Objective. Dysregulated production of cytokines has a critical role in systemic lupus. The aim of this work is to identify, by a comprehensive analysis of IL-1 family cytokines and receptors in sera, a correlation between cytokines/receptors’ levels and the clinical and serological features of the disease. Methods. A full clinical evaluation was performed in 74 SLE patients. C3, C4, anti-dsDNA and anti-C1q antibodies were measured. Cytokines of the IL-1 family (IL-1, IL-1, IL-33, IL-18), soluble receptors (sIL-1R1, sIL-1R2, sIL-1R3, ST2/sIL-1R4) and antagonists (IL-1Ra, IL-18 binding protein -IL-18BP-) were measured in sera by multiarray ELISA assay. Free IL-18 was calculated as the amount of IL-18 not inhibited by IL-18BP. Data were analysed by non parametric tests and by multivariate analysis, using partial least squares models. Results. Total IL-18, IL-18BP, sIL-1R4 and IL-1Ra levels were higher in SLE vs. controls. Total and free IL-18 and sIL-1R4 were higher in active vs. inactive patients and correlated with ECLAM, anti-C1q and anti-dsDNA antibodies.sIL-1R2 was higher in inactive patients, negatively correlated with ECLAM and anti-C1q antibodies, positively with C3 levels. PLS identified sIL-1R4, sIL-1R2 and anti-dsDNA as variables distinguishing active from inactive patients; sIL-1R4, IL-18BP and anti-dsDNA identified patients with active nephritis; sIL-1R4, C3, IL-18 and free IL-18 identified patients with haematological involvement. Conclusion. The data support the use of IL-18, sIL-1R2 and sIL-1R4 as biomarkers of disease activity and organ involvement, and suggest that a failure in the inhibition of IL-1 activation may be a critical event for the active stages of SLE.
IL-1 family cytokines and soluble receptors in systemic lupus erythematosus
Maria Laura Manca;Francesca Angelotti;Federico Pratesi;Ilaria Puxeddu;Paola Migliorini
2018-01-01
Abstract
Objective. Dysregulated production of cytokines has a critical role in systemic lupus. The aim of this work is to identify, by a comprehensive analysis of IL-1 family cytokines and receptors in sera, a correlation between cytokines/receptors’ levels and the clinical and serological features of the disease. Methods. A full clinical evaluation was performed in 74 SLE patients. C3, C4, anti-dsDNA and anti-C1q antibodies were measured. Cytokines of the IL-1 family (IL-1, IL-1, IL-33, IL-18), soluble receptors (sIL-1R1, sIL-1R2, sIL-1R3, ST2/sIL-1R4) and antagonists (IL-1Ra, IL-18 binding protein -IL-18BP-) were measured in sera by multiarray ELISA assay. Free IL-18 was calculated as the amount of IL-18 not inhibited by IL-18BP. Data were analysed by non parametric tests and by multivariate analysis, using partial least squares models. Results. Total IL-18, IL-18BP, sIL-1R4 and IL-1Ra levels were higher in SLE vs. controls. Total and free IL-18 and sIL-1R4 were higher in active vs. inactive patients and correlated with ECLAM, anti-C1q and anti-dsDNA antibodies.sIL-1R2 was higher in inactive patients, negatively correlated with ECLAM and anti-C1q antibodies, positively with C3 levels. PLS identified sIL-1R4, sIL-1R2 and anti-dsDNA as variables distinguishing active from inactive patients; sIL-1R4, IL-18BP and anti-dsDNA identified patients with active nephritis; sIL-1R4, C3, IL-18 and free IL-18 identified patients with haematological involvement. Conclusion. The data support the use of IL-18, sIL-1R2 and sIL-1R4 as biomarkers of disease activity and organ involvement, and suggest that a failure in the inhibition of IL-1 activation may be a critical event for the active stages of SLE.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
