Doris Levitz

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.

Combined alveolitis and asthma due to hexamethylene diisocyanate (HDI), with demonstration of crossed respiratory and immunologic reactivities to diphenylmethane diisocyanate (MDI)

A worker exposed intermittently to hexamethylene diisocyanate (HDI) developed episodes of dyspnea, wheezing, and fever on working days. Complete lung function tests performed when the subject was asymptomatic were normal except for increased airway responsiveness to histamine, which significantly improved after a 3 wk period off work. At that time, specific inhalation challenges with HDI were carried out. After being exposed for 5 min, the subject developed general malaise, cough, fever, and leukocytosis, together with a mixed restrictive and obstructive breathing defect. We demonstrated a subsequent increase in airway hyperexcitability, which lasted for 2 mo. The subject was also challenged with diphenylmethane diisocyanate (MDI) for 15 min. A late obstructive reaction was documented. Increased levels of specific IgG antibodies against HDI-human serum albumin (HSA) and MDI-HSA were demonstrated.

Occupational asthma secondary to inhalation of garlic dust

An atopic patient in whom the inhalation of occupationally encountered garlic dust precipitated asthma is reported. Studies revealed the presence of immediate skin-test reactivity to garlic extract, and specific IgE anti-garlic antibodies were detected in the patients serum by the polystyrene tube solid phase radioimmunoassay (PTRIA) technique. Bronchial challenge with garlic dust also resulted in an immediate asthmatic response typical for an IgE-induced mechanism.

Syndromes in Workers Exposed to Trimellitic Anhydride: A Longitudinal Clinical and Immunologic Study

A longitudinal study of workers involved in the manufacture of trimellitic anhydride has been in progress since 1977. Trimellitic anhydride is a low-molecular-weight, reactive chemical used in the manufacture of plastics. Initial studies done in 1976 defined three syndromes due to inhalation of trimellitic anhydride: asthma-rhinitis, a late respiratory systemic syndrome, and an irritant response. Also, serologic techniques were developed to measure total antibody and IgE antibody to trimellityl human serum albumin. From 1977 to 1981, 64 workers were assessed. Six workers presented with asthma-rhinitis, high levels of IgE antibody, and skin test reactivity to trimellityl human serum albumin; five workers developed the late respiratory systemic syndrome; and one worker had both immunologic syndromes. These serologic measurements detected or were predictive of an immunologic respiratory illness and were useful in monitoring workers involved in the manufacture of trimellitic anhydride.

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

The Enzyme-Linked Immunosorbent Assay Method for IgG Antibody to Purified Protein Derivative in Cerebrospinal Fluid of Patients with Tuberculous Meningitis

Three patients with culture-proven Mycobacterium tuberculosis meningitis were studied. Analysis of cerebrospinal fluid with an enzyme-linked immunosorbent assay (ELISA) method measuring IgG antibody to purified protein derivative rapidly yielded positive results, whereas results of acid-fast smears were negative and cultures took several weeks before growth appeared. We did serial studies of cerebrospinal fluid and sera from one patient. Initially, greater amounts of IgG antibody to purified protein derivative were present in the cerebrospinal fluid than in the serum. The antibody level in the cerebrospinal fluid paralleled the patients clinical course, cerebrospinal fluid cell count, protein level, and glucose level. Cerebrospinal fluid samples from 33 hospitalized control patients were negative for antibody to purified protein derivative. The ELISA method measuring IgG antibody to purified protein derivative should be evaluated as a means of early diagnosis and management of patients with suspected tuberculous meningitis.

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 170 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.

A model of immunologic lung injury induced by trimellitic anhydride inhalation: Antibody response*

We studied lung injury induced in Sprague-Dawley rats by trimellitic anhydride (TMA) inhalation. Groups of 40 male and 20 female rats were exposed to TMA by inhalation at target concentrations of 0, 10, 30, 100, and 300 micrograms/m3, 6 hours per day, 5 days per week, for 2 weeks. Rats in each exposure group were sacrificed after 10 exposures or rested for 12 days and either sacrificed or received a 6-hour TMA challenge at their initial exposure levels and sacrificed at 24 hours. At each sacrifice, serum antibody to radiolabeled trimellityl rat serum albumin (RSA-TM) was measured by an ammonium sulfate technique, and lung pathology was determined. After 10 days of exposure, external hemorrhagic lung foci were directly related to the exposure concentration of TMA. Serum antibody binding of RSA-TM correlated with exposure concentration, hemorrhagic lung foci, and lung weight. There was healing of lung lesions 12 days after exposure with a return of lung lesions only 18 hours after the 6-hour inhalation challenge. A correlation between serum antibody to RSA-TM, hemorrhagic foci, and lung weight existed after challenge. This model clarifies two clinical entities observed in exposed workers, the late respiratory systemic and the pulmonary disease-anemia syndromes.

Comparison of the radioallergosorbent test and a quantitative solid-phase radioimmunoassay for the detection of ragweed-specific immunoglobulin E antibody in patients undergoing immunotherapy☆

Commercially available radioallergosorbent test (RAST) was compared with a quantitative solid-phase polystyrene tube radioimmunoassay (PTRIA) for the detection of ragweed-specific IgE antibody in sera of patients undergoing ragweed immunotherapy. Both assays showed good replication over a wide range of IgE antibody activity. The RAST was limited in the ability to discriminate between sera with high levels of specific IgE antibody. In addition, RAST gave falsely low values of IgE antibody activity in the presence of high levels of blocking antibody.

Polymerized whole ragweed: Human safety and immune response

Abstract 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.