Immunological studies in tropical splenomegaly syndrome

Serum protein levels, serum immunoglobulin levels and the incidences of positive serological tests were measured in 169 natives with tropical splenomegaly syndrome and compared with results in 30 Caucasians and 62 normal natives.Serum levels of total protein, globulin, gamma-globulin, IgA and IgM; and positive tests for rheumatoid factor, thyroglobulin antibodies, euglobulin and cryoprotein were all higher in all groups of natives than in Caucasians. The highest levels occurred in natives with marked splenomegaly, especially the serum level of IgM. The mean serum IgM in natives with splenomegaly was 11 times that in Caucasians.The polyclonal nature of this hyperimmunoglobulinaemia was confirmed by serum electrophoresis and immunoelectrophoresis. Analytical ultracentrifugation also confirmed the presence of macroglobulinaemia; New Guinea natives resembling Africans with ‘Ie syndrôme splénomégalie-macroglobulinémie’.Tropical splenomegaly syndrome is thought to represent an unusual immunological response to repeated infection with malarial parasites of varying antigenicity. It is suggested that some of the IgG malarial antibody molecules become attached to unparasitized red cells with minimal alterations in both the IgG molecule and the red cell. The changes in the IgG molecule are then postulated as the initial stimulus to the rheumatoid factor detected in 36·1% of natives with splenomegaly with the S.S.C.A.T. The alterations in the red cell are postulated as the initial stimulus to the production of cold haemagglutinins detected with Cynomolgus monkey cells in 90% of natives with splenomegaly.Such changes could also account for the presence of antibodies against tanned red cells but there is no obvious explanation for the presence of thyroglobulin antibodies in 35·5% of natives with splenomegaly. The clarification of these postulates will involve confirmation of the malarial aetiology of tropical splenomegaly syndrome and demonstration of the attachment of IgG malarial antibody molecules to unparasitized red cells.