Background/Purpose: The anti-BAFF monoclonal belimumab is approved for the treatment of systemic lupus erythematosus (SLE) since 2011. Effects of belimumab on anti-double stranded (ds)DNA levels, as well as serum levels of B cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL), both belonging to the tumour necrosis factor (TNF) ligand superfamily, have been demonstrated in previous studies. We investigated whether belimumab treatment impacts levels of other cytokines of interest in SLE (i.e. IFN-α2, IL-6, IL-10 and IL-17A), autoantibodies (i.e.anti-dsDNA, anti-TRIM21, anti-SSA (Ro60), anti-SSB, anti-Sm, anti-SmRNP, anti-U1-RNP, anti-histone, anti-ribosomal P, anti-PCNA antibodies), and circulating immune complexes (ICs).

Methods: Longitudinally collected serum samples for up to 24 months of treatment from 78 belimumab-treated patients with SLE from the Karolinska, Skåne and Linköping University hospitals were analysed. Serum cytokine levels were measured using Luminex xMAP technology (Milliplex Map kit HCYTOMAG-60K-04; EMD Millipore Corp., Billerica, USA). Nuclear antigen autoantibody specificities were determined by addressable laser bead immunoassay (ALBIA) using the Connective profile MX117 FIDIS kit (Theradiag, Paris, France). Circulating C1q-binding ICs were measured using enzyme-linked immunosorbent assay (ELISA) (Quanta Lite, Inova, San Diego, USA). P values < 0.05 derived from paired Wilcoxon signed rank tests between baseline and follow-up time points were considered statistically significant.

Results: In patients with detectable cytokine levels at baseline, serum levels of IFN-α2 were lower at month 6 (median: 8.9; IQR: 1.5–54.9 pg/mL) compared with baseline (median: 28.4; IQR: 20.9–100.3 pg/mL; P=0.043). Levels of IL-6 showed decreases from baseline (median: 7.1; IQR: 2.9–16.1 pg/mL) to month 6 (median: 0.5; IQR: 0.5–6.3 pg/mL; P=0.018) and throughout the 24-month follow-up. Levels of IL-10 (baseline median: 12.6; IQR: 2.8–29.7 pg/mL) showed more rapid decreases as soon as from month 3 (median: 1.8; IQR: 0.6–9.1 pg/mL; P=0.003) and remained significantly lower than baseline levels over the 24-month follow-up. Only one patient had detectable levels of IL-17A at baseline. In patients with positive autoantibody levels at baseline ( >40 international or arbitrary U/mL), levels of anti-dsDNA (P< 0.001), anti-Sm (P=0.002), anti-SmRNP (P=0.028), anti-U1-RNP (P< 0.001) and anti-ribosomal P (P=0.012) antibodies decreased as soon as from month 3 and remained significantly lower than baseline levels over the study period. Anti-histone antibody levels showed decreases at month 3 (P=0.008) and month 6 (P=0.003) from treatment initiation, but were not significantly changed compared to baseline at later time points. In patients with baseline circulating ICs 10.8 mg Eq/mL or higher (reference value), IC levels showed decreases at month 3 (P=0.028), month 6 (P=0.009) and month 12 (P=0.021), but not at month 24 (P=0.345).

Conclusion: In our cohort, belimumab treatment lowered IFN-α2, IL-6, IL-10 and circulating IC levels, as well as levels of multiple autoantibodies against nuclear components.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/cytokine-and-autoantibody-profiles-during-treatment-with-belimumab-in-patients-with-systemic-lupus-erythematosus/