Evaluation of recombinant and native timothy pollen (rPhl p 1, 2, 5, 6, 7, 11, 12 and nPhl p 4)- specific IgG4 antibodies induced by subcutaneous immunotherapy with timothy pollen extract in allergic patients.
BACKGROUND
Allergen immunotherapy is a widely accepted treatment for IgE-mediated allergies. The evaluation of immunotherapy-induced IgG4 antibodies based on allergen extract is questionable because the amount of allergen-extract-specific IgG4 to individual disease-eliciting allergens cannot be determined using crude allergen extracts. In this study, we examined the specific IgE and IgG4 serum binding profiles to individual Phleum pratense allergens in grass-pollen-sensitive patients who had received grass-pollen-specific immunotherapy (SIT).


METHODS
The study included 33 patients from North-West Italy. All suffered from seasonal rhinoconjunctivitis and/or asthma. A modified "cluster" regimen of injections of a standardized aluminium-adsorbed P.pratense extract, with once-weekly visits and 10 injections for 5 weeks followed by 3 weeks of maintenance injections was instituted. Patients' sera were analyzed for specific IgE and IgG4 reactivity to individual P. pratense allergens (recombinant Phl p 1, Phl p 2, Phl p 5, Phl p 6, Phl p 7, Phl p 11, Phl p12 and native Phl p 4) and natural P. pratense extract using the Pharmacia CAP system.


RESULTS
IgE reactivities to new allergen components were not detected by CAP in treated patients after 15 weeks and a cumulative dose of approximately 65 microg of the major allergen Phl p 5. Patients lacking specific IgE reactivity towards individual allergens at the start of SIT did not produce significant levels of specific serum IgG4 to serum IgE-negative allergens. On the other hand, an increase in specific IgG4 only to allergens to which patients were previously sensitized was observed. Significant increases in specific IgG4 levels to rPhl p 1 (p < 0.05), 2 (p < (0.01), 5 (p < 0.0001), 6 (p < 0.0001), 7 (p < 0.05), 11 (p < 0.05) and nPhl p 4 (p < 0.01) were observed after P. pratense extract immunotherapy. No significant rPhl p 12-specific IgG4 antibody increase was documented after treatment.


CONCLUSIONS
These findings suggest that Phl p 12 was underrepresented in the extract used, as indicated by the low specific IgG4 response induced by this grass-pollen-specific vaccine. Thus, the simple detection of specific serum IgG4 antibodies a few weeks after the start of SIT could represent a valuable tool to estimate the presence of relevant allergens in a given immunotherapeutic allergen extract.
Allergy Unit, National Health Service, Cuneo, Italy. immunoway@libero.it
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Rossi
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Monasterolo
D000293:Adolescent; D000328:Adult; D000485:Allergens / Q000737:chemistry / Q000276:immunology*; D001249:Asthma / Q000276:immunology / Q000628:therapy; D002648:Child; D003233:Conjunctivitis, Allergic / Q000276:immunology / Q000628:therapy; D003888:Desensitization, Immunologic / Q000379:methods; D005260:Female; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology* / Q000628:therapy; D007073:Immunoglobulin E / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D031784:Phleum / Q000737:chemistry / Q000276:immunology*; D010936:Plant Extracts / Q000737:chemistry / Q000276:immunology; D011058:Pollen / Q000737:chemistry / Q000276:immunology*; D006255:Rhinitis, Allergic, Seasonal / Q000276:immunology / Q000628:therapy
D000485:Allergens; D007074:Immunoglobulin G; D010936:Plant Extracts; D007073:Immunoglobulin E