Results of repeated IgE titre determinations for the early diagnosis of tumour recurrence in the otolaryngological area (author's transl)

Repeated serum IgE determinations in 292 tumour patients, in parallel with clinical check-ups, show the great diagnostic significance of the serum IgE level. The IgE titre variations give an insight into the tumour-host relationship and, in particular, into the current state of activity of the tumour patients who were found to be tumour-free after specific therapy have constant serum IgE values on repeated examination. The serum IgE level declines significantly during radiotherapy and after operative therapy. Tumour recurrence or metastases cause a sharp increase in the serum IgE level already before clinical manifestations can be ascertained. Hence, this method contributes through continued immunological checks towards an early diagnosis of tumour activity.     

Clinical pharmacokinetics of carboplatin and MCNU in malignant brain tumor and normal brain tissues

We measured the concentrations of MCNU and CBDCA in the serum, brain tumor and normal brain tissue. Six patients with malignant glioma were treated with intravenous chemotherapy using 80mg/m2 MCNU and 300mg/m2 CBDCA during surgery. After drug administration, specimens of serum, tumor and normal brain tissue were collected every 30 min and then the drug concentration in each sample was measured. The highest MCNU levels in all samples were obtained immediately after administration which followed by gradual decrease. On the contrary, the mean CBDCA levels in the tumor and normal tissue remained almost at a constant level, although serum CBDCA level declined rapidly as MCNU. As expected, MCNU seemed to have advantages in the treatment of brain tumors as it distributed with higher concentration in the tumor tissue than in the serum and normal brain tissue. On the contrary, CBDCA in the tumor tissue did not exceed the concentration in the serum. Nevertheless, it remained longer in the tumor tissue with a constant level, suggesting that CBDCA can achieve an effective area under the concentration versus time curve (AUC) in the brain tumor tissue to kill tumor cells.     

Elevated serum levels of soluble CD30 in patients with atopic dermatitis (AD)

The immunopathology of AD is still unclear, but evidence for an immune response polarized towards Th2 activity has been provided. The CD30 molecule belongs to the tumour necrosis factor (TNF) receptor family and is expressed on activated T cells with a sustained expression in Th2 cells. This molecule also exists in a soluble form (sCD30). Elevated serum levels of sCD30 have been found in patients with Hodgkin's disease, chronic hepatitis B infection and HIV infection. Studies were undertaken to compare the serum levels of sCD30 in patients with AD (n=49) and healthy non-atopic controls (n=94). The presence of sCD30 was analysed with ELISA. A significantly higher concentration of sCD30 was noted in AD patients, median sCD30 level 29 U/ml (range 1-708 U/ml), compared with healthy non-atopic controls (P<0.001), where the median level was 11 U/ml with a range of 1-1042 U/ml. No correlation was found between sCD30 levels and total serum IgE, or between the AD patients' SCORAD values and concentration of sCD30. sCD30 levels were also analysed in 20 AD patients, which during ketoconazole treatment had improved their clinical scores and reduced their serum IgE and eosinophil cationic protein levels. However, no significant decrease in sCD30 levels was noted after treatment. The results show that patients with AD have elevated levels of sCD30, but without correlation to total serum IgE or disease activity.     

In vitro and in vivo effect of glucocorticoids on IgE and IgG subclass secretion

Hydrocortisone (HC) as well as its synthetic derivatives have been shown to strongly enhance interleukin-4 (IL-4)-induced in vitro IgE synthesis. To investigate possible effects on IgG subclasses, peripheral blood mononuclear cells (PBMC) were incubated with different glucocorticosteroids in the absence or presence of IL-4. The glucocorticoids alone led to a strongly enhanced secretion of IgG1, IgG2 and IgG3, but not IgG4. The addition of IL-4 induced marked increases in IgG1 and IgG4, no changes in IgG3, but a consistent decrease in IgG2 synthesis. In order to find out whether these profound in vitro effects of corticosteroids are also reflected by changes in antibody serum levels during steroid treatment, 10 healthy volunteers took 25 mg prednisone for 7 consecutive days. We could not observe any significant changes of IgE or IgG subclass serum levels during or after this period. However, cell cultures performed after the glucocorticoid treatment revealed a marked decrease in the ability to produce IgG4 and a significantly lower potential to produce IgE in response to IL-4 alone or IL-4 and HC. We conclude that, although strongly implicated by the in vitro results, glucocorticosteroid treatment does not result in an increased allergy risk.     

IgA levels and carrier rate of pathogenic bacteria in 27 children previously tonsillectomized

The object of the present paper is to present laboratory and clinical data on 27 children of ages between 6 and 11 years, who in connection with tonsillectomy 2 1/2 years earlier had been found to have low serum and saliva IgA levels, low serum IgE levels, and a considerable lack of IgA and IgE plasma cells in the excised tonsils; correlation between deficiency in IgA and culture of pathogenic bacteria from the tonsils was significant. From a clinical point of view, 22 of the children had benefit of the tonsillectomy and had no longer a tendency towards a development of recurrent infections. The remaining 5 patients continued to complain of recurring respiratory infections; in addition, levels of serum and saliva IgA were low. Furthermore, 4 or these 5 children harboured pathogenic bacteria in their throats. Many of the 27 patients still had low serum IgA and IgE levels as compared with levels in healthy, age-related controls; in 3 patients, however, the IgE levels in serum had risen considerably parallel with the development of atopic diseases. Saliva IgA was rather constant after tonsillectomy as compared with the preoperative levels, though it had risen in some of the children. As regards serum IgG and IgM, these immunoglobulins had decreased significantly, and the question is raised, whether it might had been due to the tonsillectomy, either by the removal of chronically infected organs or by the removal of important immunological tissue.     

Early IL-2/sIL-2R surge following surgery leads to temporary immune refractoriness

High serum level of immunoreactive but not biologically active IL-2 was detected 1 day after surgery in patients undergoing major operation (abdominal, open-heart), in proportion to the tissue injury caused by surgical trauma. IL-2 values were highest in those patients who underwent open-heart surgery and received blood transfusions. In all patients they declined in the third and fourth post-operative days. Elevated serum levels of soluble IL-2 receptors (sIL-2R) were already present 1 day after operation, and peaked in the third and fifth post-operative days after mitogen triggering. Blood lymphocytes derived from operated patients secreted reduced amounts of both IL-2 and sIL-2R compared with control lymphocytes. The extent and duration of this reduction were also proportional to the tissue trauma and were affected by blood transfusions. Based on these data we suggest that early post-operative systemic immunological activation (appearance of IL-2 in the serum) is followed by elevation of sIL-2R, which then interferes with IL-2-dependent immunity. Blood lymphocytes are probably not involved in the post-operative immunological activation. The trigger for and the site of IL-2/sIL-2R synthesis are not yet clear.     

A wall-incorporated valve for preserving continence: an experimental evaluation of a new technique

The purpose of the present study was to analyse whether sex, age, skin test reactivity, cigarette smoking and occupational exposure were related to the total serum immunoglobulin (Ig)E concentrations (kU x L[-1]), in a general population sample. We studied 1,905 subjects (915 males, 990 females) of a general population sample (n=2,841, 8-73 yrs) participating in the second cross-sectional respiratory epidemiological survey in the rural Po Delta area (near Venice, North Italy). Distribution of total serum IgE concentrations was skewed, thus a log-transformation was performed to obtain a Gaussian shape. Significantly higher values of IgE were found in males compared to females. In general, a peak of IgE concentration was found at 8-14 yrs. IgE values tended to be lower in older than younger adults. Significantly higher serum IgE levels were shown in subjects with a positive skin-prick test index (ST+) than in those with a negative skin-prick test index (ST-). There was a significant relationship of total IgE levels with skin reactivity to pollens and house-dust mites. In both sexes higher values of IgE were found in current smokers than in ex-nonsmokers, regardless of skin-test reactivity. There was no significant difference in IgE values between ex- and nonsmokers. Passive smoking and occupational exposure were significantly related to increased IgE values. Our results confirm that in a general population sample immunoglobulin E concentrations are related not only to skin-prick test reactivity to common aeroallergens, but also to other risk factors for chronic obstructive lung diseases, such as sex, active/ passive smoking and occupational exposure.     

Report of the first workshop on the genetic map of bovine chromosome 1

Allergic bronchopulmonary aspergillosis (ABPA), occurring primarily in patients with asthma or cystic fibrosis (CF), is a hypersensitivity reaction to Aspergillus fumigatus (Af), and is characterized by increased serum IgE levels and peripheral blood and pulmonary eosinophilia. We evaluated the IgE and cytokine profile in ABPA through enzyme-linked immunosorbent assay (ELISA), and evaluated eosinophil activity with the eosinophil peroxidase (EPO) assay. IgE and cytokines were measured in supernatants from cultures of peripheral blood mononuclear cells (PBMC) from three subject groups: ABPA patients, patients with asthma, and healthy individuals. All cultures for the three subject groups were studied in the presence and absence of two purified Af antigens (the 35-kD antigen and heat shock protein 1). We found that increased in vitro levels of IgE in unstimulated PBMC culture supernatants correlated significantly with serum IgE concentrations in ABPA patients. We measured a decrease in IgE levels of up to 75% of baseline values in supernatants from PBMC cultured with Af antigens. Interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) concentrations in cultures with Af were increased in ABPA, whereas concentrations of IL-4 did not differ in the three subject groups. An inverse relation was noted between the changes in IgE and IFN-gamma measured in 4 of 5 ABPA patients. The PBMC supernatants also promoted EPO activity in purified eosinophils from ABPA patients, and to a lesser extent in purified eosinophils from healthy subjects. These results show that the 35-kD antigen and HSP1 from Af downregulate IgE in vitro but are capable of inducing eosinophilia in ABPA. Further studies could result in the characterization of epitopes leading to these disparate effects. An identification of the IgE-down-regulating epitopes in Af antigens might have therapeutic significance.     

IgE antibody during infection with the ovine abomasal nematode, Teladorsagia circumcincta: primary and secondary responses in serum and gastric lymph of sheep

A monoclonal antibody to ovine IgE was employed in an ELISA to investigate the IgE antibody responses in serum and gastric lymph to a primary infection of Teladorsagia circumcincta, and following challenge in previously infected sheep. During a primary response, IgE antibody to antigens derived from the infective third stage (L3) and adult (L5) worms were negligible, with low levels of IgE antibody detected in serum and lymph. In contrast, there was a pronounced IgE antibody response in 2/4 sheep to L3 antigens during 2-8 days after challenge of previously infected animals but low levels of IgE antibody to L5 antigens. This response was confirmed in a second but similar experiment, where relatively high levels of IgE antibody was detected to antigens from L3. Antibody levels were higher in lymph than in serum from the same animals, and Western blots of L3 antigen following SDS-PAGE under reducing conditions revealed several bands of MW26-96KD which reacted with the IgE antibody from gastric lymph. Immunohistochemical staining indicated that these IgE antibodies may be reacting with allergens associated with the surface cuticle of the worms.     

The effect of T cell depletion with Campath-1M on immune reconstitution after chemotherapy and allogeneic bone marrow transplant as treatment for leukaemia

Thirty asthmatic children were examined allergic reaction against egg white, gelatin and vaccine solution before and after vaccination using skin prick test. We also measured the levels of specific IgE and IgG antibody against gelatin. The changes in clinical symptoms before and after vaccination were investigated in 25 asthmatic children by evaluating symptom and treatment score. The results were as follows; 1. In one subject who had delayed type of skin reaction to gelatin, the adverse reaction was also recognized at the skin site around 24 hrs after vaccination. In this subject, the levels of serum specific IgE and IgG to gelatin became positive after 5 months. 2. Specific IgE antibodies to gelatin were not detected in all subjects before and after vaccination. 3. The mean values of asthma symptom score before and after vaccination were 3.3 +/- 4.2 and 1.5 +/- 3.3 respectively. Those of treatment score before and after vaccination were 75.6 +/- 35.2 and 76.0 +/- 35.0 respectively. These results suggest that skin testing with gelatin and vaccine solution is useful as a screening method for predicting adverse reactions in asthmatic children and that influenza vaccination can be performed safely in skin test negative children.     

Raised serum immunoglobulin E in Wegener's granulomatosis

Five patients with Wegner's granulomatosis were found to have significantly raised serum immunoglobulin E (IgE) levels. The rise in IgE was not related to the extent of clinical involvement, was not part of a generalized serum immunoglobulin rise, and was not associated with eosinophilia. Raised serum IgE may be a clue to the pathogenesis of this disease.     

Comparison among delayed-type skin tests, serum IgE levels and peripheral blood CD4 in HIV-positive patients

Three groups of HIV-positive men and a control group of healthy subjects were evaluated simultaneously by delayed-type skin tests with recall antigens detection of CD4 cell counts in peripheral blood and the IgE serum levels. Delayed-type skin test reactivity and CD4 cell counts in peripheral blood decreased while IgE serum levels increased as immune imbalance progressed with the worsening of HIV infection (p = 0.003 between controls and HIV-positive patients). The existence of atopy did not significantly influence IgE serum levels in the groups of HIV-positive patients (p < 0.2). Candidin appeared as a useful antigen in the delayed-type skin tests considering that it was the only antigen that remained positive with low values of CD4 cell counts (< or = 250/mm3). The detection of serum IgE levels as well as the performance of delayed-type skin tests with recall antigens are useful tools to evaluate immunological status whereas the number of CD4 in peripheral blood is critical for determining the initiation of antiretroviral therapy.     

Indication of linkage of serum IgE levels to the interleukin-4 gene and exclusion of the contribution of the (-590 C to T) interleukin-4 promoter polymorphism to IgE variation

Previous segregation analysis of a sample of 234 randomly selected Australian families showed evidence for a recessive major gene controlling serum immunoglobulin E (IgE) levels independently of the specific response to allergens (SRA). Since linkage has been recently reported between serum IgE levels and the 5q candidate region spanning the interleukin-4 (IL-4) gene, we investigated whether the recessive major gene detected by segregation analysis was linked to the IL-4 region and whether polymorphisms within the IL-4 gene were associated with IgE levels. Both sib-pair method and combined segregation and linkage analysis using the regressive models were applied to our data. Whereas there was no evidence of linkage of total IgE levels to the IL-4 region, an indication of linkage (P values ranging between 0.01 and 0.03) was found between IgE levels adjusted for SRA and two IL-4 polymorphisms: one dinucleotide repeat in intron 2 of the IL-4 gene and a single nucleotide (-590 C to T) polymorphism in the IL-4 promoter. However, the putative IL-4 linked gene did not appear to be in linkage disequilibrium with either of these two polymorphisms. A contribution of the IL-4 promoter polymorphism, presumed to be a potential functional variant influencing IgE variation, was also excluded.     

Prediction of myocardial infarction in dyslipidemic men by elevated levels of immunoglobulin classes A, E, and G, but not M

BACKGROUND: Immune mechanisms have been suggested to play an important role in the development of coronary atherosclerosis and its thrombotic complications. We evaluated the predictive value of the levels of various serum immunoglobulin classes in middle-aged men at increased risk of myocardial infarction. METHODS: Using nested case-control design and logistic regression analysis, we estimated the association between serum immunoglobulins and the risk of coronary end points (nonfatal or fatal myocardial infarction or sudden cardiac death) in dyslipidemic men (levels of non-high-density lipoprotein cholesterol >5.2 mmol/L [>201 mg/dL]) participating in the Helsinki Heart Study. The cases consisted of 135 subjects in whom a coronary end point occurred during the 5-year observation period of the study, and the controls were 135 subjects who did not suffer coronary end points during this period. Levels of IgA, IgE, IgG, and IgM were determined in serum samples collected at study entry. RESULTS: Levels of IgA, IgE, and IgG, but not IgM, were significantly higher in cases than in controls. After adjustment for other risk factors, such as age, smoking, and blood pressure, the risk of coronary disease showed a significant relation to the levels of IgA, IgE, and IgG. The risk in the highest quartile of each distribution as compared with the lowest quartile was 2.2-fold for IgA (95% confidence interval, 1.0-4.5), 2.8-fold for IgE (1.3-5.9), and 2.8-fold for IgG (1.3-5.9). Hypertriglyceridemia and a low level of high-density lipoprotein cholesterol were associated with increased risk of a coronary end point only if the levels of IgA, IgE, or IgG were also elevated. CONCLUSION: Elevated levels of IgA, IgE, and IgG are associated with myocardial infarction and cardiac death in men with dyslipidemia. The present data suggest that, for dyslipidemia to cause coronary atherothrombosis, an immune response reflected by elevated levels of these immunoglobulin classes is an important determinant.     

Control of IgE responses. V. Oral administration of a synthetic derivative of the inner bacterial cell wall (SDZ 280.636) to sensitized mice induces isotype specific suppression of peak hapten specific IgE antibody forming cell responses, serum IgE levels and immediate hypersensitivity responses

SDZ 280.636, a nontoxic diacyl glycerol derivative of muramyl dipeptide (MDP), a component of the inner bacterial cell wall, which is suitable for use in man, suppressed hapten specific IgE antibody forming cell (AFC) responses in spleen, serum levels of hapten specific IgE and hapten specific immediate hypersensitivity (i.h.) responses in skin, when fed to mice at the peak of a hapten specific IgE AFC response. In addition, serum levels of IL-6 appeared increased while IFN gamma was decreased. To induce these IgE responses, BALB/c mice were injected i.p. with BPO-KLH (benzylpenicilloyl-keyhole limpet hemocyanin) (10 micrograms) in aluminum hydroxide gel (alum) on days 0, 21 and 42. Mice were fed (gavage) with either MDP or SDZ 280.636 (1.0 or 10 mg/kg) on day 44, or on days 44, 46 and 48, and killed on days 46 or 50. Numbers of BPO specific AFC in spleen, and serum levels of BPO specific immunoglobulins (IgG1, IgE and IgA) were determined (ELISPOT assay, ELISA). In addition, BPO specific IH responses were measured in these animals. Mice were injected in the right pinna with BPO-BSA (0.1 microgram) and in the left pinna with an equal volume of saline (0.05 ml). At 2 hr, pinnae were measured using a micrometer caliper. We found that 1 feeding with either MDP or SDZ 280.636 abrogated IgE AFC responses and dramatically suppressed serum levels of IgE, both in isotype specific fashion, and suppressed IH responses (> 50%). 3 feedings with SDZ 280.636 also abrogated IgE AFC responses and further decreased serum levels of IgE. In contrast to SDZ 280.636, 3 treatments with MDP had opposite effects in that IgE AFC responses and serum levels of IgE dramatically increased. A single treatment with SDZ 280.636 appeared to increase serum levels of IL-6 up to three fold, while IFN gamma levels decreased. Our data suggest that SDZ 280.636 may be useful in the therapeutic and prophylactic management of human atopic disease such as allergic rhinitis, asthma, and other atopic diseases.     

Bronchial asthma: clinical course, serum IgE and skin tests

We studied a group of 38 asthmatic patients to correlate the clinical evolution with results of IgE in serum, RAST and skin tests. Results reveal that almost 70% of the studied patients present important positivity in skin tests or RAST which confirms that the majority of asthmatics have an allergic component in their etiology. The determination of IgE in serum showed not to be a definitive exam to confirm allergic etiology. Only 25% of asthmatic patients with severe evolution presented skin tests or RAST strongly positive.     

A model to refine the selection of children with otitis media with effusion for adenoidectomy

The selection of children with otitis media with effusion for adenoidectomy has been criticized on a number of grounds. In spite of the widespread popularity of the procedure there are few objective guidelines to help the otolaryngologist make a decision which is therefore usually subjective. We present a scientifically derived model using a Generalized Linear Interactive Modelling (GLIM) technique from a population of 122 children who underwent either adenoidectomy or no pharyngeal surgery. The outcome parameter studied was otoscopic clearance in an unoperated ear 1 year after treatment. This was related principally to the operation type (P < 0.001) and to the age at which the operation was performed (P < 0.005). Using a probability of clearance threshold of 50% the model was tested on a prospective population of 166 children and outcome was correctly predicted in over 72%. This model enables the surgeon to determine the probability of clearance of effusion following adenoidectomy in an individual child. At a probability threshold of 50% adenoidectomy would be offered to children with bilateral otitis media with effusion aged between 4.33 and 8.00 years. Over the age of 8 years the probability of clearance occurring spontaneously increases beyond 50%. By careful selection of the probability of clearance thresholds it was possible to produce otoscopic resolution in over 80% of those selected to undergo adenoidectomy. The model also enables the otolaryngologist to determine the proportion of children with established disease that require adenoidectomy at his own chosen probability thresholds which will ensure that a more effective resource allocation is achieved.     

The relative paucity of IgE in human milk

The levels of IgE were determined in paired samples of serum and milk when whey obtained 3 to 8 days of postpartum, from 16 human lactating mothers who had reported a history of allergy to a variety of common allergens. Two assay procedures were employed to measure total IgE, a double-antibody assay and a commercially available solid phase assay (RIST). In addition, each sample of serum and whey was tested for specific IgE antibodies to a variety of allergens by the RAST test. The levels of total serum IgE were between 30 and 2300 I.U./ml and relatively good agreement was observed for both the double-antibody and RIST methods. In contrast, total IgE levels in milk whey were either undetectable (less than 3.0 I.U./ml in 14 of 16 subjects) or very low when analyzed by the double-antibody method, but were very high (400 to 1650 I.U./ml when analyzed by the RIST method. However, IgE added to milk whey could be measured by the double-antibody procedure indicating that the low levels detected in milk were not a fault of the double-antibody assay. It was assumed that the RIST test was subject to nonspecific interference by factors in milk whey which caused the determination of high, but incorrect, levels of IgE. Specific IgE antibodies were detected in the serum of 10 of 16 subjects but were not present in milk whey. A comparison of the whey/serum ratios of albumin, IgA, and IgE suggested that little, if any, IgE is selectively synthesized or secreted in the mammary gland.     

Studies of immunoglobulins, bentonite flocculation and IgE, IgG and IgM antibodies in serum from patients with trichinosis

Serial serum samples were obtained from two patients from a family of four who ingested raw pork at a known time and in whom trichinosis developed. Single and occasionally two serum samples were obtained from other patients with proved trichinosis. Studies of these serum samples showed that elevations of serum immunoglobulin E (IgE) levels do occur but not in all serum samples and that even when these levels are elevated, they are not high enough to be of diagnostic value. This is also true for serum immunoglobulin M (IgM). Using a solid phase radioimmunoadsorbent test, IgE, IgG and IgM antibodies were detected in the serums. The IgE antibody activity appeared early but was not present in all samples. The IgM antibody activity appeared later than the IgE and IgG antibody activity, and there was a statistically significant correlation between IgM antibodies as determined by radioimmunoassay and the bentonite flocculation titers suggesting that the bentonite flocculation is due to IgM antibody. IgM antibodies detected by radioimmunoassay were positive in all serum samples from patients with trichinosis except for a sample obtained 3 days after the onset of symptoms. The early increase in IgG antibodies and the occurrence of these antibodies in all serum samples obtained more than 3 days after onset of symptoms suggest a potential diagnostic use if serial samples are available early in the course of the disease.     

Comparative value of skin tests and IgE antibodies in the serum in patients with chronic vasomotor rhinitis

In order to assess values of skin testing and determination of pulp, as a credible indicator considering sensibilisation of an organism, 61 patients suffering from chronic vasomotor rhinitis were tested. By application of "prick" test, skin test results were positive in 30 patients and negative in 31. Presence of specific IgE antibodies in the serum was assessed in all patients by "ELISA" test. In 51 patients (83.6%) both kinds of findings corresponded. In 26 patients both skin parameters were negative while in 10 patients (16.40%) findings did not correspond. It was established that for Dermatophagodies pteronyssinus specific IgE antibodies are determined in serum when pap is 5 mm wide. Grasp pollen always caused strong local reactions, regularly more than 10 mm. Considerably high levels of IgE antibodies was also established while other pollens did not show such correspondence.