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PubMed2006

Enhancing efficacy, safety, and convenience of immunotherapy: a workshop presentation.

OBJECTIVE: To discuss issues in delivering appropriate allergen immunotherapy. DATA SOURCES: Review of Immunotherapy Collegium II workshop presented at the 2005 Annual Meeting of the American College of Allergy, Asthma and Immunology. STUDY SELECTION: Topics discussed during Immunotherapy Collegium II. RESULTS: In the past, dosage schedules, levels, and rates of acceleration were linked to skin test results. The most recent published schedules for administration of immunotherapy do not reflect the initial reaction to the skin test, but leave it to the treating physician to factor in the results of testing with plans for administration in both increments and frequency. However, there are no official recommendations for physicians relevant to using a skin test to gauge patient sensitivity. Rather, allergists are advised to set up a maintenance concentrate and then make suitable dilutions when immunotherapy is initiated. CONCLUSION: Although recommendations are lacking regarding the use of a skin test to gauge patient sensitivity, official recommendations are clear in other areas of immunotherapy, such as the use of premedication. It is important that standard terms be adopted by all physicians who prescribe allergen immunotherapy and that modified allergens and/or oral immunotherapy be explored in the future to make immunotherapy more comfortable.

Desensitization, Immunologic↗

PubMed2006

Sublingual immunotherapy: a comprehensive review.

Sublingual immunotherapy (SLIT) has been used with increasing frequency in Europe and is viewed with increasing interest by allergists in the United States. To address this interest, a Joint Task Force of the American College of Allergy, Asthma and Immunology and the American Academy of Allergy, Asthma and Immunology's Immunotherapy and Allergy Diagnostic Committees reviewed the available literature on SLIT and prepared this report. The task force concluded that despite clear evidence that SLIT is an effective treatment, many questions remained unanswered, including effective dose, treatment schedules, and overall duration of treatment. Until these have been determined, an assessment of the cost/benefit ratio of the treatment cannot be made. SLIT does appear to be associated with few serious side effects, but it has not been administered in high-risk asthmatic patients, nor in the studies reviewed has it been administered as a mixture of non-cross-reacting allergens. Furthermore, there is currently no allergy extract approved for this use in the United States, nor is there a Current Procedural Terminology code for billing purposes. All of these factors should be given careful consideration by anyone contemplating initiating SLIT treatment for their allergic patients.

Administration, Sublingual↗

PubMed1981

[Antibody response pattern (specific IgE and IgG) of insect sting allergic patients in immunotherapy with venom preparations].

The concentrations of venom specific IgE (Phadebas-RAST) and IgG (Phadebas IgG-RAST) were monitored in sera of 22 patients with histories of systemic anaphylactic reactions following insect stings who underwent immunotherapy with venom extracts (bee venom and/or yellow jacket venom). Analysis of the immunological parameters during immunotherapy revealed great individual variation in the degree of response concerning both specific IgE and IgG antibodies. Nevertheless, four typical patterns of immune response could be found. The majority of the patients were able to produce high titers of IgG "blocking" antibodies without an IgE increase. Another group of patients had a marked rise in both specific IgG and IgE following the initial phase of hyposensitization. In contrast, one patient received venom injections without a significant IgG or IgE response. Finally, a small group of patients has a marked increase in specific IgE while synthesis of IgG was not observed. This IgE rise was the cause of systemic reactions in this group after the venom injections. Regular monitoring of venom specific IgE and IgG is useful in evaluating the degree of protection for the patient. Since an increasing IgG/IgE ratio must be obtained during immunotherapy, a knowledge of this relationship serves to adapt the individual treatment schedule.

Adolescent↗

PubMedDate not supplied

Immunotherapy with standard bacterial and bacterial ribosomal antigens in childhood bronchial asthma.

UNLABELLED: In this study we compared the therapeutic effectiveness of a lyophilized bacterial vaccine (LBV) with that of a vaccine prepared from bacterial ribosomal antigens (ARB) in 150 children with bacterial bronchial asthma. The immunological response of the patients was assessed clinically at 6 months, 1 year and 3 years, by determining the intensity and frequency of the bronchospasm. The serum immunoglobulin levels, the only immunologic parametres studied, were determined at basal conditions and following immunotherapy. CLINICAL RESULTS: after 360 days we detected a better clinical response in those patients who received the ribosomal vaccine (ARB), whereas after 3 years there was no difference in the clinical response between this group of patients and the group who received the bacterial vaccine (LBV). Immunological results: we were not able to show a statistically significant increase in immunoglobulin levels during the three years of immunotherapy with the two vaccines. However, those patients who possessed a deficit in IgG displayed a statistically significant increase in IgG levels after 360 days (t = 3.58, p less than 0.01), and an even greater increase after 1080 days (t = 7.86, p less than 0.001), of treatment with the standard bacterial vaccine. The ribosomal vaccine produced a significant increase in IgG levels (t = 9.59, p less than 0.001) after 1080 days also in patients with a deficit in IgG. In patients with a previous deficit in IgA we did not observe an increase in serum IgA levels during immunotherapy with the bacterial vaccine, but with the ribosomal vaccine these patients displayed significantly higher levels of IgA (t = 13.09, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Bacterial↗

PubMed2004

[Specific immunotherapy. Hyposensitization with allergens].

Successful allergen-specific immunotherapy (SIT) induces complex immunologic chan-ges resulting in reduced allergic inflammatory reactions. SIT has long-term effects in mild forms of inhalant allergies and is effective even when standard pharmacotherapy fails. Moreover, the risk to develop additional allergic sensitizations and the development of asthma is significantly reduced in children with allergic rhinitis. SIT is the treatment of choice in patients with systemic reactions to hymenoptera venoms. Although the exact effector mechanisms of SIT still have to be clarified, the most probable effect is a modulation of regulatory T cells associated with a switch of allergen-specific B-cells towards IgG4 production. The critical point to insure efficacy and safety is the selection of patients and allergens, task best performed by a specialist trained in allergology. Further details are available in the position papers of the German allergy societies - DGAI(Deutsche Gesellschaft fiir Allergologie und Klinische Immunologie) and ADA (Arzte-verband Deutscher Allergologen) - which can be found at www.dgaki.de.

Adolescent↗

PubMedDate not supplied

Immunologic evaluation of 24 month course of sublingual immunotherapy.

58 patients under 12 years of age, positive to mites (Dermatophagoides pteronyssinus and D. farinae) according to prick, in vitro specific IgE and challenge tests, suffering from asthma and rhinitis, have been randomly assigned on a double blind basis to receive per os either a biologically standardized extract of mites (active therapy TA = 30 patients) or a saline buffered solution (placebo TP = 28 patients). The serologic results are interesting. The specific IgE level differences of significance are, in comparison with the placebo group. In particular, we did observe the increase of the specific IgE level in the placebo group during the autumn, whereas after 12 months and after 24 months of active treatment there was a clear (p < 0.01) decline in serum specific IgE antibody. In the active group, there was a significant increase in IgG antibodies level after 12 and 24 months and a significant increase in IgG4 level after 24 months. In the placebo group, the level of IgG antibodies was unchanged. In the actively treated patients, a significant increase of CD8+ values and a significant reduction of the ratio CD4+/CD8+ was observed.

Administration, Sublingual↗

PubMed2006

Immunological mechanisms of sublingual immunotherapy.

Administration of allergen-specific immunotherapy by the oral route, sublingual immunotherapy (SLIT), has been shown to be effective, with an improved safety profile compared with subcutaneous administration. However, the precise mechanisms underlying the induction of immune tolerance by SLIT remain unclear. Contact of the allergen with the antigen-presenting cells in oral mucosa is likely to be critical. Mucosal Langerhans cells can capture the allergen and transport it to local lymph nodes, which may favour the induction of T lymphocytes that suppress the allergic response. In addition, the production of blocking IgG4 antibodies and the involvement of mucosal B cells appear to play a role. There is a growing evidence to support the role of regulatory T cells in controlling the development of asthma and allergic disease. Nevertheless, there remains a lack of firm evidence that SLIT induces regulatory T cells, although preliminary in vitro data suggest that SLIT may increase interleukin-10, which has a clear role in suppressing the allergic immune response. Further studies are required to determine the involvement of regulatory T cells, the role of different dendritic cell subsets, mucosal B cells as well as the potential use of adjuvants during SLIT.

Administration, Sublingual↗

PubMed1984

Grass pollen immunotherapy: a single year double-blind, placebo-controlled study in patients with grass pollen-induced asthma and rhinitis.

Fifteen grass pollen--sensitive asthmatic patients were selected from 200 patients with grass pollenosis on the basis of positive SPTs and RASTs that were restricted to grass pollens (except Bermuda grass), no previous IT, and residence and occupation in an area monitored by serial pollen counts. They underwent a double-blind trial of specific IT with a mixture of three grass pollen--aqueous extracts (velvet, sweet vernal, and timothy) or placebo. After 10 mo, the mean maintenance dose of pollen extract (assayed by RAST inhibition) in eight actively treated patients was 6000 RAST units (range 3000 to 8000) and the mean total dose was 18,700 RAST units (range 10,200 to 30,000). Results were assessment done by the following clinical and immunological data: (1) during the pollen season, daily symptom scores; (2) PD 20% FEV1, IgE antibody to timothy by RAST in serum and in nasal secretions, serum IgG antibody to purified timothy allergen D by solid-phase radioimmunoassay, and the four IgG subclass antibodies by enzyme immunoassay were all measured before treatment and before and after the pollen season. Symptom scores of both treated patients and controls correlated with pollen counts (R = 0.88, p less than 0.05 and R = 0.71, p less than 0.05, respectively). There was a significant difference between the mean symptom score values of treated patients versus controls (Kruskal-Wallis test, p less than 0.001). No significant differences or changes either in the PD 20% FEV1 or IgE antibody to timothy in serum and nasal secretions were found in the two groups before or after IT.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed2004

The potential role of allergen-specific sublingual immunotherapy in atopic dermatitis.

Atopic dermatitis is a chronic inflammatory skin disease associated with increasing prevalence, morbidity, and cost in developed Western countries. Frequently associated with respiratory allergy during adulthood, atopic dermatitis often represents the first phenotypic appearance of atopy in early childhood when the allergic 'march' starts and progressively moves toward food allergy, asthma, and rhinitis. At present, a consistent body of evidence supports the view that atopic dermatitis may represent the skin compartmentalization of a systemic allergic inflammation. Lymphocytes infiltrating early lesional skin express a T helper (Th) 2 pattern of cytokine secretion (increased levels of interleukin [IL]-4 and/or IL-13 and decreased levels of interferon-gamma) as well as the typical Th2-type chemokine receptor CCR4, specific to the thymus and activation-regulated chemokines. Keratinocytes from patients with atopic dermatitis produce thymic stromal lymphopoietin, a novel cytokine that supports the early lymphocyte development in mouse models, and activates dendritic cells involved in the pathogenesis of allergic diseases in humans. Increased levels of circulating hemopoietic precursor cells have been reported in atopic dermatitis, as in allergic asthma and rhinitis. Furthermore, the recognition of CD34+ hemopoietic precursor cells, and evidence for cellular differentiation/maturational events occurring within atopic dermatitis skin lesion infiltrates, are consistent with the recent reinterpretation of the Th2/Th1 paradigm, where Th2 cells appear to belong to the early stages and Th1 to the ultimate stages of a linear, rather than divergent, pattern of lymphoid differentiation. This more detailed understanding of the immunologic derangements contributing to the atopic dermatitis pathogenesis has led to growing interest in allergen-specific immunotherapy for the disease. Due to the complexity intrinsic to atopic dermatitis and the lack of consensus-based guidelines for standardized outcome measure, only eight studies are available in the literature for a qualitative evaluation of this treatment approach. Two of these studies were double blind and placebo controlled, and six were cohort studies. Immunotherapy was found to be effective in one controlled study and five observational reports. Uncertain results were provided by one low-powered, controlled study, and negative outcomes were raised by a unique study performed with oral immunotherapy, which is not an effective route of mucosal allergen administration. Thus, more efficacy studies are required before immunotherapy could be recommended for the routine treatment of atopic dermatitis. Allergen-specific sublingual immunotherapy, given its excellent safety profile and ability to interfere with the systemic aspects of allergic inflammation, appears a good potential candidate for the pathogenetic treatment of the disease.

Administration, Sublingual↗

PubMed1985

The subclass nature and clinical significance of the IgG antibody response in patients undergoing allergen-specific immunotherapy.

The purpose of this paper is to discuss the methodological difficulties in quantitation of human IgG subclass antibodies to allergens, to describe the subclass nature of the IgG antibody response in patients undergoing allergen-specific immunotherapy, and to discuss the possible immunological functions and clinical significance of allergen-specific IgG antibodies of different subclasses. Based on results obtained by use of assays with documented specificity it is concluded that the IgG antibody response during allergen-specific immunotherapy is IgG1 and IgG4 restricted, although low levels of IgG2 and IgG3 antibodies to some allergens may occur. In most patients the early IgG antibody response is IgG1 dominated and the late IgG4 dominated. A too early or too pronounced IgG4 dominated antibody response seems to indicate a poor clinical outcome of immunotherapy with inhalant allergens, whereas a pronounced early IgG1 antibody production has been found to be associated with a decrease in synthesis of IgE antibodies to an insect venom. It is therefore proposed that an early IgG1 dominated response is necessary to induce suppression of the ongoing IgE antibody production, which in its turn may be a prerequisite for long-lasting clinical effect. The possibility of induction of an early IgG1 dominated response in every patient by use of alternative immunotherapy procedures is discussed.

Allergens↗

PubMed1986

[Mites: the principal respiratory allergens of house dust].

The Mites are the most frequent of the lung allergens. Three families have a prime importance. The Pyroglyphidae (of which Dermatophagoides pteronyssinus, Dermatophagoides farinae and Euroglyphus maynei are a part), the Acaridae and the Glyciphagidae which comprise the stock acariens responsible for certain occupational asthmas. After the discovery of the role of mites in respiratory allergy numerous studies have specified the ecological conditions favourable to their development (temperature, relative humidity, the nutritional environment) and have emphasised the beneficial role of altitude and the importance of the characteristics of the habitat. Another avenue of research consists in culture of the acariens, to isolate by immunological chemical purification techniques the glycoproteins responsible to their allergic activity, The studies led to the identification of the major allergens most frequently responsible for sensitizing man. Thus for Dermatophagoides pteronyssinus two major allergens have been identified by different teams. Certain common allergens in different species explain the crossed sensitivity which are frequently observed. One of the major allergens of Dermatophagoides pteronyssinus, the allergen P, is contained in faecal particles of the acariens. These particles are identified in the domestic environment and are easily made into a suspension by normal household activities. Current preventative methods are orientated towards the effect of exclusion of the acariens on the respiratory symptomatology. The diminution of the mite numbers, a reduced frequency of crisis after complete eviction of the allergens from the home and diminished bronchial reactivity to pharmacological mediators after very prolonged eviction. The use of acaricides or of fungicides would merit more numerous controlled studies with a view to showing their efficacy on the respiratory symptomatology of sensitive subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Allergens↗

PubMed1999

[Therapeutic measures for anaphylactic reactions in the course of allergen-specific immunotherapy].

Allergologic emergencies that are caused by an overwhelming immunologic systemic reaction during immunotherapy are guessed to occur in 1:1,000,000 to 1:100,000. These anaphylactic or anaphylactoid reactions are induced by the liberation of different mediators. The symptoms are determined by the kind, the quantity and the relation of these mediators and by the individual predisposition. In general, these symptoms can be detected on the skin, the lungs, the cardiovascular system and the gastrointestinal tract. The early treatment of circulatory and pulmonary disturbances is decisive for the prognosis of the patient. The severity of symptoms is graded from 1 to 4. An adequate therapy has to be given immediately according to the severity of the symptoms in a step-wise approach. Initially, an interruption of the allergen exposition is important, as is an oxygen supply and placement of intravenous accesses. In the specific drug-therapy a few substances have proved to be reliable. Catecholamines (adrenaline, dopamine, noradrenaline), histamine-antagonists, glucocorticosteroids, theophylline and volume substitutes belong to this group, but not the intravenous application of calcium.

Anaphylaxis↗

PubMed2005

Comparison of 2 maintenance doses (100 microg vs 200 microg) in Hymenoptera venom immunotherapy: influence of the maintenance dose on the immunologic response.

BACKGROUND: In Hymenoptera venom immunotherapy, the maintenance dose is usually 100 microg. However, persistent systemic reactions to sting challenges could be treated by an increase in the maintenance dose to 200 microg with success, suggesting greater efficiency. OBJECTIVE: To compare the effects of 2 monthly maintenance doses (100 microg vs 200 microg) on skin test sensitivity and venom specific IgE antibody levels. METHODS: Twenty-two patients receiving Vespula venom immunotherapy were enrolled in this retrospective study. After rush therapy, the 100-microg maintenance dose initially administered was maintained (group 1, n = 13) or was increased to 200 microg (group 2, n = 9). RESULTS: Levels of venom specific IgE antibody and skin test results measured before the onset of immunotherapy were comparable in both groups. Unlike in group 1, a maintenance dose of 200 microg resulted in significant decreases in venom specific IgE antibody levels and skin test sensitivity. CONCLUSIONS: Increasing the monthly maintenance dose to 200 microg results in a greater degree of change in venom specific IgE antibody levels and skin test sensitivity than when maintaining a 100-microg dose. Our data strengthen those of previous clinical studies showing the usefulness of a 200-microg maintenance dose in the case of clinical failure of a 100-microg dose.

Adult↗

PubMed1997

Pharmacokinetics of allergens after local administration.

The authors review the status of knowledge on absorption and kinetic of allergens administered on nasal mucosa. Intranasal administration is well known in pharmacology, and has been used for a long time for peptide drugs, mainly hormones. The immunological response to intranasally administered antigens have been studied in some experimental models: bovine Rnase, dextran, KLH, tetanus toxoid. These studies showed in atopic people a greater absorption of antigens by nasal mucosa compared to normal individuals, a difference that might be of importance in the pathogenesis of atopic diseases. The absorption rate of peptides through nasal mucosa has been studied biologically by PK-test with Rnase and peanut allergen, and a consistent passage of intact molecules has been observed. Using as tracer 125I-labelled human albumin, transport across the nasal mucosa has been demonstrated in 3/9 normal subjects, 1/9 patients with extrinsic asthma and 9/10 patients with atopic rhinitis. In experimental animals (rabbits) the passage of allergens through the nasal mucosa has been confirmed using 125I-labelled Parietaria allergens that showed a peak in the bloodstream 60 min after administration. It is concluded that peptide molecules such as allergens can be absorbed through the nasal mucosa and reach the bloodstream, and that in atopic patients nasal permeability is enhanced.

Administration, Intranasal↗

PubMed1989

Survey of whole body-extract immunotherapy for imported fire ant- and other hymenoptera-sting allergy. Report of the Fire Ant Subcommittee of the American Academy of Allergy and Immunology.

A survey of 5300 allergists was conducted to determine the number and geographic distribution of patients receiving immunotherapy for imported fire ant (IFA) allergy in the United States and Canada. Responses were received from 1293 physicians who reported a total of 2573 patients being treated in 28 states. Most patients were from the southeast, but some patients were reported to be receiving IFA immunotherapy in areas outside the boundaries of known IFA infestation. Although IFA is a widespread health hazard in the southeast, it appears to exert an uneven impact on allergy practice in this region. Of the 1293 physicians responding to the survey, 117 (9%) reported the use of whole body extract (WBE) in the treatment of 1746 patients with winged Hymenoptera-sting allergy. Continued use of WBE immunotherapy was reported by physicians from all regions of the United States and from Canada. The largest numbers of patients receiving winged WBE immunotherapy were reported from Texas (641), Pennsylvania (246), Florida (129), and Canada (127). The results of this survey suggest a need for continuing medical education regarding (1) the magnitude of the health hazard posed by the IFA and (2) the efficacy of venom versus WBE in the treatment of winged Hymenoptera-sting allergy.

Animals↗

PubMed2001

Case report of venom immunotherapy for a patient with large local reactions.

BACKGROUND: Inadvertent Hymenoptera stings reportedly elicit large local reactions in up to 17% of the general population. Current practice parameters do not recommend venom immunotherapy (IT) for these cases. OBJECTIVE: The goal of this case study was to investigate the clinical and immunologic consequences of venom IT in a newly sensitized individual with large local reactions using an intentional sting challenge before and after treatment to document changes in reaction severity. METHODS: A 47-year-old man became honeybee venom (HBV)-allergic with progressively larger reactions at honeybee sting sites with subsequent stings. Then, a sting on his forefinger produced a large (62 cm) local reaction with swelling throughout the arm that persisted for more than 4 weeks with severe pain. He refused steroid therapy and voluntarily requested venom IT with honeybee-sting challenges to monitor clinical parameters and immunologic changes in his skin and serum before and 7 months post-HBV maintenance IT. RESULTS: A single pre-IT bee sting challenge produced an 11.4-cm wheal with 13-cm erythema at the sting site after 15 minutes, followed by several weeks of edema that involved the entire arm. After rapid escalation of venom IT to maintenance in 7 weeks, a post-maintenance IT sting challenge with two honeybees produced a 3-cm diameter erythema with no wheal at 15 minutes and no late-phase induration. Complete loss of any visible reaction at the field sting site resulted after 13 months of maintenance venom IT. A HBV-specific IgG antibody level >3.5 microg/mL and IgG/IgE antibody molar ratio >500 persisted over the period of venom IT, with venom skin reactivity diminishing 100-fold. CONCLUSIONS: These results support venom IT use in the treatment of Hymenoptera venom-sensitive individuals who experience large local reactions and are at risk for repetitive inadvertent stings.

Bee Venoms↗

PubMed1997

Long-term follow-up of nasal immunotherapy to Parietaria: clinical and local immunological effects.

BACKGROUND: Local nasal immunotherapy (LNIT) with extracts in powder has been demonstrated clinically effective and devoid of side-effects in several controlled trials; nevertheless, no data concerning the long-term effects of LNIT are presently available. METHODS: In a recent double-blind, placebo-controlled study of LNIT to Parietaria pollen we observed, by means of specific nasal provocation test (SNPT) that LNIT is able to modify the local allergic inflammatory response. In the present study we followed up the same patients in open fashion for 2 further years. RESULTS: The results confirmed the clinical efficacy of LNIT and showed that it is strictly dependent on pre-seasonal administration: in fact, after LNIT discontinuation a clinical relapse was observed. A certain long-lasting protective effect on SNPT parameters (nasal symptoms and neutrophils infiltration) was also observed, whereas an increase of eosinophils count and ICAM-1 expression on nasal epithelial cells appeared as possible markers of clinical relapse. CONCLUSION: The present study suggests that pre-seasonal LNIT can be taken in consideration in selected subjects as prophylactic treatment for pollen-induced rhinitis. In addition, the results obtained provide informations about the duration of clinical efficacy and add data about the local allergic inflammation and its modulation.

Administration, Intranasal↗

PubMed1992

Clinical and immunological effects of immunotherapy with alum-absorbed grass allergoid in grass-pollen-induced hay fever.

A double-blind, placebo-controlled study of immunotherapy was conducted in 19 patients with grass-pollen hay fever to evaluate the efficacy and safety of a formalinized depot grass allergoid. The patients were assessed before and during IT by clinical (symptom-medication scores during the grass- pollen season, specific nasal and skin reactivity) and immunological (specific IgE, IgG, IgG1 and IgG4 antibodies) parameters. High doses of grass allergoid, corresponding to a cumulative pre-seasonal dosage of 46,050 PNU, were administered, with only one systemic reaction. The actively treated patients had significantly lower symptom-medication scores than placebo (p less than 0.01) during the month of May and showed a significant decrease in specific skin (p less than 0.01) and nasal (p less than 0.05) reactivity, and a significant early increase in specific IgE (p less than 0.01), IgG (p less than 0.0005), IgG1 (p less than 0.001) and IgG4 (p less than 0.05), with a subsequent decrease of IgE and IgG1. No differences were detected in any of these parameters in the placebo group. A correlation was found between high IgG4/IgG1 ratio and the specific skin reactivity decrease (r = 0.691, p less than 0.05), whereas a high IgG4/IgG1 ratio was associated with higher symptom-medication scores (r = 0.654, p less than 0.05). Possible explanations of these apparent discrepancies are proposed.

Adolescent↗