Type I interferon-mediated skewing of the serotonin synthesis is associated with severe disease in systemic lupus erythematosus.
Level 4 - case-series / case-control
Case-control observational study with in vitro mechanistic assays
PubMed 25897671 · doi:10.1371/journal.pone.0125109
What was done
Researchers evaluated serotonin synthesis and degradation pathways in patients with systemic lupus erythematosus (SLE; n=148) compared to healthy volunteers (n=79). Serotonin levels were quantified in serum and plasma using liquid chromatography and ELISA, and intracellularly in platelets using flow cytometry. Type I interferon (IFN) activity in patient sera was assessed with a reporter assay, and indoleamine 2,3-dioxygenase (IDO) activity was estimated via the kynurenine/tryptophan ratio measured by liquid chromatography. In vitro experiments tested the ability of SLE sera to induce IDO expression in WISH cells.
What was found
Compared to healthy controls, SLE patients exhibited significantly decreased serotonin concentrations in serum (p=0.01) and platelets (p<0.0001). Patients with active type I IFN signatures showed lower serum serotonin (p=0.0008) and increased IDO activity (p<0.0001). In cell culture, SLE sera induced IDO expression in WISH cells in a type I IFN-dependent manner (p=0.008). Platelet activation also contributed to decreased serotonin availability (p<0.05). Lower serum serotonin levels significantly correlated with severe SLE phenotypes, including the presence of anti-dsDNA antibodies and lupus nephritis. Specific absolute concentrations and effect sizes were not reported in the abstract.
Why it matters
This study identifies a mechanism whereby type I interferon up-regulates IDO and shifts tryptophan metabolism away from serotonin production, associating reduced serotonin levels with severe clinical manifestations in SLE.
Limits
The study is an observational case-control design, which cannot establish causality between altered serotonin metabolism and lupus pathogenesis. Exact numerical values, confidence intervals, and potential confounders such as patient medications were not reported in the abstract.
Cited by
- supports Pro-inflammatory cytokines affect tryptophan metabolism and serotonin synthesis.