Nonspecific binding of IgE to allergens.

Nonspecific IgE binding to allergens was observed in testing myeloma IgEs, namely, IgE-VL and IgE-PS, chimeric IgE (IgE-JW8), and the recombinant IgE Fc epsilon peptide CH1-CH4, in two different immunoassays. This binding was concentration-dependent but detectable only at higher IgE concentration. In RAST inhibition, IgE-allergen interactions could be reduced by using either matching or nonmatching allergens. In order to test whether the nonspecific binding of IgE to allergens was due to carbohydrate interaction, myeloma IgEs and the chimeric IgE were desialized with neuraminidase. Desialized samples were equally well recognized by xenogenic antibodies as native IgEs, but binding of IgE to Fc epsilon receptors on basophils was affected by the treatment, as shown in the histamine-release assay. Desialization of IgE affected also its binding capacity to allergens in RAST: binding of chimeric IgE was reduced, but nonspecific binding of myeloma IgE-VL was enhanced. Hence, nonspecific allergen-IgE binding may be partly due to a lectin-like interaction, but may depend mostly on the tertiary structure of IgE. Thus, nonspecific IgE-allergen interactions might present a problem 1) at high IgE concentration, and 2) depend on the grade of sialization of IgE, which might affect its conformation. This may explain why patients with elevated total IgE levels often have multiple weak positive RASTs with non-cross-reactive allergens.

Structure and function of IgE myeloma protein VL from an atopic patient.

In a woman suffering from IgE myeloma, hay fever and polyvalent respiratory and skin allergy the IgE monoclonal protein VL was isolated and investigated with respect to structural and functional properties. The amino acid sequence of 22 isolated peptides--especially of the biologically significant C2-C3 part--corresponded with that originally described by Bennich et al. (Immunol Rev 1978;41:3-23; Prog Immunol 1974;13:49-58). However, in mass spectrometry the sugar residues on ASN 99 (219) and 252 (371) were deficient in sialic acids. The native IgE VL protein precipitated with high intensity all mannose-specific lectins as concanavalin A (Con A) and was able to release histamine after triggering by these lectins. The same lectins also elicited more histamine release and more positive skin reactions in atopic than in healthy persons. In sera from atopic patients the binding of IgE on Con A Sepharose 4B column was stronger than in normal persons. It is suggested that changes in the IgE glycosylation state may contribute to IgE-mediated pictures of clinical allergy by the nonimmunological pathway.

An epidemiologic-immunological inquiry into the incidence of altered immunity in children of school age.

The authors examined 536 children 10 years of age to evaluate their immune status and the development of allergies and recurrent respiratory inflammations. Altered resistance was found in as many as 47% of children, pollen allergy and atopic eczema in at least 10.5%, habitual rhinitis in 15.2%, asthma in 3.5% and recurrent inflammatory infections in 13.1%. A higher rate of alterations was found where environmental conditions were deteriorated. Elevated IgE, changes in IgG, IgA and IgM as well as increased levels of acute phase proteins suggest a relationship between the degree of immune impairment and clinical manifestations. Our results imply there are large numbers of children with altered immunity and point to the fact that in common practice only 14% of them are attended to by the clinical immunologist and thus receive causal treatment. It is therefore concluded that, in line with the expansion of noxious factors which accompany our civilization, more attention should be given to the development of immunity in the young population.

[Sperm agglutination antibodies studied in infertile couples at the Women's Clinic in Plzen 1980-1988]. / Spermaglutinacní protilátky vysetrované u neplodných páru na zenské klinice v Plzni v období 1980-1988.

The authors assessed sperm-agglutination antibodies in infertile couples in 1980-1988, using the Kibrick test: in sera from 699 female patients, a positive result was found in 142 (20%) women, in sera from 352 men, in 6 (1.7%) sperm-agglutination antibodies were detected. Using the microagglutination test, they examined sera of 3501 sterile women; in 273 (6.8%) they found sperm agglutination up to 1:16, above titre 1:32 in 12 (0.4%) of the patients. Using the same test, they examined sera of 2803 men and found sperm-agglutination up to 1:16 in 21 (0.7%) and above 1:32 in 6 (0.3%). The most frequent type of sperm agglutination is aggregation of the heads; aggregation by tails or mixed agglutination are less frequent. In 3252 sterile women where no sperm-agglutination antibodies were found Kremer's test was negative in 1145 patients. The authors analyzed in 196 sterile women the ovulation mucus by the microagglutination test and found a high anti-spermatozoidal activity in 24 (12%) women. Concurrently an indirect MAR test was made. Antibodies against sperm cells were found in 24 (12.2%) of specimens in sIgA, in 8 (4.1%) in IgG, in 2 (2%) in IgM and in one sample (0.5%) in IgE. The indirect MAR-test in sera of 325 sterile women revealed a predominance of anti-spermatozoidal antibodies in IgG, in men in IgA. In seminal plasma the authors detected antibodies against sperm cells in sIgA. In seminal plasma the authors detected antibodies against sperm cells in sIgA and IgE.

Immunoglobulins and some serum proteins in children with altered resistance coming from areas with variously polluted atmosphere.

In four areas with different types of atmospheric pollution 534 children of school age were examined for serum immunoglobulins (IgG, IgA, IgM and IgE), saliva IgA (sIgA), lysozymes (LYS) and acute phase reactants (alfa-l-antitrypsin - A1AT, alfa-2-macroglobulin -A2M, ceruloplasmin -CPL, transferrin - TRF). The children were divided into two groups: those with altered resistance (AR) comprising allergoses of all types and recurrent or persistent infections and those without the above health problems, i.e. healthy (H). There were more children with AR in areas with higher atmospheric pollution than in control areas. The frequency of AR was higher among boys than among girls. In the control area BN, a number of parameters in the AR group differed significantly from those in the H group. In areas with substantial atmospheric pollution these differences were generally less pronounced. Significant differences were found between the control and polluted areas in many indicators. In the area KO characterized by an intermediate degree of industrial pollution the means of the tested parameters were habitually elevated, whereas in the heavily polluted areas they were decreased. The most sensitive tests for evaluating differences between the areas were the levels of A1AT, LYS, and IgE, while the variations of sIgA, sLYS and CPL were less pronounced.

[Plasmapheresis--a therapeutic method for immunity-related infertility?]. / Plazmaferéza--lécebná metoda imunologické príciny neplodnosti?

In a 30-year-old woman with primary idiopathic sterility the immunological cause of infertility was assessed (spermagglutination antibodies in serum and in the ovulation mucus of the uterine cervix). The patient was treated without success by condom therapy, general and local immunosuppression. Therefore treatment by means of membrane separation plasmapheresis was started during two preovulation periods. Serum spermagglutination antibodies class IgM declined from the original titre of 1:1024 to 1:16, immediately after homologous inseminations they rose, however, to the original titre and the patient did not become pregnant.

Humoral defending mechanisms in children of smoking parents.

In autumn and spring a group of 132 ten-year-old school children (54.5% from families of smokers) were examined for blood content of immunoglobulins (IgG, IgA, (gM, in autumn including also IgE), lysozyme (LYS) and the so called acute reactants (alpha-1-antitrypsin = A1AT; alpha-2-macroglobulin = A2M; transferrin = TRF; ceruloplasmin = CPL); and for saliva sIgA and sLYS. Autumn examination detected significantly higher mean values of IgE in children from families of smokers, while other mean differences remained insignificant. Spring examination revealed significant differences in the means of IgA levels children from families of smokers (FS) had significantly lower levels of IgA while their saliva sIgA values were significantly higher. Mean spring CPL levels in FS were significantly higher. Analysis of distribution curves of autumn examination showed a significant shift of A1AT towards higher values in boys from FS. Girls from FS exhibited a shift of LYS towards lower values. Spring examination in boys FS evidenced a shift of CPL and sIgA values towards higher values; the curve of serum IgA levels split distinctly into two subgroups. In girls from FS the only change observed during the spring examination was a shift of A2M levels towards higher values with an indication of a split. To conclude, passive smoking in school children is responsible for a number of significant changes, the latter being more frequent and marked in spring when the children's organism is weakened by many other unfavourable circumstances. More significant changes were seen in boys.

Human exposure to nickel and cobalt: biological monitoring and immunobiochemical response.

Thirty-eight production workers exposed to Ni and 35 exposed to Co were examined for the content of Ni and Co in hair, the serum concentration levels of immunoglobulins, IgG, IgA, IgM, and IgE, and serum proteins, alpha 2-macroglobulin (A2M), transferrin (TRF), alpha 1-antitrypsin (A1AT), ceruloplasmin (CPL), lysozyme (LYS), and alpha 1-glycoprotein (A1GP). Atomic absorption analysis of hair revealed that the respective geometric mean values of Ni and Co in Ni-exposed workers were 216.75 and 3.31 micrograms X g-1 and in Co-exposed workers 34.5 and 96.81 micrograms X g-1. These values were significantly higher than respective control values found in nonexposed individuals matched by age (Ni: 3.31 and Co: 0.38 micrograms X g-1). These findings suggest that hair analysis is a suitable method for the biological monitoring of exposure to these two metals. Tests for serum proteins revealed that nickel workers differed from controls by exhibiting significantly elevated IgG, IgA, and IgM levels; cobalt workers by a significant elevation of IgA level; and both exposed groups by a significant drop in the IgE level. A significant rise in the concentration (P less than 0.001-P less than 0.005) was also recorded in the case of A1AT, A2M, CPL, and LYS. The possible biomedical implications of these immunobiochemical findings are critically analyzed.

Seasonal variations in the level of immunoglobulins and serum proteins of children differing by exposure to air-borne lead.

A semicohort of children, initial age about 11.5 years, from an exposure area near a secondary lead smelting plant (E group children) was examined for some humoral immune response parameters in the blood and saliva and compared to a group of control children matched by age living in a relatively unpolluted rural area (Co group children). All examinations were performed every autumn and spring over a period of 2 successive years, and the data included in the final analysis were only from children who had completed at least 3 of the 4 examination series performed. To sum up, children from area E showed a clearcut elevation of mean blood lead (Pb) levels with marked seasonal fluctuations peaking in spring; Pb levels in the blood of Co group children had no such season-related fluctuation patterns and tended to slightly decline over the two years of observation. Delta-aminolevulinic acid dehydratases (ALAD) levels in area E were of distinctly lower mean values than in area Co, but no correlation with mean blood Pb levels could be observed. Levels of IgG were more or less inversely correlative with Pb levels in both sexes, levels of IgM showed a distinct downward trend in E group children at all samplings. Total serum protein (SP) levels of children from area E showed a reverse correlation with plumbemia, secretory IgA (sIgA) concentrations showed a decrease in E group children of both sexes, but the values tended to converge with control values. Levels of alpha 1-antitrypsin (A 1-AT) showed marked season-related fluctuation patterns in Co children, the curves in E group children turned steeply upward from the third examination series on. Ceruloplasmin (CPL) levels in E group children had a clearcut upward trend at three subsequent blood samplings, the curves in Co group children continued to drop. Children from area E showed markedly higher frequency rates of abnormal values than did children from Co area.

Ketotifen action upon the immunity state in bronchial asthma.

Alterations of the entire immunity profile of bronchial asthma patients have been studied following a half-year long Ketotifen treatment. It was observed that this drug leads to the normalization of the immunity state in a whole series of parameters and that it thus contributes on a large scale to the reestablishment of normal regulation. These findings may be utilized for expanding the possibilities of application of this preparation upon other immunopathological states that bronchial asthma and the atopic diseases.