Background The cytokine IL-38 (IL-1F10) is a member of the IL-1 superfamily, which binds to IL-36R. IL-38 polymoprhisms have been associated with spondylitis and rheumatoid arthritis, and while IL-38 function is poorly understood, it has been reported to inhibit Th17 responses.
Objectives Clinical associations of serum IL-38 have not been reported. Here, we investigated associations of serum IL-38 in SLE.
Methods Serum was obtained from patients with SLE (≥ACR 4) followed in a longitudinal cohort in which disease activity (SLEDAI-2k) and drug treatment details were recorded with each sample. IL-38 was quantified by ELISA.
Results 142 SLE patients (median age 42 (20-80) years, disease duration 103 (18-439) months) were studied at baseline, 115 of whom were also studied in two consecutive subsequent clinic visits. 28 age- and gender-matched healthy control individuals were also studied.
IL-38 (0-5928 pg/ml) was detectable in 128 (13.4%) baseline SLE samples. Mean serum IL-38 was significantly higher in SLE compared with controls (p=0.0031). Significantly higher IL-38 was observed in patients with active disease (SLEDAI ≥4, n=84, p=0.0438). Baseline IL-38 was significantly higher in patients with subsequent persistently active disease (PAD; Nikpour 2009) (p=0.0057), and time-adjusted mean IL-38 measured longitudinally was also significantly higher in patients with PAD (p=0.0226). Detectable IL-38 was associated with a 1.7 fold increased risk of PAD (RR=1.669, 95%CI 1.255-1.938, p=0.0096). Mean serum IL-38 was increased in patients with renal (p=0.0170) or CNS (p=0.0189) lupus, and detectable IL-38 was associated with increased risk of renal disease (RR=1.605, 95%CI 1.153-2.234, p=0.0280) and CNS disease (RR=2.233, 95%CI 1.174-4.249, p=0.0349).
Conclusions These data are the first report of IL-38 in SLE. Serum IL-38 is strongly associated with markers of adverse outcome including disease activity and renal and CNS disease. Further investigation of the role of IL-38 in SLE is justified.
Nikpour, M., Urowitz, M. B., Ibañez, D., & Gladman, D.D. (2009). Frequency and determinants of flare and persistently active disease in systemic lupus erythematosus. Arthritis & Rheumatism, 61(9), 1152–1158.
Disclosure of Interest None declared
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