PubMed Health⌕ Search

Biomedical subjects

D G Marsh

Publications and source records attributed to D G Marsh.

At least 109 records · Page 6Linked to original sources
PubMed1984

Demonstration of auto-anti-idiotypic antibody cross-reacting with public idiotypic determinants in the serum of rye-sensitive allergic patients.

The present study documents the presence, in the serum of one allergic individual, of auto-anti-idiotypic antibodies cross-reacting with public idiotypic determinants expressed on human IgE and IgG anti-Rye I antibodies. Sera from rye-sensitive patients were tested for specific IgG and IgE antibodies to Rye I by double antibody. The IgG fraction, isolated from the serum of a patient with a history of previous hyposensitization therapy, was repeatedly absorbed on Rye-I-Sepharose as well as on IgM- and IgG-Sepharose to remove anti-Rye I antibodies as well as any possible anti-heavy or light chain activity. This IgG fraction, named anti-idiotypic fraction (a-IdF), blocked in a dose-dependent fashion the reaction of IgG and IgE anti-Rye I antibodies with Rye I antigen. The a-IdF also blocked the binding of anti-rye antibodies to Rye I antigen in the serum of 20 unrelated allergic patients, indicating that these anti-Rye I antibodies bore public idiotypic determinants.

Adolescent↗
PubMed1983

Inheritance of immunoglobulin E: genetic model fitting.

Total serum immunoglobulin E (IgE) concentration was measured on 316 members of five pedigrees selected through breast cancer probands. Sex- and age-adjusted natural logarithm-transformed IgE level was not found to differ between individuals with breast cancer or with cancer of any site and other relatives. Likelihoods of the polygenic and of one-locus, two-allele major gene and mixed models were computed. The analysis provided evidence for the presence of a polygenic component in the determination of IgE; it did not show evidence of a major gene effect.

Alleles↗
PubMed1983

The inheritance of immunoglobulin E: genetic linkage analysis.

Linkage analyses between 21 genetic markers including HLA-A, B, and the postulated locus for determining total serum IgE levels were done to try to clarify the inheritance of total IgE levels and to map the locus. A total of 316 individuals from five Mormon kindreds were studied, and data from an additional 204 Amish individuals from 11 families were analyzed for possible HLA linkage. Segregation analyses of both data sets did not give clear definition of the mode of inheritance of total IgE levels, but purely environmental models were rejected. Linkage analyses gave significant evidence against HLA linkage with the codominant, recessive, or dominant model of inheritance for total IgE levels. No significant evidence for linkage with any of the genetic markers was obtained. Since total serum IgE levels are correlated with allergies, understanding the genetics of total IgE levels is important to understanding the genetics of allergic disease in man.

Blood Group Antigens↗
PubMed1983

The structuring of an allergy index based on IgE-mediated skin sensitivity to common environmental allergens.

We computed skin-test sensitivity levels in 485 adults puncture-tested with eight standardized, high-quality inhalant allergens tested at single concentrations. In order to quantitate the "average" IgE-mediated skin sensitivity of each subject, we used both nonparametric and parametric statistical methods to generate two "allergy indices" (Allergy Index I and Allergy Index II) based on sensitivity end-point data from the subpopulations of individuals positive to six of the eight allergens. For the 192 skin test-positive subjects, Allergy Index I and Allergy Index II were significantly correlated with each other (rs = 0.98, p less than 0.001) and with the number of positive skin-test reactions (rs congruent to 0.9, p less than 0.001) as well as with log[total serum IgE] (r congruent to 0.4, p less than 0.01). In 102 ragweed-positive subjects, log[specific IgE to ragweed] was significantly correlated with ragweed-specific "ragweed indices I and II" (r congruent to 0.6, p less than 0.01). Furthermore, the average daily symptom scores reported by 14 ragweed-positive subjects during the ragweed pollination season were significantly correlated with ragweed indices I and II (p less than 0.05). We propose the use of Allergy Index II in epidemiologic and genetic studies of allergic phenotypes as well as in clinical decisions for diagnosis and immunotherapeutic intervention.

Adult↗
PubMed1983

Antigens of Ambrosia elatior (short ragweed) pollen. III. Crossed radioimmunoelectrophoresis of ragweed-allergic patients' sera with special attention to quantification of IgE responses.

Short ragweed allergenic extract has been studied by means of crossed radioimmunoelectrophoresis (CRIE) with the use of sera from 37 allergic patients and the relevant control sera. In this study 22 of 52 antigens, detectable in crossed immunoelectrophoresis (CIE) against polyspecific rabbit anti-ragweed IgG, were able to bind specific human IgE to their corresponding immunoprecipitates. This binding was semiquantified by comparison with the binding of a standard serum pool. Nine antigens were identified as important allergens, including the previously isolated components, AgE, AgK, and Ra6. Certain allergens (e.g., AgE, AgK, and Ag 31) bound IgE in almost all patients' sera, whereas others showed a bimodal distribution for sera of responder and nonresponder patients. The total CRIE score was found to correlate significantly both with ragweed-specific serum IgE antibody determined by RAST (rs = 0.88; p less than 0.001) and with total IgE level (rs = 0.55; p less than 0.01). Patient's CRIE scores to AgE also correlated significantly with their specific IgE antibody to AgE measured by RIA (r = 0.47; p less than 0.01) and with skin-test sensitivity to AgE (r = 0.44; p less than 0.05). It was concluded that CRIE is well suited for identification of important ragweed allergens without the previous need for laborious isolation procedures.

Adult↗
PubMed1983

Isolation and properties of a new short ragweed pollen allergen, Ra6.

Two chromatographic forms (A and B) of the rapidly released short ragweed (Ambrosia elatior) pollen allergen Ra6 were isolated to antigenic ultrapurity by a combination of membrane filtration and ion exchange and gel filtration chromatography. Both Ra6 forms had a m.w. of 11,500 by gel filtration chromatography and 8000 by SDS-PAGE, and each consisted of two cathodically migrating bands on agarose electrophoresis at pH 8.5. Amino-terminal amino acid sequencing analysis detected two similar sequences (sequence 1 and sequence 2), which were present in different proportions in each of the chromatographic forms of Ra6. Among a ragweed-positive population sample (n = 101), 21% had specific IgE antibody (ab) and 42% specific IgG ab toward Ra6A; among ragweed-negative subjects (n = 260), 10.8% had IgG ab. We were unable to discriminate between Ra6A and Ra6B immunologically with the use of hyperimmune animal antisera or IgE and IgG ab from five Ra6-allergic humans. It appears that Ra6 is composed of at least four closely related isoallergens of similar size but slightly different charges and amino acid sequences, which appeared to be antigenically and allergenically indistinguishable according to present evidence.

Allergens↗
PubMed1982

HLA-Dw2: a genetic marker for human immune response to short ragweed pollen allergen Ra5. I. Response resulting primarily from natural antigenic exposure.

Ultra-pure short ragweed pollen allergen Ra5 (5,000 mol wt) was used to investigate the relationship between human leukocyte antigen (HLA) type and IgE and IgG antibody (Ab) responses to Ra5 in two groups of Caucasian subjects, totaling 447 people. Using highly sensitive radioimmunoassay procedures to measure serum IgE and IgG Ab, qualitative responses to Ra5 in both groups were found to be strongly associated with HLA-Dw2 (P less than 0.0001). For example, 95% of 38 people with IgE Ab vs. 22% of 139 ragweed-allergic persons having no detectable IgE Ab to Ra5 were Dw2+. Quantitative log [IgE Ab] and log[IgG Ab] responses to Ra5 were highly correlated with Dw2 (P = 10(-5) to 10(-14)) in four separate multiple regression analyses, examining the relationship between HLA type (and other variables) and Ab levels in the two study groups. Further studies showed that the primary association of Ra5 response was with Dw2 rather than DR2 and that various combinations of A3, B7, and Dw2 were less strongly associated than Dw2 alone.

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↗
PubMed1982

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.

Allergens↗
PubMed1982

A genetic study of total IgE levels in the Amish.

Relevant to the investigation of genetic factors involved in allergic response is the mode of inheritance of IgE levels, an important factor in allergic disease. Serum total IgE levels in 208 Pennsylvania Amish individuals from 23 nuclear families were studied. Males had a significantly higher mean in IgE level than females. There was also a significant negative relationship between age and IgE levels. Segregation analysis was used to fit a major gene model to the age- and sex-adjusted data. The environmental model was rejected (x2 = 41.12, p less than 0.005). The Mendelian codominant model was not rejected x2 = 8.84, p approximately or equal to 0.03) and gave a better fit to the data than the Mendelian dominant or recessive model.

Adolescent↗
PubMed1982

Antibody responses following immunotherapy with cat pelt extract.

IgG antibody responses to a major allergen, cat allergen 1 (cat 1), and to a minimally allergenic protein, cat albumin (alb), were studied in patients who had received 4 to 11 mo of immunotherapy with three concentrations of crude cat pelt extract. A double-antibody radioimmunoassay utilizing 125I-labeled antigen was used to measure IgG and IgE antibody. The high-dose group (HDG)(n = 5), which was composed of the active-treatment group of a previously reported double-blind study, received a mean cumulative dose of 3440 microgram cat 1 and 10,660 microgram alb. The intermediate-dose group (IDG) (n = 6) and low -dose group (IDG)(n = 5) received 70 and 0.930 microgram of cat 1 and 217 and 2.86 microgram of alb. IgE antibody to cat 1 before treatment was measurable in most patients. IgE antibody to alb was either no measurable or of a low level. Mean (geometric) before-and-after IgG levels (U/ml) to cat 1 in the HDG, IDG, and LDG were 420 and 7794, 158 and 1388, an 191 and 1365, respectively. Mean before-and-after IgG levels (U/ml) to alb in the HDG, IDG, and LDG were 72 and 348, 1.9 and 4584, and 0.4 and 508, respectively. Two patients (HDG) had no IgG antibody to alb after treatment. Another patient (HDG) had 82,364 U/ml IgG antibody to alb and precipitating antibody by gel diffusion. Very intense IgG antibody response to both cat 1 and alb were seen over a wide range of immunizing doses.

Adult↗
PubMed1982

Two isoallergens of short ragweed component Ra5.

Two isoallergenic forms of short ragweed (Ambrosia elatior) allergen Ra5 were isolated in ultrapure form by a combination of molecular sieving (through Amicon hollow-fiber cartridges), cation-exchange chromatography, and gel filtration. The two forms, Ra5A and Ra5B, exhibited charge differences by CM-Sephadex chromatography and agarose electrophoresis at pH 8.5. The A form as identical to conventional Ra5 by its physical and chemical properties and was more cationic than the previously undescribed B form. Ra5A and Ra5B had identical m.w. of 5000 by SDS-PAGE. Their amino-terminal sequences of 30 residues showed no differences from each other or from the previously published sequence of the major form of Ra5. The two forms were antigenically indistinguishable when using hyperimmunized animal antisera to Ra5 and crude ragweed extract. Although the IgG and IgE ab of most Ra5-responder patients could not discriminate between the two Ra5 forms, significant small differences in binding to Ra5A and Ra5B were consistently observed in 10 to 15% of the patients studied. Further analysis of the Ra5A preparation suggested a purity of at least 99.5% and probably greater than or equal to 99.9%.

Allergens↗
PubMed1981

A genetic-epidemiologic study of human immune responsiveness to allergens in an industrial population: I. Epidemiology of reported allergy and skin-test positivity.

Four hundred six subjects, comprising a 10% random sample of all employees, and a sample of "self-reported" allergic employees of a light industrial plant participated in an epidemiologic study of allergy. Puncture skin testing with a wide variety of crude allergens revealed a significantly higher prevalence of IgE-mediated sensitivity in males than females (29% males and 7% females in a random group; 60% males and 30% females in a self-reported allergic group); however, reported prevalence rates for "allergy" and different allergic symptoms were generally not different between males and females. Interestingly, reported asthma was greater in skin-test-positive subjects than in skin-test-negative subjects. We also noted a decrease in skin-test positivity with increasing age in self-reported allergic subjects. This was significant in the case of several crude allergens but not in the case of positivity to at least one allergen. We also found evidence that people born in and who have been resident in "Zone I) (MD, PA, Del, NJ, or DC) for most of their lives exhibit a greater prevalence of skin-test positivity than people who were born in and have lived for much of their lives in the northeastern United States (east of the Mississippi River and to the north of South Carolina) other than in Zone I.

Adolescent↗
PubMed1981

Human immunoglobulin E and immunoglobulin G antibody responses to the "minor" ragweed allergen Ra3: correlation with skin tests and comparison with other allergens.

We report here the use of antigen-binding assay to measure serum IgE and IgG binding activity (BA) for the "minor" ragweed antigen, Ra3. These studies were carried out in ragweed-allergic individuals, many of whom had been skin tested with Ra3 as well as with the "major" ragweed allergen, antigen E (AgE). IgE BA for Ra3 showed a weak quantitative correlation with skin-test sensitivity to Ra3. More strikingly, there was a threshold of skin sensitivity (< 10(-3) microgram/ml) above which serum IgE BA was likely to be detectable. Serum IgG BA for Ra3 measured in parallel with IgE BA was found in all sera that showed detectable IgE BA for Ra3. By contrast, 11/13 ragweed-allergic individuals who were skin-test negative for Ra3 showed no detectable IgG BA for Ra3. These results support the view that the known genetic controls over Ra3 sensitivity control IgG antibody as well as IgE antibody responses. Individuals receiving injections of ragweed extract showed increases in IgG BA for Ra3 following therapy. Among nine persons who had no IgG BA for Ra3 before treatment, four out of nine developed a low degree of IgG BA for Ra3. However, the patients who developed IgG BA did not develop detectable IgE BA for Ra3.

Adolescent↗
PubMed1981

Rapidly released allergens from short ragweed pollen. I. Kinetics of release of known allergens in relation to biologic activity.

Study of the kinetics of in vitro release of known antigens from short ragweed pollen revealed a slow release of AgE (1.5% to 4% release after 16 min) but a rapid release of other highly allergenic components. The rapidly released allergens in 16-min pollen extracts were found to be mainly highly basic proteins including the well-characterized Ra5 molecule along with several hitherto uncharacterized components. Considering previous data that suggest that particles of a similar size to ragweed pollen grains remain in the nose only about 6 to 8 min following inhalation, it is difficult to explain the apparent anomaly between the high biologic potency of 16-min extracts and their low AgE content. Increase in the pH of the extracting buffer from the physiologically normal nasal plH of 5.5 to 6.5 to about pH 8.0 to 8.5 (characteristically found in rhinitis) increased the proportion of AgE released after 16-min extraction by about 10-fold, suggesting that response to allergens in ragweed and other inhalants may enhance AgE release and thereby aggravate allergic symptoms. Detailed comparison of the allergenic activity of AgE and of 16-min and 4-day ragweed extracts in 38 ragweed-sensitive subjects suggested that allergens other than AgE were together more important than AgE in causing ragweed allergy in most patients, although large patient-to-patient differences in relative response were observed. Our data emphasize the need to reevaluate materials used in both diagnosis and treatment of ragweed allergy. The importance of AgE relative to other ragweed pollen components with respect to induction of allergic symptomatology deserves to be placed in a more balanced perspective.

Allergens↗
PubMed1981

Rapidly released allergens from short ragweed pollen. II. Identification and partial purification.

We have identified several basic allergens in 16-min extracts of short ragweed (Ambrosia elatior) pollen and obtained a partially purified fraction (G50 II) using a combination of ion-exchange (CM-Sephadex C25) and gel-filtration (Biogel P30 and Sephadex G50) procedures. G50 II was allergenically and antigenically distinct from known allergens antigen E, Ra3, and Ra5. It gave a highly symmetrical peak on Sephadex G50 (fine), corresponding to a molecular weight of 11,500 daltons, and a single band on SDS polyacrylamide gel electrophoresis under both reducing and nonreducing conditions. However, two cathodic antigens were detectable by both agarose electrophoresis and crossed immunoelectrophoresis. Allergenic activity of G50 II, assessed by puncture testing in ragweed-sensitive subjects, showed a characteristic pattern of response independent of patient response to AgE, Ra3, and Ra5. The major antigenic and allergenic component of G50 II is designated Ra6.

Allergens↗