SOLUBLE ADHESION MOLECULES IN CHILDREN WITH HEMOLYTIC UREMIC SYNDROME

Atypical hemolytic uremic syndrom (aHUS) is a rare severe life-threatening form of thromboticmicroangiopathy. aHUS is thought to be primarily mediated by dysfunctional complement regulation, dueto mutations or genetic rearrangement of the complement components, or regulatory factors, as well asautoantibody production to the complement factors. These alterations promote uncontrolled complementactivation by the alternative pathway on the surface of endothelial cells, followed by endothelial dysfunction,microthrombosis and organ damage, especially, renal pathology. Many studies showed that the biomarkersof endothelial activation/dysfunction including intercellular adhesion molecule type 1 (ICAM-1) andvascular cell adhesion molecule type 1 (VCAM-1) were associated with severe disease and could predictcomplications and clinical outcomes in different disorders. Increase of these biomarkers was observed inaHUS as well. Until recently, aHUS resulted in unfavorable outcomes, with high death rates in acute phase,and up to 2/3 patients progressed to the end-stage renal failure. Understanding the role of complementdysregulation in aHUS pathogenesis has led to major changes in therapeutic approaches. Eculizumab(a humanized anti-C5 monoclonal antibody) inhibits the terminal complement pathway. This drug hasrevolutionized treatment and improved prognosis in aHUS. Those patients who received eculizumab haveshown sharp decreae in the C3 levels. However, the questions concerning duration of targeted therapy in remission still remains unclear. The aim of the present study was to evaluate serum С3, sICAM-1, sVCAM-1 levels in the children withaHUS remission supported by eculizumab maintenance treatment, or without it. Serum C3, sICAM-1 andsVCAM-1 levels were determined in 25 children with aHUS (14 treated with eculizumab and 15, withouteculizumab). A control group included 17 children with a history of typical HUS. Serum levels of C3, sICAM-1and sVCAM-1 were within normal age ranges in all the groups. The children treated with eculizumab showeddecreased C3 levels (99±20 mg/l vs 112±15 mg/l, and 123±40 mg/l, respectively), and increased sICAM-1levels (483±103 ng/ ml vs 343±50 ng/ml and 401±91 ng/ml, respectively) compared to other groups (p < 0.05).No differences in sVCAM-1 levels were revealed in the groups. Hence, no signs of subclinical complementactivation or endothelial disfunction were revealed in the group free of eculizumab therapy. Normal C3,sICAM-1 and sVCAM-1 levels