Idiotypic determinants and antiglobulins in multiple myeloma.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to I Schedel.
Explore the source record for details and available documents.
Using sera from patients with rheumatoid arthritis and antiglobulin preparations obtained from such sera, inhibition of human lymphocyte cytotoxicity in antibody-dependent (ADCC) and spontaneous cell-mediated cytotoxicity (SCMC) reactions against an allogeneic melanoma cell line (IGR3) has been demonstrated. Fractionation of effector cell preparations indicated that Fc-receptor-bearing lymphocytes were operative in both reactions. Removal of phagocytic and adherent cells from the effector cell population resulted in more pronounced inhibition of SCMC and ADCC reactions by rheumatoid sera. The results indicate that antiglobulin preparations from human sera containing rheumatoid factor activity can effectively block the cytotoxic activity of Fc-receptor-bearing effector lymphocytes (K cells) in vitro. On analogy with the inhibition of ADCC and SCMC reactions by immune complexes and aggregated IgG, antiglobulin complexes present in the antiglobulin preparations are responsible for this effect.
Antiglobulin factors of the IgG class were measured in human sera by a modified immunoadsorbent-technique involving absorption to and elution from insoluble preparations of horse IgG. 32 mg of horse IgG insolubilized with bisdiazotized benzidine were used for quantitative immunoadsorption of IgG antiglobulins from 100 mul serum. Different IgG-antiglobulin concentrations could be obtained in two control groups differing in age. Elevated IgG-antiglobulins levels were found both in seropositive (mean value 23.21 +/- 7.08 mug/ml serum) and seronegative (mean value 20.06 +/- 8.39 mug/ml serum) RA patients. High values of IgG-antiglobulins were found in chronic liver disorders, particularly in the group of CAH patients (mean value 25.10 +/- 6.1 mug/ml serum).
Sera from 50 healthy adults, from 21 patients with multiple myeloma (MM) and from 11 patients with benign monoclonal hyperglobulinaemia (BMH) and from 28 patients with sarcoidosis were examined for the presence of anti-IgG-activity by passive haemagglutination technique. 62% of healthy adults (titre less than 2) and all of the sera from patients with MM and BMH (titres 32-512) as well as 42% of the sera from sarcoidosis patients were found to be anti-IgG positive. The anti-IgG positive sera showed also anti-(Fab)2-activity (with the exeption of 2 sera from sarcoidosis patients). No significant differences could be found between anti-Ig activity in sera from MM patients with BMH. There was also seen no correlation of anti-Ig with the clinical course of the disease. After column chromatography we could detect the partially simultaneous presence of anti-Ig with anti-Fc-specificity (MW ca. 900,000) and with (Fab)2-specificity (MW 150,000 or less than 90,000). Antibody dependent cytotoxicity (using melanoma cell lines as targets) was significantly inhibited by the isolated anti-Ig-fractions with low molecular sizes (MW less than 90,000). From these results it seems possible that anti-immunoglobulins may play a role in the clinical course of the disease.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
The effectiveness of (Fab')2 G-Anti-D regarding elimination of D-incompatible fetal erythrocytes, and suppression of the formation of specific antibody, was investigated in 16 probands. Using 51Cr labelled D-incompatible fetal erythrocytes and simultaneous HbF-cell counting, fast elimination of incompatible red cells, and selective accumulation in the spleen, were observed after injection of small doses of (Fab')2 G-Anti-D. None of the probands showed active formation of anti-D after 3-12 months. The doses of the (Fab')2 G-Anti-D preparation used were similar to those employed in routine use of IgG-Anti-D. The results emphasize the importance of fast immunelimination of potentially antigenic red cells and thus point to a peripheral mechanism of anti-D prophylaxis by specific anti-D.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
40 adults with symptomatic HIV-1 infection (AIDS related complex [ARC] WR 2B-4B or AIDS WR 5-6) were randomized into two groups, receiving either 200 mg of an i.v. immunoglobulin preparation (ivIg)/kg body weight every other week or no such treatment. Medical care and antibiotic therapy were comparable in the two groups. Frequency of opportunistic infections, "B"-symptoms, number of T-helper cells, change of disease stage (Walter Reed Classification, WR), delayed cutaneous hypersensitivity, onset and clinical course of Kaposi's sarcoma, neurological manifestations and proportion of patients alive at the end of the observation period were evaluated. After an average observation period of 13.8 months, decreased mortality was observed in ivIg treated patients of WR 5-6 (p less than 0.004). Frequency and microbial spectrum of opportunistic infections, the most frequent cause of death, were not influenced significantly by ivIg treatment. No statistically relevant differences concerning the other parameters were observed. A similar beneficial effect of ivIg in WR 2B-4 patients has not become apparent so far.
The incidence of infections caused by gram-negative bacteria is increased in patients with multiple myeloma due to secondary humoral immunodeficiency. In order to diagnose patients with increased susceptibility to gram-negative infections, serum antibodies against common determinants of lipopolysaccharides (lipid A and core-polysaccharide) were determined by a rapid enzyme-linked immunosorbent assay (ELISA). It was possible to define a group of patients at high risk of contracting gram-negative infections using this test. Intravenous IgG preparations used as a substitute were shown to contain antibodies against these common antigens. However, it is suggested that the clinically recognized efficacy of these preparations could be due to their containing anti-LPS antibodies.
A computer simulation of the morbidity and mortality rates of the "Acquired Immunodeficiency Syndrome" in the Federal Republic of Germany was performed. Since sexual intercourse is the main mode of transmission, the population was divided into six groups with different sexual behaviour. In several variations of the program it is demonstrated that during the next 15 years up to 41,000 AIDS patients can be expected. The importance of female prostitutes and male bisexuals as "vectors" who may transmit the infection into exclusively heterosexual groups is shown. Using this program, the effect of prophylaxis against infection as well as of changes of sexual behaviour within the population at large can also be examined.
Urinary excretion of Cytomegalovirus and the presence of serum antibodies against CMV were examined in 79 HIV-1-infected patients at different stages of the disease, as well as in 27 heterosexual and 52 male homosexual controls and correlated to clinical and laboratory results. HIV-1-infected and healthy individuals differed significantly with regard to cutaneous delayed type reactions, absolute numbers of CD4+ cells and CD4+/CD8+ ratios. IgG antibodies against CMV were found in 87% of homosexual and in 52% of heterosexual controls, and in all HIV-1-infected homosexuals. CMV excretion in the urine was exclusively found in HIV-1-infected individuals where the incidence correlated with the CDC-defined disease stage (stage II: 6%, stage III/IV A: 22%, stage IV B/C: 55%). HIV-1-infected patients excreting CMV in the urine also exhibited distinctly decreased numbers of CD4+ cells and significantly decreased CD4+/CD8+ ratios compared to those without CMV viruria.
The etiology of inflammatory rheumatic diseases is unknown. The hypothesis, that bacteriae may play a part in the induction of a rheumatic synovialitis is further substantiated by the detection of Endotoxin (Lipid A) in the synovial membranes of five of eleven patients with early synovitis (disease duration shorter than 6 months) by using anti Lipid A monoclonal antibodies. Endotoxin (Lipid A) is a component of gram-negative bacteriae and Chlamydiae. It is a potent immunogen, and could be the link between infection of the gut or the urogenital system and the rheumatic synovialitis.
Circulating immune complexes were determined in rheumatoid arthritis and systemic lupus erythematosus using a semiautomated PEG-precipitation laser-nephelometer technique. Immunoglobulins IgA, IgG and IgM as well as complement proteins C3c and C4 were quantitatively determined in 2.75% PEG-precipitates. The PEG-precipitates obtained from the sera of healthy controls, SLE patients, and RA subjects displayed different protein patterns. In RA sera a significant elevation of all investigated proteins was found. In SLE sera, a significant increase of IgG, IgA, IgM, and C3 was found, whereas C4 was significantly reduced as compared to the controls. Typical values for a calculated IgG/C4 ratio in circulating immune complexes were obtained for RA and SLE. In RA this ratio remained unchanged in different activity stages and was found in seropositive as well as in seronegative sera. Thus circulating immune complexes from SLE and RA sera differ with respect to the degree of complement-dependent solubilization.
In addition to the well-known rheumatoid factors or antiglobulins belonging to different immunoglobulin classes, a new type of antiglobulin has been found in serum and synovial fluid from patients with rheumatoid arthritis. 15/20 sera and 6/6 synovial fluids contained serologically active material with a molecular weight of approximately 95.000 Daltons. Using chromatographic and affinity chromatographic methods as well as specific precipitation techniques, the (Fab')2 character of these antiglobulins could be ascertained. These antiglobulins may arise through enzymatic degradation of IgG or monomeric IgM antiglobulins, or may be the product of partial intracellular degradation of phagocytosed immune complexes with subsequent extrusion of such material. An in vitro blocking effect of (Fab')2 type antiglobulins on SCMC or ADCC reactions was not found.
The aim of this study was to assess the efficacy of pentaglobin, a polyclonal polyvalent immunoglobulin containing IgG, IgM, and IgA, in therapy of septicotoxic diseases. Fifty-five patients with sepsis were divided into 2 perspective randomized groups. Group 1 (27 patients) were infused pentaglobin containing specific antibodies to bacterial endotoxin determinant. Immunoglobulin therapy was carried out during the first 3 days after the group was selected for study. In the other group (n = 28) no immunoglobulin therapy was carried out. During 6 weeks from the beginning of the study one patient out of 27 in group 1 (4%) died because of sepsis, whereas in group 2 nine patients died out of 28 (32%) (p < 0.01). A reliably higher titer of circulating endotoxins and a lower titer of antibodies to endotoxin determinant were revealed during the first 48 hours of experiment in the serum or plasma of patients who died in the course of the follow-up period, in comparison with the survivors.