Skin test reactivity in infancy

Skin tests represent a major tool in the diagnosis of reaginic allergy; however, their interpretation does not appear to be without difficulty in children under the age of 3 yr. Seventy-eight infants from birth to 24 mo were prick tested and compared with 30 nonallergic adult subjects. Skin tests were performed without bleeding by use of two strengths of histamine hydrochloride (1 and 10 mg/ml), a mast cell degranulating agent (codeine phosphate, 50 mg/ml), and allergenic extracts. Negative control solution elicited a small wheal (less than 1.5 mm) in two infants who were excluded from further results. A clear and significant (p less than 0.001) hyporeactivity to both histamine and codeine phosphate was observed in infancy, especially before the age of 6 mo. Six infants were allergic and presented positive prick tests to either food or inhalant allergens. These tests were confirmed by serum specific IgE and a suggestive clinical history. The size of the allergen-induced prick test wheal ranged from 2 to 5 mm in diameter, suggesting that prick test wheals may be smaller in infants. This study confirms that prick tests can be performed and interpreted without difficulty in infants, keeping in mind the small wheal size induced by both positive control solutions and allergen-induced prick tests.     

Functional assessment of alveolar macrophages: comparison of cells from asthmatics and normal subjects

Alveolar macrophages (AM) were obtained by bronchoalveolar lavage (BAL) from seven healthy nonallergic, nonasthmatic donors, I5 patients with allergic bronchial asthma, and six patients with aspirin-sensitive asthma. AM were purified by adherence over 2 hr and cultured for an additional 24 hr. Functional assessment of viable cells was carried out for zymosan phagocytosis and for prostaglandin (PG) E₂-PGF_2α thromboxane (Tx) B2 release by resting and zymosan-stimulated AM. The eosinophil count in BAL fluid from allergic asthmatics was higher than that from control subjects (3.9% ± I.6% vs 0.4% ± 0.3%, p < 0.05) and still greater in BAL from patients with aspirin-sensitive asthma (21.7% ± 9.0%, p < 0.0I). After the 24 hr of incubation, the AM viability was inversely correlated to the percentage of eosinophils in BAL fluid (r = -0.54, n = 21, p < 0.02). Zymosan phagocytosis was significantly lower by viable cells from both allergic asthmatics and aspirin-sensitive patients as compared with cells from normal donors (p < 0.05). Zymosan phagocytosis induced a twofold to threefold increase in the release of PGE₂, PGF_2α, and TχB₂ from AM of normal subjects (p < 0.01) but only a onefold to twofold increase from AM of allergic asthmatic patients. The stimulated AM from aspirin-sensitive patients released smaller quantities of each product than AM from normal subjects or allergic asthmatic patients (p < 0.05). We conclude that the viability and functional activity of AM are impaired in asthmatic patients and that these deficits correlate with the percent eosinophilia in the BAL; it is therefore suggested that they may be due to an interaction between eosinophils and AM in the bronchoalveolar lumen.     

Clinical and immunologic survey in beekeepers in relation to their sensitization

Beekeepers often present allergic symptoms and represent a natural and experimental model of anaphylaxis and specific immunotherapy. Two hundred BKs were investigated. Both allergic and nonallergic subjects were selected very carefully in terms of immunologic status and exposure to bee stings. They were surveyed by a questionnaire, the titration of total serum IgE, and bee venom-specific IgE and IgG. Skin tests to HBV were performed in 176 subjects. Skin test sensitivity to HBV and allergic symptoms were significantly (p less than 0.0001) related to the estimated number of annual stings. BKs did not have allergy for more than 200 bee stings received in a year, and skin tests were negative in all cases. Many subjects who received between 50 and 200 annual stings had positive skin tests, and 9% of them had a systemic allergic history. Systemic anaphylaxis was present in 20% of BKs who received between 25 to 50 annual stings, and in 45% of BKs who are stung less than 25 times a year. Specific IgE was present in 42% of BKs whatever the number of stings received, but the titer was lower when the number of stings increased. The presence of specific IgE in subjects who are stung numerous times and who do not present allergic symptoms at the time of the stings suggests that outbreaks of anaphylaxis may be possible in nonallergic BKs. Specific IgG titrated by the Pharmacia IgG-RAST was less than 150 U/ml in most allergic subjects and over this level in most nonallergic BKs.(ABSTRACT TRUNCATED AT 250 WORDS)     

Egg allergy, influenza vaccine, and immunoglobulin E antibody.

In a study of 70 patients with asthma, rhinitis, and eczema, those giving a definite history of allergic reactions to egg more frequently showed positive skin tests to egg extracts (p = less than 0.003), the wheal diameters of which were significantly larger (p = less than 0.01) than in patients with only a possible or no such history. Patients with a definite history of egg allergy had significantly higher levels of specific IgE antibody against egg yolk, egg white, and allantoic fluid than patients in the other two groups (p = less than 0.005). Seven patients, all of whom had given a definite history of allergy to egg, were found to have positive skin prick tests to influenza vaccine, at the concentration used in medical practice. Two of these patients had previously been given influenza vaccine and both had developed adverse reactions. Of the 22 patients giving a definite history of allergy to egg, the 7 (35 per cent) with positive skin tests to influenza vaccine had significantly larger skin tests and higher levels of specific IgE antibody to the egg extracts than the group as a whole (p = less than 0.001). Allergic reactions to influenza vaccine are likely to occur in patients who have a definite history of allergy to egg and large skin prick test reactions or high levels of specific IgE antibody to egg extracts. Those at risk can best be identified by skin prick testing with egg extracts and undiluted influenza vaccine.     

Microtiter solid-phase radioimmunoassay for specific immunoglobulin E

A microtiter solid phase-radioimmunoassay (MSPRIA) for perennial rye grass-specific IgE is described. The assay is carried out in flexible polyvinyl chloride "u" microtiter plates by sequentially incubating antigen, albumin, test sera, and finally radiolabeled antihuman IgE. Wells are cut free of the plate with a hot wire-cutting apparatus and counted individually in a gamma counter. The amount of radioactivity bound is proportional to the amount of specific IgE in the serum. The MSPRIA is shown to be antigen and antibody specific, reproducible, and easily done. Rye-specific IgE levels assayed with the MSPRIA correlated with quantitative end point titration skin testing using perennial rye grass antigen performed on 31 volunteers with a maximum correlation coefficient of 0.92. The MSPRIA was compared with the radioallergosorbent test (RAST) method using sera from the same 31 volunteers. The rye-specific IgE levels assayed by MSPRIA correlated with those assayed by RAST with a correlation coefficient of 0.95. The MSPRIA is well suited for mass screening and represents a useful method for measuring specific IgE.     

Bronchial response to inhaled prostaglandin F2α in patients with common or aspirin-sensitive asthma

The effect of aerosolized prostaglandin F₂α (PGF₂α) on specific airway resistance (SRaw) has been measured in patients with common (n = 10) or aspirin-sensitive asthma (n = 5). In all subjects PGF₂α caused a dose-related increase in SRaw, but considerable individual differences in sensitivity were observed. The patients with aspirin intolerance did not differ from regular asthmatics in terms of their response to PGF₂α. Two types of reactions to PGF₂α could be distinguished from their time-course: immediate and short-lasting (3 cases) or delayed and long-lasting (12 cases). Inhalation of a β-adrenergic drug rapidly and completely reversed the effect of PGF₂α, suggesting that the increase in SRaw was due to bronchospasm. In 7 subjects the inhalation of an anticholinergic drug (SCH 1000) prior to PGF₂α inhibited to a large extent the effect of the latter, suggesting that the cholinergic system played an important role in the bronchial response to PGF₂α. In 9 subjects no correlation was found between the bronchial sensitivity to carbachol and PGF₂α.     

Detection of immediate hypersensitivity in rabbits by direct basophil degranulation.

The direct in vitro antigen-induced degranulation of rabbit basophils based on a simplified one-step method for the staining of these cells is reported. Degranulation was assessed by counting the number of basophils before and after exposure to antigen at 37 degrees C in the presence of Ca++. The degranulation was IgE-mediated, as shown by its passive transfer to nonimmunized rabbits by IgE-containing serum; also, the reaction was dependent on the presence of Ca++ ions and normal cell metabolism. The technique allowed the detection of serum factors capable of blocking the degranulation. It provided a means for following IgE sensitization at the cellular level, which is a better index of immediate hypersensitivity than the presence of circulating specific IgE.     

Elevated serum immunoglobulin E in bronchial carcinoma: its relation to the histology and prognosis of the cancer

Total IgE and specific IgE antibodies against six common allergens were measured in the sera of 217 unselected patients with bronchial carcinoma. Their median total IgE level was significantly increased as compared to the median levels found in two control populations consisting of 246 individuals representing the adult general population and 143 patients with benign pulmonary disorders. The frequency of serological atopy, i.e., the presence of specific IgE antibodies, was also significantly increased in the cancer population as compared to the controls. In contrast, the incidence of possible clinical atopy was about five times higher in the general population than in the cancer group. Patients with bronchial carcinoma typed as adenocarcinoma had the best prognosis and also had nonelevated IgE levels in contrast to patients with bronchial carcinoma typed as squamous cell carcinoma, small or large cell carcinoma. The favourable prognosis with nonelevated IgE levels also was demonstrated in patients with squamous cell carcinoma. It is suggested that the elevated IgE levels in bronchial carcinoma reflect impaired cellular immunity.     

Anaphylactic reactions to modified fluid gelatins

Use of modified fluid gelatins as a plasma expander is of interest in human clinical medicine due to osmotic pressure similarities with plasma proteins. However, adverse reactions such as urticaria, edema, and/or anaphylactic shock occur and can lead to diagnostic problems. In addition, mechanisms of these reactions are poorly understood. We report three cases of anaphylactic shock studied by skin tests and, for the first time, in vitro leukocyte histamine release (LHR). Intradermal skin tests were significantly positive for concentrations of 1:1000 to 1:10 of the commercial preparation used before the reaction in each patient. Thirty control subjects were negative even for the undiluted preparation. Positive LHR was obtained from patients' leukocytes washed and then incubated in Tris-albumin Ca++ Mg++ buffer with serial dilutions of fluid gelatins; controls were negative. Addition of D2O (50%) caused significant increase of LHR in patients but had no effect on controls. In conclusion, skin tests and LHR might be valuable in diagnosis of patients reactive to gelatins. Furthermore, these findings suggest release of mediators from mast cells or basophils, but discrimination between immunologic and idiosyncratic pharmacologic mechanism was not obtained.     

Serum IgD concentrations in children with atopic diseases

When serum IgD was measured by electroimmunodiffusion (EID) in 60 children with atopy and in 55 normal children, the children with atopy had a mean serum IgD level of 2.47 mg. per 100 ml. and a standard error of the mean of 0.32 mg. per 100 ml. In contrast, the control group of normal children had a mean level of 3.59 ± (S.E.M.) 0.48 mg. per 100 ml. This difference was not statistically significant. IgD levels in the two groups could not be correlated with sex or diagnosis, but there was a significant (p < 0.05) correlation with age in the group with atopy. Further statistical analysis indicated that the lower mean IgD level in the atopic group was related to the lower mean age in this group. The study also demonstrated that EID is more sensitive than single radial diffusion (SRD) for the measurement of IgD in the serum of normal and atopic children.     

Transient hypogammaglobulinemia, elevated immunoglobulin E levels, and food allergy.

Four infants presented with the combination of food allergy, transient hypogammaglobulinemia (THI), and elevated serum IgE levels. Food allergy was documented by history, positive skin tests for immediate hypersensitivity, radioallergosorbent test, histamine release studies, and lymphocyte transformation in response to food allergens. THI was probably secondary to decreased production since there was no evidence of protein loss from the gastrointestinal tract. Immunologic studies revealed normal B cell number and function in vitro. T cell number and proliferative response to mitogens and antigens were normal but T cells were deficient in their ability to generate helper factors necessary for B cell maturation into immunoglobulin secretory cells. The THI and the deficient production of T cell--helper factor resolved after the age of 20 to 24 mo. A defect in immunoregulation may be responsible for the immunologic abnormalities observed in these patients and their propensity to develop IgE antibodies to food allergens.     

Effect of beta adrenergic blockade on bronchial sensitivity to inhaled acetylcholine in normal subjects

Dose-responses curves were established in 10 normal subjects by measuring, with a body plethysmograph, the changes of specific airway conductance (SGaw) produced by aerosolized acetylcholine. Doses of acetylcholine producing a 50 per cent decrease of control SGaw (ED₅₀) were found to be largely variable among individuals. β-adrenergic blockade with intravenous propranolol (0.2 mg per kilogram) resulted in a mean potentiation of the acetylcholine effect (mean ED₅₀ after propranolol was significantly lower than mean ED₅₀ before). This potentiating effect of propranolol, however, was also subjected to individual variations, suggesting individual variability of the sympathetic system. The range of variation in acetylcholine sensitivity was not narrowed by propranolol treatment and no correlation was found between initial acetylcholine sensitivity and propranolol potentiation. This suggests that variability of the sympathetic system is not the main factor in determining individual variation in acetylcholine sensitivity. Even when propranolol was very effective in increasing airway sensitivity, this sensitivity was still less marked than usually encountered in asthmatic patients. This suggests that β-adrenergic blockade cannot create, if alone, the bronchial hypersensitivity characteristic of asthma.     

Aging and serum immunoglobulin E levels, immediate skin tests, RAST

The changes of the serum IgE levels, specific immediate skin-test responses, and RAST measurements with age were evaluated. A total of 331 unrelated individuals were studied, consisting of 166 subjects with ragweed allergic rhinitis and/or asthma, 67 with idiopathic (intrinsic) asthma, and 98 who appeared in good health with no clinical evidence of atopic diseases. All subjects were evaluated by history and physical examination, intradermal skin testing to the common aeroallergens, measurements of IgE antibody to common aeroallergens with the RAST, and serum IgE levels. Results demonstrated a significant decrease in serum IgE levels with aging in atopic individuals. This decline was exponential in character. In addition, a tendency for RAST and immediate type skin-test responses for selected antigens and histamine to decrease with age was observed.     

Immunodeficiency diseases and expression of HLA antigens

The role of HLA antigens in lymphocyte differentiation is strongly suggested by the existence of a recently identified immunodeficiency associated with, and probably resulting from, the lack of expression of HLA-A, B, and C antigens as well as /gB₂ microglobulin on various cells of hematopoietic origin. This “bare lymphocyte syndrome” has been described in a family where the transmission appeared to be autosomal recessive, and the responsible gene was not borne by the sixth chromosome.Another infant with a severe combined immunodeficiency disease has been treated with fetal liver and thymus transplants (FLTT). A persisting chimerism has been documented: T cells derived from the donor and B cells from the host. Despite complete HLA-A, B, and DR mismatch, T and B cells did cooperate resulting in significant antibody production, and defense against viral infection has been normal. Such an observation may suggest that “allogeneic restriction” of T-cell effector functions can be circumvented.     

Increased serum immunoglobulin E levels following allogeneic bone marrow transplantation

IgE levels were determined before and serially after allogeneic bone marrow transplantation (BMT) in 12 patients. Six patients had aplastic anemia, four leukemia, and one each Wiskott-Aldrich syndrome and infantile agranulocytosis. IgE levels increased sharply (7- to 2,000-fold) in 10 of the 12 as early as 14 days after BMT. They all returned to baseline levels by 60 days. In six of these patients, the rise accompanied clinical and biochemical evidence of acute graft-versus-host disease (GVHD). All of the patients who received rabbit antihuman thymocytic serum (ATS) in preparation for transplantation and were tested for IgE antirabbit serum antibody by radioallergosorbent test (RAST) (n = 6) developed a strongly positive RAST which paralleled their total IgE levels. These high IgE levels detected during the period of acute GVHD may be a manifestation of a transient lack of suppressor T cell activity.     

Spontaneous paroxysmal electroclinical patterns in rat: a model of generalized non-convulsive epilepsy

During quiet wakefulness of 63 adult Wistar rats, 24 exhibited synchronous paroxysmal bursts consisting of spikes and spike and wave discharges, recorded in the amygdala and frontoparietal cortex. Discharges were associated with a sudden immobility of the rat and rhythmic twitches of vibrissae or cervicofacial musculature. As soon as the phenomena stopped, the animal resumed its previous behavior. Paroxysmal electroclinical attacks could be observed as long as the animal survived. Similar electrical discharges have been observed previously in rodents by other authors and interpreted as an epileptic phenomenon. Preliminary pharmacological results confirm this interpretation and emphasize the similarity between our findings and the human petit mal epilepsy.     

IgE synthesis in man. II. Comparison of tetanus and diphtheria IgE antibody in allergic and nonallergic children.

Specific IgE and IgG antibodies were quantitated in 91 allergic and 80 nonallergic age- and sex-matched children between 4 and 17 yr of age. Statistically significant increased antidiphtheria and antitetanus IgE antibodies (p < 0.01) measured by the radioallergosorbent test (RAST) were noted in allergic compared with nonallergic subjects. Of the allergic children with total serum IgE >500 U/ml, 19 of 52 (37%) and 25 of 52 (48%) had elevations (>2 SD above nonallergic control mean) of serum antitetanus or antidiphtheria IgE antibody, respectively, whereas only 2 of 35 allergic children with serum IgE <500 U/ml had elevation (>2 SD) of these antibodies. Antitetanus and antidiphtheria IgG antibodies were measured by passive sheep red blood cell (SRBC) hemagglutination. Geometric mean antitetanus IgG antibodies were higher in allergic (4.9 AU/ml) as compared to nonallergic (1.7 AU/ml) children (p < 0.001). Geometric mean antidiphtheria IgG antibodies were higher (0.31 AU/ml) in nonallergic and lower in allergic (0.10 AU/ml) subjects (p < 0.01). These data suggest that allergic individuals with markedly elevated total serum IgE have unique antibody responses following routine immunization with tetanus-diphtheria (Td) toxoids and tetanus-pertussis-diphtheria (DPT) which are manifest by enhanced specific IgE synthesis.     

Enumeration of T cell subsets in atopic dermatitis using monoclonal antibodies

Peripheral blood lymphocytes from 22 patients with atopic dermatitis, 17 age-matched healthy controls, 10 patients with other skin diseases, and 14 patients with either asthma or allergic rhinitis were characterized by reactivity with monoclonal antibodies to the surface antigens of helper-inducer (T4) and suppressor-cytotoxic (T8) T cell subsets and to a common T cell antigen (T3). In contrast to healthy controls and controls with other skin diseases or respiratory allergic disease, patients with atopic dermatitis had a reduced percentage of T3-positive (T3+) cells (p < 0.01) and T8-positive (T8+) cells (p < 0.001) but not of T4-positive cells (T4+) (p > 0.05). A selective increase in the ratio of T4+ cells over T8+ cells was observed in 17 of 22 patients with atopic dermatitis but not in any of the controls. Thus there is a loss of circulating suppressor-cytotoxic T cells in the majority of patients with active atopic dermatitis.