Preventive role of atopy in lung cancer

Incidence of atopic disease, serum and sputum IgE, and sputum IgA levels were studied in lung cancer patients, and compared with those in lung benign disease patients and normal controls. A significantly lower prevalence of personal atopic history was observed in the cancer group in comparison with the other two experimental groups. Patients with lung cancer showed significantly higher serum IgE levels than benign-disease and normal control individuals. At the same time, patients with epidermoid lung carcinoma had significantly increased levels of serum IgE and sputum IgA than those with lung adenocarcinoma.     

The relationship of a topic disease and immunoglobulin levels with special reference to selective IgA deficiency

We have confirmed that the presence of IgE in selective IgA deficient patients does not give protection against increased susceptibility to infections. Atopic individuals with selective IgA deficiency may have higher levels of IgE than non-atopic individuals. Immunoglobulin levels for G, A or M tend to be lower in atopic individuals than in normal individuals.     

A study of serum immunoglobulins including IgE and reaginic antibodies in patients with bronchial asthma in relation to the spectrum of the disease

Immunoglobulins G, A, M, D, and E were studied in the sera obtained from sixty-nine bronchial asthma patients, who were graded objectively according to atopic score. Among other associated atopic diseases, they often had allergic rhinitis. Ninety-one per cent of these patients had elevated serum IgE levels and the mean level of serum IgE was more than 3.5 times higher than that observed in the normal subjects. Moreover, as their atopic score increased, the serum IgE levels were also elevated, and every patient with high atopic score, had elevated serum IgE levels: This indicates the association of atopic state with serum IgE level. Furthermore, reaginic antibodies were studied in some of these patients by intradermal tests, Prausnitz-Küstner (PK) reaction, conjunctival and bronchial provocation tests. Intradermal and PK tests were comparable and proved to be the most sensitive method of detecting reagins. The intensity of these reactions correlated significantly with serum IgE level, although this relationship is not invariably present. The reaginic activities in the sera of the patients with atopic bronchial asthma also compared well with the positive bronchial test (induced asthma) by inhalation of specific aerosol although this association is also not always present. Eleven patients with high atopic score had isolated serum IgA deficiency. There was a significant rise of mean serum IgM in comparison to the controls.     

Relationship between antigen-specific IgE antibody (RAST) and total serum IgE levels.

Although the total serum IgE level is generally higher in atopic than in non-atopic individuals, high total serum IgE levels and atopic diseases are not invariably associated. In 42 atopic patients with the total serum IgE levels less than 100 U/ml, 27% of RAST against 14 allergens were positive whereas in 45 atopic patients with the total serum IgE levels greater than 500 U/ml, 57% of RAST against 14 allergens were positive. The mean RAST values against four grass antigens expressed as a percentage of antigen-disc bound radioactivities were significantly lower in the group with the lower total serum IgE levels. Low or normal total serum IgE levels are likely to be found in atopic patients who are allergic to a relatively few grass antigens.     

Total serum IgD is increased in atopic subjects

We have developed a sandwich-type ELISA system for measuring total IgD levels in the serum of atopics and non-atopic controls. In this ELISA system, affinity purified goat anti-human IgD was used for capture. Results were superior to those obtained with monoclonal anti-human IgD antibody. No cross-reactivity could be demonstrated to IgG, IgM, IgA or IgE. The assay showed minimal non-specific binding even with initial serum dilutions of 1:2. The results obtained were reproducible among replicates (Mean CV +/- SEM = 0.03 +/- 0.002; n = 251), between dilutions (CV = 0.08 +/- 0.006; n = 108), and between assays (CV = 0.05 +/- 0.12; n = 5). We used routine radioimmunoassay for measuring total serum IgE. Using these assays total serum IgD and IgE levels were measured in 75 atopic patients and 33 normal subjects. None of the atopics had recent immunotherapy. As expected, the geometric mean serum IgE in atopics (373 ng/ml) was significantly higher than that in normal subjects (49 ng/ml) (P less than 0.01). However, geometric mean serum IgD was also significantly higher in atopics (20.3 micrograms/ml) than that in normal subjects (8.4 micrograms/ml) (P less than 0.02). In both atopic and normal groups, mean serum IgD level did not differ significantly on the bases of age, sex or asthmatic status. Furthermore, total serum IgD was not significantly correlated with total serum IgE (r = 0.14; P = 0.14; n = 108), indicating that immunoregulatory control of the basal levels of the two isotypes is not linked.(ABSTRACT TRUNCATED AT 250 WORDS)     

Serum IgE in non-atopic adults and in dermatitis patients

Total serum IgE was determined with the PRIST technique, and specific reaginic antibodies against 10 allergens were measured in 163 healthy adults with no personal or family history of symptoms indicative of atopy (Group A). 103 non-atopic adults with a family history of atopic diseases were similarly investigated (Group B). When all subjects who at the second interview presented with a history of atopic symptoms and those with positive RAST results were excluded, the geometric mean serum IgE value for Group A was 14.5 (SD = 2) - 94.4 U/ml and for Group B 14.4 (SD = 2) - 130.2 U/ml. There was no significant difference in the IgE values between men and women. Subjects under 40 years of age had significantly higher IgE values than subjects over 40 years. In the series of 276 dermatitis patients the geometric mean IgE value for the men was significantly higher (46.8) than for the women (28.8 U/ml). There was a highly significant difference in the mean serum IgE levels between the patients with a personal history of atopic diseases and the other patients. Patients with present atopic disease had significantly higher mean IgE values than those with past atopic disease while no significant difference was discernible in the mean IgE levels between the non-atopic patients from atopic families and those with no personal and family atopy. Three years later, total serum IgE was controlled in subjects with initial IgE levels greater than 100 U/ml. During this time, eight subjects had developed an atopic disease. In most cases, there were only slight variations in the IgE values.     

Serum IgE levels in normal subjects and allergy patients among the Chinese in Singapore.

Serum IgE was determined in four groups of Singapore Chinese consisting of 292 normal subjects, 15 patients with atopic dermatitis, 39 with drug allergy and 14 with bronchial asthma. The results were compared with the findings of similar groups in western countries. In the normal subjects the range and means (numerical and geometrical) of serum IgE were four to seven times higher in the Singapore Chinese than reported in the western countries. However, the circulating levels in atopic dermatitis and bronchial asthma patients were comparable. In drug allergy moderate IgE elevation was noted. The serum IgE levels of the normal subjects and patients with atopic dermatitis and bronchial asthma were markedly lower than those found in nearby Papua New Guinea. The significance of these observations is discussed.     

Milk whey-specific immune complexes in allergic and non-allergic subjects

We developed an antigen- and isotype-specific ELISA for the rapid detection of native serum immune complexes (IC). It is a sandwich assay, in which a solid phase antigen-specific capture antibody selectively binds the antigen-specific IC via the antigen. The isotype of the bound IC is then identified using an enzyme-labelled indicator antibody. Using this sensitive assay system, we were able to detect native serum milk whey-specific immune complexes (SMIC) of the IgG, IgE and IgA isotypes. Detectable amounts of native serum SMIC of all three isotypes were found in sera of the majority of both atopic and non-atopic subjects. The ELISA was then used to compare the levels of native IgE SMIC in sera of milk RAST positive atopic patients with those found in milk RAST negative atopic patient sera. Milk RAST positive patient sera were found to have significantly higher mean levels (P less than or equal to 0.005) of native IgE SMIC than milk RAST negative sera. Sera of other atopic individuals were also found to contain significantly higher mean levels (P less than or equal to 0.005) of native IgG and IgA SMIC than non-atopic donors. IgE IC may specifically be involved in adverse symptoms seen in milk allergic patients.     

The relationship between atopy and salivary IgA deficiency in infancy.

In a prospective study, infants born to atopic parents had a significantly higher prevalence of salivary IgA deficiency at all ages studied than control infants, and the mean non zero IgA level of the potentially atopic infants was significantly lower at 8 and 12 months than of control infants. Of the infants with atopic parents, the prevalence of IgA deficiency was not significantly greater in those who manifested atopic disease during the study period than in those who did not, but the levels were significantly lower at 4 months.     

Humoral and cellular immunity in asthma

Parameters of humoral and cellular immunity have been measured in 91 asthmatic patients. Mean serum levels of IgG and IgE were raised. IgG levels were higher in those with a family history of asthma. IgE levels were higher in those with a past history of atopic eczema, but intrinsic and extrinsic asthma could not be differentiated on the basis of IgE levels. Thirteen of 74 patients failed to respond to tetanus immunization, while only 1 failed to respond to Salmonella typhi H antigen. Tetanus nonresponders had a raised mean serum IgA level, reduced spontaneous lymphocyte tritiated thymidine uptake, and reduced thymidine uptake in fetal calf serum. Eight of 87 patients failed to mount delayed hypersensitivity reactions to a battery of five intradermal antigens. The tritiated thymidine uptake of lymphocytes stimulated with phytohemagglutinin was normal in autologous serum, but reduced in fetal calf serum. The data support the hypothesis that asthma may be associated with immunodeficiency states.     

Serum IgG, IgA, IgM, IgE, salivary IgA levels and lung function in a healthy male population from the Italian Air Force: a preliminary study

The reliability of total IgE quantitation in predicting atopic states was evaluated in a highly homogeneous group of 315 male subjects between 19 and 22 years of age, in apparent good health. A parallel evaluation of the other major Ig classes (serum IgG, IgA, IgM and salivary IgA) and a series of lung function tests were also performed. Forty-eight subjects (15%) referred history of allergy (41 respiratory and seven cutaneous). Twenty-one percent of these had IgE greater than 440 IU/ml, a value reported as abnormally high. No significant association was found between atopy and any of the lung function tests performed. Clinical history or IgE levels were not related to other Ig classes. Conversely, serum but not salivary IgA levels were significantly reduced in tonsillectomized subjects. From the present data it appears that neither IgE determinations nor performing lung function tests can be considered reliable substitutes for an accurate history and evaluation of clinical parameters.     

Serum IgG, IgA, IgM, and IgE levels and allergy in Filipino children in the United States

The serum levels of IgE, IgG, IgA, and IgM of 27 American-born Filipino children 5 to 17 years of age were measured and found to be significantly higher than those of a control group of 24 Caucasian children of similar age distribution and attending the same general pediatric clinics. The geometric mean of serum IgE of the Filipinos was 227 U. per milliliter and of the Caucasians, 69 U. per milliliter (p < 0.01). The geometric means of other serum immunoglobulin levels of the Filipinos by comparison with the Caucasians were: IgG, 1,303 and 1,010 mg. per 100 ml. (p < 0.01); IgA, 195 and 120 mg. per 100 ml. (p < 0.001); and IgM, 141 and 92 mg. per 100 ml. (p < 0.02), respectively. The incidence of atopic disease was higher in the Filipino study group (48 per cent) than in the Caucasian control group (25 per cent); eczema was especially prevalent in the Filipino group. Elevated serum IgE levels were associated with atopic disease in both racial groups; however, there was no correlation between serum level of IgG, IgA, or IgM and atopy.     

Jejunal plasma cells and in vitro immunoglobulin production in adult coeliac disease.

IgA, IgE, IgG and IgM plasma cells in small bowel mucosal biopsies from 15 controls, 16 untreated and 14 treated coeliac patients and five patients with selective serum IgA deficiency (four of whom also had coeliac disease) were quantified using an indirect immunoperoxidase technique. The IgA, IgG and IgM plasma cell counts were significantly increased in the untreated coeliac patients. The cell counts were intermediate in the treated coeliac group. These changes were in parallel to production in vitro of IgA and sIgA, IgG, and IgM by cultured mucosal biopsies from the same patients. The IgA deficient patients had very few mucosal IgA cells but elevated IgG and IgM plasma cell numbers; again these changes were reflected in the production in vitro of immunoglobulins. IgE plasma cell counts were very low in all patients and there were no differences between patient groups. The changes in cell counts and mucosal immunoglobulin production were not reflected in serum IgA, IgM and IgG concentrations but serum secretory IgA was significantly elevated in the untreated coeliac patients compared with controls, with the treated coeliac patients being intermediate. The raised mucosal plasma cell counts reflect the local mucosal production of immunoglobulin but not the immunoglobulin concentrations of serum, emphasising the importance of studying the immune function of the gut itself in coeliac disease rather than immunological abnormalities in serum.     

The natural history of shrimp hypersensitivity

Sera collected sequentially during a 24-month interval from 11 individuals with shrimp hypersensitivity and 10 nonhypersensitive control subjects were evaluated for shrimp-specific IgE, IgG, IgM, and IgA reactivity. Shrimp-hypersensitive subjects underwent double-blind, placebo-controlled shrimp challenges; seven exhibited positive challenges, and four subjects reported the subjective symptom of oropharyngeal pruritus. Shrimp-specific IgE levels in all subjects were relatively constant during the 24 months of this study and not affected by shrimp challenge, although some fluctuation in the shrimp-specific IgG, IgM, and IgA reactivity were noted, apparently unrelated to shrimp challenge. Shrimp-specific IgE and IgG, but not IgM and IgA, were significantly higher in the group with shrimp hypersensitivity as compared to the control subjects. Moreover, the challenge-positive subjects had higher levels of both shrimp-specific IgE and IgG than subjects reporting pruritus. The levels of shrimp-specific IgG correlated directly with shrimp-specific IgE reactivity. These studies indicate that serum levels of shrimp-specific IgE are significantly elevated in shrimp-hypersensitive subjects who exhibit positive food challenges, and these baseline levels did not appear to be altered long term by isolated shrimp challenge. Furthermore, baseline shrimp-specific antibody (IgG, IgM, and IgA) levels noted in normal subjects were not markedly affected by frequent ingestion of shrimp.     

Immunoglobulin in health and disease. III. Immunoglobulins in the sera of patients with amoebiasis

The serum immunoglobulins IgG, IgA, IgM and IgE were determined together with indirect haemagglutination test in normal subjects and in patients with intestinal and extra-intestinal amoebiasis. The IgG level in intestinal amoebiasis was found to be significantly higher than that of extra-intestinal. Although in intestinal amoebiasis, the concentrations of IgE were comparatively higher than extra-intestinal group, the IgE levels in both groups of amoebiasis were seen to be much higher than that of the normal group. No significant difference was found in the IgA and IgM levels between the three groups of cases. Indirect haemagglutination test was positive in both intestinal and extra-intestinal amoebiasis, but negative in normal subjects.     

Hypergammaglobulinaemia E in HOdgkin's disease and its relationship to atopy or a familial predisposition to atopy

We have found a normal incidence of atopy among patients with Hodgkin's disease (HD). Atopic HD patients had serum IgE levels and allergen specificities similar to those observed in an atopic but otherwise normal population. An atopic family background increased the number of weakly positive allergen responses in otherwise non-atopic HD patients. This effect of atopic background is known to be true for normal healthy subjects. serum IgE was raised in a third of the non-atopic HD patients but they showed neither an increase in allergen specificity nor a more frequent atopic family background than patients with normal IgE. IgE was the most frequently raised immunoglobulin class and was due to its increased synthesis. We concluded that the hyper-IgE which occurs in non-atopic HD patients is distinct from the increase in allergen-specific IgE which occurs in atopy.)     

Predictable clinical disorders related to serum and saliva Ig-levels and the number of circulating T cells in asthmatic children

An examination was made of 221 children with bronchial asthma, who were divided into six groups according to serum and saliva Ig levels and the number of circulating T cells. Absence or small amounts of IgA and low or low-normal numbers of T cells were associated with (1) atopic dermatitis, (2) hypersensitivity to house dust mite and animal danders, (3) previous hospital admissions due to respiratory tract infections with pathogenic bacteria and (4) a high family incidence of allergic diseases. In a group of patients with IgA deficiency and elevated serum and saliva IgM, respiratory tract infections were not common, and furthermore, in another group of IgA-deficient patients with normal numbers of circulating T cells, atopic dermatitis was rare. In the latter patients, allergic rhinitis occurred very frequently, and in that respect they resembled a group of patients with combined high IgM/high IgE levels. Another group of asthmatic children with normal Ig levels represented an intermediate type of patient with regard to hypersensitivity to different allergens and family incidence of allergy on the one hand, and the occurrence of atopic dermatitis and allergic rhinitis on the other. Investigations on Ig levels and circulating T cells in asthmatic children may provide important clues into disease classification and mechanisms of such patients.     

The concentrations of IgA and free secretory piece in the nasal secretions of patients with recurrent respiratory infections.

The concentrations of total IgA, 11S IgA, total and free secretory piece (SP) were measured in the nasal secretions of 39 patients with recurrent upper and lower respiratory tract infections during an infection free period. In all of eight patients who had selective serum IgA deficiency (less than 0.05 g/l) IgA was also undetectable in their nasal secretions and the mean concentration of free SP was significantly raised. However, the mean concentrations of 11S IgA, SP and free SP in nasal secretions of patients with normal or low (greater than 0.05 g/l but below the normal range) serum IgA were not significantly different from those of 10 healthy normal subjects. In patients with detectable nasal secretory IgA, 11S IgA concentrations correlated significantly (r = 0.57; P less than 0.001) with concentrations of free SP. One patient with normal serum IgA was found to have a large excess of free SP and therefore may have had a relative defect in local IgA production.     

Raised IgE levels in beta-thalassaemia: correlation with splenectomy and hepatitis B virus infection.

IgE values obtained in 117 beta-thalassaemia patients were significantly higher than in age matched normal subjects. In 31 patients (26.5%) IgE levels were above 2 s.d. of normal values for age, but the frequency of IgE with reaginic activity was lower in patients (5.1%) than in controls (11.9%). The highest values were observed in splenectomized patients who were also positive for one or more serological markers of hepatitis B virus infection. The increase of IgE levels was directly correlated with the number of years after splenectomy, and patients with biopsy proven chronic liver disease had higher IgE levels than those without evidence of liver damage. On the other hand, IgE levels were not correlated with the number of transfusions, age, IgG, IgA, IgM levels or T cell subsets and mitogen responsiveness. These results show that beta-thalassaemia patients develop elevated IgE levels to which splenectomy and hepatitis B virus infection contribute in a synergistic manner.     

IgG subclass distribution of antibodies against S. aureus teichoic acid and alpha-toxin in normal and immunodeficient donors

IgM, IgG, IgA and IgE class and IgG and IgA subclass levels were determined in 18 IgG2 deficient and six IgG3 deficient donors. IgG2 deficiency was associated with concomitant IgG4, IgA (in particular IgA2) and IgE deficiency. This pattern is compatible with a regulation defect of the downstream switch in the heavy chain locus on chromosome 14. IgG3 subclass deficiency was not associated with further deficiencies. Specific anti-teichoic acid antibodies were lacking in most IgG2 deficient donors supporting the notion that anti-teichoic acid antibodies are normally of this subclass. This was also confirmed in a subclass-specific ELISA using sera from normal donors although substantial amounts of specific IgG1 antibodies were also noted. Two IgG2 deficient donors had normal IgG titres (IgG1 in the subclass specific ELISA) and the lack of IgG1 anti-teichoic acid antibodies in most IgG2 deficient donors may suggest a lack of maturation of the appropriate idiotype. IgG antibodies to alpha-toxin, a pure protein, were within the lower normal range in a large proportion of IgG2 deficient donors but largely normal in the IgG3 deficient donors.