IgG subclasses in respiratory disorders: cystic fibrosis.
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Age Factors↗
Biomedical subjects
R B Moss
Publications and source records attributed to R B Moss.
Underestimation of specific immunoglobulin E by microtiter plate enzyme-linked immunosorbent assays.
We developed an ELISA by use of monoclonal anti-IgE to measure allergen-specific IgE. We measured perennial ryegrass (PRG) specific immunoglobulin E (sIgE) with conventional single incubations and with the recently reported transfer method to decrease interference in the assay. Paired sera in 10 patients before and during immunotherapy with PRG extract were analyzed for PRG sIgE with single serum incubations and with the sum of five serial serum incubations. A standardized reference serum and patient sera were incubated 12 hours and then transferred to a second well, incubated 12 hours more, and transferred again. The process was repeated until five pairs of wells had been incubated with each serum dilution. Color was developed, and optical density was measured. PRG sIgE was calculated by interpolation from the reference curve. Evidence of interference was inferred when less PRG sIgE was detected by single incubation than by transfer. Inhibition of 71.3% occurred in the sera drawn during immunotherapy. Inhibition of 32.9% was found before immunotherapy. Also, a late peaking of the well-to-well curve of optical density was observed in nine of 10 sera drawn during immunotherapy (the exception had not reached full strength), whereas all of the sera drawn before immunotherapy had normal curves. This suggests that sIgE determinations performed in microtiter plate format with single incubations will usually underestimate the sIgE level. This drawback needs to be kept in mind by the clinician interpreting the results of these assays.
Enzyme-Linked Immunosorbent Assay↗
Cystic fibrosis and neuroblastoma.
Two cases of coexistent cystic fibrosis and infantile thoracic neuroblastoma are presented. In one patient, neuroblastoma was congenital, and diagnosis of cystic fibrosis was made at 3 months of age; in the other, the diagnosis of cystic fibrosis was made at 7 months of age, preceding that of neuroblastoma by 4 months. In both infants, surgical resection of the tumors have been successful. Recent advances in the genetic aspects of neuroblastoma, including translocation and activation of the oncogene N-myc, are discussed. Current recombinant DNA technology, which can identify translocation of N-myc and allow localization of the cystic fibrosis gene if the translocation occurs near the cystic fibrosis allele, is being applied to these cases.
Cystic Fibrosis↗
Allergy to semisynthetic penicillins in cystic fibrosis.
Allergic reactions to anti-Pseudomonal penicillin derivatives are an increasing problem in therapy of cystic fibrosis lung disease. We evaluated 15 patients, ages 12 to 37 years, with documented allergic reactions to carbenicillin, ticarcillin, or piperacillin. Intradermal skin test reactions were positive for benzylpenicillin in seven patients, penicilloyl-polylysine in one, and ticarcillin or piperacillin in eight, for a total of 11 of 11 tested. Results of radioallergosorbent testing to penicilloyl conjugates were positive in eight of 14 patients and equivocal in four others. Overall, skin tests or RAST results were positive in 13 of 15 patients. All patients were desensitized with a semisynthetic penicillin by continuous serial intravenous infusion of 10-fold dose increments, beginning with 10(-6) of the therapeutic dose. Desensitization was successful in 25 of 26 instances. After intravenously administered therapy, maintenance of desensitization with dicloxacillin orally was unsuccessful in four of six patients. We conclude that (1) allergy to semisynthetic penicillins in cystic fibrosis usually is IgE mediated; (2) such allergy can be evaluated by skin testing; (3) it can be safely and in most cases successfully treated by intravenous desensitization; and (4) allergic patients should be desensitized on each subsequent admission for intravenously administered therapy.
Adolescent↗
Grass pollen immunotherapy: a single year double-blind, placebo-controlled study in patients with grass pollen-induced asthma and rhinitis.
Fifteen grass pollen--sensitive asthmatic patients were selected from 200 patients with grass pollenosis on the basis of positive SPTs and RASTs that were restricted to grass pollens (except Bermuda grass), no previous IT, and residence and occupation in an area monitored by serial pollen counts. They underwent a double-blind trial of specific IT with a mixture of three grass pollen--aqueous extracts (velvet, sweet vernal, and timothy) or placebo. After 10 mo, the mean maintenance dose of pollen extract (assayed by RAST inhibition) in eight actively treated patients was 6000 RAST units (range 3000 to 8000) and the mean total dose was 18,700 RAST units (range 10,200 to 30,000). Results were assessment done by the following clinical and immunological data: (1) during the pollen season, daily symptom scores; (2) PD 20% FEV1, IgE antibody to timothy by RAST in serum and in nasal secretions, serum IgG antibody to purified timothy allergen D by solid-phase radioimmunoassay, and the four IgG subclass antibodies by enzyme immunoassay were all measured before treatment and before and after the pollen season. Symptom scores of both treated patients and controls correlated with pollen counts (R = 0.88, p less than 0.05 and R = 0.71, p less than 0.05, respectively). There was a significant difference between the mean symptom score values of treated patients versus controls (Kruskal-Wallis test, p less than 0.001). No significant differences or changes either in the PD 20% FEV1 or IgE antibody to timothy in serum and nasal secretions were found in the two groups before or after IT.(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
Sudden death in adolescent asthma.
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Adolescent↗
Microtiter immunoenzymatic assay (micro-ELISA) for antigen-specific IgG4 subclass antibody.
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Antibodies, Bacterial↗
Isolation and characterization of circulating immune complexes in cystic fibrosis.
A methodology for the isolation and immunologic characterization of IgG-containing circulating immune complexes (IgG-CIC) as detected by the 125IClq-binding assay (ClqBA) is described. We applied this methodology to sera from patients with cystic fibrosis (CF), both positive and negative for IgG-CIC. We used latex-fixation-positive rheumatoid arthritis sera and normal human sera as positive and negative controls, respectively. All IgG-CIC-positive serum samples from CF patients were found to contain antibodies against Pseudomonas aeruginosa in the isolated complexes. Some patients also had antibodies in CIC specific for Staphylococcus aureus and Candida albicans. CIC specificity corresponded to respiratory tract colonization for each patient.
Antibodies, Bacterial↗
125I-Clq-binding and specific antibodies as indicators of pulmonary disease activity in cystic fibrosis.
We studied the incidence and levels of circulating immune complexes by the 125I-Clq-binding assay in patients with cystic fibrosis in relation to clinical respiratory status and specific IgG and IgE antibodies to Pseudomonas aeruginosa. Staphylococcus aureus, Aspergillus fumigatus, and Candida albicans. Overall prevalence of CIC was 43%, but 86% of serially studied patients had evidence of CIC at some time. Patients with acute respiratory exacerbations and deteriorating pulmonary function had a higher incidence of CIC (76%) as compared to stable patients (36%, P less than 0.01), as well as significantly higher levels of CIC. Acute exacerbations were also associated with significant increases in IgG antibody to Pseudomonas (P less than 0.005) but not in other antibodies. CIC did not correlate with Pseudomonas-specific IgG nor with any other specific antibody studied. A variety of age-related differences in specific antibody levels were seen. The episodic appearance of CIC is common in CF and is usually associated with exacerbation of lung disease.
Adolescent↗
Immune complexes and humoral response to Pseudomonas aeruginosa in cystic fibrosis.
We studied the humoral immune status of 51 patients with cystic fibrosis (CF) as compared to 25 patients with other respiratory diseases (RD). CF patients had higher serum concentrations of IgG and IgA (p less than 0.001), C5, and CH50 (p less than 0.05), than did RD patients. Twenty-three % of CF patients had increased IgE concentrations. Of 32 CF and 1 RD patients colonized with mucoid Pseudomonas aeruginosa (PA), 91% had serum precipitins to PA, whereas no precipients were found in patients not colonized with mucoid PA. Fifty-one % of CF patients had circulating immune complexes detected by 125I-C1q binding (for CF patients mean values +/- SD, 14.5 +/- 12% versus 7.5 +/- 3.4% for RD patients; p less than 0.005). Complexes were correlated with higher serum IgA concentrations but not other immunoglobulins, complement components, response to PA, or pulmonary function at time of assay. Extra vascular formation of complexes was suggested by uniform absence of plasma C3 activation in vivo.
Adolescent↗
Chronic neuropathy presenting as a floppy infant with respiratory distress.
Respiratory distress was the presenting feature in a 4-month-old male infant suffering from Déjérine-Sottas disease, an inherited sensory-motor polyneuropathy. This unusual but potentially benign disorder can be diagnosed upon peripheral nerve biopsy by noting extensive demyelination with "onion bulb" formation. Polyneuropathy should be considered in the differential diagnosis of infantile neuromuscular weakness including or solely involving bulbar and respiratory muscles.
Biopsy↗
Maxillary sinusitis as a surrogate model for CF gene therapy clinical trials in patients with antrostomies.
BACKGROUND: Assessing the biological activity and clinical efficacy of gene therapy is critically important in cystic fibrosis (CF). It is widely accepted that clinical testing using surrogate markers including pulmonary function will be useful in assessing clinical efficacy. One problem with pulmonary surrogate markers of CF disease is the large number of patients and length of time required to demonstrate clinical efficacy. An alternative to pulmonary testing of new CF treatments is use of the maxillary sinuses as a surrogate model of CF lung disease. Using CF sinusitis as a surrogate model for testing clinical efficacy of new treatments is attractive because CF upper respiratory disease is similar to the lower respiratory disease with respect to electrophysiology and microbiology. METHODS: Sinusitis recurrence in untreated sinuses was analyzed during a prospective, randomized, unblinded, dose-escalation, within-subjects, phase I clinical trial of the adeno-associated virus mediated cystic fibrosis transmembrane conductance regulator (AAV-CFTR) gene transfer. RESULTS: Clinical symptoms combined with sinus endoscopy proved useful in the diagnosis of unilateral and bilateral sinusitis recurrence. Sinusitis recurred at a rate of 45% during one month of follow-up. IL-8 concentration rose in sinus fluids from affected sinuses. Bacterial cultures and increased sinus leukocytes corroborated recurrent sinusitis. Sinus CT scans were also useful in diagnosing recurrent sinusitis in this surrogate model of CF infectious exacerbations. CONCLUSIONS: CF sinusitis as a surrogate for lung disease is particularly well-suited for phase II clinical trials of gene transfer agents, with the potential for measuring clinical efficacy in relatively small numbers of patients over relatively short periods of time.
Adult↗
Drug allergy in cystic fibrosis.
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Anti-Bacterial Agents↗
In vitro enhancement of natural cytotoxicity by atrial natriuretic peptide fragment 4-28.
The presence of atrial natriuretic peptide (ANP) binding sites in the thymic cortex, medulla, and splenic white pulp suggests that this peptide may have immunoregulatory activity. We examined the effect of ANP on human natural killer (NK) cell activity. ANP significantly augmented NK cell cytotoxicity after twenty-four hours of incubation but had no effect on NK activity after short-term incubations of one hour. In addition, atrial natriuretic peptide did not effect the expression of natural killer or T cell surface markers. This study demonstrates that atrial natriuretic fragment 4-28 enhances natural killer cell activity.
Antigens, CD↗
Safety and immunogenicity of REMUNE in HIV-infected Thai subjects.
The safety and immunogenicity of REMUNE, an HIV-specific immune based therapy for HIV infection, was evaluated in a cohort of 30 HIV infected subjects in Thailand. This therapy utilizes a gp120 depleted inactivated virus (HZ321), which exhibits a high degree of conservation with the core antigens of both type B' and E strains of HIV, the predominant Thailand isolates. The treatment was well tolerated, with no serious adverse events reported over the course of the 4-month trial. Treatment in which four doses were administered with REMUNE appeared to boost HIV-specific immune responses, with approximately 75% of the treated subjects demonstrating an increase in either the repertoire or the intensity of the serological response to HIV as measured by Western blot. CD4%, viral load, and weight remained stable over the course of the 4-month study relative to baseline values. Viral subtyping of this cohort revealed a predominance of type 'E'. These data suggest that REMUNE is safe and immunogenic in seropositive Thai subjects and supports further study of the therapeutic potential of REMUNE to treat HIV-1 infection.
AIDS Vaccines↗
Evaluation of the immunologic cross-reactivity of aztreonam in patients with cystic fibrosis who are allergic to penicillin and/or cephalosporin antibiotics.
The immunogenicity, allergenicity, and cross-reactivity of aztreonam were investigated in 19 patients with cystic fibrosis (CF) who are allergic to beta-lactam antibiotics. Skin tests with benzyl-penicilloyl polylysine (BPO), minor determinant mixture, and the drug responsible for the previous allergic reaction were positive for 26%, 53%, and 79% of the patients, respectively. Serum IgG, but not IgE, antibodies to BPO were detected in nine of 14 patients. Eighteen patients whose skin tests with aztreonam were negative were treated. One developed bronchospasm. The others tolerated aztreonam, with an improvement in clinical score greater than or equal to 1 month after treatment (P less than .001). One patient without previous exposure had positive aztreonam skin tests and was later treated uneventfully after iv desensitization. Treatment with aztreonam did not result in IgG or IgE antibody responses in vitro. However, two patients had anaphylactic reactions on reexposure. In patients with CF, allergy to beta-lactam antibiotics is primarily drug-specific. But despite reduced immunogenicity and cross-reactivity, aztreonam should be administered cautiously to patients with CF who are allergic to other beta-lactam antibiotics because it is potentially allergenic with repeated use.
Adolescent↗
Long-term follow-up of HIV-1-infected Thai patients immunized with Remune monotherapy.
PURPOSE: The purpose of this 2-year follow-up study was to investigate the long-term effect of Remune as monotherapy for HIV-1 infection. BACKGROUND: Participants previously enrolled in the phase II double-blind, randomized, adjuvant-controlled study of the HIV-1 Immunogen (Remune) were followed for 2 years. Open-label immunization with Remune monotherapy was given to each participant every 12 weeks. Remune, a gp 120-depleted HIV-1 that was inactivated in beta-propiolactone and irradiation, was emulsified with mineral oil (incomplete Freund's adjuvant). METHOD: In Study 2101B, the effect of four doses of Remune given every 12 weeks over 40 weeks was compared to placebo in 297 asymptomatic type E HIV-infected patients [Churdboonchart et al., 2000]. A group of 17 volunteers were separated into a subset study and another 57 were excluded from analysis due to discontinuation or addition of other treatments. This 2-year follow-up study continued with open-label dosing of HIV-1 Immunogen every 12 weeks for the remaining 223 patients. Changes in CD4+ cells, CD8+ cells, and body weight were monitored at each patient visit. RESULTS: Overall, immunizations were safe; common adverse events were tolerable injection site reactions. CD4+ T-cell counts remained stable over the 132-week observation period for this cohort with a slight increase of 36.01 cells/microL. CD8+ T-cell counts showed an increase from baseline during the follow-up period (415.21 cells/microL). Furthermore, we also observed an increase in body weight from baseline (1.08 kg) at week 132. In addition, baseline CD4 count appeared to predict CD4 count at week 132 (slope = 0.31, p <.0001). CONCLUSION: These results suggest that long-term treatment of HIV-1 infection with Remune monotherapy is safe and results in a stabilization of CD4+ counts. Furthermore, it is likely that HIV-1 therapeutic immunization may show its greatest clinical benefit in participants with higher CD4+ cell counts. Such an approach may have important ramifications in developing countries where access to antiviral drugs is limited and also in early chronic HIV-1 infection when CD4+ cells are still over 300 cells/microL in order to limit the cost and toxicity.
AIDS Vaccines↗
IgG subclass antibody markers in grass pollen immunotherapy.
Rye grass immunotherapy was clinically effective in seasonal allergic asthma and induced serologic changes different from those of natural exposure. These included the blunting of the seasonal rise in IgE antibody and much greater increases in blocking IgG antibodies. Blocking antibody responses to rye grass antigens were restricted to the IgG1 and IgG4 subclasses. Nonatopic individuals had similar preseasonal levels of IgG1 antibodies, but low or undetectable levels of IgG4 or IgE, compared to allergic subjects. Immunotherapy induced increases in both IgG1 and IgG4 antibodies, but IgG4 was dominant and the rise was much more dramatic. Rye grass extract contained at least eight IgE binding allergens and 11 IgG binding antigens, by far the most important of which was antigen I. IgE and IgG binding antigens generally showed concurrence in individuals, but heterogeneity between individuals for non-Rye 1 antigens. Finally, while IgG4 quantitatively dominated the blocking response, early clinical benefits might involve IgG1 antibodies, suggested by an observed inverse correlation between individual symptom medication scores individuals and IgG1 antibody levels.
Antibodies, Monoclonal↗