Studies of perennial ragweed immunotherapy.

Perennial ragweed immunotherapy was studied in 24 patients with ragweed pollenosis. Cellular responsiveness was determined by measuring the cellular reactivity and sensitivity to ragweed antigen E (RW-AgE) by RW-AgE-induced leukocyte histamine release. Serum blocking antibody content was determined by measuring the serum RW-AgE binding capacity by ammonium sulfate coprecipitation of bound RW-AgE. Specific IgE (anti-RW-AgE) concentration was determined by polystyrene tube radioimmunoassay. Cellular responsiveness decreased with continuing immunotherapy, as did the specific IgE concentrations. The serum RW-AgE binding capacity, in contrast, increased as treatment continued. The absence of demonstrable correlations between RW-AgE binding capacity and cellular reactivity, cellular sensitivity, and specific IgE concentrations contrasted impressively with the demonstration of multiple significant correlations between the change in the RW-AgE binding capacity and the other parameters studied. The degree of increase in RW-AgE binding capacity correlated significantly with the degree of decrease in both the specific IgE concentration (p is less than 0.04) and the cellular sensitivity to RW-AgE (p is less than 0.003). these findings suggest that the active process of blocking antibody production, rather than the passive presence of blocking antibody, is related to the process which decreases the specific IgE concentration and the degree of cellular responsiveness and therefore results in clinical improvement.     

Variation with season and with polymerized ragweed immunotherapy in IgE against ragweed antigen E in plasma and eluted from the basophil surface in patients with ragweed pollenosis

Sixteen patients with ragweed pollenosis were studied immediately before and after the 1979 ragweed season with measurement of total plasma IgE, specific plasma IgE against ragweed antigen E (IgE-a-AgE), molecules of IgE-a-AgE eluted per basophil, total antibody binding of AgE (blocking antibody), and maximum percentage histamine release in response to AgE. Thirteen received immunotherapy with polymerized ragweed and the measurements were repeated just before and after 1980 ragweed season. The patients kept symptom score diaries for each ragweed season. With season before immunotherapy, plasma IgE-a-AgE and total IgE rose. The ratio of specific to total IgE has been demonstrated to correlate with the IgE-a-AgE molecules eluted per basophil. This ratio, molecules of IgE-a-AgE eluted per basophil, and histamine release did not change. With immunotherapy, there was a significant decrease in symptom scores and a marked increase in blocking antibody. Specific IgE in plasma remained the same as total IgE fell from October 1979 to July 1980. Thus, there was a modest increase in ratio and in the number of IgE-a-AgE molecules eluted per basophil. With these changes, there was no alteration of histamine release. With season, after immunotherapy, there was not significant change in any parameter measured.     

Attenuation of allergen sensitivity early in the course of ragweed immunotherapy

During the course of an open immunotherapy (IT) study of ragweed (RW)-allergic patients, nasal mediator release was studied by provocation testing. All subjects had a history of seasonal RW rhinitis, positive skin puncture test to RW, and RW-specific IgE by RAST. Nasal challenge was performed with serial dilutions of RW extract, before and after 12 weekly injections, providing a cumulative dose of 0.22 microgram of Amb a I. Serum IgE and IgG and basophil histamine release with RW were also measured. By 12 weeks of IT, when only 1% of the usual maintenance level dose had been administered, mean histamine release and TAME-esterase activity in nasal washes decreased significantly (p less than 0.05 and p less than 0.01). Prostaglandin D2 release did not change. Skin sensitivity decreased (p less than 0.05), whereas RW-specific IgE increased (p less than 0.05). No significant change in basophil histamine release was observed for RW or a control antigen. Only six of 40 subjects had an RW-specific IgG rise greater than 0.05 microgram/ml. Changes in nasal sensitivity did not correlate with the increases in IgE or IgG or with the change in skin test sensitivity. These present data indicate that there is a significant decline in nasal sensitivity to inhaled RW very early in the course of IT. There is, however, no indication of a relationship between the decreased nasal sensitivity and the production of RW-specific IgG antibodies.     

A controlled study of the effectiveness of the Rinkel method of immunotherapy for ragweed pollen hay fever

In a double-blind study, we compared the effects of the Rinkel method of immunotherapy with ragweed pollen extract and placebo on symptoms of ragweed hay fever and immunologic parameters in 24 ragweed-sensitive patients. Each had a skin-test end point by Rinkel serial dilution titration to ragweed pollen extract at 1:312,500 w/v or greater dilution, a 2+ skin test to ragweed AgE at 0.1 μg/ml or greater dilution, and in vitro leukocyte histamine release by ragweed pollen extract. None had had immunotherapy for at least 7 yr. Patients matched on the basis of leukocyte histamine release by ragweed were assigned to two treatment groups (12 patients in each group). One group received ragweed pollen extract, and the other, placebo, both administered by the Rinkel method between June and October, 1978. Treatment doses were derived from skin-test end points. The median maintenance (“optimal dose”) for patients receiving ragweed pollen extract was 0.53 ml of 1:312,500 w/v and the mean cumulative dose of ragweed pollen extract given during the study contained 0.094 μg of ragweed AgE. Symptom-medication scores of all patients rose and fell with ragweed pollen counts. No significant differences were observed in mean daily symptom-medication scores, antiragweed IgG or IgE levels, leukocyte histamine release by ragweed, total IgE levels, or skin-test end-point dilutions with ragweed pollen extract between the group receiving ragweed pollen extract and the group receiving placebo. Despite the absence of specific effect on symptom-medication scores and measured immunologic variates, 10 of the 12 ragweed-treated patients and 10 of the 12 placebo-treated patients were of the opinion that their hay fever symptoms during the ragweed pollen season were less severe in 1978 than in 1977 and that they had been helped by Rinkel method immunotherapy. Under the conditions of the study, Rinkel method immunotherapy with ragweed pollen extract was no more effective than placebo given in an imitation of the Rinkel method.     

The effect of cromolyn sodium powder as a treatment for ragweed pollinosis

The effect of treating ragweed pollinosis with intranasal cromolyn sodium powder was evaluated in 26 patients in a double-blind clinical study. Thirteen matched patient pairs were treated by either nasal insufflation of cromolyn sodium powder, 20 mg three times daily, or by a placebo powder. Patients were monitored for severity of symptoms by means of daily symptom diaries collected weekly throughout the pollen season. Serum samples were obtained in July prior to the ragweed season and following the ragweed season during the first and fourth weeks of October for the determination of ragweed-specific IgE antibody levels by the radioallergosorbent test. A significant reduction in symptom severity was observed in the treated patients with high preseasonal levels of IgE antibody to ragweed. Initially the levels of IgE antibody to ragweed did not differ between the two groups. IgE antibody levels increased in both groups after pollen exposure, but the treated group showed a significantly greater rise in IgE antibody levels. The results suggest that treatment with cromolyn sodium enhanced IgE antibody response to pollen exposure and significantly reduced the severity of hay fever symptoms in patients with high preseasonal levels of IgE antibody to ragweed.     

Measurement of the absolute levels of IgE antibodies in patients with ragweed hay fever: Effect of immunotherapy on seasonal changes and relationship to IgG antibodies

The effect of immunotherapy with aqueous ragweed pollen extract on changes in IgE antibody was analyzed in 40 untreated patients with ragweed hay fever and compared to changes in 63 treated patients. Treated patients received cumulative doses prior to and during treatment ranging from 1.4 × 10⁵ to 4.8 × 10⁶ protein nitrogen units (PNU). IgG antibody to ragweed antigen E (AgE) was measured by radioimmunoprecipitation, while IgE antibody to allergens in crude ragweed extract was measured by the radioallergosorbent test (RAST). The RAST procedure was calibrated using a serum whose content of IgE antibody in nanograms per milliliter had been determined by immunoabsorption, and with this method the absolute quantities of IgE antibodies to ragweed allergens could be measured. Control experiments indicated that the IgG antibodies in the sera of the treated patients did not interfere with the measurements of IgE antibodies. The levels of IgE antibody in serum varied from less than 5 ng/ml to approximately 3,000 ng/ml. IgE antibodies decreased from October, 1973, to July, 1974, and rose sharply from July to October, 1974, following the pollination season. In both untreated and treated patient groups the magnitudes of the decreases were related (p < 0.001) to the levels of IgE antibody in October, and the magnitudes of the rises were related to the levels of IgE antibody in July. In the treated patients with IgE antibody less than 71 ng/ml in October, the rate of decrease (October to July) was less than in the untreated patients. Comparison of the rises in IgE antibody from July to October revealed that these were partially suppressed in the treated group (p < 0.001), and this effect was most marked in patients with July levels less than 36 ng/ml. Levels of IgG antibody to AgE in the treated patients were approximately 70-fold greater than in untreated patients and showed little change over the study period. The levels of IgG and IgE antibody in the treated patients were positively correlated (p < 0.001) at all time periods, and patients with high levels of IgG antibody also had greater declines and rises in IgE antibodies. The results indicate that immunotherapy is associated with (1) a reduction in the seasonal decrease in IgE antibody from October to July in patients with the low levels of IgE antibody, (2) a partial suppression of the rises in IgE antibody from July to October, and (3) that both these effects are related to the level of IgE antibody before the change. In many treated patients both IgE and IgG antibodies were low in spite of parenteral administration of ragweed extract. This result is consistent with the view that overall humoral immunologic reactivity to ragweed antigens is reduced in these patients.     

Comparison of the in-vivo and in-vitro response to ragweed immunotherapy in children and adults with ragweed-induced rhinitis

In order to compare results of allergen immunotherapy in paediatric and adult populations, 22 children with a history of ragweed hay fever were matched with an equal number of adults for skin sensitivity to ragweed and all were given a 1-year course of immunotherapy with a partially purified ragweed extract. Biological responses were measured by nasal challenges with ragweed before therapy was started, after 12 weekly injections and when the maintenance dose had been reached and also by methacholine bronchoprovocation tests before and after 12 months of therapy. Skin-test sensitivity to ragweed and control allergens, and ragweed-specific IgE and IgG antibody responses were measured at the same intervals as the challenges and at the end of the study. The effect of the therapy on clinical symptoms was not evaluated. Before therapy the groups of adults and children were comparable by all indices, except for TAME esterase activity in nasal washes during ragweed nasal challenge which was significantly lower in children. During treatment, mediators released during sequential nasal challenges declined to undetectable levels in most patients and changes in nasal ragweed sensitivity were comparable in both groups. Ragweed IgE increases after 12 weeks of therapy and IgG levels at maintenance therapy tended to be higher in the children, but neither difference was statistically significant. At the end of the study IgE and IgG antibody levels were comparable in both groups. Results of methacholine inhalation tests did not change significantly in either group. The decrease in skin sensitivity to ragweed was similar in both groups. We conclude that ragweed immunotherapy leads to immunological and biological consequences that are comparable in children and adults.     

Local nasal immunotherapy: efficacy of low-dose aqueous ragweed extract

In previous studies preseasonal local nasal immunotherapy (LNIT) with moderate doses of aqueous ragweed extract (mean total dose 59 micrograms of AgE and 139 micrograms of AgE) was an effective treatment for ragweed hay fever; however, local adverse reactions during therapy were common. This study evaluated the clinical and immunologic responses to LNIT by use of lower doses of aqueous ragweed extract in order to minimize these adverse reactions. Patients were administered preseasonal LNIT for 7 wk and received a mean total dose of 4.7 micrograms of AgE. During the ragweed season, symptom/medication scores (SMS) of the treated patients were equivalent to SMS of untreated patients. Serum ragweed-specific IgE and nasal secretory ragweed-specific IgA rose slightly in the treated patients but not to the extent observed in previous studies. After the ragweed season treated and untreated patients had a substantial increase in serum ragweed IgE antibody titers. No correlation could be found between antibody responses and SMS. This study indicates that LNIT with lower doses of aqueous ragweed extract is clinically ineffective.     

Polymerized whole ragweed: An improved method of immunotherapy

A single-blind study compared the effectiveness of glutaraldehyde-treated polymerized ragweed with nonpolymerized monomeric ragweed. These studies are an extension of those previously reported for polymerized AgE using a readily available ragweed preparation containing all ragweed antigens. Nineteen ragweed-sensitive patients were randomized into 2 groups; 10 received the polymerized form and 9 received the monomeric form. Four parameters were followed: serum-specific IgE against antigen E, total blocking antibody against antigen E, local and systemic reactions to injection therapy, and symptom score indices. Pretreatment levels of antigen E-specific IgE and blocking antibody activity were similar in both groups. After a total of 15,000 protein nitrogen units (PNU) had been given, blocking antibody activity in the monomer group rose from a mean of 173 ng AgE bound per ml to a mean of 2,813. The rise in blocking antibody activity in the polymer group was from a mean of 181 ng AgE bound per ml to 1,574. At 15,000 PNU, blocking antibody activity levels were not statistically different in the 2 groups. After 1 year of treatment, no consistent decrease in postseasonal specific IgE rise could be shown in either group. Forty times less erythema and 15 times less induration were found with polymerized ragweed. There were 7 systemic reactions with the monomer and none with the polymer. Both groups experienced symptomatic improvement with treatment.     

Local intranasal immunotherapy for ragweed allergic rhinitis II. Immunologic response

Local nasal immunotherapy (LNIT) was administered in a double-blind study to 67 subjects. Twenty-three received an unmodified ragweed extract (RW), 24 received a glutaraldehyde polymer of ragweed extract (PRW), and 21 received placebo. Serum ragweed-specific IgE (S-IgE), ragweed-specific nasal secretory (NS-) IgE, secretory IgA (SIgA) and IgG, and NS-albumin were measured. RW therapy caused a significant increase in ragweed-specific S-IgE (p < 0.005) and NS-SIgA (p < 0.05). PRW therapy caused a significant rise in ragweed-specific NS-SIgA (p < 0.001), NS-IgE (p < 0.05), and NS-IgG (p < 0.01). Ragweed-specific S-IgG was not affected by any of the treatments. There was no consistent correlation between NS-antibody levels and symptom/medication scores.     

Diagnostic tests in ragweed hay fever. A comparison of direct skin tests, IgE antibody measurements, and basophil histamine release

In 87 patients with both spring and fall hay fever symptoms the radioallergosorbent test (RAST) technique for specific IgE antibodies to ragweed was compared with basophil histamine release and direct intradermal skin testing by the threshold dilution technique. The three techniques gave good agreement except with the leastsensitive patients, some of whom had a positive skin test but undetectable histamine release or IgE antibodies. Twenty-one patients who were highly sensitive to ragweed as measured by all three techniques were followed without specific immunotherapy. There was significant agreement between the level of positivity of all three tests and the symptom index obtained during the ragweed season. In 14 of the 21 patients there was a significant correlation between daily ragweed pollen counts and daily symptom indexes during the season. On the other hand, among the 16 least-sensitive patients (as judged by histamine release) the correlation between daily ragweed pollen counts and symptom indexes was significant in only 3 patients. Other significant allergens could not be identified in the latter group, and the cause of their symptoms is not clearly identified but appears not to be ragweed. The RAST is a quantitative technique that gives diagnostically useful information in ragweed hay fever, although not significantly different from basophil histamine release or carefully performed skin testing. The convenience to the patient may, however, offer a noticeable advantage.     

Controlled evaluation of allergoid in the immunotherapy of ragweed hay fever

Immunotherapy with ragweed allergoid administered in a clustered regimen, placebos in a clustered regimen, and unaltered ragweed extract (allergen) in a weekly regimen were compared in three groups of hay fever patients carefully matched for ragweed sensitivity. The allergoid and placebo comparison was performed double-blind and the unaltered ragweed extract comparison was single-blind. In terms of antigen E (AgE) equivalents, doses were about 50 times higher in the allergoid-treated group than in the allergen-treated group. Whereas there was no immunologic response to placebos, the allergoid regimen produced a more rapid serum IgG antibody response, with significantly higher posttreatment levels than those in the allergen regimen. Initial IgE antibody rises and subsequent slow declines were similar. Symptom-medication scores were similar in the two specifically treated groups and significantly less than scores reported by the placebo group (p less than 0.01). Due to an overestimate of the initial allergoid doses, systemic reactions occurred mostly in the early visits with allergoid treatment, whereas systemic reactions appeared late in the allergen treatment. The overall incidence was similar. In a second year, after 8 mo of no injections, a preseasonal booster regimen with both materials produced virtually no untoward reactions. During the period of no injections, IgG antibody declines were modest and, after boosters, IgG antibody levels rose promptly. Clinical results in both groups were again excellent, with an advantage for allergoid.     

Preseasonal IgE ragweed antibody level as a predictor of response to therapy of ragweed hay fever with intranasal cromolyn sodium solution.

Intranasal administration of a 4% solution of cromolyn sodium for the treatment of ragweed hay fever was tested in an 8-week double-blind matched-pair study involving 66 patients. Patients on active drug received 5.2 mg into each nostril 6 times daily; control patients received a placebo spray. The treated group showed a significant reduction in mouth breathing (p less than 0.001), stuffy nose (p less than 0.002), runny nose (p less than 0.003), and postnasal drip (p less than 0.035). Patients receiving the active drug also reported fewer sneezing episodes (p less than 0.003) and nose blowing episodes (p less than 0.015). One patient using cromolyn solution developed nasal ulceration, tongue swelling, coughing, and wheezing. Other side effects were minimal and occurred with equal frequency in both groups. In the treated group relief of symptoms was most marked in patients with high preseasonal levels of IgE ragweed antibody. Intranasal 4% cromolyn solution appears to be an effective drug for the treatment of ragweed hay fever; measurement of the preseasonal level of IgE ragweed antibody is a useful screening test to identify patients most likely to achieve a maximal beneficial response to treatment.     

Seasonal changes in serum and nassal IgE concentrations

Sequential changes in serum and nasal IgE concentrations were examined in both hyposensitized and nonhyposensitized patients with ragweed hay fever. Concentrations as low as 0.1 ng. per milliliter of IgE in nasal washings could be measured directly by a modification of the double antibody radioimmunoassay. Serum IgE levels rose during the ragweed pollination season in all allergic groups, with the hyposensitized patients showing a more sustained elevation of serum IgE. Nasal IgE concentrations in allergic subjects were consistently elevated as compared to nonallergic subjects. The IgE content of nasal washings varied directly with total protein content. Because the protein content in turn varied widely from patient to patient, nasal IgE concentrations were expressed in terms of an IgE:total protein ratio ($\text{IgE}\text{TP}$). Nasal $\text{IgE}\text{TP}$ rose in most allergic patients during the ragweed pollination season, with the hyposensitized patients again showing a more sustained elevation. There was a strong correlation between nasal $\text{IgE}\text{TP}$ and serum IgE in the allergic patients. The results are interpreted in terms of the local production of IgE by cells in the nasal tissues and are consistent with the hypothesis that IgE, like IgA, is a secretory immunoglobulin.     

Regulatory role of prostaglandin E in allergic histamine release with observations on the responsiveness of basophil leukocytes and the effect of acetylsalicylic acid

This study examined the relationship between prostaglandin E (PGE) production and antigen-induced histamine release by leukocytes of asthmatic patients. The maximum amount of antigen-induced histamine release from leukocytes of different donors did not correlate with serum ragweed-specific IgE levels and correlated inversely with the basal PGE release from cultured leukocytes. The relationship betwen maximum histamine release and serum ragweed-specific IgE levels appeared to be influenced by the degree of PGE release. Patients with lower histamine release relative to ragweed-specific IgE levels had elevated PGE release. Based on these findings it can be hypothesized that spontaneously produced PGE might be a determinant of the responsiveness of basophil leukocytes to immunologic stimulation. This hypothesis was supported by demonstration of a positive correlation between the degree of inhibition of total basal PGE production in leukocyte suspensions during a short period of incubation and the degree of enhancement of antigen-induced histamine release by acetylsalicylic acid (ASA). The results indicate that, although the presence of IgE antibody in the blood may be the prerequisite for allergic histamine release from human leukocytes, endogenous PGE may be an important regulator of the release reaction. The results also suggest that idiosyncratic reactions to ASA and other nonsteroidal anti-inflammatory drugs observed in the allergic population may be at least partly due to impairment of the regulator function of endogenous PGE in the IgE-mediated histamine release reaction.     

Studies of HLA antigen frequencies, IgE levels, and specific allergic sensitivities in patients having ragweed hayfever, with and without asthma.

In order to study genetic and immunological features which might be important in the pathogenesis of asthma, forty-one ragweed allergic seasonal asthmatics were first matched with forty-one ragweed allergic nonasthmatics on the basis of similar total IgE levels. No significant differences were observed in their sensitivity to ragweed antigen E (measured by histamine release), or in their skin response to ragweed antigens E, Ra3 and Ra5. An increased frequency of HLA-B5 was observed in nonasthmatics as compared to asthmatics (P = 0-03). Although frequencies of HLA-A1 and B8 were also elevated in nonasthmatics and HLA-B40 in asthmatics, these differences were not significant. The forty-one asthmatic patients were than paired with forty-one nonasthmatics patients were then paired with forty-one nonasthmatics on the basis of leucocyte sensitivity to ragweed antigen E. Similar HLA differences were found which were non-significant. No significant difference in total IgE levels were found between the two groups. Whereas no differences in IgE synthesis or antigen sensitivity was found in the two populations, the frequency of HLA antigens needs further study in larger groups.     

Preseasonal intranasal immunotherapy with nebulized short ragweed extract

We determined the effect of preseasonal intranasal short ragweed (SRW) immunotherapy in a double-blind, nonpaired, 20-wk study involving 33 SRW-sensitive patients. Patients were selected on the basis of an elevated IgE serum antibody level, a positive intradermal skin test, and a positive intranasal challenge to SRW antigen. SRW-treated patients sprayed SRW solutions intranasally six times a day for 12 wk preseasonally. Placebo-treated patients used nebulized solutions containing buffer or histamine that were interchanged randomly throughout this period. The SRW-treated group reported more preseasonal symptoms than the placebo-treated group (p < 0.003); however, during the SRW pollination season, the SRW-treated group reported significantly less sneezing, nasal congestion, rhinorrhea, red/itchy eyes, itchy nose/throat, and cough/wheeze. Supplemental antihistamine usage was similar in both groups. The treatment did not affect serum IgE antibody levels to crude SRW, AgE, Ra3, or Ra5 in either group at any time during the study. No significant production of IgG antibody to SRW was seen in either group. One SRW-treated patient developed acute sinusitis after 2 wk of treatment; otherwise no side effects other than symptoms of hay fever were noted. Although intranasal SRW immunotherapy may offer an effective and less costly alternative to parenteral immunotherapy, reduction in hay fever symptoms during the pollination season was achieved at the expense of provoking these symptoms during the preceding weeks.     

Ragweed hay fever: treatment by local passive administration of IgG antibody

To determine whether the local administration of IgG antibodies might reduce the symptoms of ragweed hay fever, we tested the effect of this treatment in fourteen patients in a double-blind pilot trial. The patients were randomly divided into two groups, treatment and placebo, and their symptoms and medication usage were determined during the ragweed pollination season. One group used a nasal spray consisting of phosphate-buffered saline (PBS) containing human serum albumin, whereas the other used PBS containing purified IgG from a subject with a high titre of IgG antibody to partially purified ragweed antigen E. Treated and control groups used comparable quantities of nasal spray, and neither noted any ill effects. Comparison of individual symptoms of hay fever, medication usage, and total symptom scores showed no significant differences between the groups except a lessening of eye symptoms (P<0.05) in the treated group. The results suggest that nasal administration of IgG antibody up to five times daily does not alter the severity of symptoms in ragweed hay fever. Furthermore, total serum IgE protein and specific IgE levels increased comparably in both groups, suggesting that passive administration of IgG antibody does not suppress the production of IgE antibody during the pollination season.     

The role of ragweed pollen in autumnal asthma

Thirty-nine ragweed-allergic seasonal asthmatics were studied from 1972 to 1974. After quantitative skin tests, antigen E-induced leukocyte histamine release, quantitative inhalation bronchial challenge with ragweed extract to determine PD35 (provocation dose of allergen causing 35% decrease in specific airways conductance), and radioallergosorbent test (RAST) determinations were done, patients were paired based on PD35 values and randomly assigned to treatment or placebo groups, receiving either aqueous ragweed extract or placebo prior to the 1973 ragweed season. Treated patients received a mean cumulative dose of extract equivalent to 11.7 microng antigen E (4,180 protein nitrogen units [PNU]). Twenty-nine patients were followed through the ragweed season with daily symptom diaries and biweekly physician examinations. Severity of disease was not predictable by PD35 data, skin tests, leukocyte histamine release, or radioallergosorbent test (RAST) values. Although all patients were ragweed-allergic by objective tests, only 13/29 had asthma symptoms correlating with ragweed counts. Mold spore counts were related significantly to symptoms in some patients. Asthma and hay fever symptoms correlated significantly in 24/29 patients. This dose of immunotherapy caused no significant difference to be found in asthma or hay fever symptoms in treated versus placebo patients for the 1973 reporting period as determined by physician evaluations or daily symptom diaries. No patients showed significant improvement in PD35 values after treatment in 1973. Similar findings were obtained for a smaller group of patients followed through the 1974 ragweed season who received a mean dose of 31.2 microng antigen E (11,140 PNU). The failure of these patients to show a response to immunotherapy could be due to a combination of the relatively low dose of ragweed extract and their sensitivity to other allergens.     

Polymerized whole ragweed: Human safety and immune response

Polymerized ragweed (PRW) has been shown to have reduced allergenicity while maintaining immunogenicity. In order to evaluate whether the reduced allergenicity would permit high initial doses and rapid progression to maintenance, two groups of subjects with ragweed pollenosis were placed on immunotherapy with PRW standardized for antigen E (AgE) content. Group I, 28 subjects, received an initial dose of 100 protein nitrogen units (PNU) (1 μg AgE) and reached a maintenance dose of 1,000 PNU (10 μg AgE) in four weekly injections. In the first 10 wk each subject received 7,850 PNU (78.5 μg AgE). Group II, six subjects, received an initial dose of 100 PNU (1 μg AgE) and after 11 weekly injections received 30,000 PNU (300 μg AgE). No anaphylactic reactions occurred in the study groups. In group I, three large immediate-type local reactions and nine large late-type reactions occurred in 110 injections. Anti-AgE antibody activity in group I rose from a pretreatment mean value of 264 ng AgE bound per milliliter serum to a posttreatment value of 3,182. The major rise occurred after only 4 wk of therapy. In group II, anti-AgE antibody activity rose from 66 to 2,123 after the 11 wk of therapy. IgE antibody to AgE did not change to any extent in either group, and histamine release in response to AgE measured in group II patients did not change. Symptom score evaluation of group I patients revealed a marked decrease in symptoms after therapy with PRW. Immunotherapy with PRW can be initiated at higher doses, with rapid attainment of maintenance dosage with safety resulting in a brisk immune response and symptomatic improvement.