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.