Team Ingrid Lundberg

Our team conducts research about myositis, a chronic, rheumatic, autoimmune disorder of unknown cause that affects approximately 1000 people in Sweden.

Myositis - disease mechanisms and effects of treatment

Myositis is a chronic, rheumatic, autoimmune disorder of unknown cause that affects approximately 1 000 people in Sweden. It is characterized by progressive muscle weakness and muscle fatigue particularly affecting thigh, shoulder, and neck muscles. In the most severe forms problems with swallowing may occur. Other organs are frequently involved like the skin, lungs, joints and heart suggesting that this is a systemic inflammatory disease.

Treatment is based on high doses of glucocorticoids in combination with immunosuppressive drugs and with physical exercise. The disease manifestations and prognosis vary between individual patients but overall the myositis disorder is associated with a high degree of morbidity leading to a low health related quality of life and a high mortality. Thus there is a high unmet need of improved treatment, and to achieve this we need to improve the knowledge on underlying pathophysiology and here we want to contribute.

Major research focus

Our research in myositis is focused on disease mechanisms that could explain (1) why you develop myositis, (2) why the muscles become weak and (3) why the lungs are often affected. This will be accomplished through longitudinal studies of patients with myositis and by combining clinical outcome measures and investigations of molecular expression in repeated muscle biopsies and in peripheral blood after different interventions, both pharmacological and exercise.

We also aim to understand immune specificities of myositis in order to find targets for new therapies. One aim is to understand why the muscle becomes a target of the immune reaction leading to muscle weakness and muscle damage. Another aim is to understand the link between the inflammation in muscle and in the lung, which is often affected in patients with myositis.  We also aim to understand the role of exercise to improve muscle health, improve aerobic capacity, reduce inflammation to improve quality of life and prognosis. In addition, our aim is to improve our understanding of patients’ experience of living with myositis, specifically what symptoms patients experience as most debilitating and important to improve and how to assess these symptoms by patient-reported and objective measurement tools.

To accomplish our goals we combine clinical, epidemiological research with molecular research on patient samples. We follow patients at Karolinska University Hospital in a systematic way and collect clinical data and biological samples. We are part of a Swedish Myositis Network, SweMyoNet, and of an international myositis network, where we contribute to the international myositis registry EuroMyositis, www.euromyositis.eu in which more than 5 900 patients with myositis have been enrolled.

We are also part of an international collaboration, MYOGEN, on genetic and environmental risk factors for myositis. In addition, we are part of the international myositis collaborations IMACS and OMERACT. In the rheumatology research laboratory at Center for Molecular Medicine, Karolinska Institutet, we analyse the biological samples, muscle biopsies, peripheral blood samples, sera, and plasma. We use immunological tools, such as T cell tetramers and muscle cell cultures to learn about the role of the autoimmune reactions in myositis.

The Myositis team

The Myositis research group
Photo: Lars Klareskog. From left: Maryam Dastmalchi, Karin Lodin, Charlotta Preger, Antonella Notarnicola, Begum Horuluoglu, Lara Dani, Angeles Shunashy Galindo Feria, Kristofer Andreasson, Weng Ian Che, Helene Sandlund, Mei Bruton, Helene Alexanderson, Ingrid Lundberg.

Helene Alexanderson, Associate Professor

Kristofer Andreasson, Msc, RPT, PhD student

Alexandra Argyriou, PhD student

Mei Bruton, M.D., Ph.D. post doc

Maryam Dastmalchi, M.D., Ph.D. senior consultant

Anneli Dihkan, Patient research partner

Louise Ekholm, M.D,. Ph.D. consultant

Fabricio Espinosa Ortega, M.D., PhD student

Ingrid Gerhardsson, Research nurse

Karina Gheorghe, M.D., Ph.D. consultant

Eveline van Gompel, PhD student

Begum Horuluoglu, Ph.D. Post doc

Eva Lindroos, Lab technician

Karin Lodin, M.D., Ph.D. post doc

Antonella Notarnicola, M.D., Ph.D. Post doc

Gloria Rostvall, Lab technician

Helene Sandlund, Research nurse

Angeles Shunashy Galindo Feria M.D., PhD student

Anna Tjärnlund, Ph.D.

The following PhD students are also in Team Marie Holmqvist:

Lara Dani, M.D., PhD student

Weng Ian Che, PhD student

Valérie Leclair, M.D., PhD student

Collaborations

Associate professor Daniel Andersson, Department of Physiology and Pharmacology, Karolinska Institutet.

Dr Helena Andersson, Oslo University.

Associate Professor Karine Chemin, Division of Rheumatology, Department of Medicine, Solna.

Professor Hector Chinoy, Manchester University.

Associate professor Lisa Christopher-Stine, Johns Hopkins Medical Center, Baltimore, USA.

Dr Louise Diederichsen, Copenhagen.

Professor Johan Grunewald, Division of Pulmonary diseases, Department of Medicine, Solna.

Associate Prof Marie Holmqvist, Division of Clinical Epidemiology, Department of Medicine, Solna.

Professor Per-Johan Jakobsson, Division of Rheumatology, Department of Medicine, Solna.

Professor Vivianne Malmström, Division of Rheumatology, Department of Medicine, Solna.

Associate Professor Leonid Padyukov, Division of Rheumatology, Department of Medicine, Solna.

Professor Lars Rönnblom, Uppsala University Hospital.

Professor Johan Rönnelid, Uppsala University Hospital.

Associate professor Lesley-Ann Saketkoo, Tulane Medical Center, New Orleans, USA.

Dr Dag Leonard, Uppsala University.

Professor Håkan Westerblad, Department of Physiology and Pharmacology, Karolinska Institutet.

Recent key publications

Idiopathic inflammatory myopathies.
Lundberg IE, Fujimoto M, Vencovsky J, Aggarwal R, Holmqvist M, Christopher-Stine L, Mammen AL, Miller FW
Nat Rev Dis Primers 2021 Dec;7(1):86

Expert Perspective: Management of Refractory Inflammatory Myopathy.
Lundberg IE
Arthritis Rheumatol 2021 08;73(8):1394-1407

Contribution of Rare Genetic Variation to Disease Susceptibility in a Large Scandinavian Myositis Cohort.
Bianchi M, Kozyrev SV, Notarnicola A, Hultin Rosenberg L, Karlsson Å, Pucholt P, Rothwell S, Alexsson A, Sandling JK, Andersson H, Cooper RG, Padyukov L, Tjärnlund A, Dastmalchi M, , , Meadows JRS, Pyndt Diederichsen L, Molberg Ø, Chinoy H, Lamb JA, Rönnblom L, Lindblad-Toh K, Lundberg IE
Arthritis Rheumatol 2022 02;74(2):342-352

Factors Associated With Treatment Response in Patients With Idiopathic Inflammatory Myopathies: A Registry-Based Study.
Espinosa-Ortega F, Holmqvist M, Dastmalchi M, Lundberg IE, Alexanderson H
Arthritis Care Res (Hoboken) 2022 Mar;74(3):468-477

Autoantibodies against Four-and-a-Half-LIM Domain 1 (FHL1) in Inflammatory Myopathies: Results from an Australian Single-Center Cohort.
Galindo-Feria AS, Horuluoglu B, Day J, Fernandes-Cerqueira C, Wigren E, Gräslund S, Proudman S, Lundberg IE, Limaye V
Rheumatology (Oxford) 2022 Jan;():

Serum-circulating His-tRNA synthetase inhibits organ-targeted immune responses.
Adams RA, Fernandes-Cerqueira C, Notarnicola A, Mertsching E, Xu Z, Lo WS, Ogilvie K, Chiang KP, Ampudia J, Rosengren S, Cubitt A, King DJ, Mendlein JD, Yang XL, Nangle LA, Lundberg IE, Jakobsson PJ, Schimmel P
Cell Mol Immunol 2021 06;18(6):1463-1475

Distribution and trajectory of direct and indirect costs of idiopathic inflammatory myopathies.
Leclair V, Moshtaghi-Svensson J, Regardt M, Hudson M, Lundberg IE, Holmqvist M
Semin Arthritis Rheum 2021 10;51(5):983-988

Familial aggregation and heritability: a nationwide family-based study of idiopathic inflammatory myopathies.
Che WI, Westerlind H, Lundberg IE, Hellgren K, Kuja-Halkola R, Holmqvist M
Ann Rheum Dis 2021 11;80(11):1461-1466

Overall and site-specific cancer before and after diagnosis of idiopathic inflammatory myopathies: A nationwide study 2002-2016.
Dani L, Ian Che W, Lundberg IE, Hellgren K, Holmqvist M
Semin Arthritis Rheum 2021 02;51(1):331-337

Neutrophil dysregulation is pathogenic in idiopathic inflammatory myopathies.
Seto N, Torres-Ruiz JJ, Carmona-Rivera C, Pinal-Fernandez I, Pak K, Purmalek MM, Hosono Y, Fernandes-Cerqueira C, Gowda P, Arnett N, Gorbach A, Benveniste O, Gómez-Martín D, Selva-O'Callaghan A, Milisenda JC, Grau-Junyent JM, Christopher-Stine L, Miller FW, Lundberg IE, Kahlenberg JM, Schiffenbauer AI, Mammen A, Rider LG, Kaplan MJ
JCI Insight 2020 02;5(3):

Proinflammatory Histidyl-Transfer RNA Synthetase-Specific CD4+ T Cells in the Blood and Lungs of Patients With Idiopathic Inflammatory Myopathies.
Galindo-Feria AS, Albrecht I, Fernandes-Cerqueira C, Notarnicola A, James EA, Herrath J, Dastmalchi M, Sandalova T, Rönnblom L, Jakobsson PJ, Fathi M, Achour A, Grunewald J, Malmström V, Lundberg IE
Arthritis Rheumatol 2020 01;72(1):179-191

Focused HLA analysis in Caucasians with myositis identifies significant associations with autoantibody subgroups.
Rothwell S, Chinoy H, Lamb JA, Miller FW, Rider LG, Wedderburn LR, McHugh NJ, Mammen AL, Betteridge ZE, Tansley SL, Bowes J, Vencovský J, Deakin CT, Dankó K, Vidya L, Selva-O'Callaghan A, Pachman LM, Reed AM, Molberg Ø, Benveniste O, Mathiesen PR, Radstake TRDJ, Doria A, de Bleecker J, Lee AT, Hanna MG, Machado PM, Ollier WE, Gregersen PK, Padyukov L, O'Hanlon TP, Cooper RG, Lundberg IE,
Ann Rheum Dis 2019 07;78(7):996-1002

2017 European League Against Rheumatism/American College of Rheumatology classification criteria for adult and juvenile idiopathic inflammatory myopathies and their major subgroups.
Lundberg IE, Tjärnlund A, Bottai M, Werth VP, Pilkington C, Visser M, Alfredsson L, Amato AA, Barohn RJ, Liang MH, Singh JA, Aggarwal R, Arnardottir S, Chinoy H, Cooper RG, Dankó K, Dimachkie MM, Feldman BM, Torre IG, Gordon P, Hayashi T, Katz JD, Kohsaka H, Lachenbruch PA, Lang BA, Li Y, Oddis CV, Olesinska M, Reed AM, Rutkowska-Sak L, Sanner H, Selva-O'Callaghan A, Song YW, Vencovsky J, Ytterberg SR, Miller FW, Rider LG,
Ann Rheum Dis 2017 12;76(12):1955-1964

Abatacept in the treatment of adult dermatomyositis and polymyositis: a randomised, phase IIb treatment delayed-start trial.
Tjärnlund A, Tang Q, Wick C, Dastmalchi M, Mann H, Tomasová Studýnková J, Chura R, Gullick NJ, Salerno R, Rönnelid J, Alexanderson H, Lindroos E, Aggarwal R, Gordon P, Vencovsky J, Lundberg IE
Ann Rheum Dis 2018 Jan;77(1):55-62

Development of autoantibodies against muscle-specific FHL1 in severe inflammatory myopathies.
Albrecht I, Wick C, Hallgren Å, Tjärnlund A, Nagaraju K, Andrade F, Thompson K, Coley W, Phadke A, Diaz-Gallo LM, Bottai M, Nennesmo I, Chemin K, Herrath J, Johansson K, Wikberg A, Ytterberg AJ, Zubarev RA, Danielsson O, Krystufkova O, Vencovsky J, Landegren N, Wahren-Herlenius M, Padyukov L, Kämpe O, Lundberg IE
J Clin Invest 2015 Dec;125(12):4612-24

Functional Index-3: A Valid and Reliable Functional Outcome Assessment Measure in Patients With Dermatomyositis and Polymyositis.
Ernste FC, Chong C, Crowson CS, Kermani TA, Mhuircheartaigh ON, Alexanderson H
J Rheumatol 2021 01;48(1):94-100

 

Ingrid Lundberg ORCID ID: orcid.org/0000-0002-6068-9212