A comparative study of the effectiveness of the Rinkel method and the current standard method of immunotherapy for ragweed pollen hay fever

In a double-blind study, we compared the effects of the Rinkel and the current standard methods of immunotherapy with ragweed pollen extract and those of placebo on symptoms of ragweed hay fever and immunologic parameters in 43 patients highly sensitive to ragweed. Each had a skin-test end point by Rinkel serial titration at 1:312,500 w/v or greater dilution, a 2+ skin test to ragweed AgE 0.01 μg/ml, and in vitro histamine release by ragweed pollen extract. None had had immunotherapy for at least 7 yr. Patients were matched on the basis of leukocyte histamine release to ragweed pollen extract and assigned to treatment groups. Fourteen received ragweed pollen extract by the Rinkel method, 14 received placebo, and 15 received ragweed pollen extract by the current standard method weekly between February and October, 1979. Rinkel method doses were derived from skin-test end points and were advanced to 0.5 ml of the end-point dilution; current standard method doses were advanced to the highest tolerated dose. The median maintenance dose for Rinkel method patients was 0.5 ml of 1:1,562,500 w/v (0.001 μg AgE), and for current standard method patients was 0.3 ml of 1:100 w/v (11 μg AgE). An additional unmatched group of nine similar patients received Rinkel method immunotherapy in both 1978 and 1979. Under the conditions of this study, the current standard method of immunotherapy produced a significant decrease in ragweed hay fever symptom-medication scores, increase in antiragweed IgG levels, and decrease in seasonal rise in antiragweed IgE levels in comparison with the effects of either Rinkel method or placebo. The effect of the Rinkel method on these variates was not significantly different from the effects of placebo.     

Comparison of Rinkel injection therapy with standard immunotherapy

We compared the results of a controlled, double blind study of standard immunotherapy (SIT) in subjects with ragweed hay fever during 1980 with the results of our study of Rinkel injection therapy (RIT) in a group of subjects with ragweed hay fever in 1979. Both groups were of comparable sensitivity. During the 1980 hay fever season in Milwaukee, 20 subjects with atopic rhinitis due to ragweed pollen (eight from the 1979 group treated with RIT) were given SIT (Tr), while 14 matched subjects (eight from the 1979 placebo group) were treated with a histamine placebo (Pl). The same glycerinated aqueous ragweed extract and glycerinated histamine placebo were used in both studies. The mean cumulative dose of ragweed extract in the 1980 study was 5391 PNU (20.1 μg of antigen E [AgE]) as compared with 41.5 PNU (0.16 μg of AgE) in 1979. Results indicated a significantly lower weekly mean symptom score (SxSc) in the Tr group compared with that of the Pl group in 5 of the 6 wk that ragweed pollen was counted in 1980. Weekly mean medication score (MxSc) and physical exanination score (PESc) showed similar but less striking differences. The mean seasonal SxScs, MxScs, and PEScs of the SIT Tr group were significantly lower than those of the Pl group in 1980 as well as those of the RIT Tr group in 1979. The same indices were also significantly lower in 1980 by paired analyses in the subset of eight subjects treated in both years. RAST scores showed a significant decrease in the “after season” means in the Tr group as compared with the Pl group in 1980 but not in 1979 (analysis of covariance). We conclude that SIT is more effective than a placebo or RIT in reducing SxSc, MxSc, and PESc as well as in diminishing postseason RAST values. We cannot recommend therapy as proposed by Dr. H. J. Rinkel for clinical use at this time.     

Reactivity of ragweed allergens with IgE antibodies. Analyses by leukocyte histamine release and the radioallergosorbent test and determination of cross-reactivity.

Five distinct proteins with allergenic activity have been isolated from short ragweed pollen. We initially tested three of these, AgE, AgK, and Ra3, for reactivity with IgE antibodies by leukocyte histamine release and by the radioallergosorbent test (RAST). We found highly significant correlations between the reactivities of these allergens by leukocyte histamine release and by the RAST, consistent with the view that both procedures detected comparable allergenic activity. We next tested the allergenic cross-reactivity of all five ragweed allergens. AgE, AgK, Ra3, Ra4, and Ra5, by RAST inhibition. With solid-phase AgE the only nonhomologous inhibitor was AgK, which cross-reacted weakly and required a 140-fold mass excess of AgK compared to AgE. With solid-phase AgK both AgK and AgE produced significant inhibition; AgE was slightly more potent than the homologous AgK, Ra3 and Ra5 were allergenically unique, because only the homologous allergen produced 50% inhibition. Ra4 was weakly inhibited by AgE, Ra3, and Ra5 when these allergens were added in 300- to 5---fold mass excesses; this weak inhibition may represent either cross-reaction or cross-contamination. We found that RAST inhibition could be used as an assay for the individual ragweed allergens and we demonstrated the presence of all of the allergens in a whole ragweed extract. The sensitivity of the RAST inhibition assay ranged from 10 ng to 100 ng for 50% inhibition. Finally, the solid-phase ragweed allergens were used to determine the frequency of elevated IgE antibody levels in 65 patients with ragweed hay fever. Virtually all of the patients reacted with AgE (97%), while 88% reacted with AgK, 51% reacted with Ra3, 28% reacted with Ra4, and 17% reacted with Ra5. These results highlight the usefulness of the RAST as a specific and sensitive tool for immunochemical studies of allergens.     

A comparison of immunotherapy schedules for injection treatment of ragweed pollen hay fever

In 44 patients highly sensitive to ragweed, we compared weekly injections of single doses of ragweed extract (RW-Wk, 15 patients) with clustered doses of ragweed extract at 3-wk intervals (RW-Cl, 18 patients) and with placebo (11 patients) for effects on ragweed hay fever symptom-medication scores and immunologic variates. Patients were matched and randomly assigned to treatment groups. Ragweed doses were advanced to the highest tolerated dose. Doses and number of visits were lower in the RW-Cl group than in the RW-Wk group. Despite lower doses, systemic reactions were not reduced and antiragweed IgE levels increased significantly more in the RW-Cl group than those in the RW-Wk group. Both the RW-Cl and RW-Wk groups had significant increases in antiragweed IgG levels, decreases in seasonal rise in antiragweed IgE levels, and lower symptom-medication scores (p < 0.01) in comparison with the placebo group. We conclude that the RW-Cl regimen offered no important advantage over RW-Wk. Seventeen patients had previously received Rinkel-method immunotherapy with 0.5 ml of end-point dilution of ragweed extract for 1 to 2 yr without significant clinical improvement or immunologic changes. After adequate treatment with either RW-Wk or RW-Cl, these patients had significantly lower symptom-medication scores than those of the placebo group and immunologic changes similar to those of the entire active-treatment group. Therefore, treatment failures on Rinkel immunotherapy respond well to adequate dose immunotherapy by either schedule.     

A multi-institutional trial of polymerized whole ragweed for immunotherapy of ragweed allergy

Eighty ragweed-sensitive patients in four cities were recruited to study the safety and efficacy of partially purified, polymerized whole ragweed (PRW) as an improved form of immunotherapy. Groups of 20 patients in Chicago, Boston, Memphis, and St. Louis had blood drawn for immunologic studies before and after the 1978 and 1979 ragweed seasons and completed detailed daily symptom score sheets each day of the 1978 and 1979 ragweed pollen seasons. Beginning in March, 1979, all patients except one received 15 weekly injections of PRW totaling 50,000 protein nitrogen units (PNU) and containing about 500 μg ragweed AgE. One patient received 25,000 PNU. Symptom score indices of the posttreatment 1979 season were compared with those from the pretreatment 1978 season and also with the scores of similar groups of ragweed-sensitive patients in each city treated only with medication for symptomatic relief during the 1979 season. Local reactions to polymerized ragweed immunotherapy were minimal. No abnormalities in complete blood count, erythrocyte sedimentation rate, chest x-ray film, urinalysis, or rheumatoid factor occurred in the immunotherapy-treated groups. Total serum antibody binding of ragweed AgE increased 12-fold following immunotherapy. When compared either with their 1978 untreated group scores or when compared with scores from the untreated group in each city in 1979 (control group), the symptom score indices of the immunotherapy-treated groups in 1979 were significantly improved. PRW is efficacious in the treatment of ragweed hay fever and can be administered more safely and in higher doses with fewer injections than conventional extracts. It represents an improved form of immunotherapy.     

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.     

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.     

The clinical and immunologic specificity of immunotherapy

In order to study the specificity of immunotherapy for respiratory allergy, a group of patients sensitive to both ragweed and grass pollens were selected. From 87 volunteers with a history of both spring and fall hay fever, 42 patients with evidence of strong sensitivity by basophil histamine release to both ragweed pollen and mixed grass pollen extracts were selected for study. On the basis of the histamine release data, the patients were divided into two groups matched for sensitivity to both grass and ragweed pollens. In 1970, May and June symptom diaries showed the two groups to suffer quite similar severity of symptoms during the grass pollination season. One group of patients was started on a preseasonal course of immunotherapy with alum-precipitated aqueous extract of ragweed pollen while the other group received placebos containing histamine. By fall there had been a considerable rise in IgG-blocking antibodies to ragweed in the treated group. Symptom diaries in August and September showed that the treated group showed significantly less severe symptoms than the placebo group. Both groups received booster injections at 2-wk intervals from the fall of 1970 to the fall of 1971. Doses in the treated group were raised to attempt to administer the largest possible dose. Again there was no difference in the symptoms reported by the two groups during the grass pollination season, but an even greater difference emerged between the two groups during the ragweed season. The following year 1972 the same results were obtained. These data demonstrate that treatment with ragweed pollen extracts has little or no effect on grass pollen symptoms and confirm that immunotherapy is clinically as well as immunologically specific. Antibody responses to the second year of high-dosage booster injections was not greater than responses to a comparatively short preseasonal course given the first year.     

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.     

Rinkel injection therapy: a multicenter controlled study

The American Academy of Allergy sponsored a 2-yr “double blind” multicenter study of the effect of Rinkel injection therapy (RIT) compared with a histamine placebo in subjects with atopic rhinitis. Accumulated data included the symptom, medication, and physical examination scores and specific IgE antibody levels measured by the radioallergosorbent test (RAST). A total of 155 subjects (81 treated, 74 placebo) entered the project from six centers during their respective ragweed, grass, and mountain cedar pollen (from one center) seasons for a total of 11 pollen seasons. The total mean cumulative dose of extract was 18.6 PNU, which is much lower than recommended for standard immunotherapy. With one exception, none of the centers reported a consistent significant difference between the pollen extract-treated and placebo-treated groups in any of the weekly mean scores or the RAST before, during, and after the pollen seasons. For 4 wk after the height of the mountain cedar season the group treated with pollen extract showed a significant decrease in weekly mean symptom and medication scores as compared with the placebo group. The overall comparison of the mean seasonal scores for the entire study, however, showed no significant difference between the treated and placebo groups. We conclude the RIT is no more effective than a histamine placebo in influencing the weekly mean symptom, medication, and physical examination scores or IgE antibody levels.     

Capacity of purified antigens and whole pollen extracts to release histamine from leukocytes of hay fever patients

Eighty-seven consecutive patients appearing with complaints suggestive of spring and fall hay fever were subjected to basophil histamine release study with 4 antigenic preparations: whole ragweed extract, antigen E of ragweed, mixed grass pollen extract, and Group I antigen of rye grass. Among the 87 patients, 12 failed to release histamine to ragweed extract or antigen E and 16 failed to release histamine to grass extract or Group I. Among the remaining patients 5 reacted to whole ragweed extract but not antigen E and 2 reacted to mixed grass extract but not Group I. The patients with this pattern were all at the lower end of the spectrum of sensitivity for the crude extracts. These data tend to confirm that antigen E and Group I are the antigens of prime importance in the majority of hay fever patients with ragweed and grass pollen sensitivity respectively.     

Polymerized whole ragweed: A two-year follow-up of patients treated with an improved method of immunotherapy

We have previously reported, in a 1-yr study, the effectiveness of polymerized ragweed (PRW) as an improved method of immunotherapy for patients suffering from ragweed hay fever. In that study, treatment with PRW was found to be superior to treatment with monomer ragweed extract (MRW) because of the reduced allergenicity of the PRW. The current study is a 2-yr follow-up of nine patients treated with PRW and nine patients treated with MRW. After 1 yr of immunotherapy, both MRW- and PRW-treated patients received 9,000 protein nitrogen units (PNU) and after a second year of maintenance therapy both groups received a cumulative dose of 15,000 PNU. Serum blocking antibody against ragweed antigen E (AgE) was measured periodically during the study. After 1 yr of immunotherapy, blocking antibody in the PRW- and MRW-treated groups was similar with respective means of 1,300 and 1,500 ng AgE bound per milliliter of serum. At the end of 2 yr of therapy, these serum AgE binding activities rose to 2,700 and 4,100, respectively. No significant local or systemic reactions occurred in the PRW-treated group during the year of maintenance therapy. However, large local reactions prevented three of the nine patients treated with MRW from achieving a monthly maintenance schedule. A significant decrease in rhinitis symptoms was noted in both treated groups as compared with the season before immunotherapy and also to a group of patients untreated with immunotherapy during the 1978 ragweed season.     

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.     

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.     

Effect of immunotherapy on immunoglobulin E and immunoglobulin G antibodies to ragweed antigens: a six-year prospective study

The effect of immunotherapy with aqueous short ragweed (SRW) extract on IgE and IgG antibodies was tested over a 6 yr period in 47 adults with ragweed hay fever. Sera were collected each year in July and October from 1973 through 1979. In May 1976, 23 patients began immunotherapy with a lyophilized standardized SRW extract. From 1976 through 1979, treated patients received an average total dose of 4.8 × 10³ protein nitrogen units (1039 μg of AgE). IgE antibodies to SRW and ragweed AgE were measured by the radioallergosorbent test (RAST) in antigen excess using allergens bound to Sepharose. Blocking antibodies primarily of the IgG class were measured by RAST interference. In response to inhalation of ragweed pollen, untreated patients showed seasonal rises (July to October) and postseasonal falls (October to July) of IgE antibodies during the entire study period. IgE antibody levels in the untreated patients decreased with time and from 1974 to 1979 fell 41% (p < 0.003) for an average halftime of 6.2 yr. Before immunotherapy, treated patients also showed seasonal rises and postseasonal falls. Treatment with SRW extract in 1976 produced an abrupt increase in IgE and IgG antibodies and a clear-cut suppression of seasonal rises of IgE antibodies without an effect on postseasonal falls through 1978. From 1974 to 1979, IgE antibodies to AgE and SRW decreased more in the immunized group than in the control group, and by 1979 these levels showed a mean fall of 73%. Blocking antibodies increased in the treated patients and reached maximal levels by July 1978. In 1978 and 1979, the levels of IgG blocking antibodies to AgE were inversely related to the IgE antibody levels to AgE. These results indicate that adults with ragweed hay fever show regular seasonal and postseasonal changes in IgE antibodies and that IgE antibodies spontaneously decrease with time. Immunotherapy magnifies these decreases by suppression of the seasonal rises, but it does not affect the postseasonal falls.     

Index to volume 66

Eighty ragweed-sensitive patients in four cities were recruited to study the safety and efficacy of partially purified, polymerized whole ragweed (PRW) as an improved form of immunotherapy. Groups of 20 patients in Chicago, Boston, Memphis, and St. Louis had blood drawn for immunologic studies before and after the 1978 and 1979 ragweed seasons and completed detailed daily symptom score sheets each day of the 1978 and 1979 ragweed pollen seasons. Beginning in March, 1979, all patients except one received 15 weekly injections of PRW totaling 50,000 protein nitrogen units (PNU) and containing about 500 μg ragweed AgE. One patient received 25,000 PNU. Symptom score indices of the posttreatment 1979 season were compared with those from the pretreatment 1978 season and also with the scores of similar groups of ragweed-sensitive patients in each city treated only with medication for symptomatic relief during the 1979 season. Local reactions to polymerized ragweed immunotherapy were minimal. No abnormalities in complete blood count, erythrocyte sedimentation rate, chest x-ray film, urinalysis, or rheumatoid factor occurred in the immunotherapy-treated groups. Total serum antibody binding of ragweed AgE increased 12-fold following immunotherapy. When compared either with their 1978 untreated group scores or when compared with scores from the untreated group in each city in 1979 (control group), the symptom score indices of the immunotherapy-treated groups in 1979 were significantly improved. PRW is efficacious in the treatment of ragweed hay fever and can be administered more safely and in higher doses with fewer injections than conventional extracts. It represents an improved form of immunotherapy.     

Quantitative inhalation bronchial challenge in ragweed hay fevery patients: a comparison with ragweed-allergic asthmatics.

Fourteen ragweed hay fever nonasthmatic patients comparably sensitive to a group of ragweed-allergic asthmatics by skin test and leukocyte histamine release were tested by quantitative inhalation bronchial challenge with ragweed extract. The provocation dose of ragweed extract producing 35% decrease in airway conductance was determined and designated PD35. PD35 values in the hay fever patients were not significantly different from PD35 values in the asthmatic group. These data suggest that carefully performed skin tests may be as diagnostically useful as bronchial challenge in routinely confirming the allergic etiology of seasonal asthma.     

Immunologic responses to conjugates of antigen E in patients with ragweed hay fever

Allergens conjugated with several simple repeating polymers have reduced allergenicity in man, but large doses retain the ability to suppress ongoing allergen-specific IgE synthesis in strains of high-responder mice. To determine whether suppression of IgE antibodies could be induced in man, preliminary trials of immunologic responses to conjugates in man were carried out in ragweed hay fever patients treated with antigen E (AgE) coupled to methoxypolyethylene glycols ( MPEGs ) of 5000 and 2000 daltons, lauryloxypolyethylene glycol of 1200 daltons, and a random copolymer of D-lysine and D-glutamic acid of 69,000 daltons. In varying degrees all these conjugates had reduced allergenicity by basophil histamine release when these conjugates were compared with native AgE and could suppress IgE response in mice. Patients received one of these conjugates or native AgE in a series of subcutaneous injections and were observed for allergic reactions. The conjugates induced a lower rate of systemic reaction than native AgE but failed to induce early suppression of IgE antibodies. Instead, early rises in IgE antibody occurred in the several groups and were followed by a slow decline during a year or more that was similar to that observed with standard immunotherapy. Because the conjugates eventually caused local and systemic allergic reactions as the dose was raised, it was not possible to test the IgE-suppressive effects at doses similar to those used in mice. In contrast, rapid sustained rises in IgG antibodies occurred in all groups. The MPEG conjugates appeared to be more effective than native AgE in this regard. The reduced rate of systemic reaction and rapid rise in IgG antibody that was noted with MPEG conjugates make them worth further exploration as agents for immunotherapy.     

The immune response of patients with ragweed hay fever treated with polymerized ragweed antigens.

This report describes the immune response of patients with ragweed hay fever treated with polymerized ragweed antigens (PRW). Their IgG antibody responses to crude ragweed extract, antigen E, antigen K, and antigen Ra3 were determined by a solid-phase radioimmunoassay. The results indicate that PRW contains an array of clinically important antigens that are available for immunologic processing and result in an immune response in patients treated with this new form of immunotherapy for ragweed hay fever.     

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.