Changes in Superoxide Anion Production in Neutrophils from Multitransfused β-Thalassemia Patients: Correlation with Ferritin Levels and Liver Damage

Abstract

Superoxide anion production in resting and PMA- or zymosan-stimulated neutrophils was evaluated in 21 β-thalassemia patients. The results were correlated with ferritin values, hepatitis B virus serum markers, liver pathology, immunoglobulin levels and T-cell subsets. Superoxide anion generation from resting or PMA-stimulated neutrophils was significantly higher in patients than in controls. On the contrary, zymosan-stimulated neutrophils showed reduced superoxide anion production. Increased superoxide anion production in resting neutrophils showed a significant correlation to the values of ferritin. In addition, patients with biopsy-proven chronic liver disease showed significantly increased ferritin levels and superoxide anion production as compared to the remaining patients. No correlation was observed between superoxide anion production and the presence or the absence of hepatitis B virus serum markers, immunoglobulin levels and T-cell subsets. A possible role of interreactions between iron and oxygen radicals in determining liver damage in β-thalassemia patients is suggested.

Antibodies to HTLV-III and the Lymphadenopathy Syndrome in Multitransfused β-Thalassemia Patients

“…Positive sera stained at least HTLV-III infection. In previous papers we have reported a number of immunological changes in ß-thalassemics which were corre lated to splenectomy, iron overload, and hepatitis B virus infection [7,10]. In partic ular, we observed that inverted OKT4/OKT8 ratio and decreased mitogen responsiveness were present in patients who had started transfusion therapy very early in life [5], Analogously, it is possible that in hemophiliacs factor VIII concentrate modi fies the immunological status independently of HTLV-III infection [11], A careful follow up of the patients with immunological mod ifications will answer the question whether a preexisting immunological defect helps HTLV-III infection to take root [12],…”

A distinct pattern of cytokine production from blood mononuclear cells in multitransfused patients with β-thalassaemia

“…Transfusions lead to iron overload and also to immune derangements, both of which exert a negative effect on the functional integrity of the immune system in multitransfused patients with thalassaemia. There are already a large number of reports describing immune abnormalities in thalassaemia, namely defective function of polymorphonuclear neutrophils and monocytes [2,3], decrease of CD4 + cells and increase of CD8 + cells [4][5][6], diminished mitogen responses [5] and low natural killer (NK) cell activity [7,8]. These and probably other undetected abnormalities may explain the tendency for severe or unusual infections.…”

Decreased Phagolysosomal Fusion of Peripheral Blood Monocytes from Patients with Thalassemia Major

“…In multitransfused TM patients, the increase of reactive iron may induce an increase in oxygen free radicals generation [27], Different authors have ob served that in resting and stimulated phagocytes from multitransfused thalassemic patients, the production of superoxide anion is significantly enhanced, associated with serum ferritin levels [28], The impairment of phago lysosomal fusion of monocytes from TM patients could then be due to the peroxidation of membranes caused by oxygen free radicals. Probably, a slight increase of serum ferritin levels is enough to alter phagolysosomal fusion, explaining the lack of association between the grade of monocyte phagolysosomal dysfunction and ferritin levels.…”