In children with transfusion-dependent thalassemia, inflammation and neuronal damage biomarkers are associated with affective and chronic fatigue symptoms

Abstract

AbstractBackgroundPatients with transfusion-dependent thalassemia (TDT) are vulnerable to neurotoxicity due to frequent blood transfusions and the subsequent iron overload (IO) and inflammation. As a result, affective (depression and anxiety) and chronic fatigue syndrome (CFS) symptoms may develop.AimsTo investigate the potential association between TDT and neuronal injury, as assessed with serum concentrations of neuronal damage biomarkers, including neurofilament light (NFL), glial fibrillary acidic protein (GFAP), neuron-specific enolase (NSE), and nestin.MethodsWe investigated the associations between those CNS injury biomarkers, neuro-immune markers (C-reactive protein (CRP), interleukin (IL)-6, and IL-10), calcium, magnesium, copper and zinc, and the Fibro-Fatigue (FF), the Children’s Depression Inventory (CDI), and the Spence Children’s Anxiety Scale (SCAS) scores in 126 children with TDT and 41 healthy children.ResultsTDT children show significant increases in IO, FF, CDI, and SCAS scores, serum NSE, GFAP, NF-L, CRP, copper, IL-6, and IL-10, and lowered magnesium, zinc, and calcium as compared with healthy children. There were significant correlations between the CDI score and NFL, NSE and GFAP; SCAS score and NFL, and FF score and NFL and GFAP. The neuronal damage biomarkers (except nestin) were significantly associated with inflammatory, erythron (hematocrit and hemoglobin) and IO (iron and ferritin) biomarkers.ConclusionsTDT is characterized by intertwined increases in neuronal injury biomarkers and neuropsychiatric symptoms suggesting that TDT-associated neurotoxicity plays a role in affective symptoms and CFS due to TDT. Inflammation and neurotoxicity are novel drug targets for the prevention of affective symptoms and CFS due to TDT.