OP0175 Interferon signature might serve as early biomarker for development of lupus and correlates strongly with myxovirus-resistance protein a

2018 
Background Incomplete systemic lupus erythematosus (iSLE) marks a group of patients with typical features of SLE, who do not meet classification criteria. Up to 55% progress to SLE, but there are no predictive markers available. Interferon (IFN) type-I is an important early mediator in SLE. The majority of SLE patients show upregulation of interferon-inducible genes. Levels of IFN-related soluble markers, which are more easily applicable, are also increased in SLE. Objectives To measure IFN signature and IFN-related soluble markers in iSLE patients to determine if these can serve as predictors of SLE. Methods Thirty iSLE patients (ANA titer ≥1:80, disease duration RNA was isolated from whole blood using PAXgene tubes, reversely transcribed to cDNA and quantitatively analysed by Real time PCR. IFN score was calculated based on cumulative expression of 12 IFN-related transcripts (IP-10, IFI44L, IFIT3, LY6E, MX1, SERPING1, IFITM1, IRF7, STAT1, C1QA, IFI16 and IRF9). A positive IFN-score was defined as >2 SD of the mean of the control group. Levels of IFN-related mediators, including IFN-γ induced protein 10 (IP-10) and Myxovirus-resistance protein A (MxA) were measured using ELISA. Statistical significance between groups was tested with Mann-Whitney U tests. Correlations of continuous data were calculated using Spearman’s r test. Results Baseline characteristics are shown in table 1. An increased IFN score was present in 55% of iSLE patients (p=0.05) and 46% of SLE patients (p=0.07) (figure 1a).In iSLE, IFN score correlated positively with ESR (r=0.52, p=0.004), SSA titer (r=0.64, p=0.02) and cumulative number of ENA (r=0.57, p=0.001), and negatively with leukocyte count (r=-0.38, p=0.04), Hb (r=-0.39, p=0.04), and C4 (r=-0.47, p=0.01). SLEDAI, clinical symptoms, nor use of hydroxychloroquine were correlated with IFN score. Levels of MxA correlated strongly with IFN score in both iSLE (r=0.78, p Conclusions IFN-signature is present in 55% of patients with iSLE and correlates with ESR, autoantibody number, leukopenia, anaemia and hypocomplementemia. Interestingly, MxA levels correlated strongly with IFN-gene upregulation and thus might be a suitable and easily applicable surrogate marker for IFN type-I activity. iSLE patients with IFN upregulation might be those at most risk for disease progression; longitudinal data however should be awaited. Disclosure of Interest None declared
    • Correction
    • Source
    • Cite
    • Save
    • Machine Reading By IdeaReader
    0
    References
    0
    Citations
    NaN
    KQI
    []