SERUM-ASSOCIATED IMPAIRMENT OF PHAGOCYTIC ACTIVITY AGAINST Klebsiella pneumoniae BY MONOCYTE-DERIVED MACROPHAGES FROM HEMOGLOBIN E/β-THALASSEMIA SUBJECTS

Abstract

Bacterial infection is one of the leading causes of death in thalassemia patients.  This study aimed to quantify macrophage phagocytic activity against Klebsiella pneumoniae in moderate-to-severe  HbE/β-thalassemia subjects and investigate its correlation with ferritin and uric acid levels.  Understanding this is crucial to understanding their susceptibility to infection.  This cross-sectional study comprised hemoglobin E (HbE)/beta-thalassemia subjects (n = 19) and healthy participants (n = 7) as controls.  Exclusion criteria were cancer, current infection, diabetes, or receiving immunosuppressive treatment.  HbE/beta-thalassemia subjects had a median serum ferritin and uric acid level of 1,221 ng/ml and 6.0 mg/dl  respectively, significantly higher than that of 119.6 ng/ml and 4.4 mg/dl respectively for healthy controls (p-value = 0.0002 and 0.0259 respectively).  To evaluate the phagocytic activity of monocyte-derived macrophages (MDM), the percent heated-inactivated carboxyfluorescein succinimidyl ester-stained Klebsiella pneumoniae-ingested MDM was measured by flow cytometry.  The MDM phagocytic activity of HbE/β-thalassemia subjects and healthy controls is not significantly different (19.63 vs 8.77 %, respectively; p-value = 0.063); however, following the addition of autologous serum, the increase in phagocytic activity was significantly smaller in the former relative to the latter group (Δ36.97 vs Δ63.46 % respectively; p-value <0.01). A linear regression analysis showed no correlation of ferritin or uric acid level with MDM phagocytic activity of HbE/β-thalassemia subjects.  Our results suggest that HbE/β-thalassemia subjects have reduced phagocytic activity against K. pneumoniae compared to healthy controls, possibly contributing to their increased susceptibility to infection.  Future studies should explore other factors affecting phagocytic activity in β-thalassemia.