AB0494 Increased levels of interferon alpha and interleukin-10 as clinical activity biomarkers in systemic lupus erythematous patients
Authors: E Grau Garcia, M Fernandez Matilla, CM Feced Olmos, E Sánchez Labrador, FM Ortiz-Sanjuan, N Fernández-Llanio, E Sugreñes Tovar, K Arévalo Ruales, R Negueroles Albuixech, J Ivorra Cortes, JJ Fragio Gil, I Martínez Cordellat, R Mazarío González, I Chalmeta Verdejo, L Gonzalez Puig, C Alcañiz Escandell, C Nájera Herranz, I Cánovas Olmos, E Vicens Bernabeu, JE Oller Rodriguez, JA Castellano Cuesta, V Fornés Ferrer, D Marín Hervás, JA Román Ivorra
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Systemic lupus erythematous (SLE) is an autoimmune disease characterized by immune system disruption, including deregulation of cytokine production. Interferon alpha (INF1A) is considered a key molecule in SLE etiopathogenesis, being responsible of the differentiation of dendritic cells from monocytes, and indirectly of interleukin 10 (IL10) upregulation. The B lymphocyte stimulating factor (BLyS) is involved in autoantibodies production and clinical activity, and is regulated by other cytokines as IL10 and INF1A. <h3>Objectives</h3> To analyze the association among INF1A, IL10 and BLyS levels and clinical activity in SLE. <h3>Methods</h3> A cross-sectional, observational study of 142 patients diagnosed of SLE according to SLICC 2012 criteria and 34 healthy controls was performed. A complete blood-test was made, and clinical data by personal interview was collected. We analyzed serum concentration of IL10, BLyS and INF1A by colorimetric methods. Patients were dichotomized as high and low levels for each cytokine based on the cytokine level above 2 SD of the mean in healthy controls. Biostatistical analysis with R (3.3.2.) was performed. <h3>Results</h3> In our SLE patients we observed higher values of IL10, BLyS and INF1A than controls (P&lt;0.001, P=0.005 and P=0.043 respectively), showing an average values in patients of 13.39±27.73 pg/mL INF1A, 9.99±15.84 pg/mL IL10 and 1811.31±1757.81 pg/mL BLyS. The mean clinical activity measured by SLEDAI was 5.91±5.06. Statistical analysis indicate that INF1A levels are correlated to IL10 levels (P=0.001) and BLyS levels (P=0,034). Due to this finding, we categorized SLE patients by low or high level of the three cytokines: 44 INF1A(-)IL10(-)BLyS(-); 61 INF1A(+)IL10(-)BLyS(-); 5 INF1A(+)IL10(-)BLyS(+); 18 INF1A(+)IL10(+)BLyS(-) and 14 INF1A(+)IL10(+)BLyS(+). There is a high association of increased IL10-INF1A levels and the increased of clinical activity by SLEDAI score (P&lt;0.001), and to a lesser extent with increased IL10-INF1A-BLyS levels. Patients with high IL10-INF1A and IL10-INF1A-BLyS showed a significant rise in C3-C4 consumption (P&lt;0.001 and P=0.001 respectively) and high anti-dsDNA (P=0.001 and P=0.002 respectively). Patients with increased INF1A-BLyS exhibited high anti-dsDNA (P=0.004) and ENA positivity (P&lt;0.001). In addition, patients with increased levels of IL10-INF1A-BLyS showed ANAs (P&lt;0.001) and antiphospholipid autoantibody positivity (P=0.004). <h3>Conclusions</h3> The 69% of our SLE patients displayed almost one cytokine increased, being the INF1A the cytokine that mainly is increased. However, increased IL10 levels, irrespective of whether there is also increased levels of BLyS and/or INF1A, is the cytokine which best fits to clinical activity in SLE. <h3>Disclosure of Interest</h3> None declared