Evaluation of rapid injection immunotherapy by antigen specific IgE and IgG4 antibodies

Ten children, aged 3 to 12 years old (mean 8), with house-dust-mite sensitive bronchial asthma were hospitalized and administered a course of rapid injection immunotherapy with house-dust (HD) antigen. In order to evaluate rapid injection immunotherapy, we examined total IgE, anti-HD IgE and IgG4 antibodies, anti-mite (Dermatophagoides farinae: DF) IgE antibodies, and anti-DF IgG4 antibodies in their sera serially from 56 to 80 weeks after rapid injection. The results were as follows: 1) All of their clinical courses were markedly improved by this immunotherapy. 2) Total IgE levels were unchanged. 3) Anti-HD IgE antibodies were decreased 5 weeks after rapid administration (p less than 0.01). And anti-DF IgE antibodies were also decreased (p less than 0.05). 4) Anti-DF IgG4 antibodies were increased more than twofold from 2 to 5 weeks after rapid administration (p less than 0.02). Rapid injection immunotherapy produced positive effects in some of the asthmatic children. This seemed to be attributable to the production of antigen specific IgG4 antibodies (said to be blocking antibodies) and the reduction of antigen specific IgE antibodies.     

Changes in the levels of house dust mite specific IgG4 during immunotherapy in asthmatic children

Serum levels of IgG subclass and house dust mite (Dermatophagoides pteronyssinus, Dpt) specific IgG4 were evaluated during immunotherapy in asthmatic children. Asthmatic children undergoing long-term immunotherapy (more than 2 years) posed a mean value of total serum IgG4 or Dpt-specific IgG4 antibodies significantly higher than that of patients prior to receiving immunotherapy, asthmatic (placebo) controls, or patients undergoing short-term immunotherapy (less than 1 year) (P less than 0.05). The mean levels of serum Dpt-specific IgG4 in all asthmatic groups were also significantly higher than in the non-allergic controls (P less than 0.01). Moreover, the mean level of Dpt-specific IgG4 tended to increase during immunotherapy. A significant correlation between total serum IgG4 and Dpt-specific IgG4 antibodies was noted (r = 0.6243; P less than 0.001). Serial follow-up reveals that Dpt-specific IgG4 levels usually rose significantly with clinical improvement in asthmatic children during immunotherapy. These results suggest that the anti-mite-specific IgG4 antibody may serve as an indicator for clinical outcome of mite allergy during immunotherapy.     

Imported fire ant (IFA) sensitivity: IFA-specific levels of serum IgG and IgG4

Imported fire ant (IFA) whole body extract (WBE) and venom (V)-specific IgG and IgG4 antibodies and specific IgE antibodies were evaluated in sera from 56 IFA-sensitive individuals (18 undergoing immunotherapy with IFAWBE and 38 individuals not being treated) and 44 nonatopic and atopic control subjects with no history of IFA allergy. Although there was no difference in the level of IFAWBE- or IFAV-specific IgG between treated and untreated patients, both groups had higher levels of IFAWBE- and IFAV-specific IgG (p less than 0.05) than did control subjects. Patients receiving treatment tended to have higher levels of IFAWBE-specific IgG4 than did either untreated patients (0.05 less than p less than 0.10) or control subjects (p less than 0.05). Levels of IFAV-specific IgG4 were higher in treated patients than in control subjects (p less than 0.05) but were not different between treated and untreated patients. Levels of IFAWBE- and IFAV-specific IgE antibodies did not differ between the two patient populations but were higher in both groups than in control subjects (p less than 0.05). The ratio of IgG4 to IgE (G4/E) for both IFAWBE and IFAV was calculated for all groups. The ratios of IFAWBE- and IFAV-specific G4/E were higher in treated patients and in control subjects as compared to nontreated patients (p less than 0.05). IFAV-specific G4/E ratios were lower in treated patients than in control subjects, but IFAWBE-specific G4/E ratios were the same as ratios for control subjects.(ABSTRACT TRUNCATED AT 250 WORDS)     

A double-blind study of hyposensitization with an alginate- conjugated extract of Dermatophagoides pteronyssinus (Conjuvac®) in patients with perennial rhinitis

In a 2-year double-blind placebo controlled study an immunological evaluation was carried out on 33 patients (15 males, 18 females, mean age 29.2 years) with mite-induced perennial rhinitis who were submitted to specific immunotherapy (IT) with an alginate-conjugated extract of D. pteronyssinus. The behaviour of IgE, IgG, IgG1 and IgG4 antibodies specific to D. pteronyssinus and its major allergen Der p1 was characterized by assessment of their changes in serum, and changes in IgG in nasal secretions during the treatment. The placebo-treated patients did not show any significant variation in the levels of specific antibodies, while in the actively treated patients we found: a statistically significant decrease (P less than 0.005) of specific IgE, a statistically significant increase of specific IgG (P less than 0.005), IgG1 (P less than 0.005) and IgG4 (P less than 0.005) in serum and a statistically significant increase (P less than 0.001) of specific IgG in nasal secretions. The IgG response showed an early relative predominance of the IgG1 subclass and a late absolute predominance of IgG4 subclass, that confirmed the model of IgG4 restriction in prolonged allergen stimulation. No correlation was found between immunological and clinical data.     

Specific IgE, IgG and IgG4 antibodies against house dust mite in patients with bronchial asthma

Serum levels of total IgE, specific IgE, IgG and IgG4 against house dust mite were measured in mite-sensitive asthma patients receiving immunotherapy with house dust. Serum levels of total IgE, mite specific IgE and IgG did not significantly change during the course of hyposensitization. Increased levels of mite specific IgG4 were observed in patients during immunotherapy. The increase in specific IgG4 was dependent on the total dose of house dust administered in both children (r = 0.636, p less than 0.001) and adults (r = 0.629, p less than 0.01). However, the increase of specific IgG4 in adults was not as apparent as in children. These results might suggest that mite specific IgG4 is a useful immunological marker in the immunotherapy for allergic asthma, and that IgG4 antibody acts as a blocking antibody in atopic bronchial asthma.     

Measurement of IgG subclass antibodies to the group II antigen of Dermatophagoides pteronyssinus (Der p II) in sera from children with bronchial asthma.

Seven IgG-binding components in crude mite allergen extracted from Dermatophagoides pteronyssinus (Der p) were identified by immunoblotting analysis. Of these components, the 15-kDa protein was strongly recognized by IgG from patients with bronchial asthma, whereas it was less recognized by IgG from healthy individuals. Then, the 15-kDa protein was purified by reverse-phase high performance liquid chromatography and the protein was demonstrated to induce immediate positive skin reactions in patients with bronchial asthma. The N-terminal amino acid sequence of the 15-kDa protein was also determined and was in agreement with that of Der p II. In an attempt to understand the role of IgG subclass antibody of patients with bronchial asthma, we quantitated the antibodies of IgG subclass to Der p II. The levels of antibodies of total IgG and of all IgG subclasses in patients with bronchial asthma who had never received immunotherapy were higher than those of nonatopic healthy individuals. The levels of Der p II-specific IgG1 and IgG4 in asthmatic patients were 1.97 times and 2.20 times higher, respectively, than those in the control group. The present study demonstrates that patients with bronchial asthma are able to produce antibodies of all IgG subclasses specific to Der p II in response to natural exposure to mite antigen.     

Immunotherapy for cat asthma

In 22 patients with cat asthma who were highly sensitive to cat, we compared, double-blind, the effects of immunotherapy with cat-hair and dander extract (11 patients) with effects of placebo (11 patients). Patients were matched by the dose of the cat extract expressed in Food and Drug Administration (FDA) units of Fel d I (previously called cat allergen 1) required for end point reaction in intradermal skin test end point titration (STEPT), for in vitro leukocyte histamine release (LHR), and for the dose of cat extract producing a 20% fall in FEV1 (cat-extract PD20) in bronchoprovocation test. Patients were matched also for bronchoprovocation dose of methacholine producing a 20% fall in FEV1 (methacholine PD20). Patients were randomly assigned to one of two treatment groups. During immunotherapy, doses were increased to maintenance dose of 4.56 FDA units of Fel d I, or, if this were less, to the highest tolerated dose. Systemic reactions to cat-extract immunotherapy were mild and infrequent. Before and during immunotherapy, we measured (in FDA units of Fel d I) cat-extract PD20, cat-extract intradermal STEPT, cat-extract in vitro LHR, serum levels of cat IgG and cat IgE, and methacholine PD20. After they had received 1 year of immunotherapy, patients receiving cat extract, in comparison to patients receiving placebo, had decreased cat-extract PD20 (p less than 0.01), diminished responses to cat-extract intradermal STEPT (p less than 0.025), increased IgE antibodies toward cat extract (p less than 0.01), increased IgG antibodies toward cat extract, Fel d I, and cat albumin (p less than 0.001), but no significant change in cat-extract in vitro LHR or in methacholine PD20. We conclude that cat-extract immunotherapy was well tolerated, significantly decreased skin and bronchial responses to cat extract, and significantly increased IgE antibodies to cat extract and IgG antibodies to cat extract, Fel d I, and cat albumin.     

Suppression of late-phase skin reactions by immunotherapy with ragweed extract

The cutaneous late-phase reaction (LPR) to ragweed was studied in untreated ragweed-allergic individuals and patients receiving 3 to 5 years of immunotherapy demonstrating clinical improvement. The magnitude of immediate skin reactions and the initial levels of the specific IgE and IgG antiragweed antibodies were similar in both groups. The LPR was elicited by administering a skin test with ragweed extract at 10 times the concentration required to elicit a 4 + immediate reaction and appeared as an erythematous-edematous lesion associated with pruritus. In the untreated group 94% developed an LPR (59 +/- 32 mm at 4 hours and 67 +/- 30 mm at 8 hours) at this dose. In the treated group only one third developed an LPR, one third had partial response measurable at one of these two times, and one third failed to develop any LPR (21 +/- 20 mm at 4 hours, p less than 0.002, and 20 +/- 22 mm at 8 hours, p less than 0.001). Therapy resulted in a twentyfold increase of IgG antiragweed level and in a decline of IgE antiragweed. The size of the LPR correlated inversely with the level of IgG antiragweed (p less than 0.01; r = -0.52) but not with IgE antibody. Thus, in a retrospective analysis immunotherapy was associated with the suppression of the skin LPR, and the magnitude of the LPR was correlated with the level of IgG antiragweed. We suggest that the clinical efficacy of immunotherapy is related in part to effects on the LPR.     

Immunologic analysis of steroid-dependent asthma

In order to analyze steroid-dependent asthma immunologically, IgE antibodies to mite (Dermatophagoides farinae), Candida albicans, and Aspergillus fumigatus were measured in 112 asthmatic patients. IgG and IgG subclass antibodies to mite were also measured. The rate of patients who were positive to candida IgE RAST was higher in atopic steroid-dependent patients than in atopic steroid-independent patients (P less than .01). The rate of mite-sensitive patients who had not received immunotherapy with mite or house dust was higher than in the atopic steroid-dependent patients than in atopic steroid-independent patients (P less than .05). IgG1 and IgG4 antibodies to mite were higher in mite-sensitive steroid-independent patients than in mite-sensitive steroid-dependent patients. IgE antibodies to A. fumigatus were detected only in patients with allergic bronchopulmonary aspergillosis (ABPA). Based on these results, we were encouraged to try immunotherapy with house dust mite or C. albicans if patients were steroid-dependent and sensitive to these allergens except when the patients had ABPA.     

Solid-phase radioimmunoassay for the measurement of IgG antibodies specific for the house dust mite, Dermatophagoides farinae

The sera from 65 asthmatic patients were studied for the measurement of IgG antibodies specific to the house dust mite, Dermatophagoides farinae (D. farinae) by solid-phase radioimmunoassay using polystyrene tubes coated with the antigen extract. The solid-phase radioimmunoassay had about the same sensitivity as the conventional double antibody antigen-binding assay in the detection of mite-specific IgG antibodies. The mean value of IgG antibodies was 26.1 (+/- 39.8) micrograms/ml in patients hyposensitized with D. farinae, 23.9 (+/- 29.3) micrograms/ml in those hyposensitized with house dust (HD), and 21.6 (+/- 35.6) micrograms/ml in non-treated patients. A significant difference was detected between HD-treated patients and normals (p less than 0.05). The levels of IgG antibody tended to increase with the increment of the maintenance dose of the D. farinae or HD used in immunotherapy. In addition, eight patients were evaluated for their IgG antibody levels before and after immunotherapy. In five of them, IgG antibodies increased about two to threefold above the value before immunotherapy. These results suggest that the measurement of IgG antibodies by solid-phase radioimmunoassay may be clinically useful in evaluating the effectiveness of immunotherapy.     

The change of allergen-specific IgG subclass antibodies during immunotherapy in mite-sensitive asthmatic children.

Fifty-six Dermatophagoid farinae (D.f)-sensitive asthmatic children were hyposensitized by D.f-crude extract for two years. Serum total IgG subclass antibodies and D.f-specific IgE and IgG subclass antibodies were measured by ELISA before and after 2 years of treatment. The results showed that 1) After two years of treatment, there were significantly higher levels of total serum IgG1 in both responder and non-responder groups than those before treatment (p less than 0.01). The responder group also had significantly higher values of total IgG2 and IgG4 after immunotherapy (IT) (p less than 0.05), but not in the non-responder group. 2) The serum levels of D.f-specific IgG3 and IgG4 antibodies in responder group increased significantly after IT (p less than 0.05). On the contrary, the D.f-specific IgE and IgG1 IgG1 in the responder group were significantly lower than those before IT. No signi- in the responder group were significantly lower than those before IT. No signi-body titres before and after IT was found in non-responder group. 3) There was a significant correlation between the total IgG4 and D.f-specific IgG4 antibody (r = 0.634, p less than 0.01). The correlation coefficient was 0.634. No correlation was found between the other IgG subclass antibodies and D.f-specific IgG subclass antibodies. 4) Correlations between the levels of D.f-specific IgE and IgG subclass antibodies were highly significant both in IT-responder and non-responder groups. There was a significant correlation between the levels of D.f-specific IgG1 and IgG4 in non-responders, while no relationship was observed in the responder group.(ABSTRACT TRUNCATED AT 250 WORDS)     

Isotypic and antigenic restriction of the blocking antibody response to ryegrass pollen: correlation of rye group I antigen-specific IgG1 with clinical response

To investigate the role of blocking antibodies in allergen immunotherapy (IT), we analyzed IgE, IgG, and IgG subclass 1 to 4 antibody responses to ryegrass group I antigen (RGGI) in a prospective double-blind, heterologous allergen, allergen-controlled trial of grass-pollen IT in 18 adults with seasonal rhinitis and asthma. Serum was assayed preseasonally before starting IT and again in midseason at time of documented highest natural exposure. Antibodies were measured by ELISA, and immunogenic specificities of ryegrass extract were examined by Western immunoblots. Nine subjects receiving grass-pollen IT and nine control subjects had similar clinical and immunologic status before IT. RGGI-specific IgE antibodies (sIgE) did not change from pretreatment levels in actively treated subjects but increased in control subjects (p less than 0.002). RGGI sIgG increased approximately thirteen-fold with active IT versus threefold during natural seasonal exposure (p less than 0.0005). The IgG-blocking response to RGGI was restricted to IgG1 and IgG4. Ten nonatopic subjects had similar RGGI sIgG1 but lower or undetectable sIgE and sIgG4 than the 18 atopic study subjects. Active IT dramatically increased RGGI sIgG4 (p less than 0.001) and to a lesser extent RGGI sIgG1 (p less than 0.01). Immunoblots demonstrated eight IgE-binding ryegrass-polypeptide allergens, with RGGI ubiquitous, and 11 IgG-binding polypeptides, including all eight allergens. A negative correlation between seasonal rhinitis symptom-medication scores and RGGI sIgG1 levels was found (r = -0.62, p less than 0.01), but no other immunologic parameters assayed were related to clinical improvement. Although RGGI sIgG4 predominates in the blocking response and is a useful marker of effective IT, early beneficial biologic effects may involve IgG1 antibodies.     

IgG Subclass Antibody Response in Grass Pollen-Allergic Patients Undergoing Specific Immunotherapy

All four subclasses of IgG antibodies to timothy grass pollen extract were measured by a three-layer immunoradiometric assay in sera from 20 grass pollen-allergic patients who underwent specific immunotherapy in a 3-year prospective study. Both IgG1 and IgG4 antibody levels rose significantly during the first 8 weeks of immunotherapy. IgG1 antibody level passed its peak (median 5.4 U/ml) after 12 weeks. At this time, the ratio between the medians of IgG1 and IgG4 antibodies was 2.25. IgG4 antibody level reached its peak (median 11.6 U/ml) just before termination of immunotherapy. At this time IgG1/IgG4 ratio was 0.43. Two years after the end of immunotherapy, IgG1 and IgG4 antibody levels were 0.0 and 1.8 U/ml in median, respectively. The amounts of IgG2 and IgG3 antibodies detected in the sera were less than 1.6 U/ml and were considered insignificant. Preseasonal serum IgG1 and IgG4 antibody levels did not correlate significantly with symptom scores in the subsequent season. Serum IgG4 level obtained after 12 weeks of immunotherapy was significantly correlated to symptom score in the third season, i.e. the season just after termination of therapy (rs = 0.529, t = 2.567, P = 0.02). In this work, a serum IgG4 antibody level higher than 8.0 U/ml after 12 weeks of therapy predicted poor clinical result at the end of immunotherapy with 100% sensitivity and 87% specificity. An IgG4/IgG1 ratio greater than 1.0 after 12 weeks' therapy had the same predictive value.     

Rush immunotherapy with a standardized Bermuda grass pollen extract

We carried out a double-blind clinical trial in 30 patients who were sensitized to Bermuda grass pollen. Before and after immunotherapy we performed in vivo tests (skin tests and standardized tests of specific and nonspecific bronchial hyperreactivity), in vitro tests (histamine release), and specific IgE and IgG antibodies to BGP. We found a significant decrease (P less than .001) in specific bronchial hyperreactivity and skin sensitivity to BGP in the group of patients treated with immunotherapy, a decrease in the delayed responses (P less than .05) in histamine release (P less than .01), and an increase (P less than .001) in specific IgE and IgG antibodies to BGP. The placebo group showed no changes in these parameters.     

Serum concentrations of allergen-specific IgG antibodies in inhalant allergy: effect of specific immunotherapy

The occurrence of antibodies belonging to IgG class of immunoglobulins with specificity for short ragweed and Bermuda grass in the sera of nonatopic subjects and patients with inhalant allergy (at the time of initial diagnosis, following specific immunotherapy was investigated with an enzyme immunoassay. The intra-assay and inter-assay coefficients of variation for this assay ranged from 1.74%-4.62% and 3.18%-9.12%, respectively. IgG antibodies were found in the sera of the majority of nonatopic and all of atopic subjects. The differences in the concentration of these antibodies between these three groups were statistically significant (P less than 0.001). Specific immunotherapy resulted in a rise in the serum levels of allergen-specific IgG antibodies and, following an initial period of modest increase, a decrease in the level of allergen-specific IgE antibodies. Specific IgG response correlated with both the cumulative antigen dose and the clinical benefit that accrued from specific immunotherapy (P less than 0.001). The increase in the serum concentration of specific IgG was most pronounced in patients with high RAST scores at the time of initial diagnosis (P less than 0.001). The concentrations of short-ragweed specific IgG antibodies assayed with multiple samples in three patients with ragweed hay fever appeared not to be affected by the short-ragweed season to any significant degree. We conclude that direct enzyme immunoassay for allergen-specific IgE and IgG antibodies are useful in vitro monitors of immunologic responses to specific immunotherapy for inhalant allergy.     

Allergen-specific immunotherapy with a monophosphoryl lipid A-adjuvanted vaccine: reduced seasonally boosted immunoglobulin E production and inhibition of basophil histamine release by therapy-induced blocking antibodies

BACKGROUND: Allergen-specific immunotherapy represents a causal form of treatment for IgE-mediated allergies. The allergen extract-based analyses of immunotherapy-induced effects yielded highly controversial results regarding a beneficial role of therapy-induced IgG antibodies. OBJECTIVE: We analysed allergen-specific IgE, IgG subclass, and IgM responses in patients treated with a grass pollen allergy vaccine adjuvanted with monophosphoryl lipid A (MPL), a Th1-inducing agent, and in a placebo group using recombinant timothy grass pollen allergen molecules (rPhl p 1, rPhl p 2, rPhl p 5). RESULTS: The strong induction of allergen-specific IgG1 and IgG4 antibodies observed only in the actively treated group was associated with significant clinical improvement. Therapy-induced allergen-specific IgM and IgG2 responses were also noted in several actively treated patients. An inhibition of allergen-dependent basophil histamine release was only obtained with sera containing therapy-induced allergen-specific IgG, but not with sera obtained before therapy or from placebo-treated patients. Moreover, patients with therapy-induced allergen-specific IgG antibodies showed a reduced induction of allergen-specific IgE responses during seasonal grass pollen exposure. CONCLUSION: Successful immunotherapy with the MPL-adjuvanted grass pollen allergy vaccine is associated with the production of allergen-specific IgG antibodies. These blocking antibodies may have protective effects by inhibiting immediate-type reactions and systemic increases of IgE responses caused by seasonal allergen exposure.     

Immunotherapy with cat- and dog-dander extracts. IV. Effects of 2 years of treatment

Thirty-five patients (20 children and 15 adults) with animal-dander asthma completed 2 years of immunotherapy with partly purified and standardized cat- or dog-danger extracts. The first year of the study was performed double-blind with a placebo-treated control group. These 15 patients were transferred to active treatment for a second year. All patients were followed by use of the skin prick test (SPT), allergen and histamine bronchial challenges, and tests for allergen-specific IgE, IgG1, and IgG4 levels. In the group treated with active extracts for 2 years (group A), the previously reported decrease in bronchial responsiveness to cat extract (p less than 0.001) and histamine (p less than 0.01) was even more pronounced after the second year. After 1 year of active treatment in the original placebo group (group B), a significant decrease in the bronchial responsiveness to cat extract was noted (p less than 0.001). The responsiveness to histamine was decreased only in the patients treated with cat-dander extracts (p less than 0.05). A significant decrease in the SPT (p less than 0.001) and an increase in the allergen-specific IgE (p less than 0.001) and IgG4 (p less than 0.001) was also noted in patients (group B) treated with cat-dander extracts. The side effects in the two groups (A and B) were negligible, except for some systemic side effects, especially among the children during the initial phase of immunotherapy. The symptoms were mild and responded promptly to treatment.(ABSTRACT TRUNCATED AT 250 WORDS)     

Induction of antibody responses to new B cell epitopes indicates vaccination character of allergen immunotherapy.

Whether the modulation of antibody responses can contribute to the improvement of clinical symptoms in patients receiving allergen immunotherapy represents a controversial issue. We have used purified [seven recombinant (r) and one natural] timothy grass pollen allergens as well as recombinant B cell epitope-containing fragments of the major timothy grass pollen allergen, Phl p 1, to investigate humoral immune responses in eight allergic patients receiving grass pollen-specific immunotherapy. We found that the administration of aluminium hydroxide-adsorbed grass pollen extract induced complex changes in allergen/epitope-specific antibody responses: increases in IgG subclass (IgG1, IgG2, IgG4) responses against allergens recognized before the therapy were observed. All eight patients started to mount IgE and IgG4 responses to continuous Phl p 1 epitopes not recognized before the therapy and a de novo induction of IgE antibodies against new allergens was found in one patient. Evidence for a protective role of IgG antibodies specific for continuous Phl p 1 epitopes was provided by the demonstration that preincubation of rPhl p 1 with human serum containing therapy-induced Phl p 1-specific IgG inhibited rPhl p 1-induced histamine release from basophils of a grass pollen-allergic patient. Our finding that immunotherapy induced antibody responses against previously not recognized B cell epitopes indicates the vaccination character of this treatment. The fact that patients started to mount de novo IgE as well as protective IgG responses against epitopes may explain the unpredictability of specific immunotherapy performed with allergen extracts and emphasizes the need for novel forms of component-resolved immunotherapy.     

Hymenoptera venom immunotherapy. I. Induction of T cell-mediated immunity by honeybee venom immunotherapy: relationships with specific antibody responses

The specific cell-mediated and humoral immune responses of 14 children allergic to honeybee venom were studied. An 8-day rush venom immunotherapy induced an increase in T proliferative (p less than 0.04) and T suppressive (p less than 0.003) cell-specific activities. Antibody variations, an increase in specific IgG4 (p not equal to 0.05), and a decrease in specific IgE (p less than 0.01) were observed 1 year later. Initial high T suppressive cell activity prevents T proliferative cell increase during rush venom immunotherapy. High initial levels of specific IgG1 and specific IgG4 have opposing effects on the increase in T suppressive cell activity, the former being positively correlated with intensive increase (r = 0.840; p less than 0.005), the latter negatively with T suppressive cell increase (r = -0.709; p less than 0.001). These data indicate that there are interrelationships between the cell-mediated immunity and the antibody responses in honeybee allergy.     

Immunotherapy with cat- and dog-dander extracts. V. Effects of 3 years of treatment

The effect of a 3-year course of cat or dog immunotherapy (IT) was evaluated in 32 patients with a history of asthma on exposure to cat or dog. Twenty-one subjects (14 children and seven adults) received cat IT and 11 subjects (six children and five adults) received dog IT. Bronchial challenges with allergen and histamine were performed once a year. Specific IgE, IgG1, and IgG4 were measured, and skin prick tests were done in connection with the challenges. Allergen sensitivity decreased significantly in both treated groups (p less than 0.001 and p less than 0.05 in the cat-allergen and dog-allergen treated groups, respectively). Bronchial hyperreactivity measured by the provocative concentration of histamine causing a 20% decrease in peak expiratory flow in the cat-allergen treated patients (p less than 0.001) but not in the dog-allergen treated patients. Skin sensitivity decreased in both groups (p less than 0.01 and p less than 0.05), whereas specific IgE increased initially but dropped to the pretreatment level during the second year. Specific IgG1 and IgG4 increased during the first and second year in the cat-allergen treated group (p less than 0.01 and p less than 0.001), whereas only IgG4 increased in the dog-allergen treated group (p less than 0.01). Five cat-allergen treated children and one of the adults who completed 3 years of therapy had mild systemic reactions. We conclude that cat IT ameliorated bronchial allergen sensitivity and bronchial hyperreactivity and resulted in an adequate antibody response. Dog IT was less efficacious but led to attenuation of bronchial allergen sensitivity.