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PubMed1991

Regulation of the human immune response to ragweed pollen by immunotherapy. A controlled trial comparing the effect of immunosuppressive peptic fragments of short ragweed with standard treatment.

A new allergenic preparation consisting of peptic fragments of short ragweed has been tested for its clinical effectiveness. Such enzymatically derived fragments have been shown in prior murine studies to retain the T epitopes of the original allergen but to have a severe reduction in the number of B epitopes. Three groups of ragweed hayfever patients were placed on pre-seasonal immunotherapy. One group received a conventional ragweed preparation that had been enriched for antigen E (Amb a I), designated as Pool 2. The second group was given fragments of Pool 2 (fSRW) prepared by peptic digestion and the third group was injected with histamine as a placebo. Groups treated with the fSRW and Pool 2 had significantly reduced symptom-medication scores compared with the placebo-treatment group. However, fSRW-treated patients fared significantly better than Pool 2 patients (P less than 0.02). fSRW injections caused a significant rise in preseasonal specific IgG, antibodies as well as suppression of the seasonal anamnestic specific IgE increase. Similar, but not quite as marked changes occurred with Pool 2 treatment. fSRW was well tolerated and non-toxic. Thus, allergen modification by enzymatic degradation, as demonstrated here, appears to be a promising new approach for allergen immunotherapy.

Adult↗
PubMed1986

The clinical and immunologic efficacy of immunotherapy with modified ragweed extract (allergoid) for ragweed hay fever.

A double-blind study comparing formaldahyde modified ragweed allergen (allergoid) and placebo in the treatment of allergic rhinitis was carried out. Twenty ragweed-sensitive patients were studied, ten receiving 10,710 PNU of allergoid pre-seasonally and ten receiving placebo injections. Daily symptom score sheets were kept by each patient during August and September of 1983. A significant difference in average daily symptom scores (P = 0.01) between the two groups was noted. Significant differences were also observed in symptom scores for individual weeks during the ragweed season. Post-treatment allergen-specific IgG blocking antibody was significantly higher (P = 0.001) in the treatment group compared to pre-treatment levels and when compared to the control group (P = 0.01). No significant local or systemic reactions occurred. The results suggest that the dosage protocol used in this study is appropriate as an initial treatment schedule in clinical practice.

Adult↗
PubMed1982

HLA-Dw2: a genetic marker for human immune response to short ragweed pollen allergen Ra5. II. Response after ragweed immunotherapy.

After artificial immunization (immunotherapy) with ragweed antigens, specific immunoglobulin G (IgG) antibody (Ab) response to Ra5 was significantly associated with HLA-Dw2 (P less than 0.0001). From a total of 61 treated patients, all 22 Dw2+ subjects made good IgG Ab responses to Ra5 by year 2 of therapy (21 by year 1), even though 8 of them had no detectable IgG Ab and 9 had no detectable IgE Ab before therapy. The prevalence of IgG Ab response among 39 Dw2- subjects was markedly lower; only 11 (28%) responded well after 1-9 yr of therapy. Both by univariate and multivariate statistical analysis, Dw2 was also found to be strongly associated with the quantity of IgG Ab produced. In particular, both the strength and significance of the association between Dw2 and log[IgG Ab] response to Ra5 increased over a 3-yr period of ragweed therapy (P = 10(-9) by year 3). Multiple regression analysis also revealed a weak association with HLA-B13, which became apparent only after year 2 of therapy. Genetic hypotheses for these findings are discussed. In particular, the possibility of a second Ir gene, Ir-Ra5', separate from HLA-Dw2 and possibly located elsewhere in the genome, is considered.

Allergens↗
PubMed1997

The severity of clinical symptoms in ragweed-allergic patients is related to the extent of ragweed-induced complement activation in their sera.

We have previously reported a correlation between the extent of ragweed allergen (RWA)-induced in vitro serum complement activation and the symptom scores registered daily during the ragweed (RW)-blooming season in RW-allergic patients. The present study was performed in 22 15-17-year-old RW-allergic adolescents. Serum samples were incubated with 100 micrograms/ml RWA, and the generation of different complement activation products was measured by ELISA or RIA. Symptom scores were registered for 4 weeks during the RW-blooming season. The patients were divided according to the extent (low or high) of the generation of complement activation products, and symptom scores registered in the two groups were compared by two-way ANOVA. Significantly higher symptom scores were obtained in the high than in the low complement activation group (P values: 0.049 for C1rC1sC1inh, 0.022 for C3bBbP, 0.015 for C5b-9, 0.0001 for C3a, and 0.0008 for C5a). Similar results were obtained at the measurement performed in the sera obtained from the same patients half a year before the season (P values: 0.022 for C3bBbP, and 0.005 for C5b-9). These findings indicate that complement activation induced by the allergen may enhance the clinical symptoms of RW allergy.

Adolescent↗
PubMed1991

Ragweed-specific IgA in nasal lavage fluid of ragweed-sensitive allergic rhinitis patients: increase during the pollen season.

Because the secretions of asthma and rhinitis contain toxic eosinophil granule proteins and because secretory IgA is the most potent immunoglobulin stimulus for eosinophil degranulation, we measured eosinophil-derived neurotoxin and ragweed-specific IgA and IgE antibodies in nasal lavage before and during the ragweed pollen season in 44 hay fever patients. We found IgA antibody in nanogram/milliliter concentrations before the season and rising 20-fold by the end of the season. IgE antibody was present in picogram/milliliter concentrations and did not change. Eosinophils and eosinophil-derived neurotoxin also increased. We conclude that IgA is the predominant antibody in allergic nasal secretions and increases with allergen exposure. The hypothesis that secretory IgA antibody-allergen complexes contributes to allergic inflammation by stimulating eosinophil degranulation warrants further study.

Humans↗
PubMed1988

Comparison of alum-precipitated aqueous extracts and modified ragweed tyrosine adsorbate vaccine in the treatment of ragweed hay fever.

Thirty-five ragweed-sensitive patients received immunotherapy with either alum-precipitated aqueous extracts (AP) or modified ragweed tyrosine adsorbate vaccine (Pollinex-R). Symptoms decreased with AP therapy only. Immunologically, there was a blunted specific IgE response and little specific IgG increase associated with both groups. Alum-precipitated aqueous extracts appeared to be more efficacious than Pollinex-R.

Adsorption↗
PubMed1998

HLA-DQ6 and HLA-DQ8 transgenic mice respond to ragweed allergens and recognize a distinct set of epitopes on short and giant ragweed group 5 antigens.

We have investigated the genetic and molecular basis of immune responsiveness to short ragweed (SRW) (Ambrosia artemisiifolia) extract, and group 5 allergens from short and giant (Ambrosia trifida) ragweed using transgenic mice expressing DQ6 (HLA-DQA1*0103, HLA-DQB1*0601) and DQ8 (HLA-DQA1*0301, HLA-DQB1*0302) genes in class II knockout (A beta0) mice. Panels of overlapping peptides spanning the Amb a 5 and Amb t 5 Ags were synthesized. Mice were immunized with whole SRW extract or individual peptides s.c. and lymph node cells (LNC) were challenged in vitro. Strong T cell responses to SRW extract were measured in both HLA-DQ transgenic mice, while control, HLA-DQ6-/DQ8-/H-2A beta0, mice were unresponsive. IL-5 and IL-10 were the primary cytokines produced by in vitro challenged LNC of SRW-primed transgenic mice. HLA-DQ6-restricted T cell responses were detected to all three peptides of Amb t 5 and two determinants (residues 1-20 and 11-30) on Amb a 5. In contrast, LNC of HLA-DQ8 mice did not recognize peptide 11-30 of Amb t 5 Ag, but recognized several Amb a 5 determinants. The immune response in transgenic mice was dependent upon CD4+ T cells and was HLA-DQ restricted. Primed with purified Amb t 5, both transgenics recognized peptide 21-40, and an additional DQ6-restricted epitope was found within residue 1-20. SRW-immunized HLA-DQ6 mice respond to peptide 11-30 of Amb a 5, while HLA-DQ8 mice strongly recognize peptide 1-20. These results demonstrate the specificity of HLA class II polymorphism in allergen sensitivity and pave the way for developing antagonistic peptides for desensitization.

Allergens↗
PubMed1981

Immunotherapy with short ragweed fraction A:D-glutamic acid:D-lysine polymer in ragweed hay fever.

We report the first human trial of immunotherapy employing the nonimmunogenic carrier, D-glutamic acid:D-lysine linked to short ragweed (SRW) fraction A (fraction A:D-GL). Twelve SRW-sensitive patients with no immunotherapy during the previous 19 yr received a 2-mo (7/79 to 9/79) course of fraction A:D-GL (average dose 49.5 mg, range 21 to 78 mg). We compared their symptom scores and serologic changes with two control groups of SRW-sensitive patients. Patients receiving fraction A:D-GL demonstrated at least a tenfold decrease in skin-test sensitivity to SRW and had statistically lower mean seasonal symptom scores (p less than 0.02) than untreated controls. Mean seasonal symptom scored did not differ statistically from those of control patients on year 4 of immunotherapy. In contrast to the expected suppression of IgE, we found that fraction A:D-GL stimulated both IgE and IgG responses to SRW and SRW-antigen E. These increases in IgE and IgG antibodies were significantly greater than in the control groups and appeared to be due largely to injection of fraction A:D-GL. Though fraction A:D-GL was generally well tolerated, we noted mild generalized urticaria in three patients, and large local reactions in five others. The difference between our results and the earlier results in mice may reside in the particular characteristics of this preparation of fraction A:D-GL.

Adult↗
PubMed1995

In vitro complement activation by ragweed allergen extract in the sera of ragweed allergic and non-allergic persons.

Ragweed allergen (RWA)-induced complement activation in sera of 40 RW allergic patients and of 40 non-allergic controls was investigated. After treatment of the sera with RWA, levels of C3a, C5a, C3bBbP, C1rC1sClinh, SC5b-9 and granulocyte-aggregating activity were determined. Concentration of RW-specific IgG was also measured. After RWA treatment dose-dependent complement activation was detected in sera of RW allergic and non-allergic persons. C3a generation was observed mostly in the sera of RW allergic individuals, while levels of C3bBbP and of RW-specific IgG were significantly higher in sera of allergics, and a strong correlation was found between these two parameters. In a prospective clinical study, a significant positive correlation was observed between the extent of RWA-induced alternative pathway (AP) activation and the severity of symptoms of allergic rhinoconjunctivitis that were developed in a 4-week period subsequent to blood sampling. These observations suggest that complement activation has a role in the development of the symptoms of RW allergy.

Complement Activation↗
PubMed1981

Seasonal variation of IgE antibody specific for ragweed antigen E (IgE-a-AgE) from the basophil surface in patients with ragweed pollenosis.

Seasonal elevation in total serum IgE and IgE antibody specific for antigen E (IgE-a-AgE) are well recognized in patients with ragweed pollenosis. We found that the ratio of specific IgE-a-AgE to total IgE in plasma was the only measure predictive of the number of specific IgE-a-AgE molecules per basophil. Although both total and specific IgE rose with season, the ratio did not change, the number of IgE-a-AgE molecules per basophil did not change, and histamine release in response to AgE did not increase.

Antibody Specificity↗
PubMedDate not supplied

Absence of nasal priming as measured by rhinitis symptom scores of ragweed allergic patients during seasonal exposure to ragweed pollen.

A priming effect, increasing responsiveness of the nasal mucosa as measured by nasal patency or resistance, has been reported to occur after nasal challenge on successive days. Because it has been suggested that the priming effect may be of clinical importance, we have studied whether such an effect occurs during natural pollen exposure as measured by symptom-medication scores in 29 patients with ragweed rhinitis. By Wilcoxon's signed rank test, we compared the symptom-medication scores of patients during two 7-day periods, one early in the season and one later, in which the weekly pollen count was approximately 250 grains/m3; we also compared an early and late period during which the weekly pollen count was approximately 500 grains/m3. There were no statistically significant differences in scores between early and late seasonal periods at the same pollen count. We conclude that the priming effect is not a clinically significant phenomenon during natural pollen exposure in allergic rhinitis patients.

Humans↗