Standardization of allergens by means of monoclonal antibodies.
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Allergens↗
Biomedical subjects
L Jäger
Publications and source records attributed to L Jäger.
IgE rheumatoid factor. Occurrence and diagnostic importance in comparison with IgM rheumatoid factor and circulating immune complexes.
The sera of 80 patients suffering from rheumatoid arthritis (RA)--30 of them with extraarticular manifestations (EAM) and 50 patients with articular disease only--of 25 patients with other joint diseases and of 30 normal healthy subjects, were analyzed for the presence of 1) IgE rheumatoid factors (IgE RF) by means of a solid phase radioimmunoassay and an ELISA, 2) IgM rheumatoid factors by using solid phase radioimmune techniques, and 3) circulating immune complexes (CIC) with the C1q binding test (C1q BT) and the solid phase conglutinin binding test (SPCBT). The best technique to discriminate RA patients with EAM from RA patients without EAM and patients with other articular diseases was the determination of IgE RF (73.3%, 38.0%, 0%, resp.) compared to IgM RF (86.7%, 78.0%, and 56.0%) and CIC (C1q BT: 80.0%, 66.0% and 45.0%; SPCBT: 46.7%, 22.0%, and 20.0%). The results suggest a certain role of IgE RF for diagnosis and a possible development of extraarticular manifestations in rheumatoid arthritis.
Antigen-Antibody Complex↗
Structure of respiratory allergens.
Respiratory allergens from one of the most important group of allergens. Except for professional allergens they are characterized by an enormous heterogeneity including a restricted number of major allergens. By means of modern immunological, chemical and genetic techniques some of them are, at least partially, characterized. Immunogenicity depends on a restricted area of the molecules. These epitopes seem to be in principle different for B cells (antibodies) and T cells. The strategies to improve immunodiagnosis are, therefore, not necessarily identical with those for the development of immunotherapy. The present data on selected respiratory allergens are summarized.
Allergens↗
[Determination of circulating immune complexes and of their component immunoglobulin classes M, G, and A with a C1q-ELISA].
In 353 sera (from healthy donors as well as patients suffering from rheumatoid arthritis, systemic lupus erythematosus, hepatitis, malignant melanoma) circulating immune complexes were determined by C1q-binding test and a C1q solid-phase ELISA. Using peroxidase-labelled antibodies (from rabbit) against human mu-, gamma-, and alpha-heavy chains, the immunoglobulin classes in the complexes were determined. In rheumatoid arthritis, immune complexes contain IgM more frequently (41.5%) than in systemic lupus erythematosus (10%). Immune complexes containing only IgA as immunoglobulin were found in 24 cases. Our results including binding experiments with chemically aggregated IgA suggest, that the binding of C1q to IgA is not necessarily followed by classical complement activation.
Antigen-Antibody Complex↗
Phase-I study of diacetyl-splenopentin (BCH 069).
BCH 069 is a new synthetic pentapeptide with thymic hormone-like activity. Two groups of patients received 50 mg BCH 069 or placebo by subcutaneous injection for 4 weeks 3 times weekly. The third group of patients received 50 mg BCH 069 by intravenous injection for 6 weeks 3 times weekly. The therapy was carried out during the peak of the pollen season. We observed the following clinical and biochemical activities of BCH 069: - flush symptom with a feeling of heat during intravenous administration of 50 mg/10 ml but not during 50 mg/20 ml, - decrease of triglyceride serum level, - decrease of SGOT- and SGPT serum levels, - increase of lipase serum level, - decrease of hemoglobin. - All changes of the biochemical parameters were not outside of the normal laboratory values. The disease-specific inflammatory changes were not seen in the intravenously treated group. The administration route is very important for the clinical side effect but not for drug induced biochemical changes. It can be concluded that BCH 069 is a well tolerated drug.
Alanine Transaminase↗
[Production and characterization of a high affinity monoclonal antibody with digoxin and digitoxin specificity].
A monoclonal antibody with a high affinity for digoxin (KA = 5.5 x 10(10) M-1) and digitoxin KA = 5.0 x 10(10) M-1) was produced by somatic cell fusion. This antibody, designated 2A3, displayed little cross reactivity with other glucosides and no cross reactivity with endogenous steroids. It was shown that 2A3 is a suitable tool in an enzyme immunoassay for digoxin and digitoxin.
Antibodies, Monoclonal↗
[Quantitative determination of apolipoprotein AI in serum by the use of monoclonal antibodies in a noncompetitive ELISA].
A methodical base for estimation of apolipoprotein AI (apo AI) in the serum using a monoclonal antibody in a non-competitive ELISA is described. The technical approach is adjusted to commercial materials of the DDR industry. The assay allows to determine apo AI within the range of 5-100 micrograms apo AI/I. The Vk was 4% (within), and 8% (day to day). The monoclonal antibody used is directed against a native epitope which is fully exposed in the serum. Application of the SUMAL system further improves the practicability of the method. The assay should be suitable particularly for the recognition of epitopes of apo AI in serum HDL fractions associated with an atherogenic risk. The values obtained by the ELISA correspond to those measured turbidimetrically using polyclonal antibodies.
Antibodies, Monoclonal↗
[Disease-specific and non-specific seasonal parameter changes in hayfever patients].
10 patients have been treated by subcutaneous injections of placebo three times weekly for 4 weeks within a phase-I trial of BCH-069. Immunological, hematological and biochemical parameters were observed at different times: preseasonal, seasonal and postseasonal. --Some new observations are reported, which are induced by the seasonal inflammation. For example there was a strong increase of C-reactive protein and also an increase in the triglyceride level. --The parameters could be useful for trials of new antiallergic drugs in hay fever in the future.
Adjuvants, Immunologic↗
[Clinical and immunologic aspects in patients with agammaglobulinemia].
Agammaglobulinemia is a rare disease. The concentration of these patients provides efficacy of diagnosis and treatment. Within this group the "acquired" type in adulthood (CVID, n = 31) can be separated from the X-linked agammaglobulinemia of infants (n = 6). The former is characterized by variable clinical and immunological pictures. Common to both are sinubronchial infections and extremely low levels of all classes of immunoglobulins. IgG-levels below 4 g/l are usually accompanied by a more severe disease. For the first time an osteopathy in most cases of CVID has been described. Patients with agammaglobulinemia should remain under close control with regard to their clinical data as well as to the result of the substitution by adequate preparations of immunoglobulins. A certain association with HLA-B21 could be identified. In 4 families with several afflicted members this has, however, not the case. Immunological screening in first-degree relatives provides information for genetical counseling.
Adolescent↗
Isolation of timothy (Phleum pratense) allergens using affinity chromatography with monoclonal antibodies.
The monoclonal antibody 1 D11, directed against the timothy pollen allergens I, II, III, and a further, anodically migrating component, is suitable for the isolation of these allergens by means of affinity chromatography. The purified allergens consist of glycoproteins with many different isoelectric points. Their molecular weights were estimated as approximately the same as those of the allergens in the whole timothy pollen extract. Their allergenic activity (IgE binding) was not lost during the purification steps.
Allergens↗
The international collaborative study establishing the first international standard for timothy (Phleum pratense) grass pollen allergenic extract.
A selected candidate international reference preparation of timothy grass (Phleum pratense)-pollen extract was studied together with two other freeze-dried timothy pollen allergenic extracts in a multinational study. The collaborators used RAST inhibition, histamine release, quantitative immunoelectrophoresis (crossed immunoelectrophoresis/crossed radioimmunoelectrophoresis and rockets), isoelectric focusing, and other methods. The total allergenic potencies measured in RAST inhibition were evaluated for validity of linearity and parallel-line response. The relative concentrations of some important individual allergenic components were measured. The relative potencies for the total allergenic activity and the timothy components studied in each preparation were expressed relative to the selected candidate. This preparation was established in 1983 by the World Health Organization expert committee on biologic standardization as the international standard for timothy grass-pollen extracts with assigned units of 100,000 IU per ampule.
Allergens↗
[Salicylamide-- a potential pain-remedy alternative in the analgesic asthma syndrome].
Central pathogenetic mechanism of the analgesics-asthma-syndrome is very probably an analgesics-conditioned inhibition of the prostaglandin-biosynthesis (cyclooxygenase). Salicylamide, an analgesic without effect on the prostaglandin synthesis was in the oral exposition test of 18 patients with proved analgesics-asthma-syndrome in the dosage of 500 mg subjectively and objectively tolerated without reaction. Body-plethysmographically in consistent thoracic gas volume a slight decrease of the airways resistance could be registered. At the model of the isolated trachea of guinea-pigs salicylamide, in contrast to indomethacin and phenazone (prostaglandin-synthesis inhibitory substances) did not lead to an increase of the acetylcholine-induced spasm. Salcylamide can, after a tolerability test, be recommended as alternative analgesic in the analgesics-asthma-syndrome in a dosage of 500 mg.
Analgesics↗
[House-dust allergy in bronchial asthma].
1. House dust allergy and house dust mite allergy are with 18.4 and 14.1% the most frequent causes of the atopic asthma also under our conditions. 2. In about 60% the house dust allergy is conditioned by a sensitization by constituents of mites (excretions). 3. The responsible antibodies may be established by means of the radio-allergo-sorbent-test. In about 50% results were found corresponding with the intracutaneous test. 4. In the restricted possibilities of the allergen carency the hyposensitization plays an important role. In critical choice of the patients in 50-60% a clinical improvement is to be achieved.
Animals↗
[Asthma caused by analgesics].
Asthma, caused by analgesics, a relatively frequent phenomenon in bronchial asthma conditioned by infection, often remains unrecognized and is then sometimes a danger of high degree for these patients. Pathogenetically, the asthma caused by analgesics perhaps does not underlie an immunological mechanism, but an induced by analgesics prostaglandin-E-synthesis inhibition. For this speak the results of skin tests, of the LTT with analgesics and of IgE concentration measurements. Concomitant phenomena of the asthma caused by analgesics are: initial rhinirrhoe, alcohol intolerance, polyposis nasi and NNH affections. Among the evoking noxae the pyrazolones (regard: pyrazolone containing asthma mixed preparations!) are of greatest importance. Since already the smallest doses of analgesics may evoke considerable asthmatic reactions the indication to the exposition test should be made cautiously. In an anamnestic suspicion on asthma caused by analgesics a strict avoidance of analgesics, antirheumatic drugs and antipyretic drugs is necessary. Salicyl amide does not cause in vitro a prostaglandin synthesis inhibition. Still further clinical examinations are necessary, whether it amy generally be recommended as a possible alternative of analgesics in asthma caused by analgesics.
Analgesics↗
[New viewpoints in the pathogenesis and therapy of bronchial asthma].
The bronchial asthma is a polyetiologic syndrome with increased bronchomotoric excitability. The most important forms are the allergic asthma, the infection-conditioned one, the asthma conditioned by analgetics, the exertion and the irritation asthma. Apart from the direct affections on the smooth musculature and other target cells reflectorical mechanisms play an essential part. The first above all operate in the smaller respiratory tracts and stand in the foreground in the allergic bronchial asthma. The latter have above all an influence on the larger bronchi and are to be found in a typical way in irritation asthma. However, the transitions are fluent. The differentiation of the responsible mechanisms and the localisation of the bronchial obstruction give the possibility of a more aimed treatment. An essential improvement of the -- symptomatic -- treatment might be achieved, when the factors of the increasing bronchomotoric excitability are better known.
Acetylcholine↗
[Differentiation of peripheral and central bronchial stenoses by menas of flow volume curves].
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Airway Obstruction↗
[Situation and trends of hyposensitisation treatment (author's transl)].
Since the introduction of the hyposensitization treatment by Noon and Freeman in 1911, an essential change of the hyposensibilisation technique, despite numerous recently published results, has not been able to be demonstrated up to now. In most cases, treatment is still done with and allergen mixture consisting of a variety of unknown compounds with changing composition according to own experiences concerning initial and final dosis of the allergen or the application intervals. The linkage of the allergens to chemical substances, the modification into so-called allergoids as well as the investigation of the hyposensitisation success, such as determination of blocking antibodies, the course of the titre of specific antibodies by the RAST technique, the histamin liberation from leucocytes of allergic persons after antigen contact and the lymphocyte stimulation by allergens are starting points for developing a scientific base to the hyposensitisation treatment and for introducing new results mainly from experiments on animals into the clinical practice. Standardisation of allergens, optimisation of the dosis and the application intervals as well as the further decrease of the allergenicity and the optimal choice of the adjuvants have to be regarded as the problems to be solved in the next future. On the other hand, the use of allergen determinants linked to non-immune carriers or the induction of a tolerance by another way seem to be not yet a subject with clinical relevance during the next years.
Adjuvants, Immunologic↗
[On the binding of cyclophosphamide and cyclophosphamide-metabolites to serum-albumin (author's transl)].
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Cyclophosphamide↗