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Biomedical subjects

B Teisner

Publications and source records attributed to B Teisner.

At least 55 records · Page 3Linked to original sources

Activation of classical pathway complement in chronic inflammation. Elevated levels of circulating C3d and C4d split products in rheumatoid arthritis and Crohn's disease.

Split products of complement component 3 (C3) and complement component 4 (C4) derived from activation of the alternative and classical complement pathways were measured in untreated outpatients, 20 with Crohn's disease and 19 with rheumatoid arthritis. Elevated levels of the d split product of C4 (C4d) were observed in 12 of 19 patients with rheumatoid arthritis and in 9 of 20 patients with Crohn's disease. Levels of the d split product of C3 (C3d) were increased in 14 of 19 patients with rheumatoid arthritis and in 6 of 20 Crohn's disease patients. The median values of C4d and C3d were significantly increased in both groups of patients. C3d concentrations correlated positively with C4d levels (rs = 0.51-0.56, p less than 0.005). The complement activation was not reflected in reduced plasma levels of native C3 and C4. The data indicate activation of the classical complement pathway in both rheumatoid arthritis and Crohn's disease.

Adolescent

Measurements of hCG and PAPP-A in uncommon types of ectopic gestation.

Seven out of 54 women with ectopic gestation had uncommon features such as extra-tubal implantation or multiple intratubal pregnancy. Depressed levels (less than 10th centile) or apparent absence of circulating human chorionic gonadotrophin (hCG) and pregnancy-associated plasma protein A (PAPP-A) were seen respectively in 5 and 7 of 7 women studied. Normal levels of hCG were seen in two women, one with an abdominal and one with an angular pregnancy. These data suggest that the synthesis of placental proteins in ectopic pregnancies is independent of the site of implantation and the number of embryos. Measurements of maternal levels of the 2 placental proteins seem to be applicable as auxiliary diagnostic tests for ectopic pregnancy, regardless of the site of implantation.

Chorionic Gonadotropin

Bactericidal capacity against Neisseria meningitidis of normal human serum and sera with functional deficiencies of the third and eight complement factor.

The bactericidal capacity of serum with C3 deficiency secondary to circulating C3 nephritic factor, serum with C8 deficiency and normal human serum were assessed in vitro against Neisseria meningitidis groups A-C. Normal human serum and C8-deficient serum, originating from a 28-year-old male with two episodes of meningococcal meningitis, showed significant bactericidal capacity against meningococci groups A and B. Against group C meningococci the C8-deficient serum revealed significant bactericidal capacity, whereas normal human serum showed no bactericidal effect. Serum with C3 deficiency, obtained from a 16-year-old female with two episodes of meningococaemia, showed no bactericial effect against meningococci groups A-C. Incubation of normal human serum and C8-deficient serum with isolated nephritic factor resulted in C3 depletion and abolished the bactericidal effect.

Adolescent

Heterogeneity of C4d and C3d and their complex formation with serum albumin.

High molecular weight (Mr around 175 KD) forms of C4d and C3d as well as free C4d and C3d (Mr about 40 KD) were demonstrable in normal human serum (NHS). Following in vitro C activation in NHS by delta IgG, the 40 KD C4d component increased markedly. By immunofixation it was shown that the high molecular forms of C4d and C3d reacted with biotinylated anti-human albumin IgG, whereas the 40 KD-free C4d and C3d fragments did not. Furthermore, the incorporation of anti-albumin IgG in the first dimensional gel in crossed immunoelectrophoresis caused retention of the 175 KD C4d component but not of free C4d. The 175 KD C4d had a distinctly higher electrophoretic migration velocity (post-albumin region) than the 40 KD C4d fragment. The C3d-, C4d-serum albumin complexes could not be dissociated by reducing agents (DTT, mercaptoethanol), a non-ionic detergent, or exposure to high and low ionic strength.

Complement Activation

Production of pregnancy-associated plasma protein-A (PAPP-A) by cultured tumour granulosa cells.

Ten ovarian and 2 cervical tumour cell lines were analysed for the production of pregnancy-associated proteins. Pregnancy-associated plasma protein-A (PAPP-A) was detected by radioimmunoassay in culture media of 2 out of 4 (50%) tumour granulosa cell lines (mean = 104 microIU/10(5) cells/24 h) but not in any ovarian (n = 6) or cervical (n = 2) tumour cell lines. By contrast, human chorionic gonadotrophin (hCG), pregnancy specific beta 1-glycoprotein and alpha-fetoprotein (AFP) were not detected in any of the PAPP-A positive media. Only two cell lines produced hCG (58.5 and 25.5 mIU/10(5) cells/24 h). No AFP was produced by any of these 12 cell lines, whereas placental protein 5 was positive in 7. None of these proteins were detected in the culture media of 4 cell lines. In vitro derived PAPP-A was immunologically indistinguishable from either pregnancy or ovarian follicular PAPP-A. All PAPP-A species interacted reversibly with immobilised heparin and were determined by molecular sieve chromatography to have an apparent molecular weight of 820,000 daltons. Cultured tumour granulosa cells specifically synthesised and secreted a large protein which was immunologically and physicochemically indistinguishable from in vivo (pregnancy and ovarian follicular) derived PAPP-A.

Female

Placental proteins in peripheral blood and tissues of ectopic pregnancies.

Circulating human chorionic gonadotrophin (hCG), Schwangerschaftsprotein 1 (SP-1) and pregnancy-associated plasma protein A (PAPP-A) were examined in 10 women with ectopic gestation in relation to distribution and intensity of staining for these molecules using immunohistochemical techniques applied to matched trophoblastic and decidualized endometrial tissues. All 10 women revealed strong staining for hCG and SP-1 in the syncytiotrophoblast, which was apparently unrelated to maternal levels of hCG and SP-1, levels being less than the 10th centile of the normal range in 9/10 and 7/10 women, respectively. By contrast maternal PAPP-A levels seemed to correlate with the intensity and the distribution of staining for PAPP-A. Circulating PAPP-A was undetectable (less than 5 mIU/l) in 4 patients, and below the 10th centile in the remaining 6. Using immunohistochemical techniques hCG, SP-1 and PAPP-A could not be demonstrated in any of the decidualized endometrial tissues studied.

Chorionic Gonadotropin

Immune complexes and complement activation following rupture of intracranial saccular aneurysms.

Circulating immune complexes (CIC) and complement activation (plasma C3d levels) were monitored during a 2-week period in patients with ruptured cerebral aneurysms and also in patients with cerebral hematoma unrelated to saccular aneurysms. Thirteen of 18 aneurysm patients were found to have CIC on admission as compared to three of 21 healthy blood donors (p less than 0.001). The presence of CIC in aneurysm patients was associated with a poor prognosis. Eight of nine patients who developed angiographic vasospasm had CIC on admission compared with one of four without vasospasm. Patients with vasospasm showed a twofold increase in plasma C3d levels at the time when the spasm occurred, whereas no significant changes in the C3d concentration could be demonstrated in aneurysm patients without spasm or in patients with hematoma unrelated to aneurysm rupture. These findings suggest that immunological processes involving complement-activating immune complexes are involved in the pathogenesis of cerebral vasospasm following rupture of saccular aneurysms.

Adult

Screening for complement deficiencies in unselected patients with meningitis.

Two hundred and nine patients consecutively admitted to hospital with a tentative diagnosis of meningitis were screened for complement deficiency by measuring classical and alternative pathway serum haemolytic complement activity and the plasma concentration of C3d. Abnormal test results were followed up by quantitative immunochemical measurements of individual complement components. No patients with homozygous complement deficiency were found in our material. One patient with pneumococcal meningitis with probable heterozygous C2-deficiency was identified. Patients with purulent meningitis of various etiologies or meningococcal disease had significantly increased plasma C3d concentration at admission compared to patients with serous meningitis or without meningitis. Furthermore, increased plasma level of C3d at admission in patients with purulent meningitis or meningococcal disease was associated with an increased lethality. Our findings do not support the hypothesis that complement deficiency is commonly associated with sporadically occurring meningococcal disease or purulent meningitis.

Adolescent

Measurement of C3 conversion by ELISA estimation of neo-determinants on the C3d moiety.

An ELISA assay estimating neo-determinants on the C3d moiety is described. The C3d neo-determinants were detected by incubating the sample on F(ab')2 anti-C3d-coated plates followed by development with biotin-labelled anti-C3d and enzyme-labelled avidin. The assay was compared with rocket immunoelectrophoresis (IE) and crossed IE. Serum from a factor I deficient patient showed no detectable C3d when analysed by rocket IE, but activation was evident when analysing by crossed IE or ELISA. The results suggest that the neo-determinants detected by ELISA become exposed when C3 is split into C3a and C3b and this interpretation was supported by kinetic analysis of C3 activation by the three methods.

Complement Activation

Immunohistochemical aspects of immunological cross-reaction and masking of epitopes for localization studies on pregnancy-associated plasma protein A.

The influence of antibody absorption procedures and proteolytic pre-treatment of formaldehyde-fixed placental tissue on the localization of pregnancy-associated plasma protein A by immunoperoxidase technique was examined. Apparently monospecific IgG fraction of the anti-plasma protein applied directly on fixed tissue resulted in staining of connective tissue and a thin apical rim of the syncytiotrophoblast. Further absorption of the antibody with foetal connective tissue abolished this staining reaction. Pre-treatment of the fixed placental tissue with trypsin prior to application of the antibody, which had been absorbed with connective tissue, resulted in staining within the cytoplasm of the syncytiotrophoblast exclusively. Identical staining was seen when this IgG preparation was used directly on frozen placental tissue. The results point to the importance of the specificity of the antibody preparations and of proteolytic unmasking of epitopes when fixed tissues are used for localization studies of pregnancy-associated plasma protein A by immunoperoxidase technique.

Epitopes

A family with complement factor I deficiency.

A family with inherited factor I deficiency is described. The proband was a 19-year-old Caucasian female with one episode of meningococcal meningitis and one episode of suspected septicaemia of unknown cause. Two obligate and two probable heterozygotes with factor I levels below the lower limit of the reference range were identified. None of these exhibited increased susceptibility to infectious diseases. The inheritance was autosomal codominant. In addition, molecular heterogeneity of factor H in plasma from the proband but not from any other family members was demonstrated by crossed immunoelectrophoresis. The migration of factor H component of fast electrophoretic mobility was retarded by antibodies to C3c and C3d, suggesting the presence of a fluid-phase complex between factor H and excess C3b generated by the uncontrolled activity of the amplification loop.

Adult

Comparison of different antibody preparations against pregnancy-associated plasma protein-A (PAPP-A) for use in localization and immunoassay studies.

Four antibody preparations against pregnancy-associated plasma protein (PAPP-A) were compared in order to find an explanation for the contradictory results published on tissue localization, clinical usefulness and biological function of PAPP-A. One of the preparations studied was a rabbit anti-PAPP-A antiserum which has been offered for general scientific use (Bischof et al. 1979). Only the IgG fraction of anti-PAPP-A antisera which appeared to be monospecific and had been further absorbed with fetal connective tissue gave specific uniform staining of the cytoplasm of the syncytiotrophoblast exclusively. Circulating PAPP-A could not be detected by RIA employing this IgG preparation in the non-pregnant state, or before 18 days after conception. Circulating PAPP-A could be detected in all seven pregnant women studied within 4 weeks after conception. Identical results were obtained with a commercially available IgG fraction against PAPP-A.

Animals

Relationship between levels of rheumatoid factor isotypes and complement component C3 conversion in blood from patients with rheumatoid arthritis.

Conversion of complement component C3 in plasma from rheumatoid arthritis patients was measured by two different methods. One of the methods gives an estimation of C3 conversion by ELISA measurement of neodeterminants present on the C3d moiety; the other method measures C3 split products expressing D, but not C, epitopes by rocket immunoelectrophoresis (RIE) with intermediate anti-C3c gel. Results from 20 RA patients obtained by the two methods did not correlate significantly (R = 0.52, 0.02 less than p less than 0.05). The results were compared to the level of rheumatoid factors (RFs) of IgG, IgM, and IgA class in serum. A significant correlation was found between the concentration of C3d measured by RIE and level of IgG RFs, whereas neither IgM nor IgA RFs showed correlation to complement activation. The results of the ELISA estimation of C3 activation showed no correlation with the RF level.

Arthritis, Rheumatoid

Quantitative comparison of circulating immune complexes in normal pregnancy and pregnancy related hypertension.

Using two different Clq-dependent assays for quantification of circulating immune complexes (CIC), the levels were compared in sera from 32 women with pregnancy-related hypertension and in sera of 32 matched controls. No difference in the CIC levels was observed. The levels of CIC in the hypertensive patients were not correlated to placental weight, fetal weight, or diastolic blood pressure.

Antigen-Antibody Complex

Circadian and diurnal variation of circulating immune complexes, complement-mediated solubilization, and the complement split product C3d in rheumatoid arthritis.

Nine patients with active classical rheumatoid arthritis (ARA criteria) were studied with reference to circadian variation of immunological and clinical parameters. Complement-mediated solubilization (CMS) of immune complexes (IC) and the level of circulating IC were found to be inversely related with low CMS and increased IC levels in the morning, and vice versa in the afternoon. Bed rest and exercise did not influence these fluctuations. The C3d concentration in plasma was increased but showed no diurnal or circadian periodic fluctuations when the levels were corrected for fluctuations in plasma albumin concentration. Clinical assessment by means of pain score exhibited marked variations, with high scores in the morning, and lower in the daytime, whereas measurements of Ritchie's joint index showed no consistent pattern. The circadian variations in CMS, serum IC and clinical parameters indicate the need to collect blood specimens and perform clinical examinations of patients at a fixed time of day.

Adult