Team Caroline Gronwall

Autoantibodies and autoreactive B cell in rheumatic diseases.
Our research aims to understand human autoimmune disease with focus on the adaptive immune system and different subsets of autoantibodies and autoreactive B-cells.

Caroline Grönwall

Senior research specialist
K2 Department of Medicine, Solna

Docent/Associate Professor

+46 (0)70-1701744

Autoantibodies and autoreactive B cell in rheumatic diseases.

Introduction

B-cells and antibodies have essential roles in protecting us from infectious threats. However, in autoimmunity the host immune system for unknown reasons recognize self-biomolecules as foreign, leading to development of self-reactive antibodies that instead can mediate inflammation and drive disease. Different autoimmune rheumatic diseases have been found to be associated with distinct types of autoantibodies targeting different autoantigens. In rheumatoid arthritis (RA), detection of IgG anti-citrullinated protein autoantibodies (ACPA) are used for classification of seropositive disease and autoreactivity to citrullinated antigens are implicated in the pathogenesis. Our research demonstrates that individual ACPA are multireactive to a wide range of citrullinated antigens and that some, but not all, ACPA clones also bind carbamylated and acetylated epitopes.

Major research focus

Our main research aim is to increase our knowledge about how autoantibodies and autoreactive B cells contribute to the pathogenesis of human disease. Our studies include investigations of both potentially pathogenic IgG reactivities as well as natural IgM reactivities with potentially immune-homeostatic capacities. We are using antibody engineering and high-throughput methodology to study the immunoglobulin diversity and repertoire distortions of B cells in RA and SLE. We are also studying the functional characteristics and immune activating properties of human monoclonal autoreactive antibody clones isolated from patients, and investigating how to modulate these functions in novel therapeutic approaches. Combining molecular immunology, cell phenotyping, and serology biomarker screening, we hope to better understand different patient subsets and development of disease. We are especially interested in autoreactivity to post-translational modifications (PTMs) in different classes of autoantibodies.

 

Team members

Caroline Grönwall

Senior research specialist
K2 Department of Medicine, Solna

Peter Sahlström

PhD student
K2 Department of Medicine, Solna

Former group members:

Radha Thyaganjan, PhD
Katy Lloyd, PhD
Yan Wang, PhD
Lisa Liljefors
Diana Zhou

Recent key publications

Identifying novel B-cell targets for chronic inflammatory autoimmune disease by screening of chemical probes in a patient-derived cell assay.
Sundström Y, Shang MM, Panda SK, Grönwall C, Wermeling F, Gunnarsson I, Lundberg IE, Sundström M, Jakobsson PJ, Berg L
Transl Res 2021 Mar;229():69-82

Different Hierarchies of Anti-Modified Protein Autoantibody Reactivities in Rheumatoid Arthritis.
Sahlström P, Hansson M, Steen J, Amara K, Titcombe PJ, Forsström B, Stålesen R, Israelsson L, Piccoli L, Lundberg K, Klareskog L, Mueller DL, Catrina AI, Skriner K, Malmström V, Grönwall C
Arthritis Rheumatol 2020 10;72(10):1643-1657

HLA-B*08 identified as the most associated MHC locus for anti-carbamylated protein antibody-positive/anti-CCP-negative rheumatoid arthritis.
Regueiro C, Casares-Marfil D, Lundberg K, Knevel R, Acosta-Herrera M, Rodriguez-Rodriguez L, Lopez-Mejias R, Perez-Pampin E, Triguero-Martinez A, Nuño L, Ferraz-Amaro I, Rodriguez-Carrio J, Lopez-Pedrera R, Robustillo-Villarino M, Castañeda S, Remuzgo-Martinez S, Alperi M, Alegre-Sancho JJ, Balsa A, Gonzalez-Alvaro I, Mera A, Fernandez-Gutierrez B, Gonzalez-Gay MA, Trouw L, Grönwall C, Padyukov L, Martin J, Gonzalez A
Arthritis Rheumatol 2020 Dec;():

Rheumatoid arthritis patients display B-cell dysregulation already in the naïve repertoire consistent with defects in B-cell tolerance.
Wang Y, Lloyd KA, Melas I, Zhou D, Thyagarajan R, Lindqvist J, Hansson M, Svärd A, Mathsson-Alm L, Kastbom A, Lundberg K, Klareskog L, Catrina AI, Rapecki S, Malmström V, Grönwall C
Sci Rep 2019 12;9(1):19995

Physiological and ultrastructural aspects of ion movements across the chorioallantois.
Saleuddin AS, Kyriakides CP, Peacock A, Simkiss K
Comp Biochem Physiol A Comp Physiol 1976 ;54(1):7-12

Differential ACPA Binding to Nuclear Antigens Reveals a PAD-Independent Pathway and a Distinct Subset of Acetylation Cross-Reactive Autoantibodies in Rheumatoid Arthritis.
Lloyd KA, Wigerblad G, Sahlström P, Garimella MG, Chemin K, Steen J, Titcombe PJ, Marklein B, Zhou D, Stålesen R, Ossipova E, Lundqvist C, Ekwall O, Rönnelid J, Mueller DL, Karlsson MCI, Kaplan MJ, Skriner K, Klareskog L, Wermeling F, Malmström V, Grönwall C
Front Immunol 2018 ;9():3033

Anticitrullinated protein antibodies facilitate migration of synovial tissue-derived fibroblasts.
Sun M, Rethi B, Krishnamurthy A, Joshua V, Circiumaru A, Hensvold AH, Ossipova E, Grönwall C, Liu Y, Engstrom M, Catrina SB, Steen J, Malmstrom V, Klareskog L, Svensson C, Ospelt C, Wähämaa H, Catrina AI
Ann Rheum Dis 2019 12;78(12):1621-1631

Autoimmune reactivity to malondialdehyde adducts in systemic lupus erythematosus is associated with disease activity and nephritis.
Hardt U, Larsson A, Gunnarsson I, Clancy RM, Petri M, Buyon JP, Silverman GJ, Svenungsson E, Grönwall C
Arthritis Res Ther 2018 02;20(1):36

Recognition of Amino Acid Motifs, Rather Than Specific Proteins, by Human Plasma Cell-Derived Monoclonal Antibodies to Posttranslationally Modified Proteins in Rheumatoid Arthritis.
Steen J, Forsström B, Sahlström P, Odowd V, Israelsson L, Krishnamurthy A, Badreh S, Mathsson Alm L, Compson J, Ramsköld D, Ndlovu W, Rapecki S, Hansson M, Titcombe PJ, Bang H, Mueller DL, Catrina AI, Grönwall C, Skriner K, Nilsson P, Lightwood D, Klareskog L, Malmström V
Arthritis Rheumatol 2019 02;71(2):196-209

Variable domain N-linked glycosylation and negative surface charge are key features of monoclonal ACPA: Implications for B-cell selection.
Lloyd KA, Steen J, Amara K, Titcombe PJ, Israelsson L, Lundström SL, Zhou D, Zubarev RA, Reed E, Piccoli L, Gabay C, Lanzavecchia A, Baeten D, Lundberg K, Mueller DL, Klareskog L, Malmström V, Grönwall C
Eur J Immunol 2018 06;48(6):1030-1045

Depressed serum IgM levels in SLE are restricted to defined subgroups.
Grönwall C, Hardt U, Gustafsson JT, Elvin K, Jensen-Urstad K, Kvarnström M, Grosso G, Rönnelid J, Padykov L, Gunnarsson I, Silverman GJ, Svenungsson E
Clin Immunol 2017 10;183():304-315

Autoreactivity to malondialdehyde-modifications in rheumatoid arthritis is linked to disease activity and synovial pathogenesis.
Grönwall C, Amara K, Hardt U, Krishnamurthy A, Steen J, Engström M, Sun M, Ytterberg AJ, Zubarev RA, Scheel-Toellner D, Greenberg JD, Klareskog L, Catrina AI, Malmström V, Silverman GJ
J Autoimmun 2017 Nov;84():29-45

B cells expressing the IgA receptor FcRL4 participate in the autoimmune response in patients with rheumatoid arthritis.
Amara K, Clay E, Yeo L, Ramsköld D, Spengler J, Sippl N, Cameron JA, Israelsson L, Titcombe PJ, Grönwall C, Sahbudin I, Filer A, Raza K, Malmström V, Scheel-Toellner D
J Autoimmun 2017 Jul;81():34-43

Modulation of natural IgM autoantibodies to oxidative stress-related neo-epitopes on apoptotic cells in newborns of mothers with anti-Ro autoimmunity.
Grönwall C, Clancy RM, Getu L, Lloyd KA, Siegel DL, Reed JH, Buyon JP, Silverman GJ
J Autoimmun 2016 09;73():30-41