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Biomedical subjects

D G Marsh

Publications and source records attributed to D G Marsh.

At least 91 records · Page 5Linked to original sources
PubMed1988

Association of HLA-DR3 with human immune response to Lol p I and Lol p II allergens in allergic subjects.

Associations between HLA type and IgE or IgG antibody (Ab) responses to two well-characterized, antigenetically non-crossreactive components of Lolium perenne (rye grass) pollen extract, Lol p I (Rye I) and Lol p II (Rye II) were studied in two groups of skin-test positive (ST+) Caucasoid adults. By both nonparametric and parametric statistical methods, significant associations were found between Ab responses to both Lol I and Lol II and the possession of HLA-DR3. In view of the well-known associations of both DR3 and B8 (which are in linkage disequilibrium) with many autoimmune diseases, differences in anti-Lol I and anti-Lol II mean log[Ab] levels between B8+, DR3- vs B8-, DR3- subjects and B8+, DR3+ vs B8-, DR3+ subjects were investigated. No differences were found. Our data, along with recent RFLP and DNA sequence studies, suggest that an Ia molecule involved in immune recognition of a similar major Ia recognition site of both the Lol molecules may consist of a DR3 alpha-beta I pair. Abbreviations used: Ab: Antibody. HLA: Human leukocyte antigen. Lol p I, Lol I: Group I allergen from Lolium perenne pollen (Rye I). Lol p II, Lol II: Group II allergen from Lolium perenne pollen (Rye II). Mr: Relative molecular mass. Rx: Immunotherapy with grass pollen extracts. ST: Skin test.

Allergens↗
PubMed1987

Immunochemical studies of Lolium perenne (rye grass) pollen allergens, Lol p I, II, and III.

It was reported earlier that human immune responses to three perennial rye grass (Lolium perenne) pollen allergens, Lol p I, II, and III, are associated with histocompatibility leukocyte antigen (HLA)-DR3. Rye-allergic people are often concordantly sensitive to all three of these allergens. Since earlier studies suggested that these antigens are non-cross-reactive, their immunologic relatedness by double antibody radioimmunoassay (DARIA) was studied in order to understand further the immunochemical basis for the concordant recognition of the three allergens. Direct binding DARIA studies were performed with human sera from 189 allergic subjects. Inhibition DARIA studies were carried out with 17 human sera from grass-allergic patients who were on grass immunotherapy, one goat anti-serum, and six rabbit antisera. None of the sera detected any significant degree of two-way cross-reactivity between Lol p I and II, or between Lol p I and III. However, the degree of two-way cross-reactivity between Lol p II and III exhibited by individual human and animal antisera varied between undetectable and 100%. In general, the degree of cross-reactivity between Lol p II and III was higher among human sera than among animal sera. Taken together with earlier findings that antibody responses to Lol p I, II and III are associated with HLA-HDR3, and that most Lol p II and III responders are also Lol p I responders, but not vice versa, our present results suggest the following: the HLA-DR3-encoded Ia molecule recognizes a similar immunodominant Ia recognition site (agretope) shared between Lol p I and Lol p II and/or III; in addition, Lol p I appears to contain unique Ia recognition site(s) not present in Lol p II and III. However, further epitope analyses are required to investigate these possibilities.

Allergens↗
PubMed1987

Immune responsiveness to Ambrosia artemisiifolia (short ragweed) pollen allergen Amb a VI (Ra6) is associated with HLA-DR5 in allergic humans.

The relationship between HLA type and specific immune responsiveness toward ultrapure Ambrosia artemisiifolia (short ragweed) pollen allergen Amb a VI (Ra6) was explored in a genetic-epidemiologic study of groups of 116 and 81 Caucasoid subjects who were skin-test positive (ST+) toward common environmental allergens. Specific immune responsiveness to Amb a VI was assessed by measuring serum IgE and IgG antibodies (Abs) by double Ab radioimmunoassay in both ST+ groups. Significant associations were found between IgE Ab responsiveness to Amb a VI and the possession of HLA-DR5; P values for the two groups were, respectively, 7 X 10(-7) and 1 X 10(-3) by nonparametric analyses, and 4 X 10(-11) and 5 X 10(-8) by parametric analyses. The levels of significance for the associations between HLA-DR5 and IgG Ab responsiveness were highly dependent on the extent of ragweed immunotherapy (Rx) within the patient group; by parametric statistics, the associations were 10(-11) for the group that had received relatively little Rx and 2 X 10(-3) for the group that had received more intensive Rx. These results provide further striking evidence for the existence of specific HLA-linked human Ir genes involved in responsiveness toward inhaled allergens and illustrate the usefulness of the allergy model in studies of the genetic basis of human immune responsiveness. Extension of these studies to investigation of structure-function relationships involved in antigen recognition by Ia molecules and the T-cell receptor will lead to a better understanding of human susceptibility toward immunologic diseases.

Antibody Formation↗
PubMed1987

An investigation of human immune response to perennial ryegrass (Lolium perenne) pollen cytochrome c (Lol p X).

Cytochrome c (Lol p X) was purified from the pollen of perennial ryegrass (Lolium perenne). It was used in a sensitive double-antibody radioimmunoassay to determine specific IgG and IgE antibody (Ab) levels in the sera of grass-allergic human subjects and the relationship between immune responsiveness and HLA type. A total of 139 subjects were studied, including 63 subjects treated by grass immunotherapy and 76 untreated subjects. The sera of only four subjects were found to contain anticytochrome c IgG Ab; there was no evidence of cytochrome c-specific IgE Ab in any of these patients. Based on these data, we conclude that the prevalence of IgE and IgG Ab responses to this protein is low. Because of the small number of responders, it was not possible to demonstrate a significant association between any HLA-D specificity and immune responsiveness to ryegrass cytochrome c.

Adult↗
PubMed1987

A study of the human immune response to Lolium perenne (rye) pollen and its components, Lol p I and Lol p II (Rye I and Rye II). II. Longitudinal variation of antibody levels in relation to symptomatology and pollen exposure and correction of seasonally elevated antibody levels to basal values.

This study used a standardized, dialyzed, Lolium perenne (ryegrass) pollen extract and two of its well-characterized components, Lol p I (Rye I) and Lol p II (Rye II), to characterize the longitudinal variation of both IgE and IgG antibody (Ab) levels, as well as total serum IgE levels, in 20 grass-allergic subjects followed for 13 months. Ab levels declined toward a basal level just before, and increased just after, the grass-pollination season, returning to the same basal level just before the next grass-pollination season. The least complex allergen, Lol II, demonstrated the most uniform pattern of variation in both IgE and IgG Ab levels. Total serum IgE levels demonstrated the least regular pattern of variation. Grass-pollen counts were strongly correlated with symptom-medication scores for these subjects (rs = 0.87). Initial values were correlated with the rise in total IgE and IgE Ab to Lol II across the grass-pollen season. Skin test results were correlated with initial IgE Ab levels for L. perenne pollen extract and Lol II. Finally, a procedure for correcting IgE Ab levels to basal values was proposed and tested. The correction procedure, for each IgE Ab, was based on the average rise during the grass-pollination season (or average decline after the grass-pollination season) observed for all subjects with that IgE Ab.

Adult↗
PubMed1987

Inheritance of total serum IgE (basal levels) in man.

Since allergic individuals with atopic allergy tend to have higher total serum IgE levels than do nonallergic subjects, family studies of total serum IgE levels are necessary in delineating the genetic and environmental factors involved in the expression of allergic disease. However, previous studies do not agree as to the genetic basis of total IgE production. To try to resolve this conflict, a total of 278 individuals from 42 nuclear families ascertained for large family size (at least four children) were studied. The families were not selected for the presence of allergic disease. Segregation analysis showed that the mixed model of recessive inheritance of high levels was most appropriate for these data--with approximately 36% of the total phenotypic variation in log[IgE] attributable to genetic factors, equally divided between a Mendelian component and a more general polygenic component. Thus, these data suggest some role for Mendelian control of basal IgE levels, but there is significant familial aggregation in IgE levels over and above that due to a Mendelian factor.

Analysis of Variance↗
PubMed1986

Dose of cat (Felis domesticus) allergen 1 (Fel d 1) that induces asthma.

In 10 patients with cat asthma and hay fever, we quantified the doses of cat allergen (expressed as cat allergen 1 [Cat-1] in log Food and Drug Administration [FDA] units) inspired from the ambient air of a room containing living cats required to induce a 20% drop in FEV1. These doses were compared with the doses required to cause the same change in FEV1 when the patients were subjected to bronchial challenge with aerosols of cat hair and dander extract in the conventional manner. Patients highly sensitive to cat extract by skin, leukocyte histamine release, and bronchoprovocation tests and with measurable levels of anticat IgE by RAST were exposed for up to 2 hours in a room occupied full-time by two cats. At the same time, room air was sampled by a Durham gravity sampler, by an Andersen sampler, and by lapel fiberglass filters. When hair and dander particles trapped on greased slides by gravity and Andersen samplers were stained, sized, and counted, squamous cell fragments in the less than 10 mm range were abundant. Assays of extracts from the lapel filters for Cat-1 content by radioimmunoassay and for allergenic activity by leukocyte histamine release demonstrated a significant correlation (p less than 0.05) between the results of the two assays. All patients developed rhinitis and asthma during exposure. At the time of a 20% drop in FEV1, when air sampling was stopped, the lapel filters had trapped a total of -1.86 to less than -3.04 (median -2.74) log FDA units Cat-1. These measurements of Cat-1 exposure in the room correlated (p less than 0.01) with the doses of cat extract (-1.18 to -3.15 [median -2.26] log FDA units Cat-1 equivalents) required to induce a 20% fall in FEV1 in the conventional bronchoprovocation tests.

Administration, Intranasal↗
PubMed1986

A study of the human immune response to Lolium perenne (rye) pollen and its components, Lol p I and Lol p II (rye I and rye II). I. Prevalence of reactivity to the allergens and correlations among skin test, IgE antibody, and IgG antibody data.

In a stratified random sample of 320 white adults, the prevalence of puncture skin test positivity (ST +) to Lolium perenne (rye grass)-pollen extract (LPE) was 16%. Fifteen percent of all subjects (or 84% of subjects classified LPE IgE antibody positive [Ab +]) was classified IgE Ab + to highly purified Lol p I (Rye I), and 4% of all subjects (or 26% of subjects classified LPE IgE Ab +) was classified IgE Ab + to highly purified Lol p II (Rye II). These data and similar results obtained in an allergy-enriched group of 361 subjects are consistent with previous studies that Lol I is a major allergen and Lol II is a minor allergen of LPE. Whether we studied LPE, Lol I, or Lol II, responder subjects were younger than nonresponder subjects and more male than female subjects were responders. We then investigated the quantitative interrelationships among ST, IgE, and IgG Ab responsiveness to LPE, Lol I, and Lol II in the allergy-enriched group. For each allergen, log-log correlations were strong and significant for ST versus IgE Ab and for IgE Ab versus IgG Ab. All subjects IgE Ab + to Lol I or Lol II were IgG Ab + to that allergen, supporting other evidence for a commonality in the genetic control influencing the production of IgE and IgG Abs to a given allergen. Log-log correlations among ST end points, IgE Ab levels, or IgG Ab levels were strong for LPE versus either Lol I or Lol II but weak between Lol I and Lol II, consistent with the reported lack of cross-reactivity between Lol I and Lol II. Despite these findings, almost all Lol II + subjects were Lol I + by ST (98%), IgE Ab (91%), and IgG Ab (83%), suggesting that the Ia-restricted immune recognition of both these molecules is at least in part under a common genetic control.

Adult↗
PubMed1986

Predicting skin test sensitivity and total serum IgE levels in family members.

A total of 278 individuals in 42 randomly ascertained nuclear families were studied to determine correlations among family members for skin test response and total serum IgE levels. The major aim was to determine whether these measures of allergic response in family members could be used to predict whether the last child in the family would be skin test positive. There were significant correlations in total log[IgE] levels between parents and their children and an even higher correlation between siblings. For the measurement of skin test response (allergy index), the only significant correlation was between siblings. Discriminant analysis was performed with the fourth child in the family as the index case. This was done to determine how many of the index cases could be correctly predicted to be skin test positive or negative based on family information. With just the skin test results on the parents, only three of the 13 positive index cases were correctly predicted. However, when the mean value for the skin test results in the siblings (mean allergy index) was used, eight of the 13 skin test positive index cases were correctly predicted. These results suggest that, although there is a high degree of concordance for allergic disease within families, information from other siblings may be the most useful predictor of allergic status in another child.

Adolescent↗
PubMed1986

Monoclonal antibodies to the major Lolium perenne (rye grass) pollen allergen Lol p I (Rye I).

Thirteen monoclonal antibodies (MAbs) were produced against Lol p I (Rye I), the major Lolium perenne (rye grass) pollen allergen. Spleen cells from A/J and SJL mice immunized with highly purified Lol p I (Lol I) were allowed to fuse with cells from the non-secreting Sp2/0-Ag14 myeloma cell line. Each MAb was analyzed for antigenic specificity by radioimmunoassay (RIA) using 125I-Lol I. The epitope specificities of seven of the MAbs were examined by competitive binding against a labelled standard MAb for the Lol I antigen (Ag). The dissociation constant, Kd, of one MAb (No. 3.2) that was studied most extensively was determined by double Ab RIA to be 3.5 X 10(-6) L/M. This MAb recognized the related 27,000-30,000 Group I glycoproteins found in the pollens of nine other species of grass pollens tested, including weak binding to Bermuda grass Group I (Cyn d I), which by conventional analysis using polyclonal anti-Lol I serum shows no detectable binding. Monoclonal antibody No. 3.2 was coupled covalently to Sepharose 4B and used to prepare highly purified Lol I from a partially purified rye pollen extract. Finally, an RIA was developed which permitted the analysis of the Group I components in rye grass and nine other grass pollen species. The latter assay is likely to prove useful in the standardization of grass pollen extracts according to their Group I contents.

Allergens↗
PubMed1986

A genetic-epidemiologic study of human immune responsiveness to allergens in an industrial population. III. Environmental influences on skin sensitivity and total serum IgE in a stratified random sample.

We quantitated puncture skin-test responses to 6 standardized, high-quality-inhalant allergen extracts in 320 adults - a stratified random sample, equally distributed between the sexes and among all decades between 20 and 60 years. For each subject, the 'average' IgE-mediated skin sensitivity to the entire panel of allergens (Allergy Index) was calculated. We evaluated correlations between log[total serum IgE]levels and Allergy Index versus quantitative measures of several environmental variables, including infection in childhood, residential history and smoking history. Age, sex and month bled were also included in these analyses. Although many significant intercorrelations were found among these variables, subsequent analyses by stepwise multiple regression showed that log[total IgE], age and smoking history were the best predictors of the Allergy Index and that the Allergy Index and sex were the best predictors of log[total IgE]. The negative relationship between smoking and skin-test responsiveness may reflect a tendency for allergic people to avoid the irritative effects of smoking on respiration. Our analyses, which simultaneously evaluated the effects of age, sex, Allergy Index and smoking history on log[total IgE]levels, did not support other studies which concluded that smoking significantly increases total serum IgE levels.

Adult↗
PubMed1986

Allergen nomenclature.

This article presents a nomenclature system for allergens which has been officially recommended by the International Union of Immunological Societies (IUIS). The nomenclature is based on proposals of the IUIS Sub-Committee for Allergen Nomenclature and is applicable to highly purified, well-characterized allergens and to non-purified or partially purified allergenic extracts.

Allergens↗
PubMed1986

Anti-idiotypes to anti-Lolp I (Rye) antibodies in allergic and non-allergic individuals. Influence of immunotherapy.

Anti-idiotypes (aId) reacting with anti-Lol I (Lolp I; Rye I) antibodies were detected by their ability to bind to radioiodinated F(ab')2 anti-Lol I. Sera were tested after removal of anti-Lol I and anti-heavy and light chain activity by adsorption on Lol I-Sepharose 4B and normal human serum Sepharose 4B. The binding of aId to Id was inhibited by affinity purified anti-Lol I but not by certain unrelated immunoglobulins; in some sera this binding was also inhibited by Lol I. The levels of aId were measured in serial bleedings collected over a 1 year period from Lol I-sensitive patients, allergic donors not sensitive to Lol I and non-allergic persons. In Lol I-allergic patients the levels of aId were significantly influenced by seasonal exposure to pollen and by immunotherapy with extracts of grass pollen. Moreover, in 12 out of 16 cases, there was also a significant inverse relationship between changes in serum levels of aId and of IgG or IgE anti-Lol I. Most interestingly, aId were also detected in non-allergic individuals; in this case, the levels of aId were not influenced by the pollen season. The data suggest that Id-aId interactions may play a role in the regulation of anti-Lol I antibody production.

Allergens↗
PubMed1985

The international collaborative study establishing the first international standard for timothy (Phleum pratense) grass pollen allergenic extract.

A selected candidate international reference preparation of timothy grass (Phleum pratense)-pollen extract was studied together with two other freeze-dried timothy pollen allergenic extracts in a multinational study. The collaborators used RAST inhibition, histamine release, quantitative immunoelectrophoresis (crossed immunoelectrophoresis/crossed radioimmunoelectrophoresis and rockets), isoelectric focusing, and other methods. The total allergenic potencies measured in RAST inhibition were evaluated for validity of linearity and parallel-line response. The relative concentrations of some important individual allergenic components were measured. The relative potencies for the total allergenic activity and the timothy components studied in each preparation were expressed relative to the selected candidate. This preparation was established in 1983 by the World Health Organization expert committee on biologic standardization as the international standard for timothy grass-pollen extracts with assigned units of 100,000 IU per ampule.

Allergens↗
PubMed1985

Immunochemical and genetic studies of Amb.t. V (Ra5G), an Ra5 homologue from giant ragweed pollen.

Giant ragweed pollen allergen Amb.t. V (Ra5G), a homologue of short ragweed pollen Amb.a. V (Ra5S), was isolated in ultrapure form from a 16-min extract of ragweed pollen by a combination of molecular sieving through an Amicon hollow fiber cartridge (H1P5), cation-exchange chromatography, and gel filtration. The size was found to be 4400 daltons (D) by amino acid analysis and 6000 D by SDS-PAGE, and the pI was 8.3 as determined by isoelectric focusing. There was no cross-reactivity detected between the two Amb. V antigens by immunodiffusion and IEP with the use of hyperimmune antisera raised against crude or highly purified antigens. Cross-reactivity between the two Amb. V antigens was further investigated by inhibition double antibody radioimmunoassay by using the sera of nine selected ragweed-allergic patients who had recently been immunized with either mixed short-giant ragweed pollen extract or with short ragweed extract alone and who had IgG antibodies (Ab) to Amb.t. V and generally to Amb.a. V. Unlabeled Amb.t. V did not inhibit the binding of 125I-Amb.a. V to the IgG Ab in any of the sera tested. Conversely, unlabeled Amb.a. V produced some inhibition of the binding of 125I-Amb.t. V to the patients' IgG Ab, primarily in those patients who had received immunotherapy with short ragweed alone. This weak cross-reactivity was probably a result of the primary structural homology between the two protein allergens. The sera from two groups of ragweed-allergic individuals were investigated for the presence of IgG and IgE Ab to Amb.t. V. The presence of IgG Ab was found to be associated both with previous (or current) immunotherapy with giant ragweed extract and with HLA-Dw2. The HLA association is of interest in view of the previously established association between Dw2 and response toward the homologue Amb.a. V. The result suggests the existence of a similar genetic control at the primary level of antigenic recognition of the two Amb. V antigens.

Allergens↗
PubMed1984

A genetic-epidemiologic study of human immune responsiveness to allergens in an industrial population. II. The associations among skin sensitivity, total serum IgE, age, sex, and the reporting of allergies in a stratified random sample.

We have quantitated puncture skin test responses to six standardized, high-quality, inhalant allergen extracts and histamine in 320 adults--a stratified random sample, equally distributed between the sexes and among all decades between 20 and 60 yr. Both the sensitivity of each subject toward histamine and his "average" IgE-mediated skin sensitivity to the entire panel of allergens (Allergy Index) were calculated. Allergy Index and Log [total serum IgE] values were weakly, but significantly, correlated (r = 0.453, p less than 0.001). Although both sexes reported similar prevalence rates of "allergy," we found that skin test positivity, Allergy Index, Histamine Index, and log [total serum IgE] were significantly higher (p less than or equal to 0.004) for the total population of male adults versus female adults. Skin test positivity, the Allergy Index, and log [total serum IgE] values demonstrated a tendency to decrease between 20 and 60 yr of age. Furthermore, log, age, and sex, respectively, were important predictors of the allergic state (Allergy Index) of an individual. Lastly, in various subgroups of our population, we found only weak correlations between the subjects' perceptions of their allergic status and both the Allergy Index and log [total serum IgE].

Adult↗