Iron-related disturbances of cell-mediated immunity in multitransfused children with thalassemia major.

Immunological abnormalities have been observed in many haemophiliacs receiving clotting factor concentrates. To determine whether similar changes also occur after repeated blood transfusions we estimated T cell subsets and cutaneous delayed hypersensitivity (CDH) in 50 multitransfused children with beta-thalassemia major (beta-TM). All patients were also tested for anti-HTLV-III/LAV antibodies. A diminished percentage of T lymphocytes (E-rosettes, T3+), and T4+ cells and a low T4/T8 ratio was found in patients as compared to age and sex matched controls (P less than 0.001). Negative CDH tests to specific antigens (Multi-test) were also found in a significantly larger proportion of beta-TM children (P less than 0.01). Antibodies against HTLV-III/LAV were negative in all patients. Decreased T4/T8 ratio in beta-TM children was primarily due to a reduction of T4+ cells and was inversely correlated to the patients' age, number of units of transfused blood (P less than 0.05) and especially to ferritin serum levels and annual iron balance (P less than 0.001). These findings indicate that immunological abnormalities in beta-TM patients appear to be acquired, transfusion-associated and related to iron load which depends on the appropriate chelation therapy.

Skin sensitization to 2, 4 dinitrochlorobenzene (DNCB) in the first months of life.

The skin reactivity to 2, 4 dinitrochlorobenzene (DNCB) was evaluated in 94 healthy term neonates, aged 1-30 days and in 190 infants aged 2-9 months. For contact sensitization to DNCB an initial dose of 1 mg DNCB and a challenge one of 0.1 mg were used. Sensitization was induced in 6.7% of neonates in the first 15 days of life. This proportion rose to 25.7% by the end of the first month, to 63% in the third month and to 91% in the ninth month. It is concluded that DNCB test is a safe and simple screening test for evaluating cell-mediated immunity in the first months of life. It appears to have some advantages over the skin tests using specific antigens, as a positive result with DNCB can be obtained at an earlier age.

Mechanisms of smooth muscle antibody production: a clinical study in children with infections, haemolytic syndromes, and idiopathic thrombocytopenic purpura.

Sera from 530 children suffering from various diseases and from 64 controls were tested for smooth muscle autoantibodies (SMA) by indirect immunofluorescence. A high incidence of SMA (51-86%) was found in patients with viral and bacterial infections (viral hepatitis, infectious mononucleosis, measles, mumps, chickenpox, typhoid fever, and brucellosis), independently of liver invovlvement, and in patients with acute haemolytic anaemia due to G-6-PD deficiency (48%). By contrast, the incidence of SMA from patients with beta-thalassaemia major and idiopathic thrombocytopenic purpura was no higher than in the controls. The discrepancy in incidence in haemolytic anaemias due to different causes may reflect the effect of endogenous and extrinsic agents. In the viral infections, SMA were mainly of the IgM class and gave an 'SMA-V' staining pattern. In bacterial infections (typhoid fever and brucellosis), SMA were either IgG only or IgM and IgG, and the staining pattern was also mainly 'SMA-V'. In infections which affect or may affect the liver (viral hepatitis, infectious mononucleosis, typhoid fever, and brucellosis), SMA was present at high titres (1:80-1:320), whereas in infections not affecting the liver (measles, mumps, and chickenpox) the titres were lower (less than or equal to 1:80). In most patients SMA occurred transiently and without apparent pathogenetic significance. The antigen against which infection-induced SMA is directed is not actin; its nature has yet to be identified.

Effect of blood transfusion on the immune response of children with thalassaemia.

The effect of blood transfusions on the immune response of 46 thalassaemic children was studied. Cell-mediated immune response was evaluated by performing skin tests to specific (streptokinase-streptodornase and candidin) and nonspecific (dinitrochlorobenzene and phytohaemagglutinin) antigens. Antibody response to specific antigen (tetanus toxoid) was estimated by measuring the tetanus antitoxin titre before and after vaccination. No gross impairment of cell-mediated immunity was elicited. The larger proportion of negative phytohaemagglutinin skin tests found in thalassaemic patients does not necessarily suggest a cell-mediated immunity impairment, since this skin reaction is also affected by other factors, especially the inflammatory skin response. The transfused antibodies may inhibit the recipient's sensitization and primary immune response to the homologous antigen, especially when the antibody level in the transfused blood is high whereas the secondary immune response is not affected.