Soluble Fas/FasL ratio as a marker of vasculopathy in children and adolescents with sickle cell disease

• We determined sFas/sFasL ratio in young patients with SCD.
• sFas/sFasL was elevated in patients with nephropathy or pulmonary hypertension.
• sFas/sFasL was increased in patients with frequent sickling crisis.
• sFas/sFasL levels were related to inflammation, iron overload and albuminuria level.
• SCD patients treated with hydroxyurea had lower sFas/sFasL ratio.

ObjectivesSickle cell disease (SCD) is characterized by chronic inflammation due to ischemic tissue damage, accentuated during acute complications. Fas and its ligand (FasL) are members of tumor necrosis factor receptor superfamily and a major pathway for induction of apoptosis. Fas/FasL interactions may be related to augmentation of inflammatory response. We assessed the levels of sFas and sFasL in 35 children and adolescents with SCD compared with 35 healthy controls in relation to hemolysis, iron overload, sickle vasculopathy including kidney disease.MethodsSCD patients, in steady state and asymptomatic for pulmonary hypertension, were studied stressing on hydroxyurea therapy, serum ferritin, urinary albumin creatinine ratio (UACR), high-sensitivity C-reactive protein (hs-CRP) and sFas/sFasL levels.ResultssFas/sFasL ratio was significantly higher in patients compared with controls. sFas/sFasL ratio was elevated in patients with pulmonary hypertension, nephropathy and those who had history of frequent sickling crisis or serum ferritin ⩾2500. SCD patients treated with hydroxyurea had lower sFas/sFasL ratio than untreated patients. sFas/sFasL ratio was positively correlated to transfusion index, white blood cells, hs-CRP, serum ferritin and UACR. The cutoff value of sFas/sFasL at 8.75 pg/mL could differentiate SCD patients with and without nephropathy while the cutoff value at 22 pg/mL could differentiate SCD patients with and without pulmonary hypertension risk with high sensitivity and specificity.ConclusionsFas/sFasL ratio may be considered as a marker for vascular dysfunction in SCD patients and is related to inflammation, iron overload and albuminuria level. Thus, it may be a reliable method to assess renal impairment in SCD.