Standardization of modified allergens using polymerized ragweed as a model system.
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Allergens↗
Biomedical subjects
L C Grammer
Publications and source records attributed to L C Grammer.
Six-year clinical and immunologic follow-up of workers exposed to trimellitic anhydride.
We report a 6-year study from 1979 through 1985 of workers exposed to trimellitic anhydride (TMA) in three groups of volunteers. Twenty-nine percent of workers (5/17) originally studied had immunologically induced respiratory disease. Subsequent to this evaluation, increased environmental control of TMA exposure was instituted. Since that time, there have been decreasing clinical symptoms and decreasing levels of antibody against TMA conjugated to human serum albumin. These long-term studies originally used radioimmunoassays, but enzyme-linked immunoassays against TMA-conjugated proteins are now demonstrated to be equally appropriate and are more cost-effective. With appropriate clinical and immunologic studies, immunologic airway reactions to TMA may be identified and then prevented by environmental control to decrease inhalation exposure to TMA. This is likely applicable to certain other chemical antigens that immunize by inhalation.
Air Pollutants, Occupational↗
The safety and activity of polymerized ragweed: a double-blind, placebo-controlled trial in 81 patients with ragweed rhinitis.
Eighty-one patients with ragweed pollinosis were recruited for a double-blind, histamine placebo-controlled study of the safety, immunogenicity, and efficacy of 15 weekly injections of polymerized ragweed (PRW) immunotherapy totaling 1359 allergy units. Patients were paired on the basis of cutaneous end point titration to RAST standardized extracts of giant and short ragweed. One patient of each pair was randomized to receive PRW, and the other patient, a caramelized glucose histamine placebo. Symptom and medication score diaries were completed by 68 patients. All 68 patients received the full maintenance dose. No patient dropped out because of adverse reactions, and there were no systemic reactions. Except for one patient receiving placebo who developed mildly elevated liver function tests, there were no clinically significant changes in routine laboratory tests associated with injections. By Student's test on log-transformed values, blocking antibody rose significantly in the patients receiving PRW but was unchanged in those receiving placebo. By Wilcoxon paired signed-rank test, the symptom and medication scores in the patients receiving PRW were significantly lower than scores in the patients receiving placebo. This study demonstrates the safety, immunogenicity, and activity of PRW in the treatment of ragweed pollinosis.
Adult↗
Formaldehyde reactions and the burden of proof.
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Antigens↗
Provocative challenge with local anesthetics in patients with a prior history of reaction.
Possible allergic sensitivity to local anesthetic agents remains problematic for some patients who could benefit from their use. We retrospectively reviewed all our consultations for evaluation of local anesthetic allergy from 1965 to 1985 to assess the safety and efficacy of skin testing and provocative test dosing with a variety of local anesthetic agents. Fifty-nine patients reported 70 reactions from the administration of six different local anesthetics. Fifty-four patients could name one or more local anesthetic agents they believed were responsible, and five patients named only "caine" drugs. Multiple reactions of the same type to the same agent were considered as one reaction. On the basis of their history of reaction, the patients were categorized as follows: anaphylactoid reactions (urticaria, angioedema, wheezing, or hypotension within 1 to 2 hours of exposure), possible anaphylactoid reactions (tachycardia, dizziness, syncope, breathlessness, or pruritus occurring within 1 to 2 hours of exposure), contact dermatitis (a typical eczematous skin eruption after appropriate cutaneous sensitization), and other reactions (nonanaphylactoid reactions other than those already described or those occurring more than 2 hours after exposure). Fifty-nine patients were administered local anesthetics after skin testing and provocative test dosing, including two patients who required intravenous lidocaine (Xylocaine; Astra Pharmaceutical Products, Inc., Westboro, Mass.) acutely to control cardiac arrhythmias. These two patients had reported anaphylactoid reactions to oral antiarrhythmic drugs of the local anesthetic class. Despite the history of previous reactions, there were no positive skin tests or positive provocative drug challenges in any patients.(ABSTRACT TRUNCATED AT 250 WORDS)
Anaphylaxis↗
Evaluation and management of corticotropin allergy.
Subsequent use of an adrenocorticotropic hormone (ACTH) preparation may be considered in some instances in a patient who has demonstrated a suspected or proven allergic reaction to corticotropin on prior administration. We describe a patient with multiple sclerosis with a history of anaphylaxis to porcine ACTH in whom another course of treatment with ACTH was being considered. The patient had immediate cutaneous reactivity to porcine ACTH but not to the synthetic ACTH peptide, cosyntropin. With a test-dose schedule, we were able to uneventfully administer cosyntropin to the patient. The presence of serum IgE antibody directed against porcine ACTH and absence of IgE antibody against cosyntropin were demonstrated by ELISA technique, corroborating the skin test results. These studies are consistent with previous evidence that immediate hypersensitivity reactions to corticotropin are IgE mediated and support the value of skin testing in the clinical evaluation and management of known or suspected corticotropin hypersensitivity.
Adrenocorticotropic Hormone↗
IgE against ethylene oxide-altered human serum albumin (ETO-HSA) as an etiologic agent in allergic reactions of hemodialysis patients.
Ethylene oxide (ETO) is used to sterilize hemodialyzers and other medical equipment. In an attempt to confirm a link between ETO and hypersensitivity reactions during hemodialysis (HD) we quantitated IgE and total antibody directed against ETO-altered human serum albumin (ETO-HSA) in the sera of 65 hemodialysis patients. In 24 patients who had experienced anaphylaxis during HD, the levels of IgE and total antibody against ETO-HSA were significantly higher than the corresponding levels in 41 patients who had not. Our data demonstrate an association between the presence of IgE and total antibody against ETO-HSA and immediate anaphylactic reactions to HD. In further studies we characterized the ETO-HSA antigen by immunoelectrophoresis, gel filtration chromatography, and cross-inhibition immunoassay. Our results suggested that ETO gas can alter HSA and induce new antigenic determinants on the molecule. Recently, we encountered a peritoneal dialysis patient with rash and eosinophilia. Suspecting ETO allergy, we measured serum IgE and total antibody to ETO-HSA and found both to be present. The data suggest that, in addition to the familiar HD reactions, ETO sensitization might cause other allergic diseases as well.
Anaphylaxis↗
Toluene diisocyanate respiratory reactions. I. Reassessment of the problem.
A series of workers with exposure to and respiratory symptoms from toluene diisocyanate (TDI) was compared with a group of exposed, asymptomatic workers and with normal controls using immunologic and clinical evaluations. Improved understanding of TDI-induced respiratory disease may best be achieved by categorizing the symptomatic workers into at least 3 and possibly 4 groups: immunologic TDI asthma; pre-existing chronic respiratory disease exacerbated or unaffected by TDI; asthma coincidental with TDI exposure, and possibly TDI respiratory disease secondary to toxic or inflammatory mechanisms.
Adult↗
Specificity of immunoglobulin E and immunoglobulin G against human (recombinant DNA) insulin in human insulin allergy and resistance.
Using an enzyme-linked immunosorbent assay method, we have demonstrated immunoglobulin E (IgE) and immunoglobulin G (IgG) against human (recombinant DNA) insulin in serum samples of a patient whose insulin therapy was only with human insulin. Within 12 days of initiation of human insulin for gestational diabetes, large local reactions developed in the patient in association with high levels of IgE to human insulin. As the local reactions subsided, the levels of IgE to human insulin decreased. The patient's insulin requirement was unusually high for pregnancy and tended to decrease in parallel with falling levels of IgG to human insulin, suggesting an element of immunologic insulin resistance. In addition to IgE and IgG against human insulin, we were able to demonstrate the presence of IgE and IgG against porcine and bovine insulin in the serum samples of this patient. The patient had similar immediate cutaneous reactivity to each insulin. In inhibition studies, similar amounts of porcine insulin, bovine insulin, or human insulin were found to produce 50% inhibition of human insulin binding to IgE or IgG against human insulin. Excess porcine insulin or bovine insulin resulted in total inhibition of human insulin binding to IgE or IgG. Thus even in a patient whose initial form of insulin therapy was human insulin, there was development of insulin allergy and of IgG to human insulin that may have contributed to insulin resistance. Moreover, the antigenic determinants recognized by antibody induced by human insulin may also be present on bovine insulin and porcine insulin as demonstrated in this case.
Adult↗
Occupational immunologic lung disease.
Occupational immunologic lung diseases either asthma or hypersensitivity pneumonitis, can occur in a wide variety of occupations from numerous antigens. New OILD syndromes and antigens are being reported constantly. In the case of some occupational agents that have been reported like isocyanates, formaldehyde, and Western red cedar, there is current investigation into the incidence of disease, mechanisms, and appropriate diagnostic criteria. A key principle in OILD is that prevention or at least early treatment by environmental control should be the goal. Determination of threshold limits for sensitization and adherence to these limits would be useful, for instance. In manufacturing processes in which this is not possible, workers and management in high risk industries should be educated so that affected workers are recognized early and avoidance can be instituted. Currently, there are no pre-employment screening criteria that have been shown to be very useful in predicting OILD. Prospective studies of animal handlers are underway and may provide useful information. In the case of TMA-exposed workers, prospective studies have demonstrated that serial immunologic studies are useful in predicting workers at risk for OILD and that reduction of airborne exposure will reduce prevalence. This sort of approach will probably be useful in studying other occupational agents. Such studies are complex and, to succeed, generally require cooperation and collaboration of physicians, industry, labor, industrial hygiene, and governmental agencies.
Alveolitis, Extrinsic Allergic↗
Prevention of chymopapain anaphylaxis by screening chemonucleolysis candidates with cutaneous chymopapain testing. A preliminary report.
The risk of anaphylaxis in candidates for chemonucleolysis for herniated lumbar discs is approximately 1%. An investigation was designed to eliminate or reduce the incidence of chymopapain anaphylaxis. The procedure was to restrict chemonucleolysis to patients who are prick test-negative to chymopapain at a concentration of 10 mg/ml. The authors skin-tested 292 chemonucleolysis candidates; five were positive and 287 were negative. None of the positive patients were injected with chymopapain. There were no instances of unequivocal chymopapain anaphylaxis in the skin test-negative group. This 0% incidence of anaphylaxis in skin test-negative patients was compared with a population estimate of 1%, based on historical data. The resulting value of p = 0.08 value fell short of the conventional level of significance of 0.05. The p value will reach 0.05 when the series of skin test-negative patients without anaphylaxis reaches 360. It is important that this information is readily available to physicians concerned about anaphylactic reactions to chymopapain.
Adult↗
Establishing clinical and immunologic criteria for diagnosis of occupational immunologic lung disease with phthalic anhydride and tetrachlorophthalic anhydride exposures as a model.
Using a questionnaire and serum antibody studies, we evaluated 13 workers exposed to phthalic anhydride (PA) and tetrachlorophthalic anhydride (TCPA). The questionnaire was designed to identify symptoms compatible with anhydride-induced immunologic or irritant syndromes. Specific IgG and IgE for both PA-human serum albumin (PA-HSA) and TCPA-HSA were determined by enzyme-linked immunosorbent assay in two different laboratories. In addition, 11 workers had cutaneous testing with PA-HSA and TCPA-HSA, and nine workers were interviewed. One worker was found to have PA-associated asthma and rhinitis. We conclude that a questionnaire and serologic assays for specific IgG and IgE are helpful to identify workers who have or are at risk for developing occupational immunologic lung disease such as those induced by anhydrides. However, additional evaluation may be necessary in those workers with such diseases as intrinsic asthma that may be difficult to differentiate from occupational immunologic lung disease.
Air Pollutants, Occupational↗
Pathogenesis of occupational lung disease.
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Animals↗
Soluble copolymer of wasp venom with human albumin for venom immunotherapy.
Polymerization of allergens decreases allergenicity while retaining immunogenicity, as we have demonstrated for ragweed, grass, and tree pollens. We have also polymerized bee venom with human albumin to form soluble, high-molecular-weight copolymers that are immunogenic in rabbits. We now have prepared a soluble wasp venom-albumin polymer (WVAP), molecular weight greater than or equal to 240,000 daltons, by glutaraldehyde treatment and Sephacryl S-300 column fractionation. Rabbits immunized with WVAP produced IgG to both WVAP and wasp venom (WV), as measured by ELISA. IgG against WVAP was totally inhibitable by a mixture of WV and albumin, demonstrating both retention of native antigens and absence of new antigenic determinants in WVAP. IgG against WV in serum from patients receiving maintenance doses of WV immunotherapy was inhibited by WVAP. In summary, we have synthesized a soluble, high-molecular-weight copolymer of WV that retains the immunogenicity of native WV, contains no new antigenic determinants, and has potential value in the treatment of patients with WV anaphylaxis.
Animals↗
A double-blind placebo-controlled trial of polymerized whole grass administered in an accelerated dosage schedule for immunotherapy of grass pollinosis.
Forty-four patients were entered into a study of the efficacy and safety of individually polymerized grass (IPG) immunotherapy with an accelerated dosage schedule. Patients were paired on the basis of cutaneous end point titrations to timothy, orchard, and Bermuda grass-pollen extracts. In a double-blind manner, one patient in each pair was treated in nine weekly visits with 13 injections that totaled 24,000 PNU of each grass to which the patient had cutaneous reactivity. The other patient in each pair received caramelized glucose histamine placebo. Symptom and medication score sheets were completed by 33 patients each day of the grass season. Blocking antibody rose significantly in the IPG-treated group but was unchanged in the placebo-treated group. By Wilcoxon paired signed-rank test, the symptom medication scores in the IPG-treated group were significantly lower than those in the placebo-treated group. There were no systemic reactions and no clinically significant changes in routine laboratory tests in either group. In summation, this study demonstrates the safety, immunogenicity, and efficacy of IPG therapy in an accelerated dosage schedule for treatment of grass pollinosis.
Adult↗
Methods of analysis of occupational lung disease.
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Humans↗
Safety and immunogenicity of immunotherapy with polymerized tree, grass, and ragweed in patients with multiple inhalant sensitivities.
Immunotherapy with polymerized ragweed (PRW) and individually polymerized grasses (IPG) previously has been demonstrated to be safe and effective. We conducted this trial in order to assess safety and immunogenicity of individually polymerized trees (IPT) and to assess safety of concomitantly administering IPT, IPG, and PRW in patients with multiple inhalant sensitivities. Sixteen patients with typical tree pollinosis were recruited; all but one had grass pollinosis, and all had ragweed pollinosis. Patients were treated in 12 weekly visits with allergens to which they were sensitive, 48,850 PNU of IPT; 2668 AU (50,000 PNU) of PRW; and 48,850 PNU of IPG. There were no systemic reactions and no changes in laboratory parameters, including renal and hepatic functions with injections. Blood was drawn for immunologic studies before and after the injection series. There were significant rises in IgG titers by ELISA to each tree allergen administered, oak, elm, and box elder. There were significant rises in total antibody binding of ragweed AgE and rye grass group I in patients treated with PRW and IPG, respectively. Changes in IgE to oak, elm, box elder, AgE, and rye grass group I were minimal. In summary, IPT is safe, immunogenic, and can be administered concomitantly with PRW and IPG in patients with multiple inhalant sensitivities.
Blood Proteins↗
Use of haptenizing ELISA to evaluate respiratory disease in a worker exposed to capacitor-coating powder.
We were asked to evaluate respiratory disease in a worker exposed to a powder containing unidentified components that was heated and used to coat capacitors. Because the powder was used as a coating material, we hypothesized that the capacitor-coating powder (CCP) contained either an anhydride or an isocyanate. We modified the initial step of a standard ELISA so that we could use CCP as a hapten in this assay. With this modified ELISA technique and inhibition analysis with antisera of known specificity, we determined that CCP contained a substance that cross-reacted with trimellitic anhydride. Later, we confirmed from the manufacturer that it contained benzophenone tetracarboxylic dianhydride. With the modified ELISA assay we also determined that the worker we were to evaluate did not have antibody to CCP or trimellitic anhydride. From clinical and immunologic evaluation we diagnosed chronic obstructive lung disease. Thus, this modified assay has proved useful in the evaluation of a worker exposed to a powder whose contents were not initially known and may prove useful in immunologic evaluation of workers in other industrial settings.
Adult↗