From genes to function in autoimmune diseases

Systemic lupus erythematosus (SLE) is regarded as the prototype autoimmune disease because it involves most immune cells and can affect all organs of the human body. SLE has a strong heritable component. There are more than 60 confirmed genetic risk loci for SLE that have been identified by genome-wide association studies and subsequent follow-up studies. By analysis of well characterized Swedish SLE patients, collected by the Swedish SLE Network, our group has contributed to the identification of 30 of of these loci.

Many of the genes at the SLE-associated loci belong to the type I interferon (IFN), B-cell and T-cell signaling pathways, but other pathways have also been uncovered by genetic studies. We have also contributed to genetic and epigenetic studies of Sjögren’s syndrome (pSS) which shares clinical features with SLE. In our current research on SLE and pSS we are using “next generation” DNA sequencing in combination with functional and epigenetic analyses on the RNA, protein and cellular levels to identify functional, disease-causing alleles in risk loci for SLE and other autoimmune diseases. Whole genome sequencing in families with SLE is applied to identify novel risk variants for SLE. The project involves a long-term and close collaboration with the Rheumatology research group in Rheumatology at our own Department.

Group members working in the project

  • Jonas Carlsson Almlöf

Former group members active in the project

  • Juliana Imgenberg-Kreuz

Main collaborators

Prof. Lars Rönnblom, Ass Prof.  Gunnel Nordmark, Ass Prof.  Maija-Leena Eloranta and Dr Johanna Sandling, Research group in Rheumatology, Department of Medical Sciences, and Rheumatology Clinic, Uppsala University Hospital.

The Swedish SLE Network: Clinicians and scientists from five major University Hospitals in Sweden

Prof Timothy Vyse, Kings College London, UK

Ass Prof. Tomi Pastinen, McGill University, Montreal, Canada.


Knut and Alice Wallenberg Foundation, read more about the KAW-funded project.
Swedish Research Council for Medicine & Health (VR-MH)
Swedish Research Council for Science &Technology (VR-NT) 

Recent publications

  • Imgenberg-Kreuz J, Carlsson Almlöf J, Leonard D, Alexsson A, Nordmark G, Eloranta ML, Rantapää-Dahlqvist S, Bengtsson AA, Jönsen A, Padyukov L, Gunnarsson I, Svenungsson E, Sjöwall C, Rönnblom L, Syvänen AC, Sandling JK (2018) DNA methylation mapping identifies gene regulatory effects in patients with systemic lupus erythematosus. Ann Rheum Dis
  • Almlöf JC, Alexsson A, Imgenberg-Kreuz J, Sylwan L, Bäcklin C, Leonard D,Nordmark G, Tandre K, Eloranta ML, Padyukov L, Bengtsson C, Jönsen A, Dahlqvist SR, Sjöwall C, Bengtsson AA, Gunnarsson I, Svenungsson E, Rönnblom L, Sandling JK, Syvänen A-C. Novel risk genes for systemic lupus erythematosus predicted by random forest classification. Science Reports 7(1):6236, 2017
  • Langefeld CD, Ainsworth HC, Cunninghame Graham DS, Kelly JA, Comeau ME, Marion MC, Howard TD, Ramos PS, Croker JA, Morris DL, Sandling JK, Almlöf JC, …… Rioux JD, Gregersen PK, Syvänen AC, Rönnblom L, Criswell LA, Jacob CO, Sivils KL, Tsao BP, Schanberg LE, Behrens TW, Silverman ED, Alarcón-Riquelme ME, Kimberly RP, Harley JB, Wakeland EK, Graham RR, Gaffney PM, Vyse TJ. Transancestral mapping and genetic load in systemic lupus erythematosus. Nat Commun. 8:16021, 2017
  • Morin A, Kwan T, Ge B, Letourneau L, Ban M, Tandre K, Caron M, Sandling JK, Carlsson J, Bourque G, Laprise C, Montpetit A, Syvanen A-C, Ronnblom L, Sawcer SJ, Lathrop MG, Pastinen T (2016) Immunoseq: the identification of functionally relevant variants through targeted capture and sequencing of active regulatory regions in human immune cells. BMC Med Genomics 9:59
  • Brække Norheim K, Imgenberg-Kreuz J, Jonsdottir K, Janssen EAM, Syvänen A-C, Sandling JK, Nordmark G, Omdal R (2016) Epigenome-wide DNA methylation patterns associated with fatigue in primary Sjögren’s syndrome. Rheumatology 55(6), 1074-1082
  • Imgenberg-Kreuz J, Sandling JK, Almlöf JC, Nordlund J, Signér L, Norheim KB, Omdal R, Rönnblom L, Eloranta M-L, Syvänen A-C, Nordmark G (2016) Genome-wide DNA methylation analysis in multiple tissues in primary Sjögren's syndrome reveals regulatory effects at interferon-induced genes. Ann Rheum Dis, 2016 Feb 8 [Epub ahead of print]
  • Bentham J, Morris DL, Cunninghame Graham DS, Pinder CL, Tombleson P, Behrens TW, Martin J, Fairfax BP, Knight JC, Chen L, Replogle J, Syvanen A-C, Ronnblom L, Graham RR, Wither JE, Rioux JD, Alarcon-Riquelme ME, Vyse TJ (2015) Genetic association analyses implicate aberrant regulation of innate and adaptive immunity genes in the pathogenesis of systemic lupus erythematosus. Nat Genet, 2015 Oct 26
  • Berggren O, Alexsson A, Morris DL, Tandre K, Weber G, Vyse TJ, Syvänen A-C, Rönnblom L, Eloranta M-L (2015) IFN-α production by plasmacytoid dendritic cell associations with polymorphisms in gene loci related to autoimmune and inflammatory diseases. Hum Mol Genet 24(12), 3571-3581