Cat Albumin Research Articles

Immunotherapy with cat- and dog-dander extracts: III. Allergen-specific immunoglobulin responses in a 1-year double-blind placebo study

An investigation was made of the specific antibody response to individual antigens in 40 patients taking part in a double-blind placebo study of immunotherapy with cat- or dog-dander extracts. Antigen-specific IgE levels were measured by means of CRIE, and the results were expressed as scores. The patients demonstrated IgE specificities toward 1 to 5 antigens. Cat-dander antigens Nos. 4 (cat Ag 1) and 7, and dog antigens Nos. 6 and 13, produced the highest scores, but high IgE binding was also found for dog albumin. After 1 year of treatment, the IgE responses of the two treatment groups (allergen and placebo) were statistically indistinguishable from those before the start of treatment. There was a tendency toward a reduction in score for two of the dander antigens (cat Ag 1 and dog Ag No. 13), and no new IgE specificities appeared. Antigen-specific IgG levels were measured by means of CIE with patient serum incorporated in an intermediate gel, and the results were expressed as plus/minus precipitins. Only two patients had precipitating antibodies before the start of treatment (one against cat albumin and one against cat Ag 1). During the course of treatment, the production of antigen-specific IgGs was observed in 18 22 allergen- and 1 18 placebo-treated patients. For the cat allergentreated group, the specificities were directed against cat antigens Nos. 2, 3 (cat albumin), 4 (cat Ag 1), and 7, and for the dog allergen-treated group, against dog antigens Nos. 2 (dog albumin), 13, and 20. Before and 1 year after the start of treatment, the patients' homes were subjected to dust analyses for content of cat and dog antigens. These revealed that there was no statistically significant difference between the allergen-treated and placebo-treated groups, either before the start of treatment or after 1 year of treatment. The range of cat Ag 1 and of dog albumin found was 100 to 100,000 ng/gm of dust.

Identification and clinical significance of allergenic molecules of cat origin. Part of the DAS 76 Study.

Freeze-dried extracts from cat dander and the corresponding rabbit antibodies were used for establishing the CIE reference pattern for cat dander extracts. Anti-Cat Ag 1 and anti-cat albumin were used for identification of the corresponding antigens. CRIE on sera from selected groups of American and Danish cat-allergic patients demonstrated antigen-specific IgE binding to 10 of 15 cat dander antigens (Cat Ag 1 being the major allergen). Only minor differences were found between the two groups. Four of these allergens were serum proteins. Variable amounts of many of the 10 allergens were measured by QIE in saliva, serum, urine and three cat pelt extracts. However, extremely wide ranges for content of the serum allergens and the non-serum allergens were found. This was exemplified by an albumin/cat Ag 1 ratio between 1 and 400, smallest in cat dander. Immunoabsorption using anti-cat dander, anti-cat albumin and anti-Cat Ag 1 indicated that the anti-cat dander, anti-cat albumin, and the anti-Cat Ag 1 absorbed approximately 90%, 25%, and 56%, respectively, of the dander RAST activity, and 87%, 11%, and 45%, respectively, of the saliva RAST activity, confirming the major importance of Ag 1. It is concluded that cat allergenic extracts should contain only modest amounts of serum albumin and other serum-derived antigens and that any relevant standardization must include quantification of at least Cat Ag 1 and cat albumin.

Immunotherapy in cat-induced asthma. Double-blind trial with evaluation of in vivo and in vitro responses

The efficacy of immunotherapy in cat-induced asthma was studied by use of a purified fraction of cat-pelt extract and a double-blind protocol. Nine active-treatment subjects who received a mean cumulative dose of cat allergen, 1 of 10.9 units, and eight placebo-treatment subjects completed the study. Active treatment resulted in significant reductions in bronchial sensitivity ( p < 0.05) and prick test titer ( p < 0.01). In addition, active treatment resulted in a significant delay in the onset of ocular ( p < 0.05) and pulmonary ( p < 0.02) symptoms on exposure to living cats. Significant increases in IgG antibody to cat allergen 1 ( p < 0.001) and cat albumin ( p < 0.01) also occurred with active treatment. There was no significant change in bronchial reactivity to methacholine or in the sensitivity of circulating basophils. These results confirm the validity of immunotherapy in allergic asthma where there is careful patient selection and well defined treatment preparations.

Exclusion phenomenon in the liver interstitium.

Measurements were made of hepatic interstitial fluid volume and the proportion of that space occupied by 125I-labeled lactoglobulin, albumin, and gamma-globulin in anesthetized cats. 51Cr-red blood cells and 99mTc-diethylenetriaminepentaacetic acid were used to estimate tissue blood volume and extracellular volume, respectively. Hepatic lymph was assumed to represent the interstitial fluid of the liver. The degree of exclusion of each protein increased with increasing molecular size. At normal hepatic venous pressures, the excluded volume fraction for cat albumin was 0.41. Elevation of hepatic venous pressure by 12.5 mmHg caused a fourfold increase in hepatic lymph flow with an increase in interstitial volume and a reduction in albumin exclusion. When the exclusion of heterologous (human) albumin was studied in the cat liver, much higher values were obtained than with homologous albumin. This effect may be due to polymerization of commercial human albumin on storage.

Antibody responses following immunotherapy with cat pelt extract

IgG antibody responses to a major allergen, cat allergen 1 (cat 1), and to a minimally allergenic protein, cat albumin (alb), were studied in patients who had received 4 to 11 mo of immunotherapy with three concentrations of crude cat pelt extract. A double-antibody radioimmunoassay utilizing 125I-labeled antigen was used to measure IgG and IgE antibody. The high-dose group (HDG)(n = 5), which was composed of the active-treatment group of a previously reported double-blind study, received a mean cumulative dose of 3440 microgram cat 1 and 10,660 microgram alb. The intermediate-dose group (IDG) (n = 6) and low -dose group (IDG)(n = 5) received 70 and 0.930 microgram of cat 1 and 217 and 2.86 microgram of alb. IgE antibody to cat 1 before treatment was measurable in most patients. IgE antibody to alb was either no measurable or of a low level. Mean (geometric) before-and-after IgG levels (U/ml) to cat 1 in the HDG, IDG, and LDG were 420 and 7794, 158 and 1388, an 191 and 1365, respectively. Mean before-and-after IgG levels (U/ml) to alb in the HDG, IDG, and LDG were 72 and 348, 1.9 and 4584, and 0.4 and 508, respectively. Two patients (HDG) had no IgG antibody to alb after treatment. Another patient (HDG) had 82,364 U/ml IgG antibody to alb and precipitating antibody by gel diffusion. Very intense IgG antibody response to both cat 1 and alb were seen over a wide range of immunizing doses.

Effect of sympathetic nerves on cerebral vessels during seizures.

The purpose of this study was to determine the effect of activation of sympathetic pathways during seizures on cerebral blood flow and integrity of the blood-brain barrier. We measured cerebral blood flow with microspheres and disruption of the blood-brain barrier with labeled albumin in cats. One cerebral hemisphere was denervated by cutting the superior cervical sympathetic trunk on one side. During bicuculline-induced seizures, superior cervical sympathetic nerve activity increased about threefold. Blood flow to the innervated hemibrain was significantly lower than flow to denervated hemibrain. However, in relation to the total increase in flow, this effect of nerves was minor. Blood-brain barrier permeability increased about sixfold during seizures, but there was no difference between the innervated and denervated sides of the brain. We conclude that sympathetic nerves attenuate the increase in cerebral blood flow during seizures, despite the increase in metabolism, but this effect is small. Activation of sympathetic nerves does not reduce disruption of the blood-brain barrier during seizures.

IgE antibody to cat allergens in an allergic population

Clinical cat sensitivity and IgE antibody to cat allergens were studied in 200 consecutive patients who presented themselves for an allergy evaluation. Fifty-nine percent of the patients had no evidence of allergy to cats (group 1). Twenty-three percent of the patients had positive histories of allergy to cats and a positive prick test to cat epithelial extracts (group 2). The remaining 18% had either positive prick tests or positive histories alone (groups 3 and 4). The group of patients with strong evidence of allergy to cats (group 2) was on an average younger and had a higher incidence of asthma than did group 1 patients. Significant binding of IgE antibody to various insolubilized allergen preparations was defined as that binding which exceeded the 95% confidence interval for group 1 patients. Significant binding of IgE antibody to insolubilized cat allergen 1 was present in 65%, 15%, and 10% of groups 2, 3, and 4 patients, respectively. Significant binding of IgE antibody to insolubilized cat pelt extract was present in 28%, 11%, and 0% of group 2, 3, and 4 patients, respectively. Data for IgE antibody binding to insolubilized cat serum and cat albumin revealed no significant difference between the groups. It is concluded that cat allergen 1 is an important allergen in patients with strong evidence of allergy to cats.

Allergens of mammalian origin V. Properties of extracts derived from the domestic cat.

Eight commercial cat dander extracts and two pelt extracts derived from mongrel and Siamese cats were compared. Cat allergn 1 and cat albumin were measured by radial immunodiffusion. Allergenic activity was evaluated by prick test and a modified radioallergosorbent test. In the latter, the dilution of each extract that produced 50% inhibition of binding of IgE antibodies to insolubilized cat allergen 1 (RAST 1) and insolubilized cat serum (RAST 2) was determind. The total non-dialysable solid content of the extracts did not correlate with any other parameter. Cat allergen 1 content determined by radial immunodiffusion correlated with average prick test results in ten cat-sensitive subjects and with RAST 1 activity. Cat albumin content correlated weakly with RAST 2 activity but not with any other measure of allergenic activity. Absorption of each extract with the gamma-globulin fraction of rabbit antiserum to cat allergen 1 significantly reduced prick test reactivity and RAST 1 activity, but not RAST 2 activity. These results indicate that cat allergen 1 is an important allergen in cat dander extracts and its measurement may be used to standardize the allergenic activity of such extracts.

The passage of intracisternally injected albumin and urea into perilymph.

The total protein and urea concentrations in perilymph, CSF and serum were determined following intracisternal injection of albumin and urea in cats. Total protein concentration in perilymph increased abruptly when total protein in CSF increased following injection of albumin. The total protein concentration in perilymph equalled two-thirds of the protein concentration in CSF by the first hour and remained fairly constant throughout the second and third hours although the protein concentration in CSF decreased during this time. The concentration of urea in both perilymph and serum increased as urea concentration in CSF increased. However, urea concentration in perilymph returned to the original value after 2 hours. This concentration remained constant and paralleled serum urea concentration even though the level of urea in CSF remained approximately five times higher than its initial value. The relationship between these findings and the etiological factors of clinical disorders such as antibiotic toxicit...

Milk Allergy in Infancy

Cat dandruff extract was characterized by crossed immunoelectrophoresis (CIE) and crossed radioimmunoelectrophoresis (CRIE) using sera from 27 cat-sensitive individuals. By applying a CIE/CRIE system with intermediate gel, the content of dander-specific and serum-specific allergens was established. Thirteen serum-related and eight dander-related antigens were identified in cat dandruff. Of these, eight antigens were visibly radiostained in CRIE. Five allergens were serum-specific and of these allergens cat albumin was the most important (intermediate allergen). Three allergens were dander-specific and of these three only cat allergen I fulfilled the criteria for a major allergen.