Systemic Lupus Erythematosus (SLE)
Systemic Lupus Erythematosus (SLE) is an autoimmune rheumatic disease affecting multiple organs in the body. Patients are typically diagnosed in their twenties or thirties and 90% are women. Both environmental and genetic risk factors are important in the pathogenesis of the disease, but the exact mechanisms are still partly unknown. The aim of our research is to identify and understand the underlying disease processes in order to improve care and treatment of patients with SLE.
Project description
The research group performs translational and clinical research in SLE. This is done in close collaboration with the rheumatology and nephrology department at Uppsala University hospital and today more than 300 patients participate in our studies. Further, we collaborate with research groups in Sweden and internationally. The focus of our research is to clarify the connection between genetics, the immune system and the clinical picture. Further, we investigate the regulation and function of the immune system and its connection to the overactivated interferon system seen in SLE.
Marstrand 2023. Upper row from left: Ahmed Sayadi, Dag Leonard, Lars Rönnblom, Maija-Leena Eloranta, Karin Hjorton, Sarah Reid. Front row from left: Nina Oparina, Elisabeth Skoglund, Johanna Sandling, Marcus Wallgren, Juliana Imgenberg-Kreuz. Foto: Private.
Selected publications
Reid S, Sandling KJ, Pucholt P, Sayadi A, Frodlund M, Lerang K, Gunnarsson I, Jönsen A, Syvänen A-C, Molberg Ø, Rantapää-Dahlqvist S, Rudin A, Sjöwall C, Svenungsson E, Bengtsson AA, Rönnblom L, Leonard D. The construction and validation of sub-phenotype-specific genetic risk scores in systemic lupus erythematosus: a novel approach using large-scale biobank data, medRxiv doi.org/10.1101/2025.03.11.25323758 Mar, 2025.
Sayadi A, Sandling JK, Eloranta ML; ImmunoArray Development Consortium; DISSECT Consortium; Jönsen A, Gunnarsson I, Rantapää-Dahlqvist S, Sjöwall C, Bengtsson AA, Svenungsson E, Lindblad-Toh K, Leonard D, Rönnblom L; DISSECT Consortium. Rare and common single nucleotide variants in childhood-onset systemic lupus erythematosus. Lupus Sci Med, 11 Feb, 2025.
Hedenstedt A, Reid S, Sayadi A, Eloranta ML, Skoglund E, Bolin K, Frodlund M, Lerang K, Jönsen A, Rantapää-Dahlqvist S, Bengtsson AA, Rudin A, Molberg Ø, Sjöwall C, Sandling JK, Leonard D. B cell polygenic risk scores associate with anti-dsDNA antibodies and nephritis in systemic lupus erythematosus. Lupus Sci Med. 2023 Oct;10(2):e000926.
Lundtoft C, Sjöwall C, Rantapää-Dahlqvist S, Bengtsson AA, Jönsen A, Pucholt P, Wu YL, Lundström E, Eloranta ML, Gunnarsson I, Baecklund E, Jonsson R, Hammenfors D, Forsblad-d'Elia H, Eriksson P, Mandl T, Bucher S, Norheim KB, Johnsen SJA, Omdal R, Kvarnström M, Wahren-Herlenius M, Truedsson L, Nilsson B, Kozyrev SV, Bianchi M, Lindblad-Toh K; DISSECT consortium; ImmunoArray consortium, Yu CY, Nordmark G, Sandling JK, Svenungsson E, Leonard D, Rönnblom L. Strong Association of Combined Genetic Deficiencies in the Classical Complement Pathway With Risk of Systemic Lupus Erythematosus and Primary Sjögren's Syndrome. Arthritis Rheumatol. 2022;74:1842-1850.
Lundtoft C, Pucholt P, Martin M, Bianchi M, Lundström E, Eloranta ML, Sandling JK, Sjöwall C, Jönsen A, Gunnarsson I, Rantapää-Dahlqvist S, Bengtsson AA, Leonard D, Baecklund E, Jonsson R, Hammenfors D, Forsblad-d'Elia H, Eriksson P, Mandl T, Magnusson Buche S, Norheim KB, Auglænd Johnsen SA, Omdal R, Kvarnström M, Wahren-Herlenius M, Notarnicola A, Andersson H, Molberg Ø, Diederichsen LP, Almlöf J, Syvänen AC, Kozyrev SV, Lindblad-Toh K, the DISSECT consortium, the ImmunoArray consortium, Nilsson B, Blom AM, Lundberg IE, Nordmark G, Diaz-Gallo LM, Svenungsson E, Rönnblom L. Complement C4 copy number variation is linked to SSA/SSB autoantibodies in systemic inflammatory autoimmune diseases. Arthritis Rheumatol, 2022, 74:1440-1450.
Sandling JK, Pucholt P, Hultin Rosenberg L, Farias FHG, Kozyrev SV, Eloranta ML, Alexsson A, Bianchi M, Padyukov L, Bengtsson C, Jonsson R, Omdal R, Lie BA, Massarenti L, Steffensen R, Jakobsen MA, Lillevang ST, ImmunoArray Development Consortium, DISSECT consortium, Lerang K, Molberg Ø, Voss A, Troldborg A, SJacobsen S, Syvänen AC, Jönsen A, Gunnarsson I, Svenungsson E, Rantapää-Dahlqvist S, Bengtsson AA, Sjöwall C, Leonard D, Lindblad-Toh K, Rönnblom L. Molecular pathways in patients with systemic lupus erythematosus revealed by gene centred DNA sequencing. Ann Rheum Dis. 2021; 80:109-117.
Bolin K, Imgenberg-Kreuz J, Leonard D, Sandling JK, Alexsson A, Pucholt P, Haarhaus ML, Almlöf JC, Nititham J, Jönsen A, Sjöwall C, Bengtsson AA, Rantapää-Dahlqvist S, Svenungsson E, Gunnarsson I, Syvänen AC, Lerang K, Troldborg A, Voss A, Molberg Ø, Jacobsen S, Criswell L, Rönnblom L, Nordmark G. Variants in BANK1 are associated with lupus nephritis of European ancestry. Genes Immun. 2021; 22:194-202.
Reid S, Hagberg N, Sandling JK, Alexsson A, Pucholt P, Sjöwall C, Lerang K, Jönsen A, Gunnarsson I, Syvänen AC, Troldborg A, Voss A, Bengtsson AA, Molberg Ø, Jacobsen S, Svenungsson E, Rönnblom L, Leonard D. Interaction between the STAT4 rs11889341(T) risk allele and smoking confers increased risk of myocardial infarction and nephritis in patients with systemic lupus erythematosus. Ann Rheum Dis, 2021;80:1183-1189
Reid S, Alexsson A, Frodlund M, Morris D, Sandling JK, Bolin K, Svenungsson E, Jönsen A, Bengtsson C, Gunnarsson I, Illescas Rodriguez V, Bengtsson A, Arve S, Rantapää-Dahlqvist S, Eloranta ML, Syvänen AC, Sjöwall C, Vyse TJ, Rönnblom L, Leonard D. High genetic risk score is associated with early disease onset, damage accrual and decreased survival in systemic lupus erythematosus. Ann Rheum Dis. 2020;79:363-369.
Rönnblom L, Leonard D. Interferon pathway in SLE: one key to unlocking the mystery of the disease. Lupus Sci & Med, 2019; 6(1):e000270. doi: 10.1136.
Leonard D, Svenungsson E, Dahlqvist J, Alexsson A, Ärlestig L, Taylor KE, Sandling JK, Christine Bengtsson C, Frodlund M, Jönsen A, Eketjäll S, Jensen-Urstad K, Gunnarsson I, Sjöwall C, Bengtsson AA, Eloranta M-L, Syvänen A-C, Rantapää-Dahlqvist S, Criswell L, Rönnblom L. Novel Gene Variants Associated with Cardiovascular Disease in Systemic Lupus Erythematosus and Rheumatoid Arthritis. Ann Rheum Dis, 2018; 77:1063-1069.
Hagberg N, Joelsson M, Leonard D, Reid S, Eloranta M-E, Mo J, Nilsson M, Syvänen A-C, Bryceson Y, Rönnblom L. The STAT4 SLE risk allele rs7574865[T] is associated with increased IL-12-induced IFN-γ production in T cells from SLE patients. Ann Rheum Dis, 2018; 77:1070-1077.
Imgenberg-Kreuz J, Carlsson Almlöf J, Leonard D, Nordmark G, Eloranta M-E, Padyukov L, Iva Gunnarsson I, Svenungsson E, Sjöwall C, Rönnblom L, Syvänen A-C, Sandling JK. DNA methylation mapping identifies gene regulatory effects in patients with systemic lupus erythematosus (SLE). Ann Rheum Dis, 2018; 77:736-743.
Leonard D, Eloranta ML, Hagberg N, Berggren O, Tandre K, Alm G, Rönnblom L. Activated T cells enhance the interferon-α production by plasmacytoid dendritic cells stimulated with RNA containing immune complexes. Ann Rheum Dis, 2016; 75:1728-34.
Bentham J, Morris DL, Cunninghame Graham DS, Pinder CL, Tombleson P, Behrens TW, Patrick, Gaffney PM, Martín J, Fairfax B, Knight J, Rönnblom L, Syvänen AC, Graham RR, Wither JE, Rioux JD, Alarcón-Riquelme ME, Vyse TJ . Genetic association analyses implicate aberrant regulation of innate and adaptive immunity genes in the pathogenesis of systemic lupus erythematosus. Nature Genet, 2015; 47:1457-1464.
Berggren O, Hagberg N, Weber G, Alm GV, Rönnblom L, Eloranta ML. B lymphocytes enhance the interferon-a production by plasmacytoid dendrtic cells. Arthritis Rheum, 2012; 64:3409-19.
Hagberg N, Berggren O, Leonard D, Weber G, Bryceson YT, Alm GV, Eloranta ML, Rönnblom L. IFN-a production by plasmacytoid dendritic cells stimulated with RNA-containing immune complexes is promoted by NK cells via MIP-1b and LFA-1. J Immunol, 2011; 186:5085-94.
Sandling J, Garnier S, Sigurdsson S, Wang C, Nordmark G, Gunnarsson I, Svenungsson E, Padyukov L, Sturfelt G, Jönsen A, Bengtsson AA, Truedsson L, Eriksson C, Rantapää-Dahlqvist S, Mälarstig A, Strawbridge RJ, Hamsten A, Criswell LA, Graham RR, Behrens TW, Eloranta ML, Alm GV, Rönnblom L, Syvänen AC. A candidate gene study of the type I interferon pathway implicates IKBKE and IL8 as risk loci for SLE. Eur J Hum Genet, 2011; 19:479-84
Svenungsson E, Gustafsson J, Leonard D, Sandling J, Gunnarsson I, Nordmark G, Jönsen A, Bengtsson AA, Sturfelt G, Rantapää-Dahlqvist, Elvin K, Sundin U, Garnier S, Simard J, Sigurdsson S, Padyukov L, Syvänen AC, Rönnblom L. A STAT4 risk allele is associated with ischemic cerebrovascular events and antiphospholipid antibodies in Systemic Lupus Erythematosus. Ann Rheum Dis, 2010; 69:834-40.
Gateva V, Sandling JK, Hom G, Taylor KE, Chung SA, Sun X, Ortmann W, Kosoy R, Ferreira RC, Nordmark G, Gunnarsson I, Svenungsson E, Padyukov L, Sturfelt G, Jönsen A, Bengtsson AA, Rantapää-Dahlqvist S, Baechler EC, Brown EE, Alarcón GS, Edberg JC, Ramsey-Goldman R, McGwin G Jr, Reveille JD, Vilá LM, Kimberly RP, Manzi S, Petri MA, Lee A, Gregersen PK, Seldin MF, Rönnblom L, Criswell LA, Syvänen AC, Behrens TW, Graham RR.A Large-Scale Replication Study Identifies TNIP1, PRDM1, JAZF1, UHRF1BP1, and IL10 as Novel Risk Loci for Systemic Lupus Erythematosus. Nature Gen, 2009; 41:1228-33.
Hom G,Graham RR, Modrek B, Ortmann W, Taylor KE, Garnier S, Lee AT, Chung SA, Ferreira R, Pant PVK, Ballinger DG, Kosoy R, Demirci FY, Kamboh MI, Kao AH, Tian C, Gunnarsson I, Bengtsson AA, Rantapää-Dahlqvist SB, Petri M, Manzi S, Seldin MF, Rönnblom L, Syvänen AC, Criswell LA, Gregersen PK, Behrens TW. Association of Systemic Lupus Erythematosus with C8orf13-BLK and ITGAM-ITGAX. New Eng J Med, 2008; 358:900-9.
Sigurdsson S, Nordmark G, Göring HH, Lindroos K, Wiman AC, Sturfelt G , Jönsen A, Rantapää-Dahlqvist S, Möller B, Kere J, Koskenmies S, Widén E, Eloranta ML, Julkunen H, Kristjansdottir H, Steinsson K, Alm G, Rönnblom L, Syvänen AC. Polymorphisms in the tyrosine kinase 2 and interferon regulatory factor 5 genes are associated with systemic lupus erythematosus. Am J Hum Gen, 2005; 76:528-37.
Lövgren T, Eloranta MJ, Båve U, Alm GV, Rönnblom L. Induction of interferon-a production in plasmacytoid dendritic cells by immune complexes containing nucleic acid released by necrotic or late apoptotic cells and lupus IgG. Arthritis Rheum, 2004; 50:1861-1872
Blomberg S, Eloranta M-L, Cederblad B, Nordlind K, Alm GV, Rönnblom L. Presence of cutaneous interferon-a producing cells in patients with systemic lupus erythematosus. Lupus, 2001; 10: 484-90.
Båve U, Vallin H, Alm G, Rönnblom L. Activation of natural interferon-a producing cells by apoptotic U937 cells combined with lupus IG and its regulation by cytokines. J Autoimmun, 2001; 11: 465-470.
Bengtsson A, Sturfelt G, Truedsson L, Blomberg J, Alm G, Vallin H, Rönnblom L. Activation of type I interferon system in systemic lupus erythematosus correlates with disease activity but not antiretroviral antibodies. Lupus 2000; 9: 664-671.
Vallin H, Blomberg S, Alm G V, Cederblad B, Rönnblom L. Patients with Systemic Lupus Erythematosus have a circulating inducer of interferon-alpha (IFN-a) production acting on leukocytes resembling immature dendritic cells. Clin Exp Immunol. 1999; 115:196-202.
Rönnblom LE, Alm GV, Öberg KE . Autoimmunity after alpha-interferon therapy for malignant carcinoid tumors. Ann Int Med. 1991; 115:178-183.
Rönnblom LE, Öberg KE, Alm GV. Possible induction of Systemic Lupus Erythematosus by interferon-a treatment in a patient with a malignant carcinoid tumour. J Int Med. 1990; 227: 207-210