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PubMed1998

Immunologic changes during immunotherapy in asthmatic children: increased IL-13 and allergen-specific IgG4 antibody levels.

BACKGROUND: The prevalence of allergic diseases such as asthma, allergic rhinitis, and atopic diseases has increased in recent years. Immunotherapy with allergens is a treatment documented to have an effect on regulating cytokine production and allergen-specific antibody production. OBJECTIVE: The aim of this study was to further investigate immunologic changes during immunotherapy and to explore the possible more efficient approach of immunotherapy. METHODS: Asthmatic children receiving house dust mite immunotherapy were followed to learn immunologic parameters such as allergen-specific antibody levels, proliferative response of peripheral blood mononuclear cells, and cytokine change during immunotherapy. RESULTS: The data suggested (1) IgG4 anti-mite antibody increased 8 months after immunotherapy while IgE antibody level remained the same; (2) allergen-induced, in vitro production of certain cytokines such as IL-4 and IL-10 decreased after immunotherapy; (3) IL-13 (which can induce IgG4 and IgE antibody production by B cells) increased after immunotherapy. CONCLUSION: Although this needs more study, IL-13 might play an important role in the generation of IgG4-blocking antibody during immunotherapy.

Adolescent↗
PubMed1998

Evolution of lymphocyte transformation to wasp venom antigen during immunotherapy for wasp venom anaphylaxis.

BACKGROUND: Venom immunotherapy (VIT) has proven to be safe and effective in wasp venom anaphylaxis. However, there are no good parameters to indicate when to stop venom immunotherapy. OBJECTIVE: To evaluate the relationship of the lymphocyte transformation test (LTT) to history and specific IgE determination, and to address the time course of lymphocyte transformation responses to wasp (Vespula) venom during VIT and the possible utility of LTT to determine the duration of therapy. METHODS: Peripheral blood mononuclear cells (PBMCs) of 18 individuals with a history of wasp sting anaphylaxis and a positive serum-venom-specific IgE, were stimulated with wasp venom before immunotherapy, at the end of a 5-day semi-rush immunotherapy and at 24 months during venom immunotherapy. Results, expressed as stimulation index (SI), were compared with the SI in seven asymptomatic stung controls. RESULTS: In controls the median (minimum-maximum) of the SI were 2.39 (0.52-3.39) before therapy and 2.39 (1.12-6.02) when repeated after 24 months. For patients the median (minimum-maximum) of the SI were 10.13 (1.19-44.88) before immunotherapy (d0), 2.73 (0.67-12.03) at the end of the build-up immunotherapy (d5) and 4.21 (0.88-14.66) at the end of 24 months of maintenance therapy (m24). The proliferation responses in vespid-allergic patients were significantly higher than in stung controls (P = 0.006) but only 13/18 patients showed a positive LTT result before the start of immunotherapy (sensitivity of the LTT 72%). When the LTT was repeated after a 5 day build-up hyposensitization course the SI significantly dropped as compared to the pre-treatment levels (P = 0.002). The SI of the LTT was negative in eight out of 18 patients at 24 months and the median values were significantly lower than before therapy (P = 0.03). CONCLUSIONS: Although, in the absence of sting challenge data it is not possible to draw conclusions about the predictive value of the LTT, our data may suggest that abolition of the LTT during VIT might indicate clinical insensitivity. Further studies, comparing the results of sting challenges, with the results of lymphocyte transformation will be necessary in order to evaluate the role of LTT in stopping immunotherapy.

Adolescent↗
PubMed1997

IL-5 production by allergen-stimulated T cells following grass pollen immunotherapy for seasonal allergic rhinitis.

Grass pollen immunotherapy for the treatment of seasonal allergic rhinitis ('summer hayfever') results in improvement in symptoms, a reduction in the early and late phase responses to allergen provocation and decreased tissue eosinophilia. Immunotherapy may act by altering the pattern of cytokine production by allergen-specific T cells from a 'Th2-type' (IL-4 and IL-5) profile to a 'Th1-type' (interferon-gamma (IFN-gamma)) profile. We set out to determine whether clinical improvement following specific allergen immunotherapy is accompanied by reduced production of the pro-eosinophilic and archetypal 'Th2-type' cytokine, IL-5. Peripheral blood mononuclear cells (PBMC) were isolated from (i) 13 patients who had received 6 or 7 years' continuous conventional immunotherapy with timothy grass pollen (Phleum pratense); (ii) 14 patients who had received 3 or 4 years of conventional immunotherapy followed by 3 years of placebo treatment; (iii) 12 matched seasonal rhinitic patients who had never received immunotherapy; and (iv) 17 non-atopic normal controls. PBMC were stimulated with 20 microg/ml and 200 microg/ml P. pratense extract, or 10 microg/ml of Mycobacterium tuberculosis purified protein derivative (PPD), at 2 x 10(6) cells/ml and 5 x 10(6) cells/ml. IL-5 concentrations in culture supernatants collected after 6 days' culture were measured by ELISA. IL-5 production in response to stimulation with P. pratense extract was highly reproducible and was elevated in both of the immunotherapy treated groups and the untreated rhinitics relative to non-atopic controls (P<0.005 for each group relative to non-atopic controls, under each of the four conditions tested). However, no significant reduction was observed in IL-5 production when immunotherapy treated patients were compared with untreated rhinitic controls. Moreover, abrogation of the cutaneous late-phase responses to allergen following treatment was not associated with reduced IL-5 production by allergen-stimulated peripheral blood T cells. Reduced IL-5 production by peripheral blood T cells may not be necessary for immunotherapy to be effective. Local immunodulation of T cell responses may play a role in this form of treatment.

Adult↗
PubMed1997

The effect of immunotherapy on the serum levels of eosinophil cationic protein in seasonal allergic rhinitis.

The role of serum eosinophil cationic protein levels in allergic rhinitis is controversial. It is also unclear whether with immunotherapy it is possible to reduce these serum levels in allergic diseases. We studied serum eosinophil cationic protein levels in patients with cedar-induced allergic rhinitis and compared them with non-atopic controls. The second aim of this study was to elucidate whether immunotherapy is capable of decreasing the seasonal elevation in serum eosinophil cationic protein levels in seasonal allergic rhinitis. The serum eosinophil cationic protein levels of the untreated patient group were significantly higher than those of the non-atopic controls. The levels in patients who received immunotherapy for 2 yr were also significantly higher than those of the non-atopic controls. However, the levels were not different between the patients undergoing immunotherapy for over 3 yr and the non-atopic controls. The serum levels of the 31 patients treated with immunotherapy correlated with the duration of immunotherapy. In conclusion, the serum eosinophil cationic protein levels are higher in untreated patients with seasonal allergic rhinitis and this seasonal activation in circulating eosiohophils decreases gradually during immunotherapy, but this inhibitory effect becomes apparent only after a number of years of immunotherapy. This prevention of seasonal eosinophil activation is one of the mechanisms responsible for the clinical effect of immunotherapy.

Adolescent↗
PubMed1999

Long-term clinical efficacy of grass-pollen immunotherapy.

BACKGROUND: Pollen immunotherapy is effective in selected patients with IgE-mediated seasonal allergic rhinitis, although it is questionable whether there is long-term benefit after the discontinuation of treatment. METHODS: We conducted a randomized, double-blind, placebo-controlled trial of the discontinuation of immunotherapy for grass-pollen allergy in patients in whom three to four years of this treatment had previously been shown to be effective. During the three years of this trial, primary outcome measures were scores for seasonal symptoms and the use of rescue medication. Objective measures included the immediate conjunctival response and the immediate and late skin responses to allergen challenge. Cutaneous-biopsy specimens obtained 24 hours after intradermal allergen challenge were examined for T-cell infiltration and the presence of cytokine-producing T helper cells (TH2 cells) (as evidenced by the presence of interleukin-4 messenger RNA). A matched group of patients with hay fever who had not received immunotherapy was followed as a control for the natural course of the disease. RESULTS: Scores for seasonal symptoms and the use of rescue antiallergic medication, which included short courses of prednisolone, remained low after the discontinuation of immunotherapy, and there was no significant difference between patients who continued immunotherapy and those who discontinued it. Symptom scores in both treatment groups (median areas under the curve in 1995, 921 for continuation of immunotherapy and 504 for discontinuation of immunotherapy; P=0.60) were markedly lower than those in the group that had not received immunotherapy (median value in 1995, 2863). Although there was a tendency for immediate sensitivity to allergen to return late after discontinuation, there was a sustained reduction in the late skin response and associated CD3+ T-cell infiltration and interleukin-4 messenger RNA expression. CONCLUSIONS: Immunotherapy for grass-pollen allergy for three to four years induces prolonged clinical remission accompanied by a persistent alteration in immunologic reactivity.

Adult↗
PubMed1995

The role of immunotherapy in pediatric allergic disease.

Knowledge of the mechanisms of immunotherapy has increased substantially in recent years. The development of better extracts for both injection immunotherapy and local immunotherapy continues, and techniques for the production of recombinant allergens and peptides will be important for future vaccines. Immunotherapy with conventional commercially available extracts is best documented in childhood pollen allergy and is useful in children with severe hay fever symptoms or seasonal asthma. Immunotherapy for perennial allergy has so far been most beneficial in dust mite- and cat-allergic children with asthma. Dust mite therapy is most efficacious in children with isolated dust mite allergy. Appropriate environmental measures should, however, precede immunotherapy when possible. Recent data indicate that immunotherapy has no additional benefit in children with multiple allergies and asthma who receive optimal pharmacotherapy. It is therefore preferable that immunotherapy be combined with anti-inflammatory drug therapy in most children with asthma. For safety reasons, it is important that immunotherapy be administered by physicians well acquainted with standardized extracts in a clinic or hospital where treatment for systemic reactions is available. Long-term treatment for 3 to 5 years results in a more sustained effect than short-term therapy.

Child↗
PubMed2004

Comparison of the clinical efficacy and safety of subcutaneous and sublingual immunotherapy: methodological approaches and experimental results.

PURPOSE OF REVIEW: Sublingual immunotherapy has been documented as clinically effective in controlled studies. Some concerns about the magnitude of disease severity reduction in relation to standard subcutaneous immunotherapy have been raised. The comparison with subcutaneous immunotherapy is important for giving recommendations on the use of sublingual immunotherapy in daily clinical practice. RECENT FINDINGS: Only three controlled comparative studies of sublingual and subcutaneous immunotherapy have been published. The methodology of the studies indicated that some study design deficiencies limited the interpretation of efficacy. Only one study used an optimal placebo-controlled, double-blind, double-dummy and randomized design. The studies are assessed with respect to a sufficient number of patients to detect statistically possible differences, the inclusion of patients, clearly defined outcome measures, doses of extract administered, and duration of treatment. In all three studies the reduction in disease severity was of the order of 50% with no significant difference between the two treatments. SUMMARY: The clinical efficacy of sublingual immunotherapy is based on three studies only, and a limited number of patients equal to the efficacy obtained by subcutaneous immunotherapy. Only limited information on long-term efficacy and preventative capacity are available. More data on these aspects are needed, but the restraint in using sublingual immunotherapy in the treatment strategy of allergic diseases does not seem to be evidence based. Future research should also focus on identifying which subsets of patients would most benefit from either of the two routes of immunotherapy administration.

Administration, Sublingual↗
PubMed1991

A computational approach to the description of individual immune responses. IgE and IgG-subclass allergen-specific antibodies formed during immunotherapy.

Detailed evaluation of the IgE and IgG-subclass immune response during immunotherapy can now be performed by crossed radio immunoelectrophoresis (CRIE). Some new concepts are introduced facilitating the handling of the vast amount of data obtained by quantitating the immune response. These concepts are "distance" between antibody responses and "immune response width". The 20 patients included in this study were pollen-allergic patients who underwent specific immunotherapy in a 3-year prospective study. It was found that the immune response during immunotherapy was restricted to IgG1 and IgG4 antibodies. The semi-quantitative CRIE analysis correlated with the RAST analysis for the IgE samples before start of immunotherapy, for the IgG1 samples at week 12, and for all the IgG4 samples. During immunotherapy the number of IgG1 antibodies directed to the different antigens increased towards 11 antigens and decreased towards six. For the IgG4 antibodies the number of reactions increased towards 15 antigens and decreased towards four. The increase is generally paralleled by an increase in quantitative immune response as well. For some of the antigens a rise in the IgE antibodies is contrasted by a fall in the IgG4 antibody response, and for other antigens the opposite was true, indicating a regulatory mechanism between the IgE and the IgG4 synthesis. The IgE immune response to a number of antigens, including the major allergens before the start of immunotherapy, was quantitatively diminished during the period of immunotherapy when IgG1 was present early (week 12) in the period, and for other antigens there was a rise in IgE without an early IgG1 antibody response. This suggests that IgG1 can have a regulating influence on the IgE synthesis. Finally, we have found that IgE antibodies with specificities not present in the samples taken before immunotherapy were formed during immunotherapy. These new IgE antibodies do not, however, seem to impair the outcome of treatment.

Antigens↗
PubMed2005

Allergy immunotherapy as an early intervention in patients with child-onset atopic asthma.

BACKGROUND: In patients with bronchial asthma an effective treatment is required at early stages of the disease to prevent irreversible structural changes of the airways. The objective of this study was to evaluate the beneficial effects of our routine immunotherapy as an early intervention on FEV1 in patients with child-onset atopic asthma. METHODS: Beneficial effects of successful immunotherapy on FEV1 were analyzed retrospectively in 43 unselected patients who received our routine standard subcutaneous immunotherapy with periodic FEV1 measurements and became asymptomatic. RESULTS: Although there was no significant correlation between the duration of asthma symptoms prior to immunotherapy and the changes in FEV1 before and after immunotherapy in 43 unselected patients, there was a significant inverse correlation between these two parameters in 23 patients whose asthma duration was less than 20 years. As the FEV1 increased after immunotherapy in all 14 patients whose asthma duration was less than 5 years, the 43 patients were divided into a group 1 including these 14 patients and a group 2 including 29 patients whose asthma duration was more than 5 years. The FEV1 decreased in 7 of the 29 asymptomatic patients in group 2. There was no difference in the initial FEV1 between the two groups, but the final FEV1 and the mean of the average increase in FEV1 per year by immunotherapy were significantly higher in group 1 than in group 2. CONCLUSIONS: Immunotherapy should be started as early as possible at the youngest age in order to increase a beneficial effect of successful immunotherapy on FEV1 improvement.

Administration, Cutaneous↗
PubMed2002

Immunotherapy in autoimmune diseases.

Immunotherapy has the potential to modify or re-balance the immune system and hence useful in the management of autoimmune conditions. This article aims to review clinically useful immunotherapies available for treatment of autoimmune conditions, with particular emphasis on Type I diabetes mellitus, multiple sclerosis, rheumatoid arthritis and systemic lupus erythematosus. A Medline search for the period 1992 to 2002 (10 years) using the unrestricted keywords "immunotherapy AND autoimmune" was done. Full-length articles were selected for reviews based on the contents of their published abstracts. Additional Medline searches were focussed on the keywords "immunotherapy AND diabetes mellitus", "immunotherapy AND multiple sclerosis", "immunotherapy AND rheumatoid arthritis", and "immunotherapy AND systemic lupus erythematosus". Relevant publications referenced in the reviewed literature were further included for review, if not present in the original Medline search. Immunotherapy in Type I diabetes mellitus has focussed on the induction of tolerance to beta cell antigens, and in multiple sclerosis trials of anti-alpha 4 integrins and altered peptide ligand of myelin basic protein (MBP 83-99) showed initial promising results. The use of anti-cytokine therapy (anti-TNF alpha and IL-1Ra) in rheumatoid arthritis has improved the quality of life of patients with refractory disease. The use of anti-CD20 monoclonal antibody for in vivo B cells depletion and early trials of autologous peripheral stem cell transplants represent additional immunomodulatory treatment modalities for systemic lupus erythematosus patients. Better understanding of autoimmune conditions and advances in the production of humanized monoclonal antibodies, promises better immunotherapy in the near future.

Arthritis, Rheumatoid↗
PubMed1992

Experience with RAST-based immunotherapy.

During its 80 year history, allergen immunotherapy has been used essentially as Noon and other early investigators described it. Immunotherapy is practiced mainly as an art based on uncontrolled clinical observations of individual patients treated in private practice. Dosing schedules and skin test interpretations are based primarily on the biases of the treating physicians. In an effort to improve the results obtained from immunotherapy, different approaches have evolved. Serial dilution skin endpoint titration (SET), practiced mostly by otolaryngologists, became popularized in the 1960s out of the need to optimize immunotherapy dosing regimens. SET can be viewed as a forward step in the direction of more aggressive yet safe initial immunotherapy doses. With the discovery of IgE in 1966 as the prime carrier of reaginic hypersensitivity in humans came the availability of a remarkable set of in vitro assays for the measurement of total and allergen-specific IgE reactivity. The radioallergosorbent test (RAST), which has been shown to correlate reliably with the major variants of the atopic state, was modified in 1977 in such a way as to enhance the sensitivity of the assay with minimal alteration of specificity. The modified RAST (MRT) has been carefully investigated and has shown reliable concordance with the major parameters of clinical allergy. Since its development only 14 years ago, the MRT has become a dependable adjunct for the determination of initial and in many cases final immunotherapy doses. An important contribution of RAST-based immunotherapy is that only patients with quantifiable serum titers of allergen-specific IgE qualify as candidates for immunotherapy. The fact that fewer allergens are used for treatment at higher initial doses and that potential reactors are identified before starting therapy are yet other advantages of RAST-based immunotherapy. The use of RAST as a method of allergen standardization only reinforces its value in patient management.

Allergens↗
PubMed1996

Risk management in allergen immunotherapy.

The major risk of allergen immunotherapy is the development of systemic anaphylactic reactions. The reported frequency of systemic reactions after allergen immunotherapy varies from < 1% in patients receiving conventional immunotherapy to > 36% in patients receiving rush immunotherapy. Fatal and systemic reactions to allergen immunotherapy have similar characteristics. The onset of both types of reaction occurs < 30 minutes after injection in approximately 70% of patients. The most common risk factors for fatal and systemic reactions to allergen immunotherapy include a history of asthma, increasing allergen dose, high allergen sensitivity, previous systemic reaction, and injection during an active allergen season. On the basis of findings from several studies, precautions during allergen immunotherapy have been recommended. In addition, several interventions, including premedication with antihistamines or corticosteroids, measurement of peak flow before injection, and access to an antihistamine or injectable epinephrine after an allergen injection, have been suggested as measures to prevent reactions to and improve the safety of allergen immunotherapy. However, additional studies are necessary before these regimens are implemented routinely in allergen immunotherapy protocols.

Allergens↗
PubMed2005

The effects of allergen-specific immunotherapy on polymorphonuclear leukocyte functions in patients with seasonal allergic rhinitis.

Immunotherapy plays an important role in the therapy of allergic rhinitis and bronchial asthma. However, there is not much information about the effects of allergen-specific immunotherapy (SIT) on the polymorphonuclear leukocyte functions. The aim of this study was to investigate the effects of specific immunotherapy on phagocytic and intracellular killing activities of polymorphonuclear leukocytes (PMN) derived from patients with seasonal allergic rhinitis. Twenty-four patients with seasonal allergic rhinitis documented to be sensitive to grass pollen were included in this study. Patients were divided into 3 groups. Group 1 (n=7) received conventional immunotherapy whereas patients in Group 2 (n=7) were treated with short-term immunotherapy and the third group (n=10) were given placebo during the study process. Both phagocytic and intracellular killing activities were significantly increased (p=0.002, p<0.0001, respectively) by conventional immunotherapy when compared to the first determination. In the short-term immunotherapy group, phagocytic activity was increased very significantly (p=0.0001), whereas intracellular killing activity was not affected (p=0.252). There were no changes in these parameters in the placebo group. These results suggest that allergen-specific immunotherapy has an enhancing effect on PMNs functions in the patients with seasonal allergic rhinitis. It should be clarified by further studies whether this enhancement might be considered as another beneficial effect of the immunotherapy.

Adult↗
PubMed2004

Allergen immunotherapy induces a suppressive memory response mediated by IL-10 in a mouse asthma model.

BACKGROUND: Human studies have demonstrated that allergen immunotherapy induces memory suppressive responses and IL-10 production by allergen-specific T cells. Previously, we established a mouse model in which allergen immunotherapy was effective in the suppression of allergen-induced asthma manifestations. OBJECTIVE: In this study, we examined whether immunotherapy induces a long-lasting effect and investigated the role of IL-10 in successful immunotherapy. METHODS: Ovalbumin-sensitized BALB/c mice were treated with 3 injections of ovalbumin (1 mg, subcutaneous) on alternate days. After a short interval (1 week) and after a long interval (5 weeks), mice were challenged by ovalbumin inhalation, and subsequently, airway reactivity, airway eosinophilia, ovalbumin-specific IgE, and T(H)2 cytokine profile were measured. Flow cytometry and blocking of IL-10 receptors in vivo were used to gain insight in the role of IL-10 in the beneficial effects of allergen immunotherapy. RESULTS: After a long interval between ovalbumin immunotherapy and ovalbumin challenge, the development of airway eosinophilia and hyperresponsiveness to methacholine were as strongly suppressed as after a short interval. These suppressive effects coincided with significantly reduced serum ovalbumin-specific IgE levels and T(H)2 cytokine production. On immunotherapy, the IL-5:IL-10 ratio in the bronchoalveolar lavage fluid shifted toward IL-10. In ovalbumin-restimulated lung cell and thoracic lymph node cultures from these mice, IL-5 levels dramatically decreased, whereas the percentage of IL-10(+)CD4(+) T cells was not affected. Finally, in mice treated with mAb against IL-10 receptors, the beneficial effects of immunotherapy were largely abrogated. CONCLUSION: These data demonstrate that allergen immunotherapy induces a memory suppressive effect in which IL-10 is essential.

Animals↗
PubMed1999

Immunotherapy in children with allergic asthma: effect on bronchial hyperreactivity and pharmacotherapy.

BACKGROUND: Immunotherapy has been shown to reduce allergen sensitivity to allergens such as cat and dust mite. The aim of this study was to investigate the effect of cat or dust mite immunotherapy on bronchial hyperreactivity and the need for inhaled corticosteroids in children with asthma, cat or dust mite allergy, and hay fever. SUBJECTS: Twenty-nine children, 7 to 16 years old, completed the 3-year study. They were randomly allocated to receive cat/dust mite or placebo and birch/timothy immunotherapy. METHODS: Before immunotherapy was begun and then once each year, bronchial histamine challenges were performed. Bronchial allergen challenge with the perennial allergen was done before and after the 3-year study. Pharmacotherapy was given according to a standardized protocol. RESULTS: PC20 allergen increased significantly in both the active immunotherapy group (P <.001) and in the placebo-pollen group (P <.05). PC20 histamine increased continuously in the active immunotherapy group (P <.05 and P =.002 after 1 and 3 years, respectively) and had also increased after 3 years in the placebo-pollen group (P <.05). The difference between the 2 groups was significant for PC20 allergen (P =.001) but not for PC20 histamine. There was no significant change in the dose of inhaled budesonide needed for symptom control in either of the groups. CONCLUSION: Pollen immunotherapy combined with inhaled corticosteroids results in improvement of both cat/dust mite bronchial sensitivity and hyperresponsiveness to histamine. The combination of cat or dust mite, pollen immunotherapy, and inhaled budesonide enhances this improvement. Cat immunotherapy also induces cat allergen tolerance.

Adolescent↗
PubMed1999

Local and systemic immunotherapy in nasal allergy.

Two assays have been done to evaluate the effect of immunotherapy in nasal allergy. First, a trial of nasal immunotherapy and second, the study of mediator release after vaccines. Local immunotherapy, applied directly, triggers different response mechanisms. Specific nasal immunotherapy started before seasonal or perennial symptoms peak, has been done by increasing the doses of allergen three times a week during a 3-month period and a manutention period of a weekly nasal puff of the same allergen. Symptom scores and drug consumption have been registered. The results have been compared with the scores obtained in the same patients over the same period of the same year before immunotherapy. In perennial rhinitis blockage, rhinorrea, sneezing and itching scores all decreased. In seasonal rhinitis, a similar score decrease was obtained for blockage, rhinorrea, sneezing and itching. Pharmacological scores also decreased. These data point to a short-term effect of nasal immunotherapy. Tryptase release has been evaluated in nasal washings after nasal challenge with a Parietaria (Pellitory wall) extract before and after specific systemic immunotherapy, in order to evaluate changes in mast cells reactivity. Eight patients were studied, all allergic to Parietaria. Nasal provocation tests have been done before the season with increasing doses of 10, 100 and 1000 PNU and tryptase assayed in nasal washings at 10, 20 and 30 min after provocation. Immunotherapy decreased tryptase release after nasal challenge. The data point to the effect of systemic specific immunotherapy on mast cell reactivity.

Administration, Intranasal↗
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↗
PubMed2003

Induction of IL-10+CD4+CD25+ T cells by grass pollen immunotherapy.

BACKGROUND: Immunotherapy involves the modulation of allergen-specific T-cell responses, either T(H)2-to-T(H)1 immune deviation or, in bee venom-treated patients, induction of IL-10 production by CD4+CD25+ T cells. IL-10-producing CD4+CD25+ regulatory T cells have emerged as potential mediators of immune tolerance in numerous murine models of immunopathology. OBJECTIVE: The aim of this study was to evaluate the role of IL-10 production and CD4+CD25+ T cells in the response to grass pollen immunotherapy. METHODS: PBMCs were isolated from patients after 1 year of grass pollen immunotherapy and from matched untreated atopic and healthy control subjects. After 6 days of in vitro stimulation with Phleum pratense, production of IL-10, IL-5, IL-4, and IFN-gamma and proliferation and numbers of CD4+CD25+ T cells were measured. T cells were then stimulated for a further 5 hours with phorbol 12-myristate 13-acetate and ionomycin and assessed for intracellular IL-10 by means of flow cytometry. RESULTS: Patients undergoing immunotherapy produced significantly more IL-10 than atopic control subjects (patients undergoing immunotherapy, 116 +/- 21 pg/mL [n = 11]; atopic patients, 30 +/- 5 pg/mL [n = 11]; P <.001), and the number of CD4+CD25+ cells identified after allergen stimulation was also greater in the immunotherapy group. The numbers of CD4+CD25+ T cells correlated positively with activation as measured by proliferation in both of the control groups but not in the immunotherapy group. Moreover, only T cells from patients undergoing immunotherapy were positive for intracellular IL-10, and these were almost exclusively CD4+CD25+ cells. CONCLUSION: Grass pollen immunotherapy results in a population of circulating T cells that express the IL-10(+) CD4+CD25+ phenotype in response to allergen restimulation.

Adult↗