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Biomedical subjects

O Tönder

Publications and source records attributed to O Tönder.

At least 19 recordsLinked to original sources

Plasma exchange in myasthenia gravis: changes in serum complement and immunoglobulins.

Serum concentrations of C4, IgG, IgA, and IgM were followed in 8 selected patients with myasthenia gravis (MG) during a 5-day course of plasma exchange (PE), using donor plasma as a replacement solution. C3 activation products (C3b, iC3b and C3c) and the terminal SC5b-9 complement complex were measured in 4 of the patients. All patients improved during the treatment, including 2 patients without detectable antibodies to AChR in serum. The main findings of the study were marked complement activation and an approximately 50% fall in the serum concentrations of IgM and C4 during PE, independent of the concentrations in the donor plasma. The concentrations of IgG and IgA did not change significantly. The fall in C4 during PE is presumably caused by C4 consumption. We postulate that the fall in IgM is an effect of a complement-induced vasodilatation and that PE-induced complement consumption may influence the effect of PE in patients with MG.

Adult

Plasma exchange in myasthenia gravis: effect on anti-AChR antibodies and other autoantibodies.

Plasma exchange (PE) was performed in 6 patients with myasthenia gravis (MG). Acetylcholine receptor (AChR) antibodies and other MG-correlated antibodies were quantified each day before, during and after PE. The antibody concentrations decreased during PE with a consisting increase between two exchanges. Repeated PE induced a transient decline in the AChR antibody concentration. The clinical improvement was maximal during the week after PE and correlated in time with increasing concentrations of AChR antibodies.

Adult

Hassall's corpuscles in the thymus of fetuses, infants and children: immunological and histochemical aspects.

Hassall's corpuscles (HC) were examined for immunological and histochemical markers in cryostat sections of thymus from fetuses, infants and children. HC could not be detected before 14 weeks of gestation. Receptors for the Fc part of IgG (Fc gamma R) were demonstrated by adherence of ox erythrocytes sensitized with anti-ox IgG using a closed chamber technique. Fc gamma R were also detected by immune complexes of horseradish peroxidase (HRP) and rabbit antibodies to HRP, and with an anti-Fc gamma R serum, using indirect immunofluorescence technique and indirect immunoperoxidase technique. The staining was seen along the outer cell membranes of the HC. The Fc gamma R activity was highest in early fetal life, and decreased with increasing age. Indicator cells which detect receptors for the Fc part of IgM and for the activated third component of complement did not adhere to HC. At 14 weeks of gestation, HC showed a weak alpha-naphthyl acetate esterase (ANAE) activity, while from 16 weeks the staining intensity and pattern was unchanged. In some HC, separate cells with strong ANAE activity were seen. These cells also showed endogenous peroxidase activity, and were stained by an antibody to HLA-DR antigens. Such cells were not seen until 16 weeks of gestation. HC were stained by antibodies to IgG in fetuses older than 16 weeks, and the intensity increased gradually up to 24 weeks. Antibodies to IgM weakly stained some HC in fetuses between 16 and 36 weeks of gestation, whereas antibodies to IgA stained a minority of HC in fetuses older than 24 weeks.

Age Factors

Lymphocyte subpopulations in thymus and blood from patients with myasthenia gravis.

Cell suspensions were prepared from hyperplastic thymic tissue and lymphoepithelioma from patients with myasthenia gravis and from presumed normal thymic tissue obtained at cardiac surgery. The mononuclear cells were examined for surface markers. The mean percentages of both T lymphocytes and Fc receptor-carrying lymphocytes were similar in the three groups, whereas there was an increase in C receptor-carrying lymphocytes in the samples from myasthenic patients. Sections from the thymus gland were examined for T and B markers. In the hyperplastic thymus and in lymphoepithelioma, the T lymphocytes were distributed diffusely throughout the cortex and the medulla; in the normal thymus they were predominant in the cortex. The mean percentage of T and B lymphocytes in peripheral blood from patients with myasthenia gravis was normal. Thymectomy involved a transitory decrease in T lymphocytes with a corresponding increase in B lymphocytes.

B-Lymphocytes

Complement receptors in human peripheral nerve tissue.

Cryostat sections of human peripheral nerve tissue adsorbed sheep erythrocytes sensitized with antibody and human complement (EAC). Activated complement was essential for the reaction to occur. The receptor had specificity for the C3b fragment. In order to obrain binding to nerve tissue, the indicator cells had to be coated with more complement than that required for binding to C3b receptors in spleen and renal tissue. The receptors are located within the nerve fascicles and are probably of glycoprotein nature. The receptors for C3b in peripheral nerve tissus may be of significance in the deposition of immune complexes, which may play a role in acute polyradiculoneuritis.

Complement Activation

Natural and immune antibodies to rabbit erythrocyte antigens.

Natural agglutinins to rabbit erythrocytes were found in all human sera studied. In the newborn, the antibodies were of IgG class; in the 6-month-old infants they were mainly of IgM class. Older children and adults had both IgG and IgM antibodies. Agglutinins to rabbit erythrocytes were also found in serum from fourteen of fifteen other species studied. The trichloroacetic acid extract from rabbit erythrocyte stromata (TCA-preparation) contains at least three different antigenic determinants: one which we hitherto to have found only on rabbit erythrocytes, one which is closely related to human blood group B antigen, and one which is closely related to the I antigen. The TCA-preparation did not elicit delayed hypersensitivity skin reactions in humans in spite of high titred agglutinins in serum, but did so in immunized guinea-pigs.

Adolescent

Localization of Fc receptors in human and rat malignant tissues.

Three human malignant tumors and a rat carcinoma (Walker 256), which all showed strong Fc receptor activity in tests with sheep erythrocytes (E) sensitized with rabbit IgG antibodies (A), were used to study the distribution of the receptor in subcellular fractions isolated by differential centrifugation. Smears of the three crude sediments obtained (nuclei, mitochondria rich and membrane rich) all possessed receptor activity. EA incubated in the suspension of cell fractions did not attach to Fc receptor positive tissue sections or to cells in suspension. Cells from which the surface receptors had been eluted still showed activity in sections of cell pellets. Apparently the Fc activity is connected with both external and internal membranes.

Adsorption

Evidence for non-specifically bound IgG in human tumours.

Heat eluates of homogenized human malignant and normal tissues were prepared using the continuous flow elution technique. IgG antibodies to rabbit erythrocytes served as marker antibodies for non-specifically bound IgG. Eluates of all of the 13 malignant tumours tested contained IgG. Most were eluted at 56C, but considerable amounts also at 37C and 45C. Marker antibodies were present in eluates of 4 of the tumours, indicating that at least parts of the IgG associated with malignant human tumours are non-specifically bound. Eight tumours contained too little IgG to detect marker antibodies, and one contained high amounts of IgG without marker antibodies. Eluates of normal organs contained either no or only small amounts of IgG, although apparently normal kidneys from older individuals contained some more IgG. Marker antibodies were detected in some of the eluates indicating non-specific binding.

Adult

Agglutinins to rabbit erythrocytes in extracts of human malignant tissues.

Agglutinins to rabbit erythrocytes in extracts from human malignant tissues were identified as the naturally occurring IgG antibodies in human serum to rabbit erythrocytes. This was revealed by agglutination, absorption, antiglobulin and inhibition tests, immunization of rabbits and immunochemical analyses. The agglutinins can therefore be used as convenient markers for both extracellular immunoglobulin and unspecifically bound immunoglobulin in tumour tissues. Apparently the extracts also contained small amounts of IgA antibodies to rabbit erythrocytes.

Agglutination Tests

Properties of Fcgamma receptors in normal and malignant human tissues.

Properties of the IgG receptors were studied by treating tissue sections or suspensions of peripheral mononuclear cells with various chemical reagents and determining changes in their ability to react with IgG-sensitized erythrocytes (EA). A heterogeneity of the Fc receptors was revealed. Iodoacetamide, 2-mercaptoethanol, sodium azide, EDTA, and a pH varying from 6.0 to 8.2 had no effect on Fc receptors in sections of normal lymphoreticular tissue and malignant tissue. Formaldehyde, low pH, and high salt concentrations affected receptor activity to various degrees. Receptors in liver sections and on monocytes were generally more resistant than receptors in spleen sections and on B lymphocytes. Receptors in malignant tissue behaved either like receptors in spleen or like receptors in liver. Although all tissues were sensitive to periodic acid, the Fc receptors in malignant tissue were always more resistant.

Azides

Complement receptors in human renal glomeruli.

Glomeruli in Cryostat sections of foetal and adult renal tissues adsorbed sheep erythrocytes sensitized with IgM antibody and human or mouse complement (EAC). Activated complement was essential for the reaction to occur. The receptor had specificity for the C3b fragment of C3 and is probably of protein or glycoprotein nature. Complement receptors in glomeruli may explain the deposition of complement components or complement-containing complexes in immune-complex glomerulonephritis.

Animals

Human agglutinins to rabbit erythrocytes. Characterization of an antigen.

Crude preparations inhibiting the agglutination of rabbit erythrocytes by pooled human serum were obtained by extraction of erythrocyte stromata with various solvents (chloroform/methanol, trichloroacetic acid, and so forth). Highest inhibiting activity was found in a preparation containing sphingoglycolipid; 0.8 mug inhibited 2 agglutinating units of serum. The active preparations retained their activity after 5 min of incubation in a boiling water bath and after treatment with proteolytic enzymes or neuraminidase. Treatment with periodate abolished the activity. The antigenic site is therefore probably determined by the sugars of the sphingoglycolipid.

Agglutination Tests

Tumor Fc receptors and tumor-associated immunoglobulins.

Tissue sections and cell suspensions from ten malignant tumors were tested for Fc receptors using sheep erythrocytes sensitized by rabbit IgG antibodies. Surface bound IgG on cells from the same tumors were estimated using an antiglobulin consumption test with 125I labelled human IgG as reference. The amount of IgG present per 10(6) cells varied from less than 100 ng to approximately 600 ng. When these amounts of IgG were plotted against the Fc receptor activity of corresponding tumors, seven of the tumors were distributed along a line showing an inverse linear relationship; i.e. tumors with large amounts of IgG on their cell surfaces had the lowest Fc reactivity and vice versa. Cells from three of the tumors had lower amounts of IgG on their surface than expected from this relationship. However, the lack of correlation could be explained by the focal distribution of the Fc positive tissue within non-reactive tissue. The cells from these areas presumably carry less IgG on their surface and thereby reduce the quantity of IgG calculated per 10(6) cells. Prolonged washing of tumor sections resulted in stronger Fc receptor activity, and correspondingly washed cells had lower amount of IgG on their surface. Presumably the Fc receptor can bind IgG in vivo.

Animals

Immunological and histological studies of temporal arteries from patients with temporal arteritis and/or polymyalgia rheumatica.

Biopsies from the temporal arteries of 62 out of 80 patients presenting the clinical picture of temporal arteritis and/or polymyalgia rheumatica showed morphologically active or healed arteritis. Fifty-five of these biopsies revealed anti-IgG activity as measured by the mixed agglutination test. In 21 of the 27 cases which could be completely studied, the anti-IgG activity was connected with the presence of IgA, either alone, or together with IgG or IgM, or both, and complement. All of these 21 biopsies showed morphologically active granulomatous arteritis with signs of tissue destruction. In 6 biopsies, the active component appeared to be some type of Fc receptor in the tissue. Morphologically these biopsies showed either non-granulomatous mononuclear arteritis without definite necrosis or they represented various stages of healing arteritis with no or minor signs of tissue destruction. Weak anti-IgG activity was often found in a morphological type characterized by minimal inflammatory activity. These lesions are easily overlooked and the mixed agglutination test proved to be a good diagnostic tool in such cases. Arteries without anti-IgG activity showed no signs of active arteritis.

Antibodies, Anti-Idiotypic

Effect of antiepileptic drugs on serum and salivary IgA.

IgA, IgG, and IgM concentrations were determined in sera from 100 patients under treatment for epilepsy for at least 6 months. Low IgA was found in 25% of adult sera and in an even larger percentage of sera from children. IgM concentrations were also low, whereas there was no significant difference in the IgG concentrations compared with normal sera. IgA values were normal in untreated patients but fell during treatment with phenytoin, in one patient from 1.5 to 0.2 mg/ml within 2 months. Low or undetectable salivary IgA was a common finding, especially in gingival hyperplasia.

Adolescent

Fc receptors in human placenta.

Cryostat sections of placental tissue strongly adsorbed erythrocytes sensitized with IgG antibodies of human, rabbit, and guinea pig origin. No adsorption occurred using erythrocytes sensitized with F(ab')2 fragments. The reaction was strongly inhibited by intact IgG and by Fc fragments, weakly inhibited by pFc' fragments, and not inhibited by Facb and F(ab')2 or albumin. These properties are similar to those of corresponding receptors in normal lymphoid tissues. Results obtained with sections of hydatidiform mole showed that the reaction occurred with the trophoblastic tissue. Porcine placenta had no Fc receptor activity. The presence of an Fc receptor in human placental tissue may therefore be of significance for the selective transfer of IgG from mother to foetus.

Animals

Natural antibodies in human cerebrospinal fluid to rabbit erythrocytes.

With an indirect agglutination technique using rabbit antisera to human immunoglobulin, IgG antibodies to rabbit erythrocytes were detected in 211 of 221 unconcentrated cerebrospinal fluids from patients with diseases of the nervous system and controls. The titres varied from 0.25 to 128. The highest titre in the control group was 4, the geometric mean 1.5. The titres were highest in the groups with elevated total protein, for instance inflammatory diseases with mean titre of 9.25. The titre divided by total protein concentration did not vary much in the different groups, but tended to be higher than controls in multiple sclerosis, inflammatory diseases and vascular brain lesions, and lower in the other groups. It did not increase parallel to IgG in multiple sclerosis and inflammatory diseases.

Animals

Binding of normal human IgG to myelin sheaths, glia and neurons.

The binding of normal human serum, purified IgG and IgG fragments to central nervous tissue was studied by the anti-globulin consumption (AGCT) and immunofluorescence (IF) techniques. In the AGCT, F(ab')2 fragments failed to react, whereas IgG and Fc fragments did so. In IF experiments, the binding was localized to myelin sheaths, glia and neurons; Fab monomers at a protein concentration of 1-3 mg/ml dod not react with the tissue, but purified Fc fragments at 0-0625 mg/ml did. The binding is neither tissue- nor species-specific. Lipid and protein extraction procedures indicated that the factor responsible for binding to myelin was basic protein. It was concluded that the binding of normal IgG to central nervous tissue is medicated by the Fc part of the molecule.

Animals