Prominence of IgG4 in the IgG antibody response to human filariasis.

Abstract

The four subclasses of IgG are distinct in structure, function, and degree of participation in the response to complex antigens. Because these differences could have important pathogenetic significance, we analyzed total and filaria antigen-specific IgG of each subclass in 31 patients with different clinical manifestations of Bancroftian filariasis. Subclass-specific, affinity-purified polyclonal antibodies were prepared from antisera raised in sheep immunized with purified myeloma IgG subclass proteins. These were radiolabeled (125I) and used to detect IgG1, IgG2, IgG3, and IgG4 in solid phase radioimmunoassays (SPRIA). The antigen-specific SPRIA was used with Brugia malayi adult antigen (BmA) bound to Sepharose 4B, whereas measurement of total IgG subclass levels in each serum was with goat anti-human IgG bound to the solid matrix. Quantification of total subclass levels was by reference to the WHO 67/97 standard, and of specific subclass antibody by development of standards from high titered sera. Although there were modest increases of total IgG1 and IgG2 in patients with filariasis compared with normals, the most striking finding was the extreme elevation of both total, and particularly, filaria antigen-specific IgG4. These elevations were seen for essentially all patients, but the relative proportion of the total IgG antibody response accounted for by IgG4 antibody was particularly marked (up to 95%) in patients with either microfilaremia or the tropical pulmonary eosinophilia syndrome. The meaning of this special prominence of the IgG4 antibody response to filarial infection is not yet clear, but the question of whether these antibodies play a role in immediate hypersensitivity reactions as either reagins or blocking antibodies is being investigated for its potential pathogenetic significance.