ICAM-1(CD54) and Tissue Factor (CD142) Monocytes Expression Among Sickle Cell Anemia Steady-State Children: Association with VCAM-1 and ICAM-1 Soluble and Cytokines Related to Inflamossome and Th17 Response.

There is emerging consensus that a pro-inflammatory and anti-inflammatory condition contributes to modulate the vaso-occlusive pain crisis in sickle cell anemia (SCA), that have been correlated to red blood cell (RBC), leukocytes, platelets and endothelial cell activation and with the participation of adhesion molecules. The result is a severe clinical outcome related to a chronic pro-inflammatory state with cytokine disruption equilibrium. In this study, we assessed the inflammatory potential of monocytes in venous blood samples by examining cell surface expression of ICAM-1 (CD54) and tissue factor (CD142), measurement of serum levels of cytokine, soluble adhesion molecule (ICAM-1s and VCAM-1s), biochemical markers, searching the potential value of inflammatory mediators as early markers of severity of vaso-occlusive crisis in SCA.

The study was approved by the FIOCRUZ human ethical research board and informed consents were signed by patients or official responsible. A prospective study was developed among 61 steady-state SCA patients aging 7.8±4.3 years, with 42.7% female. Monocytes were obtained after RBC lyses and labeled with monoclonal anti-CD54, anti-CD142 and analyzed by flow cytometry. Biochemical analyses for serum uric acid were measured by colorimetric method, hematologic analysis were performed using an electronic cell counter and VCAM-1 and ICAM-1 soluble molecules, IL-4, IL-8, TNF-alpha, IL-13, IL-17, IL-18, IL-23 and TGF-B were measured by ELISA. Statistical analyses were performed using STATA version 10.0.

Our results show a positive significant association between CD142 and CD54 expression on monocytes surface (r=0.296, p=0.014). The VCAM-1s and IL-18 were significantly positive associated to ICAM-1s (r=0.813, p=0.0001; r=0.315, p=0.048 respectively). The stratification of TGF-B in low and high concentration groups was statistically associated with uric acid, IL-17 and IL-23 serum levels (p=0.038; p=0.022; p=0.008 respectively). The IL-17 and IL-23 were significantly positive associated (r=0.552, p=0.0001). The serum levels of uric acid were significantly negative associated with RBC number and hematocrit (r=-0.366, p=0.0006; r=-0.283, p=0.035 respectively) and significantly positive associated with mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH) (r=0.383, p=0.004; r=0.403, p=0.002 respectively)

Inflammation, cell adhesion to vascular endothelium, and endothelial injury contribute to sickle cell anemia (SCA) vaso-occlusive crisis. Although alterations in inflammatory cytokines and biomarkers have been related, reports have been conflicting, and a conclusive role for these molecules in the disease remains to be established. Our results showed an association of tissue factor and ICAM-1 on monocytes expression with the participation of IL-18, VCAM-1s and ICAM-1s and TGF-B that had an interaction with uric acid, IL-17 and IL-23 levels, contributing to the establishment of inflammasome multiprotein complex and also with an probably alternative mechanism that include the Th17 cells response. Furthermore, additional studies will elucidate the mechanism involved with the interaction of this complex network of molecule and the endothelial activation and dysfunction described in the pathophysiology of vaso-occlusives episodes of sickle cell anemia.

No relevant conflicts of interest to declare.