THE DIVERSE EXPRESSION OF IMMUNITY IN HUMANS AT DISTINCT STATES OF ONCHOCERCA-VOLVULUS INFECTION

This study examined the development and persistence of immunity in hum ans presenting defined states of Onchocerca volvulus infection, i.e. i n exposed endemic control individuals without microfilaridermia and cl inical disease, in patients with patent or post-patent onchocerciasis, and in patients concurrently infected with Mansonella perstans. Oncho cerca volvulus antigen (OvAg)-specific cellular reactivity was signifi cantly diminished in microfilariae (mf)-positive patients, while the h ighest reactivity was measured in exposed but mf-negative endemic cont rols, those being free of any clinical signs of onchocercal disease. I n patients who became post-patent, responses to. OvAg were significant ly augmented, but did not approach entirely the magnitude observed in endemic controls. In onchocerciasis patients with concurrent mansonell iasis, cellular unresponsiveness to OvAg persisted, even when mf of O. volvulus were eliminated permanently by repeated ivermectin therapy. Cells from mf-positive onchocerciasis patients produced significantly less interferon-gamma (IFN-gamma) (P<0.01) and interleukin-5 (IL-5) (P <0.05) in response to OvAg than those taken from endemic controls or p ost-patent individuals in whom IFN-gamma and IL-5 production was simil arly high. In contrast, both OvAg-driven as well as spontaneous IL-10 secretion was higher in mf-positive patients than in endemic controls or post-patent cases. In all individuals examined, serological recogni tion of OvAg by immunoglobulins was dominated by IgG4; in mf-positive patients OvAg of 205 000-12 000 molecular weight (MW) were strongly bo und. In post-patent individuals, and similarly in endemic controls, Ov Ag recognition by IgG4 varied from intense (with numerous antigens bei ng recognized) to weak or absent antigen binding. Significantly elevat ed OvAg-specific Ige isotypes were measured in mf-positive onchocercia sis patients in comparison with endemic controls or post-patent indivi duals (with the exception of IgG3). IgG1, IgG2 and IgE were higher, bu t IgG4 was lower in endemic controls compared with post-patent onchoce rciasis patients. The ratios of IgG4/IgG1 differed (P<0.001) between e ndemic controls and mf-positive or post-patent onchocerciasis patients , with IgG4/IgG1 ratios of R<3.0 being characteristic for endemic cont rols and post-patent O. volvulus infection. In conclusion, this cross- sectional immunoepidemiological investigation showed that distinct sta tes of O. volvulus infection correlate with a particular cellular and humoral immune response. The mf-free condition appeared to be associat ed with a vigorous parasite-specific cellular reactivity and a particu lar cytokine production profile, while concurrent M. perstans infectio n depressed OvAg-specific cellular responsiveness. Antibody responses, in all likelihood, reflected the intensity and state of infection, an d not the degree of acquired immunity protective against parasite aggr egation.