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Biomedical subjects

U E Nydegger

Publications and source records attributed to U E Nydegger.

At least 19 recordsLinked to original sources
PubMed1992

Origin of anti-idiotypic activity against anti-factor VIII autoantibodies in pools of normal human immunoglobulin G (IVIg).

Therapeutic preparations of polyspecific IgG obtained from plasma pools of a large number of normal donors (IVIg) express anti-idiotypic activity against a wide spectrum of natural and disease-associated autoantibodies. The present study investigated the origin of anti-idiotypic activity against autoantibodies to factor VIII. The neutralizing activity of pools of IgG against patients' anti-factor VIII autoantibodies was not influenced by the presence of individuals with natural anti-factor VIII antibodies among donors contributing to the pool. A higher frequency of neutralizing antibodies against anti-factor VIII autoantibodies was found in aged donors as compared with young adults and in pools of IgG from multiparous women as compared with IgG from random donors. Pooling IgG from several donors synergistically enhanced the inhibitory activity of the pools. Thus, a neutralizing activity against anti-factor VIII autoantibodies was detected in pools of IgG of as few as two to four donors of whom individually tested IgG did not exhibit inhibitory activity against anti-factor VIII autoantibodies. These observations suggest that aged donors and multiparous women may be privileged sources for the anti-idiotypic activity of IVIg against autoantibodies and emphasize that the expression of anti-idiotypic activity in IVIg results from a synergistic participation of anti-idiotypes from each donor contributing to the pool.

Adult↗
PubMed1992

Natural antibodies to factor VIII (anti-hemophilic factor) in healthy individuals.

Spontaneous inhibitors of factor VIII (FVIII) are pathogenic IgG autoantibodies of restricted isotypic heterogeneity found in the plasma of patients presenting with bleeding episodes and low levels of FVIII. We now report the presence of a natural FVIII-neutralizing activity in 85 of 500 plasma samples (17%) from healthy donors. FVIII-inhibitory activity was present in F(ab')2 fragments of purified IgG and was dose-dependent. The titer of anti-FVIII antibodies in normal plasma ranged between 0.4 (threshold of detection) and 2.0 Bethesda units. Anti-FVIII IgG was also detected in normal plasma by using an ELISA. Anti-FVIII antibodies from healthy individuals did not exhibit restricted isotypic heterogeneity. Mean levels of FVIII activity did not differ significantly between individuals with and without detectable anti-FVIII antibodies in plasma. Natural anti-FVIII IgG inhibited FVIII activity in pools of normal plasma and in plasma of certain donors in the pool but did not inhibit FVIII activity in autologous plasma. These observations demonstrate that polyclonal IgG antibodies against procoagulant FVIII are present in healthy individuals. The antibodies are natural IgG autoantibodies and/or antibodies directed against epitopes associated with a so far unidentified allotypic polymorphism of the human FVIII molecule.

Adult↗
PubMed1992

Naturally occurring ABO antibodies: long-term stable, individually distinct anti-A IgG spectrotypes.

Spectrotypes of naturally occurring IgG antibodies to histo-blood group substance A were analyzed by isoelectric focusing and a newly developed, non-radioactive affinity immunoblotting assay. Specificity was tested by preabsorption of sera on red blood cells and on four different types of blood group substance A. Clonotype-banding patterns of sera from 18 different blood donors were individually distinct, most of them showing an oligoclonal pattern with less than 15 visible bands. To analyze the influence of IgG subclass composition on spectrotype patterns, IgG subclasses were measured by ABO enzyme-linked immunosorbent assay (ELISA) and were shown to be mostly IgG1 and IgG2. Anti-A IgG1 spectrotypes could be detected with four sera and were also individually distinct. A series of six and seven serum samples, respectively from two donors was used to analyze the time-related changes of anti-A IgG spectrotypes. Banding pattern of both individuals remained stable during the whole observation period of 167 and 82 days, respectively, and no differences between follow-up samples could be detected. This long-term stability of individual anti-A IgG spectrotypes is backed by constant serum levels of anti-A IgG and -IgM antibodies during the observation period as measured by ABO ELISA.

ABO Blood-Group System↗
PubMed1992

Self tolerance to human A and B histo-blood group antigens exists at the B cell level and cannot be broken by potent polyclonal B cell activation in vitro.

It is generally considered that tolerance to self antigens is less complete in B than in T lymphocytes. However, B cell tolerance through either functional inactivation (anergy) or clonal deletion has been demonstrated in transgenic mice. In the present study, we investigated whether B cells specific for self A/B histo-blood group antigens can be detected in normal humans. It is a key feature of the ABO system that all normal individuals make natural antibodies against those A or B carbohydrates which are not present in their organism. To detect B cells by the limiting dilution approach we used a specific enzyme-linked immunosorbent assay for the quantitation of anti-A/B antibodies, and a culture system in which polyclonal B cell activation occurs through cell contact with EL4 thymoma cells. As was reported for other B cell studies, we frequently detected "polyreactive" immunoglobulin (Ig)M (but not IgG) with apparent autoreactivity but of uncertain significance regarding physiologic conditions. However, A- or B-specific B cell responses occurred with selective patterns in agreement with classical blood group serology in 14 individuals with A, B, AB or 0 blood group phenotypes: 1/11,600 B cells made anti-allo A/B IgM and 1/26,500 B cells such as IgG, while only 1/104,000 B cells apparently made anti-self A/B IgM and 1/350,000 B cells such as IgG. This shows self tolerance at the B cell level. Since anergy of B cells can frequently be broken by polyclonal B cell activation in vitro, and EL4 cells are potent B cell stimulators, the present results argue for either a highly resistant anergic state or for clonal deletion of self-A/B histo-blood group-specific human B cells.

ABO Blood-Group System↗
PubMed1992

Influence of the cryoprotective agents glycerol and hydroxyethyl starch on red blood cell ATP and 2,3-diphosphoglyceric acid levels.

Because hydroxyethyl starch (HAES) is used for volume replacement therapy and as a cryoprotectant for frozen red blood cells (RBCs), this compound, in contrast to glycerol, does not require labor-intensive removal from thawed cells prior to transfusion. We here report the effect of both glycerol and HAES on the RBC organic phosphates ATP and 2,3-diphosphoglyceric acid (2,3-DPG). The CPD-A1-stabilized RBCs of 20 healthy donors (3 females, 17 males) were separately frozen in either 40% glycerol or 6% HAES, of molecular weight 200,000. ATP and 2,3-DPG concentrations were determined in CPD-A1 RBCs before addition of cryoprotectant and in cryopreserved thawed RBCs after 24 h storage at -80 degrees C (glycerol) and -196 degrees C (HAES). It appears that HAES, but not glycerol, significantly reduces ATP concentrations whereas both lead to a reduction of 2,3-DPG concentrations; this reduction was more pronounced with glycerol than with HAES. Experiments with the blood of 6 donors demonstrated that HAES affects autohemolysis by 16%, in contrast to glycerol, after which cryoprotectant autohemolysis was affected by 3.1% only. RBC recoveries were comparable using glycerol or HAES as cryoprotectants. A distinct pattern of reduction of 2,3-DPG levels by glycerol and less by HAES, and of ATP levels by HAES but not by glycerol, emerges. Our findings may be of importance if HAES is to be introduced as a convenient cryoprotectant.

2,3-Diphosphoglycerate↗
PubMed1991

Antibodies to histo-blood group substances A and B: agglutination titers, Ig class, and IgG subclasses in healthy persons of different age categories.

Isotypes and IgG subclasses of ABO antibodies from sera of 235 healthy blood donors were determined by an enzyme-linked immunosorbent assay (ELISA). Synthetic A and B trisaccharide-bovine serum albumin glycoconjugates were used for coating and monoclonal antibodies for the detection of heavy chain isotypes. Hemagglutination titers were determined in addition. Blood donors were between 20 and 67 years old, and at least 10 sera per 10-year age category and ABO blood group were included in this study. Antibody concentrations were expressed as a percentage of an internal standard, and sera with subclass-restricted anti-A and/or anti-B (anti-A/B) responses were used to normalize the ELISA values of IgG subclasses. A good correlation between the sum of the four subclasses and the total anti-A/B IgG values (rs = 0.81 for anti-A and 0.84 for anti-B) was obtained. IgG1 and IgG2 were the most predominant subclasses, but were found in various proportions in different individuals. Donor-to-donor variation exceeded age-related changes for all measured parameters. The correlation of anti-A IgM, IgG, IgA, and their sum with the agglutination titers was significant and revealed rs values of 0.70, 0.65, 0.65, and 0.80, respectively. For anti-B as well, the correlation of ELISA values with the agglutination titer was best when all three isotypes were added. We conclude that anti-A/B IgA, together with IgM and IgG, substantially contributes to the agglutination reaction. Potentially autoreactive antibodies were detected in sera of blood groups A, B, and AB.

ABO Blood-Group System↗
PubMed1991

Defining the specificity of anti-A/B IgM/G antibodies with different antigens and lectins.

The specificity of anti-histo blood group A/B antibodies is defined by the antigen used for their production and selection (in the case of mouse monoclonal antibodies, mAbs) or by the antigens present on various intestinal bacteria (for polyclonal human IgM and/or IgG, phAbs). Absorption experiments with red blood cells and free antigen have been used earlier to define specificity; here we use A/B substances of human, animal and synthetic origin as well as known reactivities of mAbs or lectins as tools to further characterize epitope properties of the A/B antigens. The signal response patterns obtained with identical phAbs anti-A/B IgM/G on three different antigens are superposable. In contrast, commercially available mAb anti-A/B IgM, when tested on the same antigens, revealed different response curves. The chemical specificity of lectins for distinct monosaccharides in terminal position was exploited to delineate the specificity of mouse ascites anti-A IgG1 and of phAbs anti-A/B IgM/G. Helix pomatia lectin inhibited the access of MB9 to porcine A almost completely whereas binding capacities of human anti-A IgM/G were inhibited by 50 and 62%, respectively. In similar experiments Bandeiraea simplicifolia lectin was seen to inhibit access of anti-B IgM/G to horse B by 34 and 58%, respectively. No inhibition was seen with lectin from Ulex europaeus or concanavalin A on plates coated with the three different A or B substances. Thin-layer chromatography (TLC) of antigens revealed one spot for the synthetic trisaccharides, whereas the human and animal blood group substances showed 2 and 3 spots, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

ABO Blood-Group System↗
PubMed1991

Review on therapeutic options in HIV associated thrombocytopenia with emphasis on i.v. immunoglobulin treatment.

Thrombocytopenia as a complicating event in human immunodeficiency infection is a rather common hematological disorder and in many aspects resembles idiopathic(immune) thrombocytopenic purpura (ITP). Consequently, treatment of severe cases is similar to treating ITP, but steroids should be administered with particular caution in patients suffering from AIDS. Alternatives to steroids are considered in the present article with emphasis on intravenous immunoglobulin as a means to favourably influence the pathogenic events on the platelet surface.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Clinical significance of platelet-associated immunoglobulins in narcotic addicts with human immunodeficiency virus infection.

Increased amounts of platelet-associated immunoglobulin G (PAIgG) have been reported in human immunodeficiency virus (HIV)-infected patients with thrombocytopenia. We have prospectively investigated PAIgG in 21 asymptomatic (group A; CDC stages IIA-IIB) and 9 symptomatic (group B: CDC stages IIIB-IV) HIV-infected narcotic addicts. In both groups only two subjects presented with a decreased platelet count. By competitive ELISA, we found a 1.8- and 2.3-fold greater total PAIgG (PAIgGtot) as measured on platelet lysates in group A and B, respectively; surface-bound IgG (PAIgGsurf) as measured on intact platelets was 2.5- and 3.0-fold greater in groups A and B, respectively, as compared to 36 controls. The ratio between PAIgGtot and PAIgGsurf was lower in HIV-infected addicts when compared to controls (P less than 0.05). This indicates that platelets from HIV-infected subjects not only have increased surface and internal pools of PAIgG, but also present with a distribution between these two pools that differs from that of normal platelets. In addition, levels of circulating immune complexes (CIC) were abnormally raised in 17/21 (81%) subjects of group A in 6/9 (66%) subjects of group B.

Adult↗
PubMed1990

Effect of IgG for intravenous use on Fc receptor-mediated phagocytosis by human monocytes.

Polyspecific IgG given intravenously at high doses (IVIG) is used for immunomodulatory therapy in autoimmune diseases such as idiopathic thrombocytopenic purpura and myasthenia gravis. It is assumed that the clinical effect is brought about in part by a modulation of mononuclear phagocyte function, in particular by an inhibition of Fc receptor (FcR) mediated phagocytosis. In the present study, the effect of IVIG on FcR-mediated phagocytosis by monocytes was analysed in vitro. Since monocytes exposed to minute amounts of surface-bound IgG displayed impaired phagocytosis of IgG-coated erythrocytes (EA), the effect of IVIG was studied with mononuclear cells suspended in teflon bags in medium containing 10% autologous serum and IVIG (2-10 mg/ml). Monocytes pre-exposed to IVIG and then washed, displayed impaired ingestion of EA when compared with control cells cultured in 10% autologous serum only. The decrease in phagocytosis was observed with sheep erythrocytes treated with either rabbit IgG or bovine IgG1 and with anti-D-treated human erythrocytes. This suggests that phagocytosis via both FcR type I (FcRI) and type II (FcRII) was decreased. The impairment of phagocytosis was dependent on the presence of intact IgG and was mediated by IVIG from nulliparous donors and from multigravidae to the same extent, suggesting that alloantibodies contained in IVIG have a minor role in modulating FcR-mediated phagocytosis by monocytes. A flow cytometric analysis using anti-FcRI, FcRII and FcRII monoclonal antibodies showed that IVIG treatment upregulated FcRI expression but did not significantly alter the expression of FcRII and FcRIII.

Animals↗