Gene expression of cytokines (TNF-α, IFN-γ), serum profiles of IL-17 and IL-23 in paediatric systemic lupus erythematosus

Abstract

Objective: Paediatric systemic lupus erythematosus (pSLE) exhibits an aggressive clinical phenotype and severe complications commonly renal involvement. This could be reflective of the ongoing chronic pro-inflammatory cytokine milieu. We examined relative gene expression of tumour necrosis factor-alpha (TNF-α), interferon-γ (IFN-γ) and serum levels of interleukin-17 (IL-17) and IL-23 and their association with SLEDAI (SLE disease activity index) score and organ manifestations in pSLE.

Methods: We enrolled 40 pSLE patients (age 5-16 years, on treatment) and 20 age-matched healthy controls. Relative gene expression levels of IFN-γ and TNF-α in the peripheral blood were determined by quantitative real-time reverse transcriptase polymerase chain reaction (RT-PCR). β actin gene was used for normalization of gene expression. Serum levels of IL-17 and IL-23 were determined by solid phase sandwich ELISA. Statistical analysis were carried out for comparing (Mann-Whitney U test) and correlating data (Univariate, multivariate analysis and Pearson correlation test) with SLEDAI scores and clinical manifestations.

Results: Over-expression of TNF-α and IFN-γ was found in 90% (36/40) and 80% (32/40) of pSLE patients, respectively. The relative gene expression of TNF-α and IFN-γ were significantly correlated with renal manifestations (p < 0.05). Further, relative expression of IFN-γ gene correlated significantly with skin manifestations and SLEDAI (p < 0.05). Serum levels of IL-17 (766.95 ± 357.83 pg/ml) and IL-23 (135.4 ± 54.23 pg/ml) in pSLE were significantly higher than in controls (IL-17, 172.7 ± 39.19 pg/ml and IL-23, 21.15 ± 10.99 pg/ml) (p < 0.05). Patients with cutaneous (p = 0.002) and haematological involvement (p = 0.003) had high serum IL-17 levels. Serum IL-17 levels correlated with SLEDAI (r = 0.447; p < 0.05).

Conclusions: In this preliminary study, we observed a persistent, strong pro-inflammatory cytokine milieu in pSLE patients which reflects ongoing inflammatory damage in different organs. The gene expression profile of these cytokines may be used for assessing organ involvement in pSLE. IL-17 may also serve as a prognostic marker in pSLE. However, longitudinal studies on treatment of naïve patients are required to corroborate these findings.