Immunoregulation in Juvenile Chronic Arthritis

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Abstract
The presence of hyperimmunoglobulinaemia and antinuclear antibodies in patients with juvenile chronic arthritis (JCA) suggests a possible role for immunoregulatory abnormalities in the pathogenesis of the disease. This is further supported by the demonstration in the sera of such patients of an autoantibody active against a suppressor inducer T cell subset. To identify immunoregulatory defects in JCA, a method of measuring concanavalin A (Con A)-inducible lymphocyte suppression of IgG production in vitro has been established. Peripheral blood mononuclear cells were cultured in the presence of either medium alone, pokeweed mitogen (PWM), Con A, or PWM together with Con A. IgG present in culture supernates at 8 days was measured by a double-antibody radioimmunoassay. Spontaneous IgG synthesis by lymphocytes from both patients and child controls was found to be more than double that of lymphocytes from adult control subjects. However, lymphocytes of children (patients or controls) did not show stimulation of IgG production in the presence of PWM. Con A-induced suppression of spontaneous IgG synthesis was reduced compared to adult controls in both patients (p <0.02) and child controls (p <0.05). Con A-induced suppression of IgG synthesis in the presence of PWM was also reduced compared to adult controls in both patients (p <0.01) and child controls (p <0.01) but was also reduced in the patient group compared to the child controls (p <0.01). Thus, spontaneous IgG synthesis in children is increased compared to adults, and IgG-producing cells appear less subject to regulation. This is particularly so in children with JCA and may be a factor contributing to the pathogenesis of the disease. It would appear that in addition to the previously described abnormality in the suppressor inducer T cell subset there is also an abnormality in the Con A-inducible suppressor T cell population.