Serum levels of cytokines and soluble antigens in polytransfused patients with beta-thalassemia major: relationship to immune status

Abstract

BACKGROUND. A series of immunological abnormalities has been described in patients with beta-thalassemia. The aim of this study was to investigate whether the measurement of serum levels of selected cytokines and soluble molecules (deriving from cell membrane antigens) involved in the immune response could be useful for a better definition of such alterations. PATIENTS AND METHODS. Serum levels of interleukin-2 (IL-2), IL-6, tumor necrosis factor (TNF), soluble (s) CD4, sCD8, sCD23 and sCD25 were measured using immunoenzymatic assays in 45 transfusion-dependent patients affected by beta-thalassemia major and correlated to conventional immunological indexes, such as peripheral lymphocyte subpopulations and circulating immunoglobulins. RESULTS. Patients with beta-thalassemia major showed increased TNF, sCD8, sCD23 and sCD25 and lower sCD4 values compared to normal controls. IL-2 and IL-6 were found to be undetectable or within the normal range in all patients. Splenectomized patients presented lower levels of sCD8 and sCD23 than those observed in unsplenectomized ones. A series of correlations involving TNF, sCD8, sCD23, sCD25, serum immunoglobulins and some lymphocyte subpopulations was observed. In addition, serum markers of immune activation (TNF, sCD23, sCD25) correlated directly with the annual blood transfusion requirement. Despite this series of immunological anomalies, no patient had a history of repeated infectious episodes. CONCLUSIONS. Polytransfused beta-thalassemic patients are characterized by a partial functional immunodeficiency determined by increased activity of CD8+ suppressor/cytotoxic lymphocytes and possibly reduced activity of the CD4+ helper/inducer subset. B-lymphocytes also appear highly activated. The allo-antigenic stimulation of transfusions seems to play a major role in the determination of these defects; however, this functional immunological imbalance does not seem to have any clinical relevance.