Timothy grass allergen components

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Booklet: Native & Recombinant Allergen Components.
Allergy - Which allergens? Phadia AB, 2006.
 
Allergen components from timothy grass, Phleum pratense, available for allergenspecific IgE antibody testing, are produced either with recombinant technique or as purified native proteins (1). The next generation of immunotherapy may be based on recombinant allergen components, possibly modified to reduce the risk of anaphylaxis. If the sensitisation profile to an allergen such as timothy is known, only those components to which the patient is actually sensitised should be relevant for therapy. This would eliminate the risk that the therapeutic reagent would induce IgE antibodies to additional components. The allergen components of timothy in IgE antibody tests may also be used for monitoring immunotherapy that is done with the natural extract.

Studies have evaluated different combinations of recombinant allergens for diagnostic use in grass pollen allergy. The fact that only a limited number of recombinant timothy grass pollen allergens account for the detection of a high percentage of patients with grass pollenspecific IgE suggests the usefulness of recombinant allergens not only for in vitro diagnosis but also for patient-tailored immunotherapy (2).

For example, a study used sera from 193 European, American, and Asian subjects to evaluate the percentage of IgE directed to rPhl p 1, rPhl p 2, rPhl p 5, and rBet v 2. The study also used natural pollen extracts from Anthoxanthum odoratum, Avena sativa, Cynodon dactylon, Lolium perenne, Phragmites australis, Poa pratensis, Secale cereale, Triticum sativum, Zea mays, IgE antibodies directed to these 4 recombinant pollen allergens was detected in 59% of these patients (3).

A similar study, examined the in vitro IgE antibody-binding capacity to the 3 recombinant timothy allergens, rPhl p 1, rPhl p 2, rPhl p 5, and birch profilin in sera from 183 patients allergic to grass pollen from different populations in Europe, Japan, and Canada. More than ninety-four percent of the patients could be diagnosed with a combination of recombinant Phl p 1, Phl p 2, Phl p 5, and Birch profilin. Sera that did not react with the recombinant allergens contained low levels of timothy grass pollenspecific IgE antibodies. The study pointed out that although considerable variability in the IgE antibody recognition frequency of the recombinant allergens was observed in certain populations, a good correlation was found between natural timothy-serum specific IgE antibodies and the combination of recombinant allergens in all 183 tested sera. The authors suggested that the addition of other recombinant allergens (e.g., recombinant Phl p 4) would only slightly improve the in vitro test sensitivity (4).

rPhl p 1, rPhl p 2, rPhl p 5 and Birch pollen recombinant allergens (rBet v 1, rBet v 2) were used for the measurement of allergen-specific IgE and IgG subclass antibody responses in fifty-five pollenallergic patients, allowing allergy diagnosis in 52 of 54 of the grass pollen and in 35 of 36 of the Birch pollen-allergic patients (5).

A larger study, evaluating sensitisation to timothy grass pollen using sera from 749 patients and a timothy extract compared to 8 recombinant timothy allergens, found that 95% had detectable IgE antibodies to the timothy extract. The prevalence of IgE antibody reactivity increased from 86.8% to 93.3% as the number of combined recombinant allergens rose from 2 to 8. The prevalences for each allergen were: rPhl p 1 = 83%, rPhl p 2 = 55%, nPhl p 4 = 70%, rPhl p 5 = 50%, rPhl p 6 = 44%, rPhl p 7 = 7%, rPhl p11 = 43% and rPhl p 12 = 15%. Monosensitisation to rPhl p 1 occurred in 6% patients and was negligible for the remaining molecules (6).

A study evaluating the same group of 8 allergens, using sera of 77 patients allergic to grass pollen, found a similar frequency of sensitisation to these allergens. This study also demonstrated a good correlation, as expected, between the calcium-binding proteins of rPhl p 7 and Bet v 4, and between the profilin of rPhl p 12 and rBet v 2. Nevertheless, as with other studies, highly variable individual sensitisation patterns were seen (7).

Clearly IgE antibody reactivity profiles will vary from country to country and will depend on the prevalence of pollen allergens. In an evaluation of the IgE antibody reactivity profile to individual recombinant and native allergens in sera from 1,177 subjects sensitised to timothy and/or birch pollen and living in Finnish and Russian Karelia, the IgE antibody reactivity to pollen extracts and 8 Timothy allergens (rPhl p 1, 2, 5, 6, 7, 11, 12 and nPhl p 4) and 3 Birch pollen allergens (rBet v 1, 2 and 4) revealed that the levels of IgE antibodies to timothy and Birch pollen were higher in Finnish (median 5.2 kUA/L) than in Russian Karelia (median 1.8 kUA/L). There was a significantly higher prevalence of IgE reactivity to 3 timothy pollen allergens in Finnish (n=57) than in Russian Karelia (n=12): rPhl p 2, 28 vs. 0%; rPhl p 5, 60 vs. 0%; rPhl p 6, 47 vs. 0%. The prevalence of IgE antibody reactivity to the birch pollen allergens was similar in the 2 populations. IgE antibody reactivity to rPhl p 2, 5, 6 and 11 was associated with hayfever symptoms (8). 

Because of patients being sensitised to minor timothy allergens, occasional subjects may demonstrate allergen-specific IgE antibodies to timothy extract but not to individual recombinants (9).

Assessing patients' sera for allergenspecific IgE and IgG4 antibody reactivity to individual recombinant P. pratense allergens after immunotherapy has been reported to be useful in defining optimal allergen extract doses. For example, a study that found no significant rPhl p 12-specific IgG4 antibody increase after immunotherapy, suggesting that Phl p 12 was underrepresented in the extract used. The simple detection of specific serum IgG4 antibodies a few weeks after the start of immunotherapy was a valuable tool for estimating the presence of relevant allergens in a given immunotherapeutic allergen extract (10). Grass pollen immunotherapy elicits an array of antibody specificities and these reflect the allergen content and the potency of allergen extracts, which may contribute to defining optimal allergen extract doses (11).

References:

    1. Andersson K, Lidholm J. Characteristics and Immunobiology of grass pollen allergens. Int Arch Allergy immunol 2003;130:87-107

    2. Laffer S, Vrtala S, Duchene M, van Ree R, Kraft D, Scheiner O, Valenta R. IgE-binding capacity of recombinant timothy grass (Phleum pratense) pollen allergens. J Allergy Clin Immunol 1994 Jul;94(1):88-94

    3. Niederberger V, Laffer S, Froschl R, Kraft D, Rumpold H et al. IgE antibodies to recombinant pollen allergens (Phl p 1, Phl p 2, Phl p 5, and Bet v 2) account for a high percentage of grass pollen-specific IgE. J Allergy Clin Immunol 1998;101(2 Pt 1):258-64

    4. Laffer S, Spitzauer S, Susani M, Pairleitner H, Schweiger C et al. Comparison of recombinant timothy grass pollen allergens with natural extract for diagnosis of grass pollen allergy in different populations. J Allergy Clin Immunol 1996;98(3):652-8

    5. Heiss S, Mahler V, Steiner R, Spitzauer S, Schweiger C, Kraft D, Valenta R. Component resolved diagnosis (CRD) of type I allergy with recombinant grass and tree pollen allergens by skin testing. J Invest Dermatol 1999;113(5):830-7

    6. Mari A. Skin test with a timothy grass (Phleum pratense) pollen extract vs. IgE to a timothy extract vs. IgE to rPhl p 1, rPhl p 2, nPhl p 4, rPhl p 5, rPhl p 6, rPhl p 7, rPhl p 11, and rPhl p 12: epidemiological and diagnostic data. Clin Exp Allergy 2003 Jan;33(1):43-51

    7. Rossi RE, Monasterolo G, Monasterolo S. Measurement of IgE antibodies against purified grass-pollen allergens (Phl p 1, 2, 3, 4, 5, 6, 7, 11, and 12) in sera of patients allergic to grass pollen. Allergy 2001;56(12):1180-5

    8. Moverare R, Petays T, Vartiainen E, Haahtela T. IgE Reactivity Pattern to Timothy and Birch Pollen Allergens in Finnish and Russian Karelia. Int Arch Allergy Immunol 2004 Dec 8;136(1):33-38

    9. Rossi RE, Monasterolo G, Operti D, Operti R, Berlen R. Evaluation of IgE antibodies to recombinant pollen allergens (Phl p 1, Phl p 2, and Phl p 5) in a random sample of patients with specific IgE to Phleum pratense. Allergy 2000;55(2):181-4

    10. Rossi RE, Monasterolo G. 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. Int Arch Allergy Immunol 2004 Sep;135(1):44-53

    11. Rossi RE, Monasterolo G, Diana A, Monasterolo S, Delucchi M. Evaluation of two grass pollen extracts for immunotherapy by serum determinations of specific IgE and IgG4 antibodies towards purified Timothy hyposensitization treatment. Allergology International 2002:51(4):233

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