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Abstract
Introduction Most SLE patients have increased expression of type-I interferon (IFN)-regulated genes, the so-called IFN-signature.1 IFN-regulated genes are subdivided in 3 modules (M1.2, M3.4 and M5.12).2 Module 1.2 is associated with disease presence and the latter two seem to be sequentially activated and to correspond with active disease.3
Furthermore, IFN-related mediators might be more easily applicable biomarkers of IFN upregulation.4
Material and methods Twenty-three iSLE patients (ANA titer ≥1:80, symptoms <5 years, ≥1 objectified clinical ACR criterium), 25 quiescent SLE patients (fulfilling ACR criteria, SLEDAI ≤4) and 11 healthy controls were included.
The IFN score was determined in monocytes, based on 14 IFN-related transcripts, representing all three IFN-modules. (M1.2: CXCL10, IFI44L, IFIT3, LY6E, MX1 and SERPING1. M3.4: AIM2, IFITM1, IRF7 and STAT1. M5.12: C1QA, CSCL2, IFI16 and IRF9). IFN-scores >95 th percentile of controls were defined as positive.
Levels of IFN-related mediators, including IFN-γ induced protein 10 (IP-10), monocyte chemo-attractant protein (MCP-1), and Myxovirus-resistance protein A (MxA) were measured using ELISA.
Results IFN-score was increased in 52% of iSLE patients and 48% of SLE patients. Of iSLE patients, 52%, 52% and 48% respectively had upregulation of M1.2, M 3.4 and M5.12 (see figure 1). In SLE patients, respectively 52%, 44% and 40% were upregulated. M3.4 and M5.12 were only upregulated if M1.2 was activated.
Both MxA and IP-10 were increased in iSLE (median 120 ng/ml and 76 pg/ml, respectively) compared with controls (median 82 pg/ml and 23 pg/ml, respectively). MxA and IP-10 did not correlate in iSLE. In SLE, MxA was increased (median 111 ng/ml), while IP-10 was not. MCP-1 levels were not significantly different between the groups.
Levels of MxA correlated with IFN-score in both iSLE (r=0.49, p=0.0171) and SLE (r=0.70, p<0.0001). Levels of IP-10 correlated with IFN-score based on the 14 genes in SLE but not iSLE.
Conclusion IFN-signature is present in 52% of iSLE patients and correlates with MxA. We hypothesise that these patients might be at risk for disease progression. Longitudinal data however should be awaited. Interestingly, MxA levels correlated strongly with IFN-score and thus could be a suitable and easily applicable surrogate marker.
