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AB0494 Increased levels of interferon alpha and interleukin-10 as clinical activity biomarkers in systemic lupus erythematous patients
  1. E Grau Garcia1,
  2. M Fernandez Matilla2,
  3. CM Feced Olmos1,
  4. E Sánchez Labrador1,
  5. FM Ortiz-Sanjuan1,
  6. N Fernández-Llanio2,
  7. E Sugreñes Tovar3,
  8. K Arévalo Ruales1,
  9. R Negueroles Albuixech1,
  10. J Ivorra Cortes1,
  11. JJ Fragio Gil1,
  12. I Martínez Cordellat1,
  13. R Mazarío González1,
  14. I Chalmeta Verdejo1,
  15. L Gonzalez Puig1,
  16. C Alcañiz Escandell1,
  17. C Nájera Herranz1,
  18. I Cánovas Olmos1,
  19. E Vicens Bernabeu1,
  20. JE Oller Rodriguez1,
  21. JA Castellano Cuesta2,
  22. V Fornés Ferrer4,
  23. D Marín Hervás4,
  24. JA Román Ivorra1,3
  1. 1Rheumatology Department, HUP la Fe
  2. 2Rheumatology Section, Hospital Arnau de Vilanova
  3. 3Medical School, UCV
  4. 4Biostatistics Unit, IIS la Fe, Valencia, Spain

Abstract

Background 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.

Objectives To analyze the association among INF1A, IL10 and BLyS levels and clinical activity in SLE.

Methods 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.

Results In our SLE patients we observed higher values of IL10, BLyS and INF1A than controls (P<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<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<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<0.001). In addition, patients with increased levels of IL10-INF1A-BLyS showed ANAs (P<0.001) and antiphospholipid autoantibody positivity (P=0.004).

Conclusions 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.

Disclosure of Interest None declared

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