|Year : 2007 | Volume
| Issue : 1 | Page : 3-5
Combination of allergens in specific immunotherapy for IgE mediated allergies
J Susmita, V Vijayalakshmi, G Suman Latha, K.J.R Murthy
Department Immunology Unit, Bhagawan Mahavir Medical Research Centre, 10-1-1, Mahavir Marg, Hyderabad-500 004., India
Department Immunology Unit, Bhagawan Mahavir Medical Research Centre, 10-1-1, Mahavir Marg, Hyderabad-500 004.
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Background : The success of immunotherapy for allergies has always been controversial. Some of the factors, which can affect the efficacy of immunotherapy, are the type and number of allergens in the vial, concentration, time, storage temperature, volume of the vial, diluent used and preservatives added.
Objective : To decipher the role of combination of allergens administered in Specific immunotherapy (SIT). Material and methods- patients who had a confirmed diagnosis of bronchial asthma, based on skin test and IgE were studied (n=50). Symptoms score on the scale of 1 to 4 were based on 2 factors- the frequency and the intensity.
Results : Based on the guidelines of Joint Task Force on Practice Parameters (USA), it was observed that 58% of the patients, who did not benefit, received the incorrect combination of allergens. On the other hand, the symptoms improved in all the patients who received the correct combination.
Conclusion : These results clearly lay emphasis on the nature of allergens and their combination used for immunotherapy. Therefore factors such as combination of allergens should be taken into consideration for management of allergies.
Keywords: Immunotherapy, Combination of allergens
|How to cite this article:|
Susmita J, Vijayalakshmi V, Latha G S, Murthy K. Combination of allergens in specific immunotherapy for IgE mediated allergies. Lung India 2007;24:3-5
|How to cite this URL:|
Susmita J, Vijayalakshmi V, Latha G S, Murthy K. Combination of allergens in specific immunotherapy for IgE mediated allergies. Lung India [serial online] 2007 [cited 2020 Aug 10];24:3-5. Available from: http://www.lungindia.com/text.asp?2007/24/1/3/44205
| Introduction|| |
Introduced almost a century ago by Noon and Freeman, Specific immunotherapy (SIT) till now holds a contentious task in the treatment of allergies. Allergen Immunotherapy is the repeated administration of a specific allergen(s) to patients with IgE mediated conditions for the purpose of providing protection against the allergic symptoms and inflammatory reactions associated with natural exposure to the allergen(s).
Immunotherapy is not a cure but can significantly lessen symptoms caused by specific substances. The success of immunotherapy has always been controversial. Some of the factors, which can affect the efficacy of Immunotherapy, are the type and number of allergens in the vial, concentration, time, storage temperature, volume of the vial, diluent used and preservatives added. The present study focuses on some of these aspects - the type, number and concentration of the allergens or the combination, to study their role in SIT.
| Material and Methods|| |
Patients who attended the Allergy clinic at Mahavir Hospital and Research Center, and who had a confirmed diagnosis of bronchial asthma, were studied(n=50). The criteria used to confirm atopic bronchial asthma in these patients were clinical symptoms combined with elevated total serum IgE levels and positive skin test responses. The study was retrospectively analyzed but the symptom review was prospective. Subjects below 12 years, above 60 years and pregnant women were excluded from this study. The consent of every patient was taken prior to skin testing and collection of blood for serum.
Skin testing was done by intradermal injection of allergens including pollen, fungal (selection was based on the local aerobiological calendar) insect and dust. Intradermal injection of buffer saline acted as negative control and histamine phosphatase as positive control. Immediate and late phase cutaneous responses were recorded at 20 min and 6-8 hrs after allergen challenge, respectively  .
Total serum IgE levels
The total IgE levels were estimated by using a commercial kit (General Biological Corp, Taiwan). The protocol is based on the principle of ELISA.
The treatment consisted of subcutaneous injections of antigens, by gradually increasing the dose of antigen from 1:5000, through 1:500 to 1:50, covered over a period of 18 months. Each vial had a mixture of 5 to 8 allergens and house dust mite was administered separately. Phenol was used at a concentration of 4% w/v.
The symptoms, cold, cough and breathlessness were scored based on 2 factors- the frequency and the intensity,on the scale of 1 to 4.
Combination of allergens
Combination of allergens indicates the mixture of antigens present in a vial. According to the clinical guidelines stated by the Joint Task Force on Practice Parameters  :
Allergens Compatible for mixing together are
1. Allergens with high protease activity (may be mixed together)
- Arthropods (dust mites)
- Fungi (mold spores)
- Insects (cockroach)
2. Allergens with low protease activity (may be mixed together)
- Grass pollen
- Tree pollen
- Weed pollen
- Animals (cat and dog allergens)
3. Other allergens
- Ragweed (may be mixed with either group above)
- Insect venoms (require a separate vial and a separate injection)
| Results|| |
Number of patients who received compatible and incompatible combinations was analyzed. [Table 1]. Decision regarding the role of a particular combination was based on their skin test positivity. Change in the symptoms scale was recorded before and after the immunotherapy and classification was done into three categories: reduced, same and increased. [Table 2]. Listing out the individual allergen combinations for each patient is not possible. The effect of compatible and incompatible combination of allergens on the allergic symptoms is shown. [Table 3]
| Discussion|| |
The present study focuses on the administration of allergens in 50 follow up subjects who were given immunotherapy. The results underline the importance of the combinations in which the allergens were mixed and administered.
Out of the 50 patients, 42% of them improved after completing the course of SIT. While in 34% of them there was no change in the symptoms, in the remaining 24% of them, the symptoms increased. A detailed analysis suggested that the ineffectual therapy in the latter two groups could be attributed to the combination of allergens used for SIT. Based on the guidelines of Joint Task Force on Practice Parameters (USA), it was observed that 58% of the patients, who did not benefit, received the incorrect combination of allergens. On the other hand, the symptoms improved in all the patients who received the correct combination. These results clearly lay emphasis on the nature of allergens and their combination used for immunotherapy.
Immunotherapy has been shown to be effective for sensitivity to a variety of pollens, fungi, dog and cat danders, dust mites, and cockroaches when given as single antigens  . However, when the patient is sensitive to more than one allergen, a mixture of allergens are used for SIT. In general, many allergen extracts (vaccines) contain mixtures of proteins and glycoproteins. There have been reports of interactions between extracts when mixed together. When mixed together, extracts such as those against Alternaria species have been shown to reduce the IgE-binding activity of timothy grass extract used as a vaccine. This effect was not demonstrated when Alternaria was mixed with ragweed in glycerin. All interactions between extracts have not been delineated fully; therefore, extracts (vaccines) that have higher proteolytic enzyme activities, such as those originating from fungi, arthropods (dust mites), and insects, should generally be kept separate from those with lesser enzyme activities such as pollen-based extracts  . According to a report by Nelson et. al.  , mixture with extracts reported to contain proteases caused loss of potency of most extracts tested.
In this regard, the number of injections to be given at each visit depends on whether all of the relevant extracts (vaccines) mixed into a single vial can convey an optimal dose of each allergen. If mixing causes excessive dilution or if there are advantages to separating allergens into separate vials, then more than one vial may be necessary for successful immunotherapy. Glycerin at a concentration of 50% may inhibit the activity of proteolytic and glycosidic enzymes that are present in certain extracts and vaccines. However, glycerin is irritating when injected and should be diluted before initiation of immunotherapy. An antibacterial agent such as phenol also should be included as a preservative  .
Cockroach and mite extracts contain digestive enzymes while moulds and insects contain proteases, which can denature other antigens. In addition to cockroach enzymes, among the moulds, alternaria, cladosporium, aspergillus, helminthosporium and penicillium are known to have protease activity that can interfere with the potency of other antigens in a mixture. Mites do not seem to have this activity as one would have thought, but this may have been due to glycerine in the diluent. There is no proteolytic activity in pollens or animal danders and this may render them susceptible to denaturation. Interestingly, moulds and cockroach may be mixed. Pollens and danders, however, should not be mixed with cockroach or moulds.
The inclusion of all allergens to which IgE antibodies are present, without establishing the possible clinical relevance of these allergens, dilutes the content of other allergens in the vaccine and can make allergen immunotherapy less effective  .
Our results showed no correlation between skin test, IgE levels and symptoms before and after immunotherapy. The relationship between immunotherapy efficacy and specific IgE antibody levels is variable  and the serum IgE levels may not reduce after SIT. Instead increase in the levels of specific IgG, was demonstrated  which may act as blocking antibodies. However, increases in allergenspecific IgG blocking antibody titer are not predictive of the duration and degree of efficacy of immunotherapy  . Investigations to detect a shift from Th2 to Th1 CD4+ lymphocyte immune response to allergen may be more relevant. Hence, skin test and IgE levels are probably useful parameters for diagnosis of allergies but not as postimmunotherapy check. As per the recommendations of the Joint Task Force on Practice Parameters (USA): "Evidence from meta-analysis of randomized controlled trials suggests that clinical parameters such as symptom scores and medication use may be useful measures of the efficacy of immunotherapy in a clinical setting. Routine periodic skin testing or in vitro IgE antibody testing of patients receiving immunotherapy is not recommended."  .
Future developments may include the production of pure allergens by molecular cloning and the development of peptide fragments of allergen that induce unresponsiveness in type 2 helper T cells  . Thus, one of the factors taken into consideration for the proper management of allergies, should be the combination of allergens.
Acknowledgements : We are thankful to Dr. Nateesa Sultana and R. Eswari for the clinical & technical help rendered during the study.
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[Table 1], [Table 2], [Table 3]