Abstract

There is increasing evidence of a correlation between interferon-inducible protein 10 (IP-10) and disease activity of systemic lupus erythematosus (SLE) and lupus nephritis (LN). We conducted a comprehensive search on IP-10 using MEDLINE, Scopus, and Cochrane electronic databases from the beginning to the end of December 2017. All studies that compared serum and/or urine IP-10 between active SLE/LN patients and any control groups were identified and included in this systematic review and meta-analysis. The mean difference (MD) of IP-10 level among active SLE and LN patients, as well as the correlation of IP-10 with disease activity, were meta-analyzed using a random-effects model. From 23 eligible studies, 15 provided adequate data for meta-analysis. Serum IP-10 was significantly elevated in patients with active SLE compared to non-active SLE patients (MD 356.5 pg/mL, 95% CI 59.6 to 653.4, p = 0.019). On the other hand, the levels of serum IP-10 was not different between active LN and non-active LN. However, serum IP-10 was positively correlated with disease activity like SLE disease activity index (SLEDAI) (pooled r = 0.29, 95% CI 0.22 to 0.35, p < 0.001). Furthermore, urine IP-10 tended to be higher in patients with active LN compared to non-active LN patients but this did not reach statistical significance (MD 3.47 pg/mgCr × 100, 95% CI −0.18 to 7.12, p = 0.06). Nevertheless, urine IP-10 was positively correlated with renal SLEDAI (pooled r = 0.29, 95% CI 0.05 to 0.50, p = 0.019). In conclusion, serum and urine IP-10 levels may be useful in monitoring the disease activity of SLE and LN. Serum IP-10 was correlated with systemic disease whereas urine IP-10 was a useful biomarker for detecting active LN.

Highlights

  • Despite the availability of new treatments directed against causative molecular targets, systemic lupus erythematosus (SLE) patients still suffer from disease flares due to the unpredictable nature of the disease

  • Gene expression studies showed that there was an overexpression of IFN-stimulated genes (ISGs) in the blood of SLE patients, which highlighted the significant role of IFN in SLE [6,7]

  • The search terms used were lupus nephritis or systemic lupus erythematosus combined with interferon-inducible protein 10, IP-10, or CXCL10, all of which were used as medical subject heading terms or keywords for each respective database

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Summary

Introduction

Despite the availability of new treatments directed against causative molecular targets, systemic lupus erythematosus (SLE) patients still suffer from disease flares due to the unpredictable nature of the disease. Throughout the years, evidence from multiple studies showed that interferon (IFN) signaling pathway had a pivotal role in SLE. Studies showed a high level of IFN in the serum of patients with SLE [3,4]. The use of IFN as a treatment in various diseases could induce autoantibodies seen in SLE [5]. Gene expression studies showed that there was an overexpression of IFN-stimulated genes (ISGs) in the blood of SLE patients, which highlighted the significant role of IFN in SLE [6,7]. Further study on ISG products has identified many promising IFN-regulated chemokines and demonstrated the correlation of these chemokines with disease activity making them possible biomarker candidates [8]

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