Caroline Grönwall Team

We study autoreactive B cells and autoantibodies in rheumatic disease with the aim to delineate how they contribute to human disease. With increased knowledge, we can understand what triggers autoreactive immune responses and how they can be modulated to improve or prevent disease. A particular interest is the diversity and function of patient-derived autoantibodies.

The complexity of human autoreactivity: understanding the clonal diversity of B cells and antibodies

B-cells and antibodies are an essential part of the adaptive immune system and play important roles in protecting us from infectious threats. Yet, in autoimmune diseases such as systemic lupus erythematosus (SLE), idiopathic inflammatory myopathies (IIM), and rheumatoid arthritis (RA), the host’s immune system – for unknown reasons – recognizes self-biomolecules as foreign. This can cause, if left untreated, devastating disease. In different diseases, distinct biomolecules are targeted by different classes of self-reactive autoantibodies. Moreover, within in each diagnosis patients display heterogeneous autoantibody profiles, which can define clinical subsets. However, much is still unknown about why someone develops autoimmunity and why patients display different clinical phenotypes and respond differently to treatment. We think that understanding the adaptive immune system is the key to solve these questions. Notably, not all autoantibodies are contributing to disease and some, in particular natural IgM, may also be beneficial and homeostatic.

In our translational laboratory, we use serology surveys, antibody engineering, and high-throughput single-cell methodology to study autoantibody profiles and immunoglobulin diversity of autoreactive B cells in rheumatic disease. By generation of human patient-derived monoclonal antibodies, we can perform in-depth analysis of the clonally dependent autoantibody functionality. High dimensional flow cytometry and functional assays are used for immunophenotyping of B cells in patient subsets and in response to immunomodulating treatment. We are also investigating B cell dysregulation and biomarkers in RA-associated B cell lymphoma.

• Investigation of anti-modified protein autoantibodies (AMPA) in rheumatoid arthritis: understanding the molecular features, clonal diversity, and function of autoantibodies to the post-translational modifications citrullination, carbamylation, acetylation and malondialdehyde modification
• Survey of SLE-associated autoantibodies, autoreactive B cells and biomarkers: understanding the association with disease manifestations and patient subsets
• In-depth understanding of myositis-associated autoantibodies and B cells in patient subsets
• Immunosurveillance of B cells responses: studies of immunoglobulin repertoires and B cell phenotypes in patient
• Investigation of the impact of targeted treatment on B cell activity and phenotype and development of functional assays
• B cell activity and dysregulation in development of B cell lymphoma: focus on autoimmune-associated lymphoma

Caroline Grönwall, PhD, Associate Professor/Docent

caroline.gronwall@ki.se

2003                MSc Engineering Biology, Linköping University, Stockholm, Sweden

2008                PhD Molecular Biotechology, Royal Institute of Technology (KTH), Stockholm, Sweden

2008- 2010    Postdoctoral researcher, Dep. of Medicine, University of California San Diego (UCSD), San Diego, CA, USA.

2010- 2014    Instructor of Medicine, NYU School of Medicine, NY, NY, USA

2014- 2019    Assistant Professor, Division of Rheumatology, Dept. of Medicine Solna, Karolinska Institutet, Stockholm, Sweden

2019-               Associate Professor, Division of Rheumatology, Dept. of Medicine Solna, Karolinska Institutet, Stockholm, Sweden

Program director, KI Allergy, Immunology, and Inflammation (Aii) doctoral program

https://staff.ki.se/doctoral-programme-in-allergy-immunology-and-inflammation-aii

Nora Euler, PhD student, nora.euler@ki.se

Wenqi Huang, PhD student, wenqui.huang@ki.se

Gökçe Günaydin, PhD

Yan Wang, PhD

Katy Lloyd, PhD

Diana Zhou

Lisa Liljefors

Radha Thyagarajan, PhD

Peter Sahlström, PhD

EU/IMI project RTCure (https://www.rtcure.com)

Swedish research council

Gustav den V:s 80-year foundation

The Swedish rheumatology association

Peter Sahlström, Diversity and Function of Anti-Modified Protein Autoantibodies in Rheumatoid Arthritis 2022

https://openarchive.ki.se/xmlui/handle/10616/48300

Caroline Grönwall, Department of Medicine Solna, Division of Rheumatology, Karolinska Institutet, Center for Molecular Medicine L8:04, Karolinska University Hospital, Stockholm, Sweden. Email: caroline.gronwall@ki.se

The human bone marrow plasma cell compartment in rheumatoid arthritis – clonal relationships and anti-citrulline autoantibody producing cells. Hensvold A, Horuluoglu B, Sahlström P, Thyagarajan R, Diaz Boada JS, Hansson H, Mathsson-Alm L, Gerstner C, Sippl N, Israelsson L, Wedin R, Steen J, Klareskog L, Réthi B, Catrina AI, Diaz-Gallo LM, Malmström V, Grönwall C. J Autoimmun. Apr;136:103022 (2023)

Divergent and dominant anti-inflammatory effects of patient-derived anticitrullinated protein antibodies (ACPA) in arthritis development. Raposo B., Afonso M, Israelsson L, Wähämaa H, Stålesen R, Wermeling F, Hensvold AH, Grönwall C, Rethi B, Klareskog L, Malmström V. Ann Rheum Dis. Jan 5:ard-2022-223417. (2023)

Autoantibodies targeting malondialdehyde-modifications in rheumatoid arthritis regulate osteoclasts via inducing glycolysis and lipid biosynthesis. Sakuraba K, Krishnamurthy A, Sun J, Zheng X, Xu C, Peng B, Engström M, Jakobsson PJ, Wermeling F, Catrina S, Grönwall C, Catrina AI, Réthi B. (2022) J Autoimmun. Dec;133:102903.

A comprehensive evaluation of the relationship between different IgG and IgA anti-modified protein autoantibodies in rheumatoid arthritis. Grönwall C., Liljefors L., Bang H., Hensvold A.H., Hansson M., Mathsson-Alm L., Israelsson L., Joshua V., Svärd A., Stålesen R., Titcombe,P.J., Steen J., Piccoli L., Sherina N., Clavel C., Svenungsson E., Gunnarsson I., Saevarsdottir S., Kastbom A., Serre G., Alfredsson L., Malmström V., Rönnelid J., Catrina A. I., Lundberg K., Klareskog L. Front. Immunol. May 20;12:627986. (2021)

Different hierarchies of anti-modified protein autoantibody reactivities in rheumatoid arthritis Sahlström P., Hansson M., Steen J., Amara K., Titcombe P.J., Forsström B., Stålesen R., Israelsson I., Piccoli L., Lundberg K., Klareskog L., Mueller D.L., Catrina A.I., Skriner K., Malmström V., Grönwall C. Arthritis Rheumatol Oct;72(10):1643-1657 (2020)

Rheumatoid arthritis patients display B-cell dysregulation already in the naïve repertoire consistent with defects in B-cell tolerance. Wang Y., Lloyd K.A., Melas I., Zhou D., Thyagarajan R., Lindqvist J., Hansson M., Svärd A., Mathsson-Alm L., Kastbom A., Lundberg K., Klareskog L, Catrina A.I., Rapecki S., Malmström V., Grönwall C. Sci Rep. 2019 Dec 27;9(1):19995. (2019)

Differential ACPA binding to nuclear antigens reveals a PAD-independent pathway and a distinct subset of acetylation cross-reactive autoantibodies in Rheumatoid Arthritis. Lloyd K.A., Wigerblad G., Sahlström P., Garimella M.G., Chemin K., Steen J., Titcombe,P.J., Marklein, B., Diana, Z., Stålesen, R., Elena Ossipova, Lundqvist, C., Ekwall, O., Rönnelid J., Mueller D.L., Karlsson M.C.I. Kaplan M.J., Skriner K., Klareskog L., Wermeling F., Malmström V., Grönwall C. Front. Immunol. Jan 4;9:3033 (2019)

 

Variable domain N-linked glycosylation and negative surface charge are key features of monoclonal ACPA: implications for B-cell selection Lloyd K., Steen J., Titcombe P.J., Amara K., Israelsson L., Lundström L.S., Zhou D., Zubarev R.A., Reed E., Piccoli L., Gabay C., Lanzavecchia A., Baeten D., Lundberg K., Mueller D.L., Klareskog L., Malmström V., Grönwall C. Eur J Immunol Jun;48(6):1030-1045. (2018)

Autoimmune reactivity to malondialdehyde adducts in Systemic Lupus Erythematosus is associated with disease activity and nephritis. Hardt U., Larsson A., Gunnarsson I., Clancy R.M, Petri M., Buyon J.P., Silverman G.J., Svenungsson E., Grönwall C. Arthritis Res Ther Feb 26; 20(1):36 (2018)

Depressed serum IgM levels in SLE are restricted to defined subgroups. Grönwall C., Hardt U., Gustafsson J.T., Elvin K., Jensen-Urstad K., Kvarnström M., Grosso G., Rönnelid J., Padyukov L., Gunnarsson I., Silverman G.J., Svenungsson, E. (2017) Clinical Immunology, Oct;183:304-315.

 

Full list of publications:

https://pubmed.ncbi.nlm.nih.gov/?term=caroline+gr%C3%B6nwall&sort=date