VIVIANNE MALMSTRÖM GROUP

Cellular immunology and rheumatic diseases

Inflammatory rheumatic disease – importance and contribution of B and T cell subsets

Many inflammatory rheumatic diseases e.g. RA (rheumatoid arthritis) are characterized by specific sets of autoantibodies and a strong genetic association to distinct HLA class II alleles, which implicate a direct role for B and T cells. Today severe cases are often treated with synthetic and biological therapies targeting different facets of our immune system including B and T cells. Still, there is no cure and we do not understand precisely how T and B cell subsets contribute to disease. We study RA but also SLE, APS (anti-phospholipid syndrome), AAV (ANCA-associated vasculitis) and IIM (myositis).

In the cellular immunology/rheumatology group we aim to

a) Identify disease-specific T and B cells from blood and sites of inflammation in research samples from well-characterized patients.

b) Investigate the functionality of different lymphocyte subsets.

c) Develop assays for immune surveillance, i.e. tracking of antigen- and subset-specific  B and T cell in the context of therapeutic intervention and as predictors for clinical outcome.

We study T and B cells in patient samples from the rheumatology clinic, and we collaborate with many research groups and teams including professors Anca Catrina, Elisabet Svenungsson, Iva Gunnarsson and Ingrid Lundberg. Our main method is flow cytometry, and we run and maintain the flow cytometry core at CMM via the work by Annika van Vollenhoven. Moreover, we have an HLA protein lab incorporated into professor Adnane Achours lab at SciLifeLab. Internationally we pursue collaborative efforts within the EU/IMI project RTCure (https://www.rtcure.com).

 

Selected publications

Carlberg K, Korotkova M, Larsson L, Catrina AI, Ståhl PL*, and Malmström V*.  Exploring inflammatory signatures in arthritic joint biopsies with spatial transctipomics. Sci Rep. 2019 Dec 12; 9(1):18975.

Ramsköld D*, Parodis I*, Lakshmikanth T, Chen Y, Zickert A, Sippli N, Mikes J, Amara K, Achour A, Brodin P, Gunnarsson I and Malmström V. B cell alterations during BAFF inhibition with belimumab in SLE patients. eBiomedicine. 2019 Feb; 40:517-27.

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. Recognition of amino acid motifs, rather than specific proteins, by human plasma cell-derived monoclonal antibodies to posttranslationally modified proteins in rheumatoid arthritis. Arthritis Rheumatol. 2019 Feb; 71(12):196-209.

Titcombe PJ, Wigerblad G, Sippl N, Zhang N, Shmagel AK, Sahlström P, Zhang Y, Barsness LO, Ghodke-Puranik Y, Baharpoor A, Hansson M, Isaelsson L, Niweold TB, Klareskog L, Svensson CI, Amara K, Malmström V* and Mueller DL*. Pathogenic citrulline-multispecific B cell receptor clades in rheumatoid arthritis. Arthritis Rheumatol. 2018 Dec; 70(12):1933-45.

Pieper J, Dubnovitsky A, James E, Gerstner C, Rieck M, Gebe JA, Achour A, Buckner JH and Malmström V Memory T cells specific to citrullinated α-enolase are enriched in the rheumatic joint. J Autoimmunity. 2018 Aug; 92:47-56.

Chemin K, Ramsköld D, Diaz-Gallo L_M, Herrath J, Tandre K, Rönnblom L, Catrina IA and Malmström V. EOMES-positive CD4+ T cells are increased in PTPN22 (1858T) risk allele carriers. Eur J Immunol. 2018 Apr; 48(4):655-669.

Malmström V, Catrina AI, Klareskog L. The immunopathogenesis of seropositive rheumatoid arthritis: from triggering to targeting. Nat Rev Immunol. 2017 Jan;17(1):60-75.

Gerstner C, Dubnovitsky A, Sandin C, Kozhukh G, Uchtenhagen H, James EA, Rönnelid J, Ytterberg AJ, Pieper J, Reed E, Tandre C, Rieck M, Zubarev RA, Rönnblom L, Sandalova T, Buckner JH, Achour A, Malmström V. Functional and Structural Characterization of a Novel HLA-DRB1*04:01-Restricted α-Enolase T Cell Epitope in Rheumatoid Arthritis. Front Immunol. 2016 Nov 14;7:494.

Pandya JM, Venalis P, Al-Khalili L, Shahadat Hossain M, Stache V, Lundberg IE, Malmström V, Fasth AE. CD4+ and CD8+ CD28(null) T Cells Are Cytotoxic to Autologous Muscle Cells in Patients With Polymyositis. Arthritis Rheumatol. 2016 Aug;68(8):2016-26.

Pandya JM, Loell I, Hossain MS, Zong M, Alexanderson H, Raghavan S, Lundberg IE, Malmström V. Effects of conventional immunosuppressive treatment on CD244+ (CD28null) and FOXP3+ T cells in the inflamed muscle of patients with polymyositis and dermatomyositis. Arthritis Res Ther. 2016 Apr 1;18:80.

Herrath J, Chemin K, Albrecht I, Catrina AI and Malmström V. Surface expression of CD39 identifies an enriched Treg subset in the rheumatic joint, which is impaired in suppressing IL-17A secretion. Eur J Immunol. 2014 Oct; 44:2979-89. 

James E*, Rieck M*, Pieper J, Gebe JA, Yue BB, Tatum M, Peda M, Sandin C, Klareskog L, Malmström V and Buckner JH. Citrulline-specific Th1 cells are increased in rheumatoid arthritis and their frequency is influenced by disease duration and therapy. Arthritis Rheum. 2014 Jul; 66:1712-22 

Fasth AER, Björkström NK, Anthoni M, Malmberg K-J and Malmström V. Activating NK-cell receptors co-stimulate CD4(+)CD28(-) T cells in patients with rheumatoid arthritis. Eur J Immunol. 2010 Feb; 40:378-87.

Vallerskog T, Gunnarsson I, Widhe M, Risselada A, Klareskog L, van Vollenhoven R, Malmström V and Trollmo C. Treatment with rituximab affects both the cellular and the humoral arm of the immune system in patients with SLE. Clin Immunol. 2007 Jan; 122:62-74.