Systemic Lupus Erythematosus (SLE)
Systemic lupus erythematosus (SLE) is a chronic autoimmune rheumatic disease that can affect multiple organs, including the skin, joints, kidneys, nervous system and cardiovascular system. The disease predominantly affects women and often develops in early adulthood. Both genetic susceptibility and environmental exposures contribute to the development of SLE. However, how these factors interact to trigger disease and influence its subsequent course is still not fully understood. Our research aims to identify and understand the molecular and environmental mechanisms that drive SLE and determine why the disease develops differently in different individuals. Ultimately, our goal is to translate this knowledge into improved prevention, diagnostics, prediction of disease progression, and more effective, individualized treatment.
Project description
Our research group conducts translational and clinical research in SLE in close collaboration with the Department of Rheumatology at Uppsala University Hospital. More than 300 patients in Uppsala participate in our ongoing studies.
An important foundation of our research is a long-standing Scandinavian SLE network, which includes approximately 2,500 well-characterized patients from Sweden and Norway. For these patients, we have extensive genetic data together with detailed clinical information on disease manifestations, autoantibodies, treatments and long-term outcomes. This unique resource enables large-scale studies of the biological factors underlying differences in disease course and treatment response.
A major focus of our research is to understand how genetic and epigenetic variation influences immune dysregulation, clinical manifestations, organ involvement and response to treatment in SLE. We also study how environmental and lifestyle factors interact with genetic susceptibility to influence the risk of developing SLE and its clinical manifestations. By combining genetic, epigenetic, immunological, environmental and detailed clinical data, we aim to identify mechanisms and biomarkers that can improve prediction of disease development, disease course and treatment response.
We have a particular interest in the type I interferon system, a central immune pathway in SLE. We investigate how genetic and epigenetic factors contribute to persistent interferon activation and how these molecular mechanisms are linked to specific disease manifestations and disease severity.
By integrating molecular, environmental and clinical data, our long-term goal is to develop precision-medicine approaches that can identify individuals at increased risk of SLE, predict patients at risk of severe disease, and help select the most effective treatment for each individual patient.
Lisbon, 2026. From left: Nina Oparina, Maija-Leena Eloranta, Holme Vestin, Dag Leonard, Lars Rönnblom, Karin Hjorton, Rezvan Kiani. Photo: Private.
Selected publications
Vestin H, Oparina N, Eloranta ML, Skoglund E, Giannakou I, Frodlund M, Gunnarsson I, Sjöwall C, Svenungsson E, Rönnblom L, Imgenberg-Kreuz J, Leonard D. Methylation and polygenic risk scores capture different features of Systemic Lupus Erythematosus. Rheumatology (Oxford) 1 Aug 2026.
Sayadi A, Eloranta a M-L, Oparina N, Wallgren M, Skoglund S, Frodlund M, Sjöwall C, Rönnblom L, Leonard D. Single-cell RNA-seq reveals a persistent interferon signature in immune cells from Systemic lupus erythematosus patients with high versus low polygenic risk scores despite antimalarial treatment. Journal of Autoimmunity 12 May 2026.
Reid S, Sandling J K, 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 A A, Rönnblom L, Leonard D. Genetic risk factors and clinical manifestations of systemic lupus erythematosus: Large-scale analysis of genetic predisposition and disease subtypes. Journal of Internal Medicine. 7 Nov, 2025.
Vestin H*, Oparina N*, Eloranta ML, Frodlund M, Gunnarsson I, Sjöwall C, Svenungsson E, Rönnblom L, Imgenberg-Kreuz J#, Leonard D#. */#contributed equally. Patients with SLE have an increased bisphenol A methylation score linked to SLE risk gene and selected clinical subphenotypes. RMD Open. 9 Sep, 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