Background/Purpose: Abnormalities in B cells and the interferon alpha (IFN) pathway have been separately implicated in the pathogenesis of systemic lupus erythematosus (SLE). B cell depletion therapy with rituximab is used to treat SLE but clinical response varies between patients. We hypothesized that the IFN inducible gene response may explain the difference in clinical responses to rituximab.

Methods: RNA was isolated from whole blood collected into Tempus tubes. Gene expression of the IFN signature genes (STAT 1, SERPING1, S100) was analysed in whole blood from 13 active SLE subjects (before and 2 months after Rituximab), and on age/gender-matched healthy controls, using real time PCR normalized to GADPH. Disease activity was evaluated according to the SLE Disease Activity Index (SLEDAI) score. Complement component C3 was measured by Nephelometry and anti-dsDNA antibodies by ELISA. Analysis of variance (ANOVA) was used to identify significant differences.

Results: Gene expression of SERPING1, but not other interferon inducible genes, was significantly higher in SLE patients before rituximab compared to healthy controls (p=0.0002) (Figure 1). Rituximab treatment led to a 25% decrease in SERPING1 expression in SLE patients (p=0.0131) (Figure 1C) which correlated with clinical response measured by SLEDAI (p=0.054), a reduction in anti-dsDNA antibodies after rituximab (p=0.037), and a trend towards an increase in C3 (p=0.062).

Conclusion: These data suggest that assessment of SERPING1 gene expression, an IFN inducible gene, is strikingly increased in SLE patients and correlated with clinical response to rituximab. These results could support therapeutic targeting of IFN to improve the efficacy of rituximab.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/the-expression-of-the-interferon-inducible-gene-serping1-is-reduced-by-rituximab-and-correlates-with-clinical-response-in-systemic-lupus-erythematosus/