pettersson U, Holmdahl R: Identification of murine loci associated with susceptibility to chronic experimental autoimmune encephalomyelitis. Nature Genetics 10, 313-317. 1995.
3. Malmström V, Michaëlsson E, Burkhardt H, Mattsson R, Vuorio E, Holmdahl R: Systemic versus cartilage-specific expression of a type II collagen-specific T-cell epitope determines the level of tolerance and susceptibility to arthritis. Proc Natl Acad Sci (USA) 93, 4480-4485. 1996.
4. Vingsbo-Lundberg C, Nordquist N, Olofsson P, Sundvall M, Saxne T, Pettersson U, Holmdahl R: Genetic control of arthritis onset, severity and chronicity in a model for rheumatoid arthritis in rats. Nature Genetics 20, 401-404. 1998.
5. Bäcklund J, Carlsen S, Höger T, Holm B, Fugger L, Kihlberg J, Burkhardt H, Holmdahl R: Predominant selection of T cells specific for glycosylated collagen type II peptide (263-270) in humanized transgenic mice and in rheumatoid arthritis. Proc Natl Acad Sci U S A 99, 9960-9965. 2002
6. Olofsson P, Holmberg J, Tordsson J, Lu S, Åkerström B, Holmdahl R: Positional identification of Ncf1 as a gene that regulates arthritis severity in rats. Nature Genetics 33, 25-32. 2003.
7. Hultqvist M, Olofsson P, Holmberg J, Bäckström BT, Tordsson J, Holmdahl R. Enhanced autoimmunity, arthritis, and encephalomyelitis in mice with a reduced oxidative burst due to a mutation in the Ncf1 gene. Proc Natl Acad Sci U S A 101:12646-51, 2004
8. Gelderman, K. A., M. Hultqvist, A. Pizzolla, M. Zhao, K. S. Nandakumar, R. Mattsson, and R. Holmdahl. 2007. Macrophages suppress T cell responses and arthritis development by producing Reactive Oxygen Species J Clin Invest 117:3020-3028.
9. Uysal H, Bockermann R, Nandakumar KS, Sehnert B, Bajtner E, Engström Å, Thunnisein M, Holmdahl R: Structure and pathogenicity of antibodies specific for citrullinated collagen type II in Experimental Arthritis. J Exp Med 2009; 206:449-462.
10. Kelkka T, Kienhoefer D, Hoffmann M, Linja M, Wing K, Sareila O, Malin Hultqvist, Essi Laajala, Zhi Chen, Júlia Vasconcelos, Esmeralda Neves, Margarida Guedes, Laura Marques, Gerhard Krönke, Merja Helminen, Leena Kainulainen, Peter Olofsson, Sirpa Jalkanen, Riitta Lahesmaa, M Margarida Souto-Carneiro and Holmdahl R. Reactive oxygen species deficiency induces autoimmunity with downstream interferon signature. Antioxid Redox Signal. 2014.
11. Khmaladze I, Kelkka T, Guerard S, Wing K, Pizzolla A, Saxena A, Lundqvist K, Holmdahl M, Nandakumar KS, Holmdahl R: Mannan induces ROS-regulated, IL-17A-dependent psoriasis arthritis-like disease in mice. Proc Natl Acad Sci USA. 2014
12. Olsson LM, Johansson ÅC, Gullstrand B, Jönsen A, Saevarsdottir S, Rönnblom L, Leonard D, Wetterö J, Sjöwall C, Svenungsson E, Gunnarsson I, Bengtsson AA, Holmdahl R: A single nucleotide polymorphism in the NCF1 gene leading to reduced oxidative burst is associated with systemic lupus erythematosus. Ann Rheum Dis 2017
13. Raposo B, Merky P, Yamada H, Urbonaviciute V, Lundqvist C, Niaudet C, Kyewski B, Ekwall O, Holmdahl  R*, Bäcklund J* (*=shared senior authors): T cells specific for posttranslational modifications escape intrathymic tolerance induction, Nature Com 2018
14. Farinotti AB, Wigerblad G, Nascimento D, Bas DB, Urbina CM, Nandakumar KS, Sandor  K, Xu B, Abdelmoaty S, Hunt MA, Ängeby-Möller K, Baharpoor A, Sinclair J, Jardemark K, Lanner JT, Khmaladze I, Borm LE, Zhang L, Wermeling F, Cragg MS, Lengqvist J, Chabot-Doré AJ, Diachenko L, Belfer I, Collin M, Kultima K, Heyman B, Jimenez JMA, Codeluppi S, Holmdahl R*, Svensson CI* (*shared senior and corresponding authors): Cartilage binding antibodies induce pain through immune complex mediated stimulation of neurons. J Exp Med 2019.
15. Zhu W, Lönnblom E, Förster M, Johannesson M, Tao P, Meng L, Lu S, Holmdahl R: Natural polymorphism of Ym1 regulates pneumonitis through alternative activation of macrophages. Science Adv, 2020
16. Fernandez Lahore G, Raposo B, Lagerquist M, Ohlsson C, Sabatier P, Xu B, Aoun M, James J, Cai X, Zubarev RA, Nandakumar KS, Holmdahl R: Vitamin D3 receptor polymorphisms regulate T cells and T cell dependent inflammatory diseases. PNAS, 2020
17. Norin U, Rintisch C, Meng L, Forster F, Ekman D, Tuncel J, Klocke K, Bäcklund J, Yang M, Bonner MY, Shchetynsky K, Bergquist M, Gjertsson I, Hubner N, Bäckdahl L, Holmdahl R: Identification of a mutation in the SH3gl1 gene demonstrate a new T cell mediated regulatory mechanism of autoimmune disease. Nature Com 2021
18. Fernandez Lahore G, Förster M, Johannesson, M, Sabatier P, Lönnblom E, Aoun M, He Y, Nandakumar KS, Zubarev RA, Holmdahl R: Polymorphism in estrogen receptor binding site causes CD2-dependent sex bias in T cell autoimmune diseases.  Nature Com 2021
19. Kissel T, Ge C, Hafkenscheid L, Slot LM, Cavallari M, Kwekkeboom JC, He Y, van Schie KA, Vergroesen RD, Kampstra ASB, Reijm S, Stoeken-Rijsbergen G, Heitman LH, Xu B, Pruijn GJM, Wuhrer M, Rispens T, Huizinga TWJ, Scherer HU, Reth M, Holmdahl R*, Toes REM* (shared corresponding and senior authorship): N-linked glycosylation of the immunoglobulin variable 1 domain affects antigen binding and autoreactive B-cell activation. Sci Adv 2021
20. Ge C, Cienciala S, Xu B, Dobritzsch D, Viljanen J, Kihlberg J, Do N N, Schneider N, Lanig H, Holmdahl R*, Burkhardt H* (* shared senior authorship):  Key interactions in the trimolecular complex consisting of the rheumatoid arthritis-associated DRB1*04:01 molecule, the major glycosylated collagen II peptide, and the T-cell receptor. Ann Rheum Dis 2021