Document resource
Objectives Systemic lupus erythematosus (SLE) is characterized by unpredictable flares that lead to significant morbidity. Early identification of impending flares could improve patient outcomes. This study investigates whether measuring dynamic levels of autoantibodies, proteins and cytokines can predict the occurrence of flares.Methods 98 SLE patients were prospectively followed for two years, with visits every three months at the outpatient clinic of UMC Utrecht, the Netherlands. Clinical parameters, including SLEDAI and presence of flare, were recorded. Blood samples were collected using a highly standardized biobanking protocol. Levels of SLE-associated autoantibodies, proteins and cytokines were measured in citrate plasma using the EliA™ platform (Phadia AB, Sweden) and ProcartaPlexTM Multiplex Immunoassay according to manufacturer’s instructions (Invitrogen, Carlsbad CA, USA). Non-parametric statistical testing was used to assess biomarker dynamics.Results 100 patients with SLE were enrolled, of whom 98 met the eligibility criteria. Baseline characteristics are presented in table 1. Throughout follow-up, 193 disease flares were documented (180 moderate and 13 severe). Analyzing the levels of biomarkers at the timepoint directly after flare occurrence, showed strongly significant association with median anti-dsDNA (5.86 vs16.76, p<0.0001), anti-C1q (6.69 vs 8.51, p=0.001), BAFF (4.75 vs 5.12, p=0.03), IL-6 (7.10 vs 8.93, p=0.03), IL-8 (1.67 vs 1.90, p=0.008) and calprotectin (656 vs 748, p=0.006) levels (figure 1). Investigating the association between the occurrence of a flare and the biomarkers levels at the timepoint before, thus spanning a time range of six months, significant differences between flare/no flare patients were found for anti-dsDNA (5.97 vs 18.25, p=<0.0001), anti-C1q (6.84 vs 8.65, p=0.002), BAFF (4.76 vs 5.21, p=0.03), IL-10 (7.41 vs 8.74, p=0.003) and IL-18 (43.47 vs 43.82, p=0.04) (figure 2).Abstract PO:02:049 Table 1Baseline characteristicsAbstract PO:02:049 Figure 1–2Conclusions Novel biomarkers for disease activity besides anti-dsDNA and anti-C1q were identified, with particular focus on BAFF, IL-6 and IL-10. Furthermore, besides anti-dsDNA and anti-C1q also BAFF, IL-10 and IL-18 could serve as biomarkers of flare prediction. As a next step, SLE-associated cytokines and chemokines will be measured in urine and, if significantly associated with flare prediction, included in a clinical decision rule. After external validation of this clinical decision rule, pre-emptive treatment to prevent flares in SLE can be feasible.