Division of Rheumatology, Department of Medicine, Karolinska Institutet, SE-171 76 Stockholm, Sweden.
Rheumatology, Karolinska University Hospital, SE-171 76 Stockholm, Sweden.
Int J Mol Sci. 2020 May 14;21(10):3463. doi: 10.3390/ijms21103463.
We investigated whether belimumab treatment impacts on levels of autoantibodies and cytokines of interest in systemic lupus erythematosus (SLE). Longitudinally collected serum samples from 78 belimumab-treated Swedish SLE patients were analysed. Serum cytokine levels were determined using Luminex xMAP technology, and nuclear antigen autoantibody specificities using addressable laser bead immunoassay. In patients with detectable levels at baseline, interferon (IFN)-α2 levels were lower at month 6 (median; interquartile range (IQR): 8.9; 1.5-54.9 pg/mL) versus baseline (28.4; 20.9-100.3 pg/mL; = 0.043). Interleukin (IL)-6 (baseline: 7.1; 2.9-16.1 pg/mL) decreased from month 6 (0.5; 0.5-6.3 pg/mL; = 0.018) and throughout a 24 month follow-up. IL-10 (baseline: 12.6; 2.8-29.7 pg/mL) showed more rapid decreases from month 3 (1.8; 0.6-9.1 pg/mL; = 0.003). Levels of anti-dsDNA ( < 0.001), anti-Smith antigen (Sm) ( = 0.002), anti-U1 small nuclear ribonucleoprotein (U1RNP) ( < 0.001), anti-Sm-U1RNP complex ( = 0.028), and anti-ribosomal P ( = 0.012) antibodies decreased from month 3 and remained decreased. Anti-Sm positivity at baseline was associated with higher probability and/or shorter time to achieve sustained SLE responder index-4 response (hazard ratio (HR): 2.52; 95% CI: 1.20-5.29; = 0.015), independently of other factors. Decline of IL-6 levels through month 3 was greater in responders. In summary, belimumab treatment lowered IFN-α2, IL-6, and IL-10 levels, as well as levels of multiple autoantibodies, however after different time spans. Notably, anti-Sm positivity and early decline in IL-6 levels were associated with favorable treatment outcome.
我们研究了贝利尤单抗治疗是否会影响系统性红斑狼疮(SLE)患者自身抗体和细胞因子的水平。分析了 78 例接受贝利尤单抗治疗的瑞典 SLE 患者的纵向采集血清样本。使用 Luminex xMAP 技术测定血清细胞因子水平,使用可寻址激光珠免疫测定法测定核抗原自身抗体特异性。在基线可检测到水平的患者中,干扰素(IFN)-α2 水平在 6 个月(中位数;四分位距(IQR):8.9;1.5-54.9pg/ml)时低于基线(28.4;20.9-100.3pg/ml;=0.043)。白细胞介素(IL)-6(基线:7.1;2.9-16.1pg/ml)从 6 个月(0.5;0.5-6.3pg/ml;=0.018)和整个 24 个月随访期间下降。IL-10(基线:12.6;2.8-29.7pg/ml)从 3 个月(1.8;0.6-9.1pg/ml;=0.003)开始更快下降。抗 dsDNA(<0.001)、抗 Smith 抗原(Sm)(=0.002)、抗 U1 小核核糖核蛋白(U1RNP)(<0.001)、抗 Sm-U1RNP 复合物(=0.028)和抗核糖体 P(=0.012)抗体从 3 个月开始下降并持续下降。基线时抗 Sm 阳性与实现持续 SLE 应答指数-4 应答的更高概率和/或更短时间相关(风险比(HR):2.52;95%置信区间(CI):1.20-5.29;=0.015),独立于其他因素。在应答者中,到 3 个月时 IL-6 水平的下降更大。总之,贝利尤单抗治疗降低了 IFN-α2、IL-6 和 IL-10 水平以及多种自身抗体水平,但时间不同。值得注意的是,抗 Sm 阳性和 IL-6 水平的早期下降与良好的治疗结果相关。