Serum levels of tumor necrosis factor α/cachectin (TNFα) were studied in a group of adult patients with sickle cell disease (SCD), which included 31 patients with homozygous SS hemoglobinopathy and 10 patients bearing double heterozygous SC hemoglobinopathy and in their matched normal controls. All patients tested did not show any form of crisis for at least 4 weeks prior to the extraction of the sample. The amount of TNFα in serum was quantitated by means of an immunoenzymatic assay with a lower limit of detection of 25 pg/ml. The percentage of sera with detectable levels of TNFα was significantly increased in SCD patients as compared with the normal controls. Mean TNFα values in individuals with detectable levels of the cytokine were also significantly higher in the whole group of SCD patients and in patients bearing either SS or SC hemoglobinopathies than in the control group. An inverse correlation was observed between the percentages of Hb F and the levels of TNFα found in the sera from the patients.
To study the capacity of peripheral blood mononuclear cells (PBMC) from patients with sickle cell disease to synthesize antibodies in vitro, the levels of IgM, IgG, and IgA were quantitated in supernatants of cultured PBMC from a group of asymptomatic adults with sickle cell disease and from normal controls. The rates of spontaneous synthesis of IgM were similar in nonstimulated cultures of PBMC from patients and controls, whereas the amounts of IgG and IgA produced spontaneously by nonstimulated lymphocytes from the patients were significantly greater than those from controls. Similar levels of IgM, IgG, and IgA were detected in the supernatants of cultures stimulated with pokeweed mitogen from patients and controls. Thus, the capacity of PBMC to respond in vitro to pokeweed mitogen was preserved in the patients. The enhanced spontaneous synthesis of IgG and IgA suggests the presence of chronic polyclonal activation of B cells and/or defective regulation of the production of antibodies.
The levels of antibodies of the IgG, IgA and IgM isotypes reacting against ovoalbumin (OVA), gliadin (GL) and cow’s milk proteins (CMP), were determined by ELISA in sera from a group of adult patients with sickle cell anemia (SCA) bearing homozygous SS hemoglobinopathy and from matched healthy donors. Only patients with steady-state disease were included in the study. Increased amounts of IgG and IgA reacting with OVA, GL and CMP were observed in the group of patients as compared with the controls. In contrast, the levels of IgM antibodies against each of the three dietary antigens were similar in patients and controls. Increased levels of IgG and IgA antibodies against dietary antigens in SCA may result from enhanced permeability of the gut mucosa to macromolecules of dietary origin as a consequence of microinfarctions, chronic polyclonal B cell activation and/or diminished inhibitory control of antibody synthesis.
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