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Novel etiology of autoimmune disorders: the role of acquired somatic mutations in lymphoid cells

Total Cost €


EC-Contrib. €






 M-Imm project word cloud

Explore the words cloud of the M-Imm project. It provides you a very rough idea of what is the project "M-Imm" about.

drug    adverse    host    immune    cells    clone    koskela    lymphocytes    prove    rheumatoid    autocytotoxicity    organ    regulator    gives    clinical    mechanisms    burden    antigen    viral    maladies    somatic    sequencing    granular    advantage    cytopenias    diagnostics    functional    acquire    therapy    group    mutations    molecular    spectrum    leukemia    ra    hypothesis    separate    society    mutational    arthritis    lymphoid    activating    driver    acquired    induce    infections    expanded    heavy    determines    breakthrough    continuum    tissues    stat3    lgl    small    mutated    engl    understand    autoreactive    proliferation    damage    med    discovered    discovery    transform    carry    expand    function    neoplastic    nk    al    lymphocyte    causes    cytotoxic    generation    examine    disease    poorly    clones    mediated    accurate    intriguing    pathogenesis    tissue    suffer    et    diseases    disorders    oncogenic    disorder    gene    autoimmune    patients    expansion    50    thought    hit    2012    sensitive   

Project "M-Imm" data sheet

The following table provides information about the project.


Organization address
postcode: 14

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country Finland [FI]
 Project website
 Total cost 2˙047˙337 €
 EC max contribution 2˙047˙337 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2014-CoG
 Funding Scheme ERC-COG
 Starting year 2015
 Duration (year-month-day) from 2015-09-01   to  2020-08-31


Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 


 Project objective

Molecular pathogenesis of most immune-mediated disorders, such as of autoimmune diseases, is poorly understood. These common maladies carry a heavy burden both on patients and on society. Current therapy is non-targeted and results in significant short- and long-term adverse effects. Large granular lymphocyte (LGL) leukemia is characterized by expansion of cytotoxic T- or NK-cells and represents an intriguing clinical continuum between a neoplastic and an autoimmune disorder. Patients suffer from autoimmune cytopenias and rheumatoid arthritis (RA), which are thought to be mediated by LGL cells targeting host tissues. My group recently discovered that 40-50% of LGL leukemia patients carry in their lymphoid cells acquired, activating mutations in the STAT3 gene – a key regulator of immune and oncogenic processes (Koskela et al, N Engl J Med, 2012). This breakthrough discovery gives insight to the pathogenesis of autoimmune disorders at large. I present here a hypothesis that a strong antigen-induced proliferation is a mutational driver, which causes somatic mutations in lymphoid cells. When mutations hit key activating pathways, autoreactive cells acquire functional advantage and expand. The target antigen of the expanded clone determines the clinical characteristics of the autoimmune disease induced. To prove this hypothesis, we will separate small lymphocyte clones from patients with autoimmune diseases and use sensitive next-generation sequencing methods to characterize the spectrum of somatic mutations in lymphoid cells. Further, we will study the function of mutated lymphocytes and examine the mechanisms of autocytotoxicity and end-organ/tissue damage. Finally, we aim to understand factors, which induce somatic mutations in lymphoid cells, such as the role of viral infections. The results will transform our understanding of molecular pathogenesis of autoimmune diseases and lead to accurate diagnostics and discovery of novel drug targets.


year authors and title journal last update
List of publications.
2016 E. I. Andersson, T. Tanahashi, N. Sekiguchi, V. R. Gasparini, S. Bortoluzzi, T. Kawakami, K. Matsuda, T. Mitsui, S. Eldfors, S. Bortoluzzi, A. Coppe, A. Binatti, S. Lagstro m, P. Ellonen, N. Fukushima, S. Nishina, N. Senoo, H. Sakai, H. Nakazawa, Y.-L. Kwong, T. P. Loughran, J. P. Maciejewski, S. Mustjoki, F. Ishida
High incidence of activating STAT5B mutations in CD4-positive T-cell large granular lymphocyte leukemia
published pages: 2465-2468, ISSN: 0006-4971, DOI: 10.1182/blood-2016-06-724856
Blood 128/20 2020-04-23
2017 Miko Valori, Lilja Jansson, Anna Kiviharju, Pekka Ellonen, Hanna Rajala, Shady Adnan Awad, Satu Mustjoki, Pentti J. Tienari
A novel class of somatic mutations in blood detected preferentially in CD8 + cells
published pages: 75-81, ISSN: 1521-6616, DOI: 10.1016/j.clim.2016.11.018
Clinical Immunology 175 2020-04-23
2018 Tilman Schneider-Hohendorf, Dennis Görlich, Paula Savola, Tiina Kelkka, Satu Mustjoki, Catharina C. Gross, Geoffrey C. Owens, Luisa Klotz, Klaus Dornmair, Heinz Wiendl, Nicholas Schwab
Sex bias in MHC I-associated shaping of the adaptive immune system
published pages: 2168-2173, ISSN: 0027-8424, DOI: 10.1073/pnas.1716146115
Proceedings of the National Academy of Sciences 115/9 2020-04-23
2017 Emma I Andersson
Characterization of mature T-cell leukemias by next-generation sequencing and drug sensitivity testing
published pages: , ISSN: , DOI:
2017 P. Savola, T. Kelkka, H. L. Rajala, A. Kuuliala, K. Kuuliala, S. Eldfors, P. Ellonen, S. Lagström, M. Lepistö, T. Hannunen, E. I. Andersson, R. K. Khajuria, T. Jaatinen, R. Koivuniemi, H. Repo, J. Saarela, K. Porkka, M. Leirisalo-Repo, S. Mustjoki
Somatic mutations in clonally expanded cytotoxic T lymphocytes in patients with newly diagnosed rheumatoid arthritis
published pages: 15869, ISSN: 2041-1723, DOI: 10.1038/ncomms15869
Nature Communications 8 2020-04-23
2018 Luca Trotta, Timi Martelius, Timo Siitonen, Timo Hautala, Sari Hämäläinen, Hanna Juntti, Mervi Taskinen, Mette Ilander, Emma Irene Andersson, Andrey Zavialov, Meri Kaustio, Riikka Keski-Filppula, Michael Hershfield, Satu Mustjoki, Terhi Tapiainen, Mikko Seppänen, Janna Saarela
ADA2 deficiency: Clonal lymphoproliferation in a subset of patients
published pages: 1534-1537.e8, ISSN: 0091-6749, DOI: 10.1016/j.jaci.2018.01.012
Journal of Allergy and Clinical Immunology 141/4 2020-04-23
2017 A Coppe, E I Andersson, A Binatti, V R Gasparini, S Bortoluzzi, M Clemente, M Herling, J Maciejewski, S Mustjoki, S Bortoluzzi
Genomic landscape characterization of large granular lymphocyte leukemia with a systems genetics approach
published pages: 1243-1246, ISSN: 0887-6924, DOI: 10.1038/leu.2017.49
Leukemia 31/5 2020-04-23
2018 Paula Savola, Sofie Lundgren, Mikko A. I. Keränen, Henrikki Almusa, Pekka Ellonen, Marjatta Leirisalo-Repo, Tiina Kelkka, Satu Mustjoki
Clonal hematopoiesis in patients with rheumatoid arthritis
published pages: , ISSN: 2044-5385, DOI: 10.1038/s41408-018-0107-2
Blood Cancer Journal 8/8 2020-04-23

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