Jacob J. Pruzansky

Immunoglobulin E—mediated asthma and hypersensitivity pneumonitis with precipitating anti-hapten antibodies due to diphenylmethane diisocyanate (MDI) exposure

Two workers are presented who were exposed to diphenylmethane diisocyanate (MDI) while coating pipes with a polyurethane foam. After a latent period of exposure, worker A developed immediate-onset asthma and worker B developed a clinical picture of hypersensitivity pneumonitis for which he was hospitalized. The antibody response of these workers to a conjugate of MDI with human serum albumin (MDI-HSA) was measured by gel precipitation, total antibody binding of 125I MDI-HSA, and specific IgG and IgE antibody by polystyrene-tube radioimmunoassay (PTRAI). Worker B had precipitating antibody to MDI-HSA by double immunodiffusion in gel. Both workers had high levels of IgG antibody specific for MDI-HSA which had some cross-reactivity with a conjugate or toluene diisocyanate and HSA. Total serum antibody binding of 125I MDI-HSA was 15 microgram/ml in worker A and 900 microgram/ml in worker B. Both workers had serum IgE antibody specific for MDI-HSA as measured by two PTRIA techniques. These results indicate that a marked immunologic response to MDI is possible in exposed workers and that hypersensitivity pneumonitis can occur subsequent to the inhalation of a low-molecular-weight chemical in the industrail setting.

Histamine release from leukocytes of hypersensitive individuals: II. Reduced sensitivity of leukocytes after injection therapy

Abstract Four ragweed-sensitive patients were treated by courses of injections of aqueous ragweed extract. Specific histamine release from peripheral leukocytes and circulating antibody to purified ragweed antigen were measured at various times. During treatment, a progressive increase was observed in the concentration of antigen required to release a significant proportion of the total cellular histamine. No marked changes occurred in any patient before a total of at least 20, 000 PNU of ragweed extract had been administered. The level of circulating antibody rose during therapy. Changes in serum antibody preceded changes in sensitivity of the leukocytes. After treatment a decrease in symptoms during the next ragweed season was reported by each of the patients.

Systemic allergic reactions to ingested antigens

Abstract Fifteen cases of systemic allergic reactions to ingestant antigens are reported. The causative antigens were identified through exhaustive exploration of historical details. These antigens were penicillin, pinto bean, halibut, rice, potato, Brazil nut, shrimp, milk, a cereal mix, garbanzo bean, tangerine, salicylsalicylic acid, and demethylchlortetracycline. The importance of determining the causative antigen is emphasized. Before the cause was determined, 8 patients had recurrent anaphylaxis. These reactions were studied by certain immunologic methods. Cutaneous tests were positive in all patients tested except the salicylsalicylic acid and the demethylchlor-tetracycline reactors. Monkey P-K or human P-K reactions were performed with sera from 9 patients who had positive skin tests. All were positive. Specific release of histamine from leukocytes was detected in 7 of 9 patients studied. These methods are useful for studying immunologic reactions, but they do not establish or confirm a definitive diagnosis of clinically significant food allergy. The clinical and immunological characteristics of the cases are discussed.

Vibratory angioedema: A hereditary type of physical hypersensitivity

Abstract A new clinical entity has been termed vibratory angioedema (VA). This is inherited as a Mendelian-dominant characteristic. The manifestations consist of local erythematous and edematotis lesions following local stimuli of a vibratory or fractional nature. Marked local reactions are accompanied by facial or generalised erythema and headache. The systemic manifestations subsequent to intense local stimulation suggested the release of a vasoactive amine. Further evidence for this was provided by detection of elevated plasma amine levels in venous blood from an extremity following an appropriate stimulus. It was not established that this material was histamine or that it was an active participant in the local or systemic reaction. VA is a hereditary, immediate-type, nonimmunologic physical hypersensitivity reaction that may be associated with vasoactive mediator release.

Living histamine-containing cells from the bronchial lumens of humans. Description and comparison of histamine content with cells of rhesus monkeys.

Cell populations obtained by bronchial lavage from human subjects were examined for the presence of cells related to the mast cell-basophil series. Such bronchial lumen histamine-containing cells (BLHCC) were identified. The BLHCC stained with toluidine blue may be identified by bright field or dark field microscopy. The BLHCC are alive as evidenced by ability to release histamine (H) after exposure to anti-IgE or calcium ionophore. Although H release from peripheral blood leukocytes by these two agents is potentiated by the presence of D2O, H release from BLHCC of the same subjects by anti-IgE or calcium ionophore was not potentiated by D2O. In studies comparing bronchial cell populations of humans and rhesus monkeys with peripheral blood leukocyte populations of the same subjects, the histamine content of the bronchial cell population was much higher in rhesus monkeys. IgE/Alb ratios of respiratory secretions and serum of the same human subjects were of the same order of magnitude in contrast to previous comparisons done on these fluids in rhesus monkeys.

Immunology and immunopathology of trimellitic anhydride pulmonary reactions

Inhaled trimellitic anhydride (TMA) reacts with airway proteins to produce trimellityl (TM) proteins. THe TM-proteins result in both systemic and local immune responses, of which various proteins present in the airway can be used for markers. Thus TM-human serum albumin (HSA), TM-IgG, and TM-IgA can be used as hapten-protein complexes for immunologic studies in sera of humans exposed to TMA by inhalation. Various immunologic assays have been established to measure antibodies against TM-proteins and have various purposes. With TM-HSA as a model antigen, total serum antibody may be measured by the ammonium sulfate technique of coprecipitation of TM-125I HSA. By solid-phase radioimmunoassays, IgE, IgG, IgA, and IgM antibodies can be measured. Lymphocyte reactivity can be measured by 3H thymidine uptake of TM-protein-stimulated lymphocytes. Biological effects of IgE antibody can be measured by allergy skin tests and leukocyte histamine release with TM-proteins such as TM-HSA. The reaction of TMA with proteins results in alteration of those proteins that include changes in charge and physical conformation, the latter resulting in an apparent change in molecular size. These changes may relate to the observations that human antibody is not merely directed against the hapten in the hapten-human protein complex but also against new antigenic determinants formed by the TM-protein complex. Correlations have been made with certain human immunologic responses and lung disease after TMA inhalation, as follows: IgE antibody against TM-proteins correlates with TMA-induced rhinitis, conjunctivitis, and asthma; high levels of total antibody, IgG, and IgA antibody appear to correlate with the late respiratory systemic syndrome, probably a variant of hypersensitivity pneumonitis; workers exposed to TMA fumes (rather than TMA powder) have the highest levels of antibody, and this may correlate with occurrence of the hemorrhagic pneumonitis seen in this group of workers; patients with no symptoms or mild irritative symptoms have the lowest or no antibody levels. The immunopathogenetic relationships may be better understood with the further development of animal models to TMA lung disease now available.

Histamine release from leukocytes of hypersensitive individuals: I. Use of several antigens

Abstract Histamine release has been obtained from washed leukocytes of allergic individuals after incubation of the cells with a variety of specific antigens. With leukocytes from highly sensitive individuals who also had positive cutaneous reactions, a large proportion of the cellular histamine was released. Binding of labeled ragweed antigen did not appear to be closely related to the other parameters studied. Individual cells may be sensitive to more than one antigen but they may not be equally sensitive to all of the antigens with which they react. Virtually complete lysis of erythrocytes by brief suspension in distilled water does not affect histamine release by the leukocytes.

Quantitation and New Antigenic Determinant Specificity of Antibodies Induced by Inhalation of Trimellitic Anhydride in Man

We have studied the immune response of chemical workers who are exposed to trimellitic anhydride (TMA), a biologically reactive anhydride used in the manufacture of plastics. Serum antibody activity t

Ascaris hypersensitivity in the rhesus monkey: I. A model for the study of immediate type hypersensitivity in the primate

Abstract Immediate type hypersensitivity to Ascaris occurs in certain rhesus monkeys. This sensitivity is probably the result of cross-reactive antibodies directed against other nematodes following natural exposure to the latter. The antibodies present in the sensitive monkeys are of a reaginic type, being heat labile and nonprecipitating. The antibodies can passively sensitize monkey skin and have been localized by dextran gel chromatography. Systemic reactivity to Ascaris antigen is present in the animals and is thought to be a type of reaginic reactivity in subhuman primates.

Human Antihapten Antibodies in Trimellitic Anhydride Inhalation Reactions: IMMUNOGLOBULIN CLASSES OF ANTI-TRIMELLITIC ANHYDRIDE ANTIBODIES AND HAPTEN INHIBITION STUDIES

Inhalational exposure to trimellitic anhydride (TMA) produces an immediate-type asthmatic or a late respiratory systemic syndrome in certain workers after a latent period of work exposure. TMA has been found to react with proteins to produce a hapten-protein complex (trimellitate [TM] protein) or become hydrolyzed in aqueous, alkaline solutions to produce a salt, NaTM. Using a solid-phase radioimmunoassay technique, antibodies of different Ig classes were detected against TM-protein conjugates. IgE antibody was detected in three of five workers with asthma. IgG and IgA antibodies were detected in most exposed workers but higher levels of antibody were found in symptomatic workers even after long periods without direct TMA exposure. IgM antibody activity against TM-human serum albumin (TM-HSA) was detected but did not differentiate symptomatic from asymptomatic workers. NaTM served as a hapten for study because it does not react with proteins to form a hapten-protein complex as TMA does. The NaTM only partially inhibited IgG antibody activity against TM-HSA and much smaller amounts of TM-HSA than of NaTM were required to neutralize IgG antibody. A similar result was found with TM-ovalbumin. The latter results suggest that some IgG antibody is directed against a TM-protein moiety, probably a TM-amino acid determinant. In contrast to IgG, marked inhibition by NaTM of IgA and IgM antibody against TM-HSA was found in the sera studied.