Human IgE responses to different splice variants of Schistosoma mansoni tropomyosin: associations with immunity.

Resistance to Schistosoma mansoni infection has been correlated with IgE responses to the adult worm. Molecular targets of this response are gaining interest as markers of immunity and as indicators of allergenic properties. Few protein families contain IgE antigens (allergens) and one of the most highly represented are the tropomyosins. Alternative splicing generates numerous tropomyosin isoforms, which in parasites is likely to induce a range of anti-tropomyosin responses in the host. Here we examine human IgE and the counteracting IgG4 responses to splice variants of S. mansoni tropomyosin (SmTpm). It was possible to show life-cycle transcription profiles for 12 of 20 predicted splice variants from the four SmTpm genes. We expressed recombinant protein of four variants of TpmII (TpmII.4, 8, 3 and 7) with considerable differences in sequence. TpmII.4 and 8 were muscle, and TpmII.3 and 7 non-muscle, types. IgE and IgG4 responses to all four proteins were measured in a population of 228 infected boys and men (7-76 years) from a region of Uganda endemic for S. mansoni. Levels of these antibodies were not dependent on age and did not change following anthelminthic treatment. IgE to TpmII.3 was common in the cohort (>60%) and IgG4 to TpmII.3 less so (33%). IgE to TpmII.7 was rare (6.5%), but IgG4 to TpmII.7 was more common (49%). In regression analysis, a detectable IgE response to TpmII.3 was associated with reduced re-infection 2 years after treatment and an IgG4 response to TpmII.7 with increased re-infection. Different isoforms generated by alternative splicing are targeted by different components of the anti-Tpm IgE/IgG4 response. Only some of these are associated with immunity.