Hyposensitization Treatment Research Articles

Impact of nickel oral hyposensitization on quality of life in systemic nickel allergy syndrome.

Nickel (Ni) oral hyposensitization treatment (NiOHT) is an effective management approach for Ni allergy. No health-related quality of life (HRQoL) data exist for the pre- and post-treatment with NiOHT in systemic nickel allergy syndrome (SNAS). The aims of this study were (a) to explore HRQoL in SNAS patients, (b) to assess changes of HRQoL after 1 year of NiOHT; (c) to evaluate psychological status of patients. SNAS patients completed the Short-Form 36-Item Health Survey and Psychological General Well-Being Index before and 1 week after the end of NiOHT. Moreover, psychological state was assessed with the Minnesota Multiphasic Personality Inventory (MMPI-2). A total of 52 patients self-reported pre- and post-treatment questionnaires. HRQoL was poor at baseline. After 1 year of NiOHT, all outcome measure scores improved by about 20% with respect to baseline data (P < 0.01 for all indices, except depressed mood). Finally, 33 patients performed the MMPI-2. High rates for hypochondriasis and depression were noted. Furthermore, most of the patients had high scores for anxiety, depression, and health concerns. This is the first study showing that NiOHT improves HRQoL of SNAS patients, which can be considered a “personalized medicine” approach.

AS01-04 - Post orgasmic illness syndrome: indications for an auto-immune pathogenesis

Post-orgasmic unwell being denoted as postorgasmic illness syndrome (POIS) was for the first time reported by Waldinger and Schweitzer in 2002 [1]. Recently, Waldinger et al. investigated 45 Caucasian males with complaints of POIS and categorized their symptoms in 5 preliminary criteria [2,3]. POIS is characterized by local mucosal manifestations (nasal congestion, itching eyes), and systemic features (flu-like syndrome with feverishness, muscle tension, exhaustion, foggy head, concentration difficulties, and mood irritability), occurring within 30–60 minutes after ejaculation. The symptoms always starts off after ejaculation, often reaching its peak severity at the second day and gradually diminishes within 1–7 days [3]. Affected males usually try to avoid ejaculating by planning intercourse or by abstaining from sexual activity. Waldinger et al. showed that 88% of the males had a positive intracutaneous (IC) skin-prick test for autologous semen and postulated that POIS is an expression of an auto-immune process. Support for this hypothesis comes from positive effects of hyposensitization treatment with diluted autologous semen in two men with POIS.

Evaluation of two grass pollen extracts for immunotherapy by serum determinations of specific IgE and IgG4 antibodies towards purified Timothy grass pollen allergens (Phl p 1, 2, 4, 5, 6, 7, 11, 12) in patients undergoing hyposensitization treatment

The diagnosis of allergic diseases with recombinant allergens allows us to detect antibodies specific for single allergens in extracts. The aim of the present study was to assess the early effect of grass pollen immunotherapy on IgE and IgG4 responses to eight purified grass pollen allergens in patients undergoing hyposensitization treatment. The sera of 22 consecutive atopic individuals undergoing cluster regimen grass pollen immunotherapy were analyzed for IgE and IgG4 antibodies specific for grass pollen allergens (Phl p 1, 2, 4, 5, 6, 7, 11, 12). Two serum samples were taken, one before the start of therapy and one between 12 and 15 weeks after the first immunization. Immunotherapy was performed with two allergy vaccines comprising a standardized extract aluminum-adsorbed grass pollen mix and a standardized extract of grass pollen mix adsorbed onto calcium phosphate. One treated patient showed a specific IgE conversion from negative (< 0.35 kUA/L) to positive in the capsulated hydrophilic carrier polymer (CAP) test for Phl p 2, 1 and 4 (1.89, 0.84 and 0.68 kUA/L, respectively). The sera of 10 of 11 patients treated with alluminum-adsorbed grass pollen extract showed a significant increase in specific IgG4 towards natural Timothy grass pollen extract and purified allergens, as well as significant IgG4 levels towards Phl p 1 ( P = 0.000238) Phl p 2 ( P = 0.000289), Phl p 4 ( P = 0.000585), Phl p 5 ( P = 0.000364), Phl p 6 ( P = 0.000346) and Phl p 11 ( P = 0.039623; Mann–Whitney U-test) 12 weeks after the onset of immunotherapy. The sera of seven of 11 subjects treated with calcium phospate-adsorbed grass pollen extract had significant IgG4 levels against Timothy pollen allergens, as well as significant IgG4 titers against Phl p 1 ( P = 0.004703), Phl p 4 ( P = 0.000282), Phl p 5 ( P = 0.015480), Phl p 6 ( P = 0.013012) and Phl p 11 ( P = 0.005178). Patients treated with aluminum-adsorbed grass pollen extract had higher levels of IgG4 towards Phl p 2, 4 and 6 and natural Timothy grass extract compared with patients treated with calcium phosphate-adsorbed grass pollen extract. Both the alluminum-adsorbed and calcium phosphate-adsorbed grass pollen extract allergy vaccines induced significant titers of specific IgG4 towards Phleum pratense pollen extract ( P = 0.008376 and 0.01148, respectively). These results indicate that grass pollen immunotherapy elicits an array of antibody specificities that reflect the allergen content and the potency of allergen extracts; this could be of pivotal importance to define optimal allergen extract doses.

Evaluation of immunotherapy‐induced changes in specific IgE, IgG and IgG subclasses in birch pollen allergic patients by means of immunoblotting

Sera from 27 birch pollen-allergic patients who had undergone hyposensitization treatment for 22-41 months were studied by immunoblotting before and after therapy, whereby the levels of IgE, IgG and IgG1-4 antibodies directed against the major allergen Bet v I and minor allergens of birch pollen were monitored. The clinical benefit of immunotherapy (IT) was evaluated using a symptom specific questionnaire. In patients with good clinical response (responders, n = 18), as defined by improvement of symptoms, anti-Bet v I IgE antibodies were found to decrease in 10/18 patients (55.5%), whereas in 6/18 (33.3%) no change and in two cases (11.2%) an increase of specific IgE was observed. In the group of patients with unsatisfactory clinical outcome (non-responders, n = 9), 3/9 patients (33.3%) showed a decrease, 3/9 (33.3%) no change and 3/9 (33.3%) an increase in levels of IgE antibodies directed against Bet v I. In the case of minor allergens, 5/18 responders (27.7%) and 8/9 non-responders (88.8%) showed specific IgE before IT. In the responder group, no increase of specific IgE could be observed after IT. In non-responders, however, an increase of IgE directed against minor allergens was seen in 3/9 patients (33.3%). In all patients, regardless of therapeutical success, IT-induced elevated levels of specific IgG, IgG1 and in particular IgG4 directed against Bet v I were found. Regarding minor allergens, a heterogeneous pattern of IgG responses without significant correlation to clinical benefit was observed. Our results indicate that changes in IgG reactivity patterns against Bet v I and minor allergens, as shown by the immunoblot technique, did not correlate with good or bad clinical outcome.

Oxatomide and specific hyposensitization treatment for perennial nasal allergy in children

Oxatomide and specific hyposensitization treatment for perennial nasal allergy in children

Allergen immunotherapy with an immunochemically characterized grass pollen extract: change in follow-up sensitization parameters

A perennial hyposensitization treatment over 2 years was performed in 18 pollen-allergic patients (14 children, 4 adults) with a standardized and purified graspollen extract. The selection for therapy was provided by allergen titration in skin prick test, conjunctival test and by the estimation of specific IgE to timothy. The reported decrease of seasonal symptoms was accompanied by reduced sensitivity in skin test and conjunctival provocation test (p less than 0.001, p less than 0.05). No consistent change in specific IgE was observed at the end of the study. Specific IgG antibodies significantly rised and persisted (p less than 0.001). A successful hyposensitization treatment with graspollen could be monitored by in-vivo and in-vitro parameters.

Lymphocyte proliferative responses to the purified Dermatophagoides farinae major allergen in untreated and hyposensitized atopic patients.

We investigated the proliferative response of lymphocytes from mite-sensitive patients (RAST D.far greater than 3.5 PRU/ml) in the presence of the major allergen Der.f.I purified from Dermatophagoides farinae. Comparative studies were carried out with peripheral blood mononuclear cells from non-atopic donors (RAST = 0), and from patients undergoing hyposensitization treatment (5 to 24 months). According to Student's t-test, there was no significant difference in the Der.f.I-induced proliferation of peripheral blood mononuclear cells from normal donors, untreated atopic patients and hyposensitized patients. In conclusion, it was impossible to discriminate between normal donors, atopic patients and hyposensitized patients with regard to their circulating lymphocyte responses to the purified major allergen Der.f.I.

IgG4 antibodies in patients with atopic dermatitis.

The role of IgG4 in atopic dermatitis was investigated by determining the total amounts of IgG4 and of IgG4 specific for ovalbumin (a food allergen), Dermatophagoides farinae mite antigen and house dust (inhalant allergens) and Candida. These were related to the amounts of total and antigen specific IgE in patients with atopic dermatitis and normal healthy controls. Most patients with atopic dermatitis had greater amounts of total IgG4 and of antigen-specific IgG4 than did normal control individuals. Patients who had received hyposensitization treatment injections had greater amounts of IgG4 than the atopic dermatitis patients not so treated. In patients treated by hyposensitization there was a large increase in the amount of blocking antibody detected by incubating the antigen with the serum overnight before injecting the mixture into the skin of a patient sensitive to the antigen. Blocking activity was also examined by partial inhibition by the serum of IgE-mediated mast cell degranulation and by injection of serum into the skin of sensitive patients before challenge with antigens. In all tests the blocking activity of the serum was related to the amount of antigen-specific IgG4 but not related to total IgG4. In patients with atopic dermatitis who were sensitive to mite antigen, severe cases had small amounts of specific IgG4 and large amounts of specific IgE but in mild cases there was an opposite trend with relatively large amounts of specific IgG4. Large amounts of IgG4 ovalbumin specific antibody were found in children and adults with atopic dermatitis and egg allergy but small amounts of IgE. In infants most of the anti-ovalbumin antibody was IgE with little or no IgG4. The work of others has confirmed that increased amounts of total and antigen-specific IgG4 occur in atopic dermatitis, and it is concluded that IgG4 is a blocking antibody for anaphylactic sensitization responses.

SUBCLASS TYPING OF SPECIFIC IGG ANTIBODIES IN ALLERGEN IMMUNOTHERAPY

Allergen immunotherapy results in the production of allergen specific antibodies. We investigated whether antibody response in one or more of the four IgG subclasses may be correlated to the clinical improvement. 10 patients suffering from systemic reactions to bee stings were hyposensitized over 3 years. All patients tolerated a bee stingchallenge one, two, and 3 years after the start of treatment, and after bee venom immunotherapy was discontinued. Almost all of the IgG antibodies were restricted to IgG1 and IgG4 subclasses. Although both rose during treatment, IgG4 were maintained at high levels when immunotherapy was discontinued. In conclusion, in serum from normal individuals IgG1 is the predominant main protective antibody. IgG4 subclass specific antibodies appear as a result of a repeat antigenic stimulation as in allergen immunotherapy. Our findings of persisting clinical protection and IgG4 predominant immune response support the protective role of IgG4 in allergic individuals undergoing a venom hyposensitization treatment.

Discontinuation of bee venom immunotherapy in children and adolescents

Sixty-six patients with a history of systemic allergy reactions to bee stings, positive skin prick test to less than or equal to 100 micrograms/ml bee venom, and positive radioallergosorbent test (RAST) results were given venom immunotherapy. IgE and IgG antibodies to bee venom were measured by RAST and enzyme-linked immunosorbent test (ELISA), respectively. IgE and IgG anti-bee venom levels rose initially, but subsequently fell during immunotherapy. In 31 patients in whom specific IgE fell to low (less than 6% counts bound) or unmeasurable levels, immunotherapy was discontinued, and sting challenge was carried out 1 to 3 years later. All patients tolerated sting challenge well. The specific IgE and IgG antibody levels did not change significantly after treatment was stopped. Our data suggest that hyposensitization treatment can be stopped when specific IgE serum concentrations have fallen to low or unmeasurable levels and specific IgG antibody values are maintained, and that in a considerable number of patients venom immunotherapy has a lasting therapeutic and immunologic effect.

Effects of a beta-receptor blocking agent (propranolol) on synthesis of IgE in vitro by peripheral blood lymphocytes from atopic patients.

Peripheral blood lymphocytes from patients with atopy were studied for IgE production in vitro. Addition of a beta-receptor blocking agent (propranolol) to lymphocytes from 9 of 10 patients with low spontaneous IgE production in vitro caused increased IgE production. In 10 tests with lymphocytes from patients, who were undergoing hyposensitization treatment for cat epithelium and/or birch pollen allergy, no spontaneous in vitro production of the relevant antigen-specific IgE antibodies was detected. However, when propranolol was added to the lymphocyte cultures in vitro, production of antigen-specific IgE antibodies was found. No such production was found when lymphocytes from patients who were not allergic to either of these antigens were studied. Szentivanyi's theory of a partial blockade of beta-adrenergic receptors in atopy and a possible linkage between this theory and the hypotheses of disturbed regulatory functions in the immune system of patients with atopy is discussed.

Influence of preseasonal treatment with L-tyrosine-adsorbed allergoids on IgE-mediated histamine release from basophils of children suffering from allergic diseases.

In 10 children suffering from allergic pollinosis and/or asthma, a preseasonal hyposensitization scheme with 3 weekly injections of a glutaraldehyde-modified, tyrosine-adsorbed grass-pollen allergen reduced the histamine release from basophils in response to increasing concentrations of antigen. The decrease in histamine release which occurred 1 week after the injection course was even maintained during the pollen season. The inhibition was only obtained when basophils were incubated with the serum of patients, but not with the serum of normals, indicating that blocking antibodies may have occurred. In contrast to what has been observed in the treated patients' group, 5 patients, who were not included in the hyposensitization scheme, showed identical histamine release curves during the whole investigation period. Specific IgE did not increase after the treatment course and shows the same behaviour as the untreated patients. Thus, as treatment with glutaraldehyde modified, tyrosine-adsorbed allergoids is safe to administer, requires only 3 injections, reduces histamine release from basophils by production of "blocking" antibodies, it appears to be a useful tool in the hyposensitization treatment.

Onset of polyarteritis nodosa during allergic hyposensitization treatment

In six of 20 consecutive patients with polyarteritis nodosa, the onset of vasculitic symptoms coincided with hyposensitization therapy for presumptive atopic (immunoglobulin E-mediated) respiratory disease. Atopic symptoms had been present for less than three months in half of the patients and over 10 years in the remainder. Active vasculitis persisted in all patients despite immediate cessation of the hyposensitization treatment. Three patients died within eight months. When compared with the 14 other patients with polyarteritis nodosa, those undergoing hyposensitization had significantly greater skin involvement and peripheral blood eosinophilia (p = < 0.05). Evidence for circulating immune complexes with decreased hemolytic complement, increased cryoglobulins or increased Clq binding was present in both groups. No single allergen was used in all patients, no antiallergen precipitating antibodies were detected and less than 16 mg of allergenic protein had been injected in five of the patients.

Onset of polyarteritis nodosa during allergic hyposensitization treatment: Phanuphak P, Kohler PF: Am J Med 1980; 68: 479–485

Onset of polyarteritis nodosa during allergic hyposensitization treatment: Phanuphak P, Kohler PF: Am J Med 1980; 68: 479–485

Studies of Rice Pollen Asthma : III. The Specific Hyposensitization Treatment with Rice Pollen Extract in Rice Pollen Asthma

Studies of Rice Pollen Asthma : III. The Specific Hyposensitization Treatment with Rice Pollen Extract in Rice Pollen Asthma

Immunogenic Properties of Modified Antigen E

Abstract It has been shown that regweed antigen E loses its major antigenic determinants after denaturation in 8 M urea, but urea-denatured (UD) antigen and an α-polypeptide chain isolated from the denatured molecules are capable of priming mouse T cells specific for native antigen. Weekly injections of 10μg UD antigen or α-chain into antigen E-primed antimals depressed the ongoing IgE antibody response, whereas injections of the same dose of antigen E failed to depress the antibody response. It was found by adoptive transfer experiments that helper activity of antigen E-primed splenic T cells was depressed by the treatment of the donors with either modified antigen or native antigen E. The same treatment of antigen E-primed animals depressed the DNA synthetic response of their splenic T cells to antigen E. The treatment of antigen E-primed animals with UD antigen resulted in a decrease of antigen E-specific IgE-B cells and IgG-B cells in their spleen, whereas the treatment with native antigen expanded the B cell populations. In view of the results obtained in the mouse, cellular basis for the immunologic effects of hyposensitization treatment is discussed.

Experimental studies on the antigenicity of house dust and properties of anti-house dust antibody (author's transl)

As the precipitating antibodies in rabbits to house dust were considered to correspond to the blocking antibodies produced by hyposensitization treatment, rabbit anti-house dust antibody was used to investigate the antigenicity of house dust producing blocking antibody in human. The summary of the obtained results were as follows: 1) By the use of rabbit anti-house dust serum it was found that house dust extract contained at least three antigenic elements and the specific activity of the antibodies to house dust was displayed by the 7S gammaglobulin and not by the 19S macroglobulin fraction in radioimmunodiffusion test. 2) Fractionation of the house dust extract by gel diffusion and radioimmunoelectrophoresis disclosed that the protein fraction contained two antigenic components. Furthermore, one of these components was deprived of its antigenecity by the action of pronase but no antigenicity was demonstrated in polysaccharide fraction. On the other hand, Morris and his co-workers were unable to detect significant loss in skin reactivity to purified house dust fraction submitted to treatment with pronase. 3) Using mite extract and candida extract, cross reactions to anti-house dust serum were investigated with gel diffusion, but reactions were negative for both while Miyamoto et al. reported a close correlation between extract of house dust and considered mites as the main allergen in house dust. 4) From these results, the allergenicity of house dust in skin test and the antigenicity of house dust to blocking antibodies in man might be dissociated in some instances.

Immunogenic Properties of Modified Antigen E

Abstract Ragweed antigen E loses its major antigenic determinant after denaturation in 8 M urea. The urea-denatured (UD) antigen and α-polypeptide chain isolated from the denatured molecule possess their own antigenic determinant(s) but lack the major determinant of the native molecule. The UD antigen and α-chain, however, are capable of priming mouse T cells specific for antigen E. Priming of A/J mice with the modified antigen enhanced both IgG and IgE antibody responses to antigen E. Both UD antigen-primed spleen cells and α-chain-primed spleen cells collaborate with DNP-primed cells to give an adoptive secondary anti-DNP antibody response to DNP-ragweed antigen in syngeneic irradiated mice. Pretreatment of A/J mice with an i.v. injection of α-chain partially suppressed both IgE and IgG antibody responses to antigen E. Weekly injections of α-chain or UD antigen to antigen E-primed animals depressed on-going IgE antibody response, and suppressed secondary IgE antibody response to antigen E. Transfer of spleen cells from animals treated with the modified antigen to irradiated recipients followed by challenge with native antigen showed that the adoptive secondary response was suppressed by injections of modified antigen to the donors. The results indicate that the immunocompetent cell population was changed by the treatment and provide an experimental model to analyze the immunologic effect of hyposensitization treatment.

57.Immunoglobulin classes of antibodies in sera of patients with sea-squirt&apos;s asthma, with special reference to the severity of the asthma attack and the hyposensitization treatment

57.Immunoglobulin classes of antibodies in sera of patients with sea-squirt&apos;s asthma, with special reference to the severity of the asthma attack and the hyposensitization treatment

Hyposensitization treatment.

Hyposensitization treatment.