Serum interleukin 38 is associated with disease severity and organ involvement in systemic lupus erythematosus. — ASN Events
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  3. Serum interleukin 38 is associated with disease severity and organ involvement in systemic lupus erythematosus.

Serum interleukin 38 is associated with disease severity and organ involvement in systemic lupus erythematosus. (#324)

Ina Rudloff 1 2 , Jack Godsell 3 , Claudia A Nold-Petry 1 2 , James Harris 3 , Alberta Hoi 3 , Eric F Morand 3 , Marcel F Nold 1 2
  1. Ritchie Centre, MIMR-PHI Institute of Medical Research, Melbourne, VIC, Australia
  2. Department of Paediatrics, Monash University, Melbourne, VIC, Australia
  3. Centre for Inflammatory Diseases, Monash University, Monash Medical Centre, Melbourne, VIC, Australia

Aims: Interleukin (IL)-38 is a member of the IL-1 cytokine family. Although knowledge on IL-38 is sparse, IL-38 gene polymorphisms have been associated with inflammatory diseases, and recombinant IL-38 inhibits IL-17 and IL-22. Intriguingly, both IL-17 and IL-22 play a role in systemic lupus erythematosus (SLE), a severe autoimmune disease. We therefore set out to investigate IL-38 in SLE.

Methods: IL-38 and IL-10 were quantified by ELISA in serum from SLE patients at admission (baseline, 142 patients) and two subsequent clinic visits (115/142). SLE disease activity index-2000 (SLEDAI-2k) and treatment details were recorded. Serum of 28 healthy donors served as controls. Moreover, we silenced IL-38 in PBMC from healthy volunteers by siRNA (siIL-38) and measured IL-6 by ELISA.

Results: IL-38 (63-5928pg/ml) was detectable in 59 out of 345 patient samples (17.1%) and IL-38 abundance in SLE samples was significantly higher than in healthy controls (p=0.003). Moreover, patients with active disease (SLEDAI-2k≥4) had 18.4-fold higher serum IL-38 than patients with non-active disease (p=0.044). Importantly, IL-38 was associated with increased risk of renal (RR=1.6, 95% CI 1.2-2.2, p=0.028) and CNS disease (RR=2.2, 95% CI 1.2-4.3, p=0.035), and when IL-38 was detectable at baseline, patients had a 1.7-fold increased risk of developing persistently active disease (RR=1.7, 95% CI 1.3-1.9, p=0.01).Remarkably, siIL-38-treated PBMC from healthy volunteers produced up to 30-fold more IL-6 than control-transfected cells when stimulated with CpG or imiquimod (n=3). Similarly, in SLE patients, the anti-inflammatory cytokine IL-10 was 5-fold higher when IL-38 was detectable, suggesting that IL-38 may be protective in SLE.

Conclusions: This study is the first to demonstrate the anti-inflammatory activity of endogenous IL-38. We moreover reveal IL-38 as the first mediator that exhibits an association with markers of SLE disease activity and renal and CNS involvement; IL-38 may thus become the highly sought-after first biomarker for SLE.