Background B-lymphocyte Stimulator (BLyS, or BAFF), a survival factor for B cells, has been previously implicated in the pathogenesis of Sjögren's syndrome (SS) and SS related lymphoproliferation (1–2). It has been also previously shown to be induced by both type I and II Interferons (IFNs) also implicated in the pathogenesis of SS (3). Belimumab, an anti-BAFF monoclonal antibody that targets BAFF, was recently found to be effective and safe in SS in the phase II BELISS trial (4–5).
Objectives To explore the possible effect of belimumab on IFN-induced peripheral blood gene expression in the phase II BELISS trial. Additionally, to evaluate whether baseline IFN signature could serve as a predictor of clinical and serological responses following belimumab treatment.
Methods Twelve patients who were enrolled in the phase II BELISS trial were studied for peripheral blood IFN signature at baseline, at w28 (10/12), and at w52 (4/12). Patients were all females, median 47.5 yrs (35–79), all positive for anti-SSA/SSB and for rheumatoid factor (RF), with a median ESSDAI score of 7 (2–27) at BELISS study entry. Peripheral blood mononuclear cells from all study participants were subjected to Real-Time PCR for 3 interferon inducible genes (MX-1, IFIT-1, IFI44) preferentially induced by type I IFN and 2 interferon inducible genes preferentially induced by type II IFN (MIG-1, GBP1). Both type I and II IFN scores were determined, as previously described.
Results No statistically significant changes were observed between baseline and w28 or w52 type I IFN scores (mean±SE: 17.8±3.2 vs 19.9±3.7 vs 20.2±1.2, respectively, p>0.05 for all comparisons by paired sample t-tests). Baseline type I IFN scores were correlated with changes in rheumatoid factor from baseline to w52, baseline mental component score of SF-36 (r=0.7/p=0.007, and r=0.8/p=0.003, respectively, by Pearson's test). When patients were subdivided in two groups, i.e. low IFN score and high IFN score, based on the baseline mean of IFN score, a significant differences were found between low and high IFN score groups as regards baseline to w52 changes in IgG (p=0.004, by Mann-Whitney), IgA (p=0.004, by Mann-Whitney), IgM levels (p=0.03, by Mann-Whitney) in favour of high IFN score group, while changes in RF levels tended to be significant (p=0.08, by Mann-Whitney). No significant changes or associations with type II IFN scores were observed.
Conclusions Type I IFN-induced peripheral blood gene expression may affect the magnitude of biological effect of belimumab in SS, and in particular on RF-positive B-cell clones. Patients showing higher IFN signature may be the optimal target for belimumab in SS.
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Disclosure of Interest None declared