Naturally occurring blocking antibodies modulate immediate hypersensitivity responses in human filariasis.

Abstract

Although the basophils and mast cells of patients with chronic helminth infection are sensitized with specific IgE antibody and frequently exposed to parasite antigens in vivo , these rarely manifest allergic reactions to their parasites. To investigate the regulatory mechanisms limiting immediate hypersensitivity responsiveness in such patients, we used the in vitro antigen-induced histamine- release (HR) reaction of human basophils as a correlate of in vivo allergic responses. For 13 patients with bancroftian filariasis HR responses were elicited by graded doses of microfilarial antigen in the absence of serum or in the presence of normal human serum, autologous serum, or serum from other infected patients. In all instances, sera from patients with filariasis contained a factor that specifically inhibited HR to parasite antigen. Normal sera had no such inhibitory effect, but sera from other filariasis patients inhibited as effectively as autologous serum. This HR blocking factor was heat stable (56°C x 2 hr) and nondialyzable. Its parasite antigen specificity was demonstrated by its inability to block the HR of patient cells triggered by anti-IgE anti-body and its lack of inhibitory effect on the Hr response of ragweed-sensitized cells reacted with ragweed antigen E. Fractionation of the sera by staphylococcus protein A-Sepharose chromatography showed that the blocking factor was an IgG antibody whose activity could be removed by specific immunoabsorption with filarial antigen. The levels of blocking antibody in the sera of these patients were high, comparable to those reported for atopic patients on immunotherapy regimens. These findings demonstrate that IgG blocking antibodies directed against parasite allergens are a regular component of the immune response to chronic filarial infection and suggest their potential role in vivo for specifically modulating allergic responsiveness to parasite antigens.