Immune reactivity is a key issue in the evaluation of the quality of recombinant allergens as potential reference materials. Within the frame of the CREATE project, the immune reactivity of the natural and recombinant versions of the major allergens of birch pollen (Bet v 1), grass pollen (Phl p 1 and 5), olive pollen (Ole e 1), and house dust mite (Der p 1 and 2, and Der f 1 and 2) was analysed. The IgE binding capacity of the allergens was studied by direct RAST and RAST inhibition, and their biological activity by basophil histamine release, using sera of allergic patients selected across Europe. For birch pollen, rBet v 1 is an excellent mimic of the natural allergen. For grass pollen, rPhl p 1 showed a significant lower IgE reactivity and was not considered a suitable candidate, whereas rPhl p 5a exhibited an immune reactivity closer to that of its natural counterpart. For olive, rOle e 1 had a lower IgE binding capacity in RAST but a higher biological activity in histamine release. For house dust mite, recombinant group 1 allergens were significantly less potent than their natural counterparts, but recombinant group 2 allergens were close mimics of their natural homologues.
We believe that immunotherapy with HKL as an adjuvant induces Thl-like TReg cells that can inhibit AHR and airway inflammation. These antigen-specific TReg cells are induced with CD8alpha+ DCs producing IL-12 and IL-10, produce IFN-gamma and IL-10, and also express T-bet and Foxp3. These Th1Reg cells are distinct from antigen-specific TReg cells induced with respiratory tolerance, which can also inhibit AHR and airway inflammation. These Th2-like TReg cells are induced with CD8alpha- DCs producing IL-10, they express IL-10, GATA3 and Foxp3. So allergen immunotherapy is effective in large part because it induces regulatory T cells. With HKL you get Th1Reg cells, and with other forms of immunotherapy you may get Th2Reg cells. We believe that with further refinements, allergen immunotherapy that rapidly induces allergen specific TReg cells will indeed be the magic bullets for allergy and asthma.
Defining the role of sublingual immunotherapy (SLIT) for the treatment of allergic rhinoconjunctivitis and allergic asthma is hampered for various reasons: Heterogeneity in study designs, different allergen extracts and dosages, imperfect assessment strategies and partially inconclusive results. A number of questions need to be addressed before replacing subcutaneous immunotherapy (SCIT) by the sublingual route: Ideal dose, treatment duration, magnitude of improvement, modification of the immune response, long-term and preventive effects. At present, SLIT might be used in adults with pollen related rhinoconjunctivitis, particularly if SCIT is not suitable for the patient (i.e. systemic effects). Only few data support SLIT for house dust mite allergy or bronchial asthma. Due to a lack of convincing results SLIT for children should only be applied in controlled studies and not in the daily routine. A more substantiated and conclusive judgment of SLIT is possibly warranted in a few years, when more studies with larger patient groups have addressed open questions concerning SLIT.
The present publication describes the actual situation anno 2005 with respect to registration of allergen products for specific immunotherapy (SIT) in Europe. It is concluded that the lack of the implementation of regulations and directives in force, is due to underestimation of the specific demands and aspects of the pathogenicity of allergic diseases at the one hand and of allergen products as a unique set of biological medicinal products at the other. The issues of regulatory nature that need careful attention and consideration in the opinion of the manufacturers are given in a number of statements. The main conclusion is that an EU-guideline for allergen products is urgently needed. A dialogue between regulatory authorities and representatives of the manufacturers, prior to the formulation of a new guideline seems of the utmost importance, as to prevent a similar stalemate as after the introduction of the foreseen regulatory measures of the past. The new guideline should include: An allergen product monograph. Recommendations for clinical development of allergen products like: Number of patients for efficacy and safety Acceptability of different efficacy parameters. Recommendations for toxicology.
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：