Recognition of tissue cyst-specific antigens in reactivating toxoplasmosis.

Current serological tests do not discriminate between asymptomatic latent Toxoplasma gondii infection and reactivating toxoplasmosis, but timely therapeutic intervention before the development of symptoms would lead to major reductions in morbidity and permanent disability. This study developed a new enzyme-linked immunosorbent assay (ELISA) for antibody to T. gondii tissue cyst antigens and screened tissue cyst antigens by Western blot analysis to test the hypothesis that antibody recognition of T. gondii tissue cyst-derived antigen is a good indicator of reactivation disease. A total of 187 sera was tested by Sabin-Feldman dye test and tissue cyst ELISA, AIDS patients and patients with ocular disease were considered separately, as the exposure to parasite antigens may be different in these two groups. The dye test did not discriminate between immunocompetent and immunocompromised T. gondii seropositive patients or between active and quiescent toxoplasmosis. Tissue cyst ELISA demonstrated a raised specific antibody response in immunocompetent T. gondii seropositive patients and in quiescent HIV positive sera. These data support th view that the tissue cyst population is in a state of dynamic equilibrium. It is proposed that, in the immunocompetent host, tissue cyst development and rupture are under some degree of immune control, but that in the immunocompromised host this equilibrium is disturbed and reactivation disease results. Data from patients with reactivating ocular toxoplasmosis demonstrate that tissue cyst-specific antibody levels are not different in active and quiescent disease and indeed they are not significantly different from immunocompetent T. gondii seronegative sera. In the Western blot analysis of 57 HIV positive patient sera, eight antigens (65, 57, 49, 47, 36, 28, 26 and 18 kDa) were consistently recognised by one third or more of the sera tested, but no single antigen was diagnostic of quiescent or active toxoplasmosis. It is concluded that tissue cyst-derived antigens are not a reliable serological marker of reactivating toxoplasmosis.