Serum interleukin-33 (IL-33) in children with active systemic lupus erythematosus: A cross-sectional study

Abstract

Interleukin-33 (IL-33) is a member of the IL-1 cytokine family and is associated with the development of different autoimmune diseases as systemic lupus erythematosus (SLE). So, the purpose of this cross-sectional study was to measure the serum IL-33 in children with SLE (c-SLE) in relation to their SLE disease activity index. This study was conducted upon 50 c-SLE patients in comparison to 50 normal matched children as a control group. Disease activity was assessed according to SLE Disease Activity Index (SLEDAI-2K). Serum IL-33 was measured by an Enzyme-linked immunosorbent assay (ELISA). Serum IL-33 was significantly higher in c-SLE patients (median: 157.47, IQR:64.49-237.57ng/l) than controls (median: 10.9, IQR: 10.04-12.51ng/L) (P= 0.001) and negatively correlated with serum C3 and C4 levels. Serum IL-33 levels were significantly higher in high disease activity status (HDAS) patients (SLEDAI-2K ≥ 10) (298.47 ± 78.84ng/l) than lupus low disease activity status (LLDAS) patients (SLEDAI-2K < 10) (112.18 ± 16.23ng/l) (P= 0.001). The receiver operating characteristic (ROC) curve analysis revealed that the best cutoff of serum IL-33 level to predict the disease activity was ≥141.3 ng/l with a sensitivity of 93%, a specificity of 90% and accuracy 97%. We concluded that serum IL-33 was higher in c-SLE patients and positively related to the disease activity index so could be used as a disease activity marker.

Associations between blood IL-33 levels and IL-33 gene polymorphisms with susceptibility to systemic lupus erythematosus: A meta-analysis

“…Of these, 13 were selected for fulltext examination based on the title and abstract, while four were disregarded because they lacked data or were review articles. Thus, nine publications satisfied our inclusion criteria [6][7][8][9][10][11][12][13][14] (Figure 1). The meta-analysis focused on five polymorphisms (rs1929992, rs1891385, rs7044343, rs1095498, and rs10975579).…”

“…5 Multiple studies have shown that IL-33 contributes to the pathophysiology of SLE by enhancing immune cell activation, cytokine release, and inflammation. [6][7][8][9][10][11][12][13][14] In response to IL-33, immune cells are known to release proinflammatory cytokines such as interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ). 15 Additionally, IL-33 supports Th2 cell differentiation and activation as well as ILC2 activation, each associated with the emergence of autoimmune and allergic disorders.…”

“…However, the role of IL-33 polymorphisms in the onset of SLE remains debatable, and inconsistent results from earlier studies have been reported. [6][7][8][9][10][11][12][13][14] A comprehensive review and meta-analysis are necessary to establish the relationship between IL-33 and SLE, as the results of previous investigations are inconclusive. This meta-analysis aimed to assess the relationship between blood IL-33 levels and/or polymorphisms and the risk of SLE.…”