Isotypic and antigenic restriction of the blocking antibody response to ryegrass pollen: correlation of rye group I antigen-specific IgG1 with clinical response.
To investigate the role of blocking antibodies in allergen immunotherapy (IT), we analyzed IgE, IgG, and IgG subclass 1 to 4 antibody responses to ryegrass group I antigen (RGGI) in a prospective double-blind, heterologous allergen, allergen-controlled trial of grass-pollen IT in 18 adults with seasonal rhinitis and asthma. Serum was assayed preseasonally before starting IT and again in midseason at time of documented highest natural exposure. Antibodies were measured by ELISA, and immunogenic specificities of ryegrass extract were examined by Western immunoblots. Nine subjects receiving grass-pollen IT and nine control subjects had similar clinical and immunologic status before IT. RGGI-specific IgE antibodies (sIgE) did not change from pretreatment levels in actively treated subjects but increased in control subjects (p less than 0.002). RGGI sIgG increased approximately thirteen-fold with active IT versus threefold during natural seasonal exposure (p less than 0.0005). The IgG-blocking response to RGGI was restricted to IgG1 and IgG4. Ten nonatopic subjects had similar RGGI sIgG1 but lower or undetectable sIgE and sIgG4 than the 18 atopic study subjects. Active IT dramatically increased RGGI sIgG4 (p less than 0.001) and to a lesser extent RGGI sIgG1 (p less than 0.01). Immunoblots demonstrated eight IgE-binding ryegrass-polypeptide allergens, with RGGI ubiquitous, and 11 IgG-binding polypeptides, including all eight allergens. A negative correlation between seasonal rhinitis symptom-medication scores and RGGI sIgG1 levels was found (r = -0.62, p less than 0.01), but no other immunologic parameters assayed were related to clinical improvement. Although RGGI sIgG4 predominates in the blocking response and is a useful marker of effective IT, early beneficial biologic effects may involve IgG1 antibodies.
D000485:Allergens; D000917:Antibody Formation; D052179:Antigens, Plant; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007073:Immunoglobulin E / Q000032:analysis; D007074:Immunoglobulin G / Q000032:analysis*; D007132:Immunoglobulin Isotypes / Q000032:analysis*; D010940:Plant Proteins; D011058:Pollen / Q000276:immunology*; D006255:Rhinitis, Allergic, Seasonal / Q000276:immunology*; D012434:Secale
D000485:Allergens; D052179:Antigens, Plant; D007074:Immunoglobulin G; D007132:Immunoglobulin Isotypes; C042814:Lol p I protein, Lolium perenne; D010940:Plant Proteins; D007073:Immunoglobulin E