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Abstract Number: 1576

Type I Interferon-Mediated Skewing Of The Serotonin Synthesis In Systemic Lupus Erythematosus Is Associated To Cardiovascular Disease

Christian Lood1, Helena Tydén1, Birgitta Gullstrand2, Cecilia Klint3, Christina Wenglén3, Christoffer T. Nielsen4, Niels H. H. Heegaard5, Andreas Jönsen1 and Anders A. Bengtsson1, 1Department of Clinical Sciences, Section of Rheumatology, Lund University, Lund, Sweden, 2Department of Laboratory Medicine, Section of Microbiology, Immunology and Glycobiology, Lund University, Lund, Sweden, 3R&D, AnaMar AB, Lund, Sweden, 4Department of Clinical Biochemistry, Immunology & Genetics, Statens Serum Institut, Copenhagen S, Denmark, 5Department of Clinical Biochemistry, Immunology & Genetics, Statens Serum Institut, Copenhagen, Denmark

Meeting: 2013 ACR/ARHP Annual Meeting

Keywords: Cardiovascular disease, Interferons and systemic lupus erythematosus (SLE)

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Session Information

Session Title: Systemic Lupus Erythematosus - Clinical Aspects II: Central Nervous System Manifestations, Therapeutics

Session Type: Abstract Submissions (ACR)

Background/Purpose: Systemic lupus erythematosus (SLE) is an autoimmune rheumatic disease characterized by increased expression of type I interferons (IFNs). Indoleamine 2,3-dioxygenase (IDO), a type I IFN-regulated protein, limits the conversion of tryptophan to serotonin in favor of kynurenine. Serotonin has been implicated in development of cardiovascular disease in the general population, but its role in SLE, a disease characterized with markedly increased cardiovascular morbidity and mortality, is not known. The aim of this study was to investigate if SLE patients had a type I IFN-mediated dysregulation of the serotonin production and whether or not this was associated to cardiovascular disease.

Methods: Serotonin was measured in serum from patients with SLE (n=148) and healthy volunteers (n=79) with ELISA and intracellularly in platelets using flow cytometry and related to cardiovascular disease adjusted for traditional risk factors. Tryptophan and kynurenine were measured by liquid chromatography.

Results: SLE patients had decreased serum and platelet levels of serotonin as compared to healthy volunteers. The serum levels were associated to type I IFNs, compatible with IFN-mediated skewing of the tryptophan metabolism. Serum serotonin levels were inversely associated to disease severity and cardiovascular disease in SLE patients, independently of traditional cardiovascular risk factors.

Conclusion:

We suggest that the serotonin system is dysregulated in SLE due to increased type I IFN production. Furthermore, the serum level of serotonin is identified as a novel risk factor for cardiovascular disease in SLE, independently of traditional cardiovascular risk factors.


Disclosure:

C. Lood,
None;

H. Tydén,
None;

B. Gullstrand,
None;

C. Klint,
None;

C. Wenglén,
None;

C. T. Nielsen,
None;

N. H. H. Heegaard,
None;

A. Jönsen,
None;

A. A. Bengtsson,
None.

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