Conventional Subcutaneous Immunotherapy Research Articles

Innovative delivery systems for epicutaneous immunotherapy.

Allergen-specific immunotherapy (AIT) describes the establishment of peripheral tolerance through repeated allergen exposure, which qualifies as the only curative treatment for allergic diseases. Although conventional subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT) have been approved to treat respiratory allergies clinically, the progress made is far from satisfactory. Epicutaneous immunotherapy (EPIT) exploits the skin's immune properties to modulate immunological response, which is emerging as a promising alternative and has shown effectiveness in many preclinical and clinical studies for both respiratory and food allergies. It is worth noting that the stratum corneum (SC) barrier impedes the effective delivery of allergens, while disrupting the SC layer excessively often triggers unexpected Th2 immune responses. This work aims to comprehend the immunological mechanisms of EPIT, and summarize the innovative system for sufficient delivery of allergens as well as tolerogenic adjuvants. Finally, the safety, acceptability, and cost-effectiveness of these innovative delivery systems are discussed, which directs the development of future immunotherapies with all desirable characteristics.

Sustained antigens delivery using composite microneedles for effective epicutaneous immunotherapy.

Allergen-specific immunotherapy (SIT) is a desirable way of therapy for various allergic diseases such as food allergy (FA). However, frequent visits for more than 3 years and potential adverse effects often hinder patient compliance. Recently, many researchers started focusing on microneedles (MNs) as a new method for SIT. In this study, we proposed an implantable MNs system produced by a two-step casting process, consisting of OVA (antigen)-loaded silk microneedles and a dissolvable, flexible polyvinyl alcohol (PVA) pedestal. Different from PVA, silk fibroin hydrogel has preferable vaccine release ability in vivo and in vitro. Once MNs are inserted into the skin, the PVA pedestal can dissolve in the interstitial fluid of the excised skin within 5 min and implant the OVA-loaded silk microneedle tips in dermal layer as a sustained antigen depot, thus inducing long-lasting immune response for at least 2 weeks. After receiving 3 doses of MN-based immunotherapy, the immune response in OVA-sensitized mice was successfully suppressed, with no apparent side effects. Compared to conventional subcutaneous immunotherapy (total dose of 150 [Formula: see text]g), MN immunotherapy ameliorated systemic anaphylaxis more effectively even at a lower dose (total dose of 30 [Formula: see text]g), demonstrating the antigen dose-sparing potential of the proposed MNs. Moreover, due to the prolonged release effect of silk-PVA composite MNs, the frequency of immunotherapy can be significantly reduced. To sum up, through prolonged skin exposure to antigen, this implantable designed MN may offer a new therapeutic strategy for FA treatment with significant improvements in efficacy and convenience. Schematic illustration of silk-PVA composite microneedles, consisting of OVA (antigen)-loaded silk microneedles and a dissolvable, flexible PVA pedestal. Once inserted into the skin, the PVA pedestal can dissolve in the interstitial fluid of the excised skin within 5 min. Subsequently, the OVA-loaded silk microneedle tips were implanted in the dermal layer as a sustained antigen depot and induced long-lasting immune response. This MNs-based immunotherapy can significantly modulate the Th1/Th2 imbalance of sensitized mice.

Accelerated/rush allergen immunotherapy.

Accelerated allergy shot schedules for inhalant and venom allergens provide individuals with allergy symptom relief but in a shorter time frame than conventional therapy. Accelerated immunotherapy (IT) protocols allow patients to reach therapeutic doses in a shorter time frame while improving adherence and reducing direct costs (e.g., fewer office visits and medications) and indirect costs (e.g., less travel time, missed work or school). Rush IT and cluster IT are believed to work through mechanisms similar to conventional subcutaneous IT (SCIT). The risk for severe systemic reactions during accelerated IT is low when appropriately administered; however, life-threatening and fatal reactions do occur. To reduce the incidence of systemic allergic reactions during cluster and rush IT protocols, premedication is recommended. It is important to exclude individuals at high risk such as those with poorly controlled asthma or those who are on β-blockers to mitigate the risk for developing systemic allergic reactions. However, accelerated SCIT regimens offer increased convenience, faster improvement in allergy symptoms, and the potential to reduce health-care costs while providing equivalent safety outcomes compared with conventional IT protocols.

Circadian and seasonal variations in subcutaneous allergen immunotherapy reactions

Circadian and seasonal rhythms play an important role in many physiological responses involving the immune system and allergic diseases1,2 and may also have implications in the safety profile of subcutaneous immunotherapy (SCIT). Although rare after administration of conventional SCIT in a clinical setting, systemic reactions (SR) occur in approximately 1 in 1000 injections, with roughly 67% classified as mild, 29% as moderate, and 4% as severe.3 Our study aimed to determine if the time of immunotherapy administration, seasonality, or demographic factors impact the rate of SR after SCIT.

Aqueous intradermal low-dose house dust mite immunotherapy in tropical settings: a valid cost-effective approach for developing nations?

Aqueous allergen injections, an effective and century-old technique, is considered a second-line approach in daily clinical practice. Inconveniences still surround conventional subcutaneous immunotherapy (SCIT) administration, such as a need for frequent injections, prolonged up-dosing schedules, elevated costs, and the unlikely possibility of a systemic reaction. The intradermal immunotherapy route (IDR) might favorably impact many of the aforementioned issues (Table 1). House dust mite (HDM) allergens are the main perennial sensitizers in the tropics, and as such, are solely employed in immunotherapy treatments. We carried out a year-long real-life study in 25 perennial allergic rhinitis children, symptomatic on exposure to house dust, employing an intradermal low-dose allergen mix consisting of 50 ng of Dermatophagoides pteronyssinus/Dermatophagoides farinae and 120 ng of Blomia tropicalis, under a unique cost-wise protocol. Basal symptoms/signs and face Visual Analog Scale (fVAS) scores were recorded for 2 weeks and later compared with those registered throughout the 1-year treatment. Serum-specific IgG4 and IL-10 levels were employed in the assessment of the immune responses. Symptoms/signs and fVAS scores were significantly reduced from days 42 and 49, respectively, and remained so until treatment completion. Increases in specific IgG4's and IL-10 levels reflected significant immune responses. Injections were well tolerated and families reported improved health status (quality of life, QoL). A unique cost-effective immunotherapy alternative for deprived allergic communities in tropical settings is depicted; further research is needed.

Effect of mobile platform in improving compliance and efficacy of subcutaneous immunotherapy in children with allergic rhinitis

Objective:To explore effect of mobile platform in improving compliance and efficacy of subcutaneous immunotherapy（SCIT） in children with allergic rhinitis（AR）. Method:From January to June 2018, 86 children diagnosed with AR and receiving SCIT were selected as research objects. According to the random sequence generated by the computer, the research objects were randomly assigned to the experimental group and the control group, with 43 cases in each group. The control group received conventional SCIT management, while the experimental group received mobile platform SCIT management relying on smart phones and computers. The SCIT shedding rate at the initial stage and the time taken to reach the maintenance period were compared between the two groups, as well as the visual simulation scale of rhinitis symptoms, four-point score and rhinoconjunctivia-related quality of life scores before and at the 6th month after the intervention. Result:There was no statistically significant difference in the initial SCIT shedding rate between the two groups（P>0.05）, and the average duration of the maintenance period of the experimental group was shorter than that of the control group, with statistically significant difference（P<0.05）. At the 6th month after intervention, there was no statistically significant difference in the scores of rhinitis symptoms by the four-point method between the two groups（P>0.05）, and there were statistically significant differences in the visual simulation scale of rhinitis symptoms and the scores of children's rhinoconjunctivia-related quality of life（P<0.05）. Conclusion:This study confirmed that the application of a mobile platform is of great significance for improving compliance and the treatment effects of SCIT in children with AR.

Transcutaneous Delivery of Immunomodulating Pollen Extract-Galactomannan Conjugate by Solid-in-Oil Nanodispersions for Pollinosis Immunotherapy.

Japanese cedar pollinosis is a type I allergic disease and has already become a major public health problem in Japan. Conventional subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT) cannot meet patients’ needs owing to the side effects caused by both the use of conventional whole antigen molecules in the pollen extract and the administration routes. To address these issues, a surface-modified antigen and transcutaneous administration route are introduced in this research. First, the pollen extract (PE) was conjugated to galactomannan (PE-GM) to mask immunoglobulin E (IgE)-binding epitopes in the PE to avoid side effects. Second, as a safer alternative to SCIT and SLIT, transcutaneous immunotherapy (TCIT) with a solid-in-oil (S/O) nanodispersion system carrying PE-GM was proposed. Hydrophilic PE-GM was efficiently delivered through mouse skin using S/O nanodispersions, reducing the antibody secretion and modifying the type 1 T helper (Th1)/ type 2 T helper (Th2) balance in the mouse model, thereby demonstrating the potential to alleviate Japanese cedar pollinosis.

Principles of Allergen Immunotherapy and Its Clinical Application in China: Contrasts and Comparisons with the USA.

Allergen immunotherapy (AIT) for allergic rhinitis (AR), asthma, and other allergic diseases has developed quickly. House dust mite (HDM), Artemisia (wormwood), Humulus japonicus (Japanese hop), Alternaria alternata, and Cladosporium herbarum are the five most common inhalant allergens in China. AIT has been performed in China for over 60years. With the support of the Chinese Medical Association (CMA) and the Chinese Medical Doctors Association (CMDA), the Chinese College of Allergy and Asthma (CCAA) was established in 2016 as a specialized branch of CDMA and is the main certification authority for AIT. Chinese allergists and scientists have made tremendous progress in the development of AIT. There have been many publications by Chinese allergists and scientists worldwide encompassing original research studies, systematic reviews, case studies, and clinical trials. Currently, conventional subcutaneous immunotherapy (SCIT) is the preferred AIT in China, but sublingual immunotherapy (SLIT) is beginning to gain recognition. An increasing number of clinical trials have been conducted to investigate the clinical efficacy and side effects of SLIT and SCIT. In China, HDM is the only commercial standardized allergen extracts in clinical use, whereas the others are crude allergen extracts. Besides standardized allergen extracts, other forms of hypoallergenic extracts are still being investigated and developed in China. Immunotherapy in China is similar to that in the USA in which allergen extracts can be mixed for SCIT. However, allergen extracts cannot be mixed for SCIT in Europe.

Risk factors and strategies in nonadherence with subcutaneous immunotherapy: a real-life study.

Allergen immunotherapy (AIT) is still the only causal treatment for allergic diseases. However, conventional subcutaneous immunotherapy (SCIT) administration schedules are time-consuming and patient nonadherence is a major barrier to achieving a satisfactory therapeutic effect. Our study aimed to analyze the causes leading to discontinuation of SCIT and to determine risk factors associated with nonadherence in respiratory allergies. This was a prospective study. Patients with respiratory allergies who had received standardized dust mite SCIT were enrolled from January 2012 to January 2014. And a follow-up study on these subjects was conducted via telephone interviews on an interval of 3 months and online communication through social network applications. Reasons for discontinuation were documented when patients claimed to stop treatment. A total of 311 patients were enrolled in the study. The adherence rate at year 3 was 64.6%. Fifty-nine patients (19.0%) dropped out in year 1, 31 (10.0%) in year 2, and 20 (6.4%) in year 3. Reasons for nonadherence included inconvenience (32.7%), ineffectiveness (25.5%), improvement of symptoms (22.7%), and adverse reactions (14.5%). Children had higher adherence than adults (70.7% vs 55.0%) (p < 0.05). The dropout reasons were different among the children and adults groups (p < 0.005). The follow-up work was carefully and thoroughly done. All the 311 (100%) patients accepted the telephone interview, and 296 (95.2%) patients submitted questions and got rapid replies from doctors online. Adherence to SCIT was less than satisfactory in the real-life study. A close communication between doctors and patients is helpful in enhancing adherence with AIT in clinical practice.

Accelerated subcutaneous immunotherapy in pediatric population – Systematic review

BackgroundAccelerated subcutaneous immunotherapy (SCIT) schedules represent an alternative to conventional SCIT, providing immunotherapy benefits in a shorter period of time. The objectives of this systematic review were to assess clinical and immunological efficacy as well as safety of accelerated SCIT build-up schedules for the treatment of respiratory allergy in pediatric patients. MethodsStudies were located by searching PubMed, using “immunotherapy” and “desensitization” as keywords. The selection of studies, published from January 1st, 2006, to December 31th, 2015, was performed in two stages: screening of titles and abstracts, and assessment of the full papers identified as relevant, considering the inclusion criteria. Data were extracted in a standardized way and synthesized qualitatively to assess efficacy and safety of accelerated schedules in respiratory allergy. ResultsEleven trials were included: two evaluated rush SCIT and nine assessed cluster SCIT. This review demonstrated that rush and cluster schedules are clinically and immunological efficacious, with faster effect than conventional schedules. No relevant difference with respect to clinical outcomes was noticed between subgroups (pediatric, adult and mixed populations). Regarding safety, most local adverse reactions were mild and there were neither life-threatening systemic reactions nor fatal events. No relevant differences in the incidence and severity of either local or systemic reactions between the accelerated schedule group and control group were registered. ConclusionsAccelerated SCIT build-up schedules are effective in the treatment of respiratory allergy in pediatric patients, representing a safe alternative to the conventional schedules with the advantage of achieving clinical effectiveness sooner.

Intralymphatic immunotherapy of pollen-induced rhinoconjunctivitis: a double-blind placebo-controlled trial.

BackgroundAllergen-specific immunotherapy represents the only disease-modifying treatment for allergic diseases. We and others have previously demonstrated that intralymphatic immunotherapy (ILIT), a less time-consuming alternative to conventional subcutaneous immunotherapy (SCIT), is safe and effective. However, this has recently been disputed. The aim of this study was therefore to expand our previous trial, further assessing the safety and efficacy of ILIT.MethodsThirty-six patients with pollen-induced rhinoconjunctivitis were randomised to receive three intralymphatic inguinal injections of active allergen (1000 SQ-U birch- or grass-pollen) or placebo. Clinical effects, safety and circulating immunological markers were assessed before, 4 weeks after treatment and at the end of the consecutive pollen season.ResultsNo moderate or severe reactions were recorded following ILIT. Patients receiving active ILIT experienced a significant improvement in self-recorded seasonal allergic symptoms, as compared to placebo (p = 0.05). In a subgroup of these patients (“improved”), a reduction in nasal symptoms following nasal allergen provocation was also demonstrated. No changes in total IgE or IgG4 were found. However, the affinity of allergen specific IgG4 following active treatment was significantly increased, as compared to non-improved patients (p = 0.04). This could be correlated with clinical improvement, on an individual level.ConclusionsThis double-blinded placebo-controlled study confirms that ILIT is a safe and effective treatment for pollen-induced rhinoconjunctivitis, markedly reducing seasonal allergic symptoms.Trial registrationEudraCT: 2009-016815-39Electronic supplementary materialThe online version of this article (doi:10.1186/s12931-016-0324-9) contains supplementary material, which is available to authorized users.

Assessment of stability and compatibility of dermatophagoides and blomia allergen mixture for sublingual immunotherapy

Background House Dust Mites are important etiological agents of respiratory allergy. Allergen mixtures are often used for specific immunotherapy in polysensitized patients, although scientific evidence to support its efficacy, safety and stability is scarce. Sublingual immunotherapy (SLIT) is being gradually accepted as an alternative to conventional subcutaneous immunotherapy. For SLIT, higher allergen doses are recommended, so the development of pharmaceutical formulations allowing the administration of such high doses is particularly relevant. Therefore, the aim of this work was to develop and evaluate liquid formulations of allergenic extracts of house dust mites: Dermatophagoides pteronyssinus, Dermatophagoides siboney and Blomiatropicalis, containing glycerol, for administration as sublingual vaccine.

Trends in Specific Immunotherapy for Allergic Rhinitis: A Survey of Chinese ENT Specialists.

PurposeSpecific immunotherapy (SIT) is a suitable but uncommon treatment option for allergic rhinitis (AR) in China. The current understanding and attitude of Chinese ENT (ear, nose, and throat) specialists in regards to SIT is unclear. This study investigates current trends in the awareness and application status of SIT among Chinese ENT specialists.MethodsWe performed a nationwide, cross-sectional survey with a specially designed questionnaire given to 800 ENT specialists in China. A member of the trained research group conducted face-to-face interviews with each respondent.ResultsMost of the respondents considered AR (96.0%) and allergic asthma (96.0%) the most suitable indications for SIT. Of all respondents, 77.0% recommended the application of SIT as early as possible; in addition, SIT was considered 'relatively controllable and safe' by most respondents (80.6%). The highest allergen-positive rate in AR was associated with house dust mite (47.7%) and obvious differences existed among geographical regions. Conventional subcutaneous immunotherapy was the most highly recommended treatment option (96.2%). 'The high cost of SIT' (86.6%) and 'lack of patient knowledge of SIT' (85.2%) were probably the main reasons for the lower clinical use of SIT in China.ConclusionsMost cases showed that the opinions of Chinese ENT specialists appeared to be in agreement with recent SIT progress and international guidelines; however, many areas still need to enhance the standardization and use of SIT in China. Clinical guidelines for SIT require improvement; in addition, Chinese ENT specialists need continuing medical education on SIT.

Local immunological mechanisms of sublingual immunotherapy

To summarize novel insights into the immunological mechanisms of sublingual immunotherapy (SLIT). Within the recent decades, several alternative noninvasive allergen application strategies have been investigated in allergen-specific immunotherapy (AIT), of which intra-oral allergen application to sublingual mucosa has been proven to be well tolerated and effective. To date, SLIT is widely accepted by most allergists as an alternative option to conventional subcutaneous immunotherapy (SCIT). Although detailed immunological mechanisms remain to be elucidated, much scientific effort has been made to shed some light on local and systemic immunological responses to SLIT in mice as well as humans. Only a few studies focused on the detailed mechanisms following allergen application to the oral mucosa as part of the sophisticated mucosal immunological network. Within this network, the pro-tolerogenic properties of local antigen-presenting cells (APCs) such as dendritic cells - which are able to enforce tolerogenic mechanisms and to induce T-cell immune responses - play a central role. Further on, basic research focused not only on the immune response in nasal and bronchial mucosa but also on the systemic T-cell immune response. Thus, much exiting data have been published providing a better understanding of immunological features of SLIT but far more investigations are necessary to uncover further exciting details on the key mechanisms of SLIT.

Immunological mechanisms of sublingual allergen-specific immunotherapy

Within the last 100 years of allergen-specific immunotherapy, many clinical and scientific efforts have been made to establish alternative noninvasive allergen application strategies. Thus, intra-oral allergen delivery to the sublingual mucosa has been proven to be safe and effective. As a consequence, to date, sublingual immunotherapy (SLIT) is widely accepted by most allergists as an alternative to conventional subcutaneous immunotherapy. Although immunological mechanisms remain to be elucidated in detail, several studies in mice and humans within recent years provided deeper insights into local as well as systemic immunological features in response to SLIT. First of all, it was shown that the target organ, the oral mucosa, harbours a sophisticated immunological network as an important prerequisite for SLIT, which contains among other cells, local antigen-presenting cells (APC), such as dendritic cells (DCs), with a constitutive disposition to enforce tolerogenic mechanisms. Further on, basic research on local DCs within the oral mucosa gave rise to possible alternative strategies to deliver the allergens to other mucosal regions than sublingual tissue, such as the vestibulum oris. Moreover, characterization of oral DCs led to the identification of target structures for both allergens as well as adjuvants, which could be applied during SLIT. Altogether, SLIT came a long way since its very beginning in the last century and some, but not all questions about SLIT could be answered so far. However, recent research efforts as well as clinical approaches paved the way for another exciting 100 years of SLIT.

Safety of a rush immunotherapy build-up schedule with depigmented polymerized allergen extracts

Conventional subcutaneous immunotherapy (SCIT) for allergy treatment needs several injections over several weeks to reach the maintenance dose. Shorter up-dosing regimens are desired but limited by the potential of side effects. This study was designed to compare the safety of Depigoid (Laboratorios LETI, Spain)-SCIT 1 day versus 3 weeks up-dosing in patients with Type 1 allergy caused by clinically relevant sensitization against tree pollen, grass pollen, and house-dust mites. A total of 303 patients with confirmed allergic rhinitis/conjunctivitis were included. A rush build-up schedule administering 0.2 mL and then 0.3 mL of the concentrate at day 1 followed by 0.5 mL at day 28 was compared with a conventional 4-week build-up schedule. The number of patients reaching the maintenance phase without systemic reactions or major deviation from treatment schedule were compared. Of the rush 91.8% and in the conventional group 90.9% reached the maintenance phase without dose modification. Neither the proportions of patients with systemic reactions (5.8% rush versus 2% conventional) nor the proportions of patients with local reactions differed significantly between the two regimens (24% rush versus 11% conventional). There was no difference with respect to the applied allergen group. The proposed rush build-up schedule for the immunotherapy treatment with depigmented allergoids without premedication is safe and not inferior to the conventional schedule.

Undertreatment of allergy: Exploring the utility of sublingual immunotherapy

Allergic syndromes are highly prevalent and are comprised of a wide variety of clinical problems, including rhinitis, conjunctivitis, atopic dermatitis and urticaria, asthma, and food allergies. Numerous studies have shown that allergic syndromes are both underdiagnosed and undertreated. This is related to many factors, including trivialization of allergic conditions by physicians and patients, failure to adhere to diagnostic and treatment guidelines, and dissatisfaction with conventional pharmacologic treatments. Immunotherapy involves the administration of allergen extracts in an attempt to induce immunologic tolerance and has been used for the treatment of allergic syndromes and the prevention of long-term complications. Conventional subcutaneous immunotherapy is effective but is also associated with a risk of serious adverse events, requires administration by a trained health care professional, and is contraindicated in certain populations. By contrast, sublingual immunotherapy has been used extensively in Europe and possesses most of the benefits of subcutaneous immunotherapy along with increased safety, tolerability, and convenience. This narrative review explores data from selected clinical studies and concludes that sublingual immunotherapy may be well suited to fill the gap posed by the undertreatment of allergic syndromes in the United States.

Allergen immunotherapy: immunomodulatory treatment for allergic diseases

Allergen immunotherapy is currently the only immune-modifying treatment for allergic disease. At the present time it is indicated for the treatment of allergic rhinitis, asthma and venom hypersensitivity. Efficacy appears to be dose dependent, and the immunological mechanisms responsible for the clinical efficacy of immunotherapy are still being elucidated. Immunological changes associated with immunotherapy include induction of T regulatory cells, increase in allergen-specific immunoglobulin G4, increase in interleukin-10 production and downregulation of the T helper 2 response. The disadvantages of allergen immunotherapy include risk of adverse events and patient time and inconvenience. Risks of immunotherapy range from large local reactions to mild systemic reactions, such as rhinitis. Fatalities from immunotherapy injections have been reported at a rate of approximately one fatality per 2.5 million injections. Conventional subcutaneous immunotherapy build-up schedules involve administration of a single-dose increase each visit and it may take several months before a patient achieves the therapeutic maintenance dose. Accelerated schedules, such as rush and cluster, will allow the patient to achieve the maintenance dose sooner but there may be a greater risk of a systemic reaction. The current focus of immunotherapy research is to develop safer and more effective vaccines. Another approach to enhancing immunotherapy safety is through an alternative delivery method. Sublingual immunotherapy is clearly safer than subcutaneous immunotherapy, but further investigation is needed to determine optimal dose and appropriate patient selection.

Inmunoterapia sublingual con extracto de epitelio de gato. Experiencia personal

Because cats are a common pet in many houses and tourist complexes in the Canary Islands, sensitization to cat epithelium is a frequent problem. A total of 19.2% of patients with intrinsic asthma are sensitized to cat epithelium. In the Canary Islands, the percentage of sensitization among patients with a household cat is 18.1%, which higher is higher than in the rest of Spain (11.9). Many patients with extrinsic asthma sensitized to house dust mites undergo conventional subcutaneous immunotherapy but evolution is unsatisfactory due to sensitization to cat epithelium (whether a cat is present or not). The aim of this study was to evaluate the clinical effectiveness of sublingual immunotherapy with extract of cat epithelium in monosensitized patients with perennial allergic rhinitis and/or bronchial asthma. Forty patients monosensitized to cat epithelium were selected. Of these, 20 were administered sublingual immunotherapy and another 20 received placebo. The following evaluation was carried out in both groups: in vivo and in vitro: symptom score, skin tests, nasal challenge with cat epithelium, specific IgE determination, specific IgG4 and eosinophilic cationic protein. After 1 year of treatment the cumulative dose was 3.6 micrograms of Fe ld I, equivalent to 10 ng/drop. Duration of treatment was 365 days. Our conclusions, based on our patients in the Canary Islands, were the following: 1. Sublingual Fel d I therapy is effective after 1 year of treatment. 2. There were no modifications in IgE, eosinophilic cationic protein or skin tests. 3. An increase in IgG4 occurred which was related to clinical improvement. 4. In general, tolerance was good, except in one patient who presented urticaria and sublingual pruritus. 5. In polysensitized patients, sublingual immunotherapy to cat epithelium is complementary to immunotherapy to dermatophagoides.

Specific IgE, IgG, and IgA antibody response to oral immunotherapy in birch pollinosis

Thirty-nine patients with birch pollinosis participated in a double-blind, placebo-controlled trial of oral immunotherapy (OIT) for 18 months. They were treated with increasing doses of freeze-dried birch-pollen antigens for 16 months, reaching a cumulative dose of 280 × 10 6 biologic units. This is about 200 times more than the dose used in conventional subcutaneous immunotherapy (IT). In the placebo-treated group, but not in the actively treated group, there was a rise in postseasonal birch-specific IgE antibody levels. A significant decline in postseasonal values after 1 year of treatment was recorded in the actively treated, but not in the placebo-treated, group. Compared to the placebo treatment, there was a significant rise in birch-specific IgG antibodies in patients administered active treatment; however, the rise was less than that usually observed during subcutaneous IT. No significant change in birch-specific serum IgA was found in either group. The changes in IgE and IgG antibody levels demonstrate that OIT affects the immune system. This supports our recent findings that OIT demonstrates a beneficial effect in the treatment of birch pollinosis in adults. But, as with subcutaneous IT, there was no clear relationship between antibody response and clinical findings in the patients. The underlying mechanisms responsible for the relief of symptoms thus remain unknown.